Palliative Network of Wisconsin Fast Facts

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Fast Facts Core Curriculum
Cancer Syndromes
#62 Early Diagnosis of Epidural Metastases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . 2-3
#135 Neoplastic
Meningitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . 4-5
#151 Hypercalcemia of Malignancy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . . .6-7
#157 Malignant Pleural Effusions: Interventional Management . . . . . . . . . . . . . . . . .

. . . . . . 8-9
#176 Evaluation of Malignant

Ascites . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .10-11
#177 Palliative Treatment of Malignant Ascites . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . 12-13
#209 Malignant Pericardial Effusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . . 14-15
#238 Management of Spinal Cord

Compression . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16-17
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FAST FACTS AND CONCEPTS #62

EARLY DIAGNOSIS OF EPIDURAL METASTASES
David E Weissman MD
Background Epidural metastases are very common in patients with advanced cancer. Cancers most
often associated with epidural spread include lung, prostate, breast, kidney, myeloma and melanoma.
They are also common in testicular cancer, lymphomas, and Hodgkin’s disease. Ovarian and pancreatic
cancer rarely lead to epidural metastases. Tumor reaches the epidural space via contiguous spread from
adjacent vertebral body metastases or, less commonly, from direct extension of tumor through the
intervertebral foramina from adjacent tissue (e.g. retroperitoneal lymphoma or posterior lung cancer).
The importance of early diagnosis Back pain is the herald symptom of epidural metastases; occurring,
on average, many weeks to months prior to any neurological damage. That is, pain occurs long before
there is any direct compression of the spinal cord, at a time when early diagnosis can be established and
treatment started. Neurological deficits from spinal cord compression are a late finding of epidural
metastases; serious damage is usually preventable by early diagnosis.
Characteristics of pain from epidural metastases Pain from epidural metastases occurs due to
vertebral body fracture, structural spine instability, periosteal or nerve root irritation. The various
descriptions of pain from epidural metastases are protean. Most commonly, patients say it is ‘dull’ or
‘aching,’ often with a sensation of ‘muscle spasm.’ Pain typically worsens gradually, so that over a period
of weeks patients require increasing analgesics and have a corresponding decrease in function. This is
in contrast to benign compression fractures, where severe pain occurs suddenly, followed by slow
improvement over weeks. If there is nerve root irritation, patients will describe neuropathic symptoms in
a radicular pattern (e.g. burning or shock-like pain, and/or dysesthesias). The pain is usually located in
the central back or paravertebral region and/or in a radicular distribution. Commonly missed radicular
symptoms are tip of shoulder pain from C7-T1 metastases; lateral or anterior rib pain from thoracic
metastases; anterior abdominal, flank or hip pain from T12-L2 metastases. Pain is often made worse by
increasing the spinal cord load that occurs with standing, coughing or valsalva. Pain in the thoracic
region is particularly worrisome due to the narrow spinal canal and minimal epidural space; patients with
thoracic metastases often complain of increasing pain when recumbant.
Diagnostic strategies The key to early diagnosis is a high index of suspicion. A good rule to use is
that the cancer patient with progressive back or radicular pain, for more than 1-2 weeks, has epidural
metastases unless proven otherwise; this is especially true in the high risk cancers (breast, prostate, lung,
myeloma). Various protocols describing diagnostic approaches have been developed to aid clinicians
(see references); all agree that in the setting of a normal neurological examination, early radiological
imaging is essential for diagnosis and treatment planning. Rodichok et al demonstrated in 1981 that plain
spine x-rays, in the region of back pain, can be an excellent first screening tool; MRI is the definitive
diagnostic study and is necessary for planning radiation or surgical intervention. If neurological signs
have become evident, emergent MRI is the diagnostic test of choice.
Summary/Key Teaching Points:
• Epidural metastases (tumor in the epidural space), occurs prior to actual spinal cord compression
and neurological damage.
• Pain will precede neurologic deficits by weeks to months.
• Early diagnosis will preserve neurological function.
• Progressive back or radicular pain is an indication for radiographic investigation to rule out epidural
metastases, especially in high risk cancers.
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References
1. Schmidt MH, Klimo P Jr, Vrionis FD. Metastatic spinal cord compression. J Natl Comp Cancer
Network. 2005; 3(5):711-9.
2. Byrne TN. Spinal cord compression from epidural metastases. NEJM. 1992; 3217:614-619.
3. Rodichok LD, Harper GR, Ruckdeschel JC. Early diagnosis of spinal epidural metastases. Am J
Med. 1981; 70:1181-1188.
4. Posner JB. Neurologic complications of cancer. Contemporary Neurology Series, Vol 45.
Philadelphia, PA: FA Davis; 1995.
Version History: This Fast Fact was originally edited by David E Weissman MD. 2nd Edition published
July 2006; 3rd Edition May 2015. Current version re-copy-edited April 2009; then again May 2015.
Fast Facts and Concepts are edited by Sean Marks MD (Medical College of Wisconsin) and associate
editor Drew A Rosielle MD (University of Minnesota Medical School), with the generous support of a
volunteer peer-review editorial board, and are made available online by the Palliative Care Network of
Wisconsin (PCNOW); the authors of each individual Fast Fact are solely responsible for that Fast Fact’s
content. The full set of Fast Facts are available at Palliative Care Network of Wisconsin with contact
information, and how to reference Fast Facts.
Copyright: All Fast Facts and Concepts are published under a Creative Commons Attribution-
NonCommercial 4.0 International Copyright (http://creativecommons.org/licenses/by-nc/4.0/). Fast Facts
can only be copied and distributed for non-commercial, educational purposes. If you adapt or distribute a
Fast Fact, let us know!
Disclaimer: Fast Facts and Concepts provide educational information for health care professionals. This
information is not medical advice. Fast Facts are not continually updated, and new safety information may
emerge after a Fast Fact is published. Health care providers should always exercise their own
independent clinical judgment and consult other relevant and up-to-date experts and resources. Some
Fast Facts cite the use of a product in a dosage, for an indication, or in a manner other than that
recommended in the product labeling. Accordingly, the official prescribing information should be consulted
before any such product is used.
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NEOPLASTIC MENINGITIS
Fareeha Siddiqui MD, Lisa Marr MD, and David E Weissman MD
Background Neoplastic meningitis (NM) – also known as leptomeningeal metastases, meningeal

carcinomatosis, or leukemic meningitis, is a common oncologic complication representing spread of tumor
cells to the subarachnoid space (SAS). It is a complication which often portends a very short prognosis.
Epidemiology NM is found in 20% of cancer patients at autopsy. Among solid tumors, NM is common
in breast cancer, small cell lung cancer, and melanoma while rare in gastrointestinal and gynecologic
cancers. 90% of solid tumor patients with NM have widespread metastatic disease. NM is found in
40-50% of patients with hematological malignancies, mostly commonly the acute leukemias and high-
grade lymphomas (such as large cell and Burkitt lymphomas).
Signs/Symptoms Tumor reaches the SAS by hematogenous spread via arachnoid vessels or direct
invasion along nerve roots. Cancer cells in the subarachnoid space have the potential to: a) settle in
dependent portions of the neuraxis (base of brain/cranial nerves or lower spinal canal), b) grow into the
surface of the brain and fill the sulci, and c) block normal paths of cerebral spinal fluid (CSF) flow. Thus,
the hallmark of diagnosis is neurological signs/symptoms at more than one level of the neuraxis:
• Brain – headaches, nausea/vomiting, seizure, hydrocephalus.
• Cranial Nerves – diplopia, hearing loss, facial numbness, dysphagia, dysphonia.
• Spinal – radicular pain, weakness (usually legs), parenthesis, bladder and bowel dysfunction.
Diagnosis Lumbar puncture typically reveals a CSF profile of high opening pressure, low glucose, high
protein, and lymphocytic pleocytosis. Sensitivity for finding malignant cells is 50- 70% for one sample,
increasing to 80-90% with three samples. MRI can identify nodular/bulky areas of disease,
hydrocephalus, and/or enhancement of the cortex/tentorium if tumor growth along the sulci leads to
neovascularization. NM commonly causes abnormal CSF flow; this can be demonstrated by a
radionucleotide cisternogram.
Prognosis and Treatment Patients with breast cancer or hematological malignancies that have not
been extensively treated with chemotherapy, have a reasonable chance at remission of their CNS
disease if their systemic cancer can also be controlled. In contrast, patients with other cancers (e.g. lung,
melanoma) typically have a dismal prognosis (1-4 months) with or without treatment. In fact, the median
survival of patients who underwent placement of an implanted intraventricular reservoir (Ommaya
reservoir) for intrathecal chemotherapy administration was only 72 days in a multicenter retrospective
analysis. Unlike spinal cord compression or brain metastases, there is no accepted role for corticosteroids
except in lymphoid malignances. Treatment options include chemotherapy and/or radiation.
• Radiation: Either cranio-spinal irradiation (entire spinal column) or focused radiation therapy to
sites of bulky or symptomatic areas (e.g. cauda equina for radicular leg pain).
• Chemotherapy: Options include systemic high-dose chemotherapy (Ara-C or Methotrexate)
intrathecal chemotherapy (1-2 times per week) administered either by repeated lumbar puncture
or via repeated puncture of an Ommaya reservoir. Commonly used intrathecal drugs include
methotrexate or Ara-C.
Summary For many patients, NM represents a pre-terminal diagnosis and no anti-neoplastic therapy is
warranted. Establishing the diagnosis in such patients may be important to help prognosticate and to
anticipate future neurological problems (e.g. seizures, headache, radicular pain). The decision whether or
not to begin anti-neoplastic treatment should be made in consultation with a medical, radiation, or
neurooncologist.
References
1. Wasserstrom WR, Glass JP, Posner JB. Diagnosis and treatment of leptomeningeal metastases
from solid tumors. Cancer. 1982; 49:759-772.
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2. Grossman SA, Trupm DL, Chen ECP, Thopson G, Cargo EE. Cerebrospinal fluid flow
abnormalities in patients with neoplastic meningitis. Am J Med. 1982; 73:641-647.
3. Kaplan JG, DeSouza TG, Farkash A, et al. Leptomeningeal metastases: comparison of clinical
features and laboratory data of solid tumors, lymphomas and leukemias. J Neurooncol. 1990;
9:225-9.
4. Demopoulos A, et al. Leptomeningeal metastases: a review. Curr Neurol Neurosci Rep. 2004;
4(3):196-204.
5. Roguski M, Rughani A, et al. Survival following Ommaya reservoir placement for neoplastic
meningitis. Journal of clinical neuroscience. 2015; article in press.
Version History: This Fast Fact was originally edited by David E Weissman MD and published in April
2005. Version re-copy-edited in April 2009; edited again by Sean Marks MD July 2015 with reference #5
added and incorporated into the text.
volunteer peer-review editorial board, and are made available online by the Palliative Care Network
of Wisconsin (PCNOW); the authors of each individual Fast Fact are solely responsible for that Fast
Fact’s content. The full set of Fast Facts are available at Palliative Care Network of Wisconsin with
contact information, and how to reference Fast Facts.
NonCommercial 4.0 International Copyright (http://creativecommons.org/licenses/by-nc/4.0/).
Fast Facts can only be copied and distributed for non-commercial, educational purposes. If you adapt or
distribute a Fast Fact, let us know!
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!

HYPERCALCEMIA OF MALIGNANCY
Fareeha Siddiqui MD and David E Weissman MD
Background Up to 30 percent of patients with cancer develop hypercalcemia. Approximately 50% of
these patients will die within 30 days of a hypercalcemia diagnosis, even if the hypercalcemia is
corrected, which suggests that hypercalcemia is a sign of hormonally advanced cancer. It is most
commonly associated with squamous cell cancers of lung, head and neck, and esophagus, breast cancer,
renal cell carcinoma, lymphomas and multiple myeloma.
Pathophysiology
• Local osteolytic hypercalcemia due to direct effect of bone metastases.
• Humoral Hypercalcemia of Malignancy – secretion of parathyroid hormone related protein
(PTHrP) by malignant tumors.
• 1,25(OH)2D (vitamin D) secreting lymphomas.
• Ectopic secretion of authentic PTH (very rare).
Symptoms/Signs Symptoms roughly correlate with the degree of hypercalcemia (corrected) and the
rapidity of rise: Mild (10.5-11.9 mg/dl); Moderate (12-13.9 mg/dl) Severe(>14 mg/dl).
• Cognitive: sedation, delirium, coma.
• Gastrointestinal: anorexia, nausea, vomiting.
• Renal: dehydration, polyuria, thirst/polydipsia.
Diagnostics
• Total serum calcium, corrected for albumin (Formula: [(4 - albumin) x 0.8] + Ca++]).
• Ionized calcium.
• Renal function, phosphate, magnesium and potassium—monitor during treatment.
Anti-Tumor Therapy Treatment of the underlying malignancy with systemic therapy (e.g.
chemotherapy) is essential for long-term management. In cases where further anti-neoplastic therapy is
not feasible, the decision to treat or not treat hypercalcemia should be made by careful exploration of the
patient’s goals of care. In advanced untreatable cancer, the decision to not treat hypercalcemia may be
very appropriate.
Supportive measures
• Saline hydration and loop diuretics: Normal saline 200-500 ml/hr increases GFR, increases
filtered load of calcium, and is calciuretic. Loop diuretics (e.g. furosemide) blocks calcium
resorption in the loop of Henle. Note: only use diuretics once dehydration has been corrected.
• Discontinue medications that can increase serum calcium (e.g. lithium, Vitamin D, supplements
containing calcitriol, thiazides, calcium antacids); remove calcium from TPN.
• Increase mobility if possible.
• Bisphosphonates are the drug class of choice for most patients. They work via blocking
osteoclastic bone resorption. Pamidronate and zoledronic acid are used in the US with full
efficacy noted 2-4 days after administration; responses last 1-3 weeks. May lead to hypocalcemia
or azotemia; use with caution in renal dysfunction. Pamidronate = 60-90 mg. Repeat only after 7
days have elapsed after 1st dose. Repeat infusions every 2-3 weeks or longer according to the
degree and of severity of hypercalcemia. Zoledronic acid = 4 mg (maximum). Wait at least 7
days before considering retreatment.
• Denosumab is a human monoclonal antibody that is a potent inhibitor osteoclast mediated bone
resorption. In repeated studies, it has led to durable responses in over 60% of patients with
hypercalcemia refractory to bisphosphonates. Its cost may be prohibitive in hospice settings.
• Other Agents: Glucocorticoids are useful in lymphoid malignancies that secrete 1,25(OH)2
Vitamin D. Calcitonin may lead to transient and reductions in serum calcium (12-24 hours). It is
administered intramuscularly or subcutaneously; initially 4 units/kg every 12 hours; may increase
up to 8 units/kg every 12 hours to a maximum of every 6 hours. Mithramycin was the standard
agent prior to bisphosphonates; now it is used only rarely due to a higher side effect profile.
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Gallium nitrate is usually impractical due to the need for a 5 day IV infusion. Renal Dialysis can
be used in cases of acute/chronic renal failure.
Summary Hypercalcemia is a common oncologic complication that often portends a very short
prognosis. The decision to attempt reversal should be made after first exploring the goals of care and
assessing the feasibility of future systemic anti-cancer treatments. Vigorous hydration and
bisphosphonates are the cornerstones of short-term hypercalcemia therapy.
Reference
1. Stewart AF, et al. Malignancy-Associated Hypercalcemia. In: DeGroot L, et al, eds.
Endocrinology. 5th Edition. Philadelphia, PA: Saunders; 2005
2. Roodman GD, et al. Mechanisms of bone metastasis. NEJM. 2004; 350:1655-64.
3. Ralston SH, et al. Cancer associated hypercalcemia: morbidity and mortality: Clinical experience
in 126 treated patients. Ann Intern Med. 1990; 112:499-504.
4. Hu MI, Glezerman IG, et al. Denosumab for treatment of hypercalcemia of malignancy. J Clin
Endocrinol Metab 2014;99:3144-3152.
5. Gucalp R, Insogna K, et al. Denosumab For The Treatment Of Hypercalcemia Of Malignancy
Refractory To IV Bisphosphonates In Patients With Hematologic Malignancies. Blood 2013;122:
2536-2536.
Version History: This Fast Fact was originally edited by David E Weissman MD and published in
February 2006. Version re-copy-edited in April 2009; revised again by Sean Marks MD July 2015 with
references #4 and #5 added and incorporated into the text.

MALIGNANT PLEURAL EFFUSIONS: INTERVENTIONAL MANAGEMENT
Vincent Thai MD and Ron Damant MD
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Background Malignant pleural effusions can cause dyspnea, cough, and reduced exercise tolerance.
Over three quarters of malignant pleural effusions are due to lymphomas or cancers of the breast, lung,
and ovary. The average survival of patients with refractory cancer and pleural effusions is 4-6 months (1).
Survival is considerably worse for patients with poor functional status due to progressive cancer. This
Fast Fact reviews key facts regarding effusion management.
Symptom Causality and Goals of Care The cause of dyspnea, even in the presence of a known
malignant effusion, is not always evident. Common confounding problems include congestive heart
failure, chronic obstructive pulmonary disease, pulmonary emboli, pericardial effusions, parenchymal lung
metastases, ascites, and radiation lung injury. A ‘diagnostic’ therapeutic thoracentensis may be indicated
to determine if removal of fluid leads to an improvement in the patient’s dyspnea. The decision to
proceed with thoracentensis should be made after considering the overall goals of care, functional status,
prognosis, and presence of co-morbid conditions. Guidelines suggest that no more than 1.5 L of fluid can
be safely removed at any one time to prevent reexpansion edema, but some authors suggest that as
much as 20ml/kg of fluid can be safely removed (2).
Management Options:
• Repeated thoracentesis is appropriate for patients with a short prognosis (weeks). The re-
accumulation rate is approximately 98% by 30 days (3). Problems associated with this approach
include the need for repeated procedures, pneumothorax, infection, and the development of
loculation.
• Chest tube drainage alone involves the use of a large-bore tube to drain the pleural cavity
followed by the tube’s removal, without sclerosis. This prevents re-accumulation in 11-40% of
patients at 30 days follow-up (4).
• Systemic chemotherapy or hormonal therapy is the best long-term management option for
treatment sensitive tumors (see Fast Facts #14, 99).
• Chemosclerosis requires chest tube insertion followed by instillation of a sclerosing agent. It has
a success rate of 70-95% with no fluid re-accumulation at 1 month (if the pleural and parietal
surfaces are apposed after drainage and pleural fluid drainage is less than 100 ml/day at the time of
instillation) (5). Heavy tumor burden, reflected by low pleural pH (<7.2) or glucose concentration (<
3.3 mmol/L), is associated with a lower success rate and shorter survival (6). Talc is inexpensive
and has the lowest re-accumulation rates (3-8% after 30 days), compared to doxycycline and
bleomycin (1). Talc is rarely associated with ARDS and systemic embolization; more common side
effects are pain and fever. Sclerosis requires a large-bore chest tube which often remains in place
for 5-7 days – a major consideration in patients with a short prognosis. Thorascopic installation of
talc is the most effective technique in highly selected patients, but it is more costly (7,8). Providing
adequate pain management is crucial for chest tube insertion and any sclerosis technique.
• Small-bore catheters can be inserted radiologically in the ambulatory setting and connected to a
drainage bag for intermittent drainage by nurses or family members at home. Chemosclerosis can
be accomplished through the small catheter. When done in the inpatient setting, sclerosis via a
small catheter has a success rate of 62 to 95%; outpatient chemosclerosis may be less efficacious
but there has been no head-to-head comparison.
• Tunneled pleural catheters are similar to small-bore catheters but involve a cuff which is tunneled
under the skin to prevent infections. In a 2012 cost analysis, tunneled pleural catheters were found
to be the most cost effective management approach when prognosis was 3 months or less (9). A
retrospective study showed symptom improvement in 96% of patients at 2 weeks post insertion;
spontaneous pleurodesis was noted in 44% of all patients (10).
• Pleuroperitoneal shunts are occasionally indicated in patients with intractable effusions and
trapped lungs. The shunt drains pleural fluid into the abdomen via a subcutaneous reservoir that
the patient must pump ~ 400 times/day. Cost, limited efficacy and frequent malfunctioning all limit
usefulness of this procedure. In addition, the development of malignant ascites can occur if the
patient lives long enough.
• Pleurectomy is only indicated in patients who are expected to have a prolonged survival. There is
significant associated morbidity (20%) and mortality (10%) (11).
References
1. Belani CP, Pajeau TS, Bennett CL. Treating malignant pleural effusions cost consciously. Chest.
1998; 113:78S-85S.
2. Putnam JB,Jr. Malignant pleural effusions. Surg Clin North Am. 2002; 82:867-883.
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3. Anderson CB, Philpott GW, Ferguson TB. The treatment of malignant pleural effusions. Cancer.
1974; 33:916-922.
4. Grodzin CJ, Balk RA. Indwelling small pleural catheter needle thoracentesis in the management
of large pleural effusions. Chest. 1997; 111:981-988.
5. DeCamp MM,Jr, Mentzer SJ, Swanson SJ, Sugarbaker DJ. Malignant effusive disease of the
pleura and pericardium. Chest. 1997; 112:291S-295S.
6. Heffner JE, Nietert PJ, Barbieri C. Pleural fluid pH as a predictor of pleurodesis failure: Analysis of
primary data. Chest. 2000; 117:87-95.
7. Shaw P, Agarwal R. Pleurodesis for malignant pleural effusions. Cochrane Database of
Systematic Reviews 2004, Issue 1. Art. No.: CD002916. DOI:
10.1002/14651858.CD002916.pub2.
8. Belani C, Einarson TR, Arikian SR, Doyle J. Cost-effectiveness analysis of pleurodesis in the
management of malignant pleural effusion. J Oncology Management. 1995; Jan/Feb:24-34.
9. Puri V, Pyrdeck TL, et al. Treatment of malignant pleural effusion: a cost-effectiveness analysis.
The Annals of Thoracic Surgery 2012; 94:374-380.
10. Tremblay A, Michaud G. Single-center experience with 250 tunnelled pleural catheter insertions
for malignant pleural effusion. Chest. 2006; 129:362-368.
11. Rusch VW. Pleurectomy/decortication and adjuvant therapy for malignant mesothelioma. Chest.
1993; 103:382S-384S.
Version History: This Fast Fact was originally edited by David E Weissman MD and published in June
2006. Version copy-edited in April 2009; revised again July 2015 with reference #9 added and
incorporated into the text.
Disclaimer: Fast Facts and Concepts provide educational information for health care professionals. This information
is not medical advice. Fast Facts are not continually updated, and new safety information may emerge after a Fast
Fact is published. Health care providers should always exercise their own independent clinical judgment and consult
other relevant and up-to-date experts and resources. Some Fast Facts cite the use of a product in a dosage, for an
indication, or in a manner other than that recommended in the product labeling. Accordingly, the official prescribing
information should be consulted before any such product is used

EVALUATION OF MALIGNANT ASCITES
Karen LeBlanc and Robert Arnold MD
Background Malignant ascites is the accumulation of abdominal fluid due to the direct effects of
cancer. This Fast Fact reviews the causes and diagnosis of malignant ascites. Fast Fact #177 will review
its treatment.
Pathophysiology The pathophysiology of malignant ascites is incompletely understood. Contributing
mechanisms include tumor-related obstruction of lymphatic drainage, increased vascular permeability,
over-activation of the renin-angiotensin-aldosterone system, neoplastic fluid production, and production of
metalloproteinases that degrade the extracellular matrix. Portal venous compression can also occur from
metastatic invasion of the liver, leading to peritoneal fluid accumulation.
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Natural History The most common cancers associated with ascites are adenocarcinomas of the ovary,
breast, colon, stomach and pancreas. Median survival after diagnosis of malignant ascites is in the range
of 1-4 months; survival is apt to be longer for ovarian and breast cancers if systemic anti-cancer
treatments are available.
Presentation and Diagnostics Symptoms include abdominal distension, nausea, vomiting, early
satiety, dyspnea, lower extremity edema, weight gain, and reduced mobility. Physical exam findings may
include abdominal distention, bulging flanks, shifting dullness, and a fluid wave. Plain abdominal x-rays
are not specific, but may show a hazy or a “ground glass” appearance. Ultrasound or CT scanning can
confirm the presence of ascites and also demonstrate if the fluid is loculated in discrete areas of the
peritoneal cavity.
There are many potential causes of ascites in the cancer patient: peritoneal carcinomatosis, malignant
obstruction of draining lymphatics, portal vein thrombosis, elevated portal venous pressure from cirrhosis,
congestive heart failure, constrictive pericarditis, nephrotic syndrome, and peritoneal infections.
Depending on the clinical presentation and expected survival, a diagnostic evaluation is usually indicated
as it will impact both prognosis and treatment approach. Key tests include the serum albumin and protein
level and a simultaneous diagnostic paracentesis, checking ascitic fluid white blood cell count, albumin,
protein, and cytology.
Classification The old classification of exudative versus transudative ascites has been updated
through the use of the serum-ascites albumin gradient (SAAG).
SAAG = (the serum albumin concentration) – (ascitic fluid albumin concentration).
A SAAG > 1.1 g/dl indicates ascites due to, at least in part, increased portal pressures, with an accuracy
of 97%. This is most commonly seen in patients with cirrhosis, hepatic congestion, CHF, or portal vein
thrombosis.
A SAAG < 1.1 g/dl indicates no portal hypertension, with an accuracy of 97%; most commonly seen in
peritoneal carcinomatosis, an infectious process of the peritoneum, nephrotic syndrome, or malnutrition/
hypoalbuminemia.
Cytological evaluation is approximately 97% sensitive in cases of peritoneal carcinomatosis, but is not
helpful in the detection of other types of malignant ascites due to massive hepatic metastasis or
malignant obstruction of lymph vessels.
References
1. Thomas J, von Gunten CF. Diagnosis and Management of Ascites. In: Berger AM, Von Roenn J,
Schuster J, eds. Principles and Practice of Palliative Care and Supportive Oncology. 3rd edition.
Philadelphia, PA: Lippincott, Williams & Wilkins; 2006.
2. Adam RA, Adam YG. Malignant ascites: past, present, and future. J Am Coll Surg. 2004;
198:999-1011.
3. Spratt JS, Edwards M, Kubota T, et al. Peritoneal carcinomatosis: anatomy, physiology, diagnosis,
management. Current Problems in Cancer. 1986; 10:553-584.
4. Becker G. Galandi D. Blum HE. Malignant ascites: systematic review and guideline for treatment. Eu
J Cancer. 2006; 42:589-97.
5. Aslam N, Marino CR. Malignant ascites: new concepts in pathophysiology, diagnosis, and
management. Arch Int Med. 2001; 161:2733-7.
Version History: Version copy-edited in May 2009; then again July 2015.
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PALLIATIVE TREATMENT OF MALIGNANT ASCITES
Background The natural history, presenting signs/symptoms, and diagnostic approach to the patient
with malignant ascites are discussed in Fast Fact #176; readers are encouraged to read this Fast Fact to
review the important role of determining the Serum Ascites-Albumin Gradient as a diagnostic and
treatment aid. This Fast Fact will review treatment approaches.
1. Diuretics: Malignant ascites (SAAG < 1.1) generally does not respond to diuretic treatment
although no randomized trials have been completed. Patients with evidence of portal hypertension
(SAAG > 1.1) are more likely to respond to diuretics.
2. Paracentesis: Paracentesis can provide immediate relief of symptoms in up to 90% of patients.

Drainage of uncomplicated large-volume ascites (4-6 L/session) can be done safely and quickly in
the outpatient setting—including the home—or at the hospital bedside; ultrasound guidance is
necessary only when there is loculated fluid.
3. Drainage catheters: For patients who require frequent paracentesis, external drainage catheters
placed through the abdominal wall allow frequent or continuous drainage of ascites fluid without
repetitive needle insertions. Patients or caretakers may perform the drainage, reducing visits to
medical clinics. Several types of catheters are available:
a. Pigtail Catheter: A simple, temporary all-purpose catheter; they are prone to complications when
used over an extended duration (peritonitis, accidental removal, leakage, occlusion), hence are
rarely used now.
b. Tunneled Catheter: A catheter that prevents infection by promoting scarring around an antibiotic-
impregnated Dacron cuff in subcutaneous tissue. Used conventionally for peritoneal dialysis, it
is placed with ultrasound or fluoroscopic guidance and has lower risks of infection and leakage
than the pigtail catheter. Complications are reduced by daily drainage for the first two weeks of
cuff healing. The PleurX catheter is FDA approved for malignant ascites and features a one-way
rubber valve to prevent leaks between draining sessions. Tunneled catheters are used in
patients with life expectancy of at least one month.
4. Vascular Shunts:
a. Peritovenous shunt (PVS) systems are designed to channel peritoneal fluid and proteins in
benign ascites back into the circulation via the superior vena cava. PVS has not been shown to
have clinically significant risk of disseminating tumor cells in malignant ascites. A PVS is placed
by interventional radiology under conscious sedation, and patients typically require 24 hours of
monitoring with a central venous line after the procedure. The best response to PVS (only about
50%) is in ovarian and breast cancers. PVS is recommended only in patients with a life
expectancy of one to four months, considering that eventual occlusion rate is up to 24%.
b. Transjugular Intrahepatic Portosystemic Shunt (TIPS) is a shunt between the portal vein and
hepatic vein, designed to reduce portal hypertension and improve sodium balance. Most
patients with malignant ascites do not have portal hypertension although TIPS might be helpful
in the occasional cancer with evidence of increased portal pressures (SAAG > 1.1).
5. Hyperthermic Intraperitoneal Chemotherapy (HIPEC): This procedure is performed by surgical

oncology specialists and entails warmed chemotherapy being infused into the peritoneal cavity for a
short period of time. Most commonly this procedure is done along with tumor debulking or cyto-
reductive surgery (CRS). However, considering that recovery from HIPEC with CRS can take 3 to 6
months, CRS-HIPEC is typically reserved for low-grade appendiceal primary cancers seeing that
these cancers are associated with a longer survival. For patients with anticipated shorter survivals,
!12
HIPEC without CRS can be done laparoscopically (and is therefore associated with less morbidity)
with high rates of ascites control.
References
1. Thomas J, von Gunten CF. Diagnosis and Management of Ascites. In: Berger AM, Von Roenn J,
Schuster J. Principles and Practice of Palliative Care and Supportive Oncology. 3rd edition.
Philadelphia, PA: Lippincott, Williams & Wilkins; 2006.
198:999-1011.
3. Spratt JS, Edwards M, Kubota T, et al. Peritoneal carcinomatosis: anatomy, physiology,
diagnosis, management. Current Problems in Cancer. 1986; 10:553-584.
4. Becker G, Galandi D, Blum HE. Malignant ascites: systematic review and guideline for treatment.
Eu J Cancer. 2006; 42:589-97.
management. Arch Int Med 2001;161:2733-7.
6. Smith EM, Jayson GC. The current and future management of malignant ascites. Clinical
Oncology. 2003; 15:59-72.
7. Pockros PJ, Esrason KT, Nguyen C, Duque J, Woods S. Mobilization of malignant ascites with
diuretics is dependent on ascitic fluid characteristics. Gastroenterology. 1992; 103:1302-1306.
8. Abeloff M, Armitage J, Niederhuber J, Kastan M, McKenna WG, eds. Clinical Oncology. 3rd
edition. New York, NY: Churchill Livingstone; 2004: 1199-1205.
9. Covey AM. Management of malignant pleural effusions and ascites. J Support Oncol.. 2005;
3:169-73.
10. White MA, Agle SC, et al. Denver peritoneovenous shunts for the management of malignant
ascites: a review of the literature in the post-LeVeen era. The American Surgeon 2011;77:
1070-1075.
11. Randle RW, Swett KR, et al. Efficacy of cytoreductive surgery with hyperthermic intraperitoneal
chemotherapy in the management of malignant ascites. Ann of Surg Onc 2014;21: 1474-1479.
Version History: Current version copy-edited in May 2009; then again July 2015 by Sean Marks MD:
references #10 and #11 were added and incorporated into the text.
Copyright: All Fast Facts and Concepts are published under a Creative Commons Attribution-NonCommercial 4.0
International Copyright (http://creativecommons.org/licenses/by-nc/4.0/). Fast Facts can only be copied and
distributed for non-commercial, educational purposes. If you adapt or distribute a Fast Fact, let us know!
information should be consulted before any such product is used.
!13
!

MALIGNANT PERICARDIAL EFFUSIONS
Vincent Thai MD
Introduction Malignant pericardial effusions (MPEs) are a rare complication of advanced cancer, but
are associated with high morbidity and mortality. This Fast Fact discusses the diagnosis and
management of MPEs.
Epidemiology and Prognosis Approximately 10% of patients with cancer develop cardiac
metastases, with ~75% of these affecting the epicardium (1, 2). Only a third of these, however, will
develop clinically significant MPEs (1). Lung and breast cancers are the most common causes. MPEs
are associated with a poor prognosis. Studies suggest a median survival of 2-3 months after a MPE is
diagnosed, with a mean survival of 5 months for solid tumors and 20 months for hematologic
malignancies (3, 4).
Physiology and Symptoms The pericardial space is normally filled with <50 ml of serous fluid. As this
volume increases due to epicardial or pericardial metastases or lymphatic obstruction, both right and left
ventricular failure can occur due to inadequate filling. Signs and symptoms include peripheral and
pulmonary edema, chest discomfort, cough, shortness of breath, and orthopnea. Severity of symptoms
depends on the volume of the MPE as well as the rapidity of its accumulation; severe cases can present
with cardiac tamponade and shock. An echocardiogram is indicated whenever a MPE is suspected. Not
only does it confirm the presence of an effusion, but its findings can dictate whether or not urgent
treatment is indicated (e.g. if signs of tamponade are evident). A diagnostic pericardiocentesis or
pericardial biopsy is sometimes needed to confirm the cause of the effusion.
Treatment Options
• Systemic chemotherapy or radiotherapy are effective for chemo- or radio-sensitive tumors such as
previously untreated breast cancer and many lymphomas. Reaccumulation rates for both modalities
are about 1/3 overall, depending on the patient’s overall course and response to therapy (5).
• Pericardiocentesis results in immediate symptom relief in most patients, however the effusion may re-
accumulate, requiring repeat pericardiocentesis (within 1-2 weeks in some series) (6).
• Pericardial sclerosis involves instilling a sclerosing agent with the intention of scarring the pericardium
to the epicardium, preventing reaccumulation of the MPE (similar to pleural effusions – see Fast Fact
#157). Multiple agents have been studied including doxyclycline, minocycline, and bleomycin.
Success rates (no reaccumulation at 30 days) are about 70-90% (7, 8). Longer term success rates
are undefined due to the poor survival of study patients. The major side effect is chest pain (50-70%),
cardiac arrhythmias, and fever (8, 9, 10). In head to head comparisons with doxycycline, bleomycin
has been shown to have fewer side effects and to lead to shorter hospitalizations (10, 11, 12).
• Surgical decompression therapies range from less invasive (balloon pericardiotomy, subxiphoid or
thorascopic pericardiostomy) to more extensive (open thoracotomy with pericardial stripping). A
pericardial ‘window’ (which allows ongoing drainage of fluid externally or internally such as into the
pleural cavity) is often created. Case series have suggested reaccumulation rates with surgical
therapies are low (less than 15% up to 10 months out) (13, 14, 15).
Decision-Making The treatment of MPEs depends on how urgently treatment is needed, the likelihood
of the tumor responding to anti-neoplastic treatments, and the anticipated survival of the patient. A
multidisciplinary approach to decision-making, involving input from medical and radiation oncology,
cardiology, and thoracic surgery is recommended. Simple pericardiocentesis may be appropriate for
patients with short prognoses (<1 month), particularly if their MPE is not expected to re-accumulate in
their remaining life-span. A symptomatic patient with no signs of tamponade and a chemotherapy-
sensitive tumor such as untreated breast cancer may receive a durable response from a
pericardiocentesis for symptom relief, followed by chemotherapy. Patients with longer prognoses (>1
month) who are expected to re-accumulate their MPEs will likely benefit most from sclerosis or surgical
decompression; there is no clear evidence currently suggesting one strategy is superior to the other.
!14
Symptom directed care without specific intervention for the MPE is an appropriate option for patients with
very short prognoses and for those who decline more invasive treatments.
References
1. Klatt EC, Heitz DR. Cardiac metastases. Cancer. 1990; 65(6):1456-59.
2. Abraham KP, Reddy V, Gattuso P. Neoplasms metastatic to the heart: review of 3314 consecutive autopsies.
Am.J.Cardiovasc.Pathol. 1990; 3:195-198.
3. Moores, D.W, Allen K.B, Faber L.P, Dziuban S.W, Gillman D.J, Warren W.H., Ilves R, Lininger L, Subxiphoid
pericardial drainage for pericardial tamponade, J Thoracic Cardiovascular Surg. 1995; 109:546-552.
4. Dosios T, Theaskos,N, Angouras D, et al. Risk factors affecting the survival of patients with pericardial
effusion submitted to subxiphoid pericardiostomy. Chest. 2003; 124:242
5. Lamont E, Hoffman PC. Oncologic emergencies. In: Hall JB, et al, eds. Principles of Critical Care. 3rd
Edition. New York, NY: McGraw Hill; 2005.
6. Laham RJ, Cohen DJ, Kuntz RE et al. Pericardial effusion in patients with cancer: outcome with
contemporary management strategies. HEART. 1996; 75(1):67-71.
7. Lashevsky I, Ben Yosef R, Rinkevich D, Reisner S, Markiewicz W. Intrapericardial minocycline sclerosis for
malignant pericardial effusion. Chest. 1996; 109(6):1452-54.
8. Maher EA, Shepherd FA, Todd TJR. Pericardial sclerosis as the primary management of malignant
pericardial effusion and cardiac tamponade. J Thoracic Cardiovascular Surg. 1996; 112(3):637-643.
9. Ben Yosef,R, Phefer,R, Ge,A, Catane,R. Management of malignant pericardial effusion Harefuah, 1988;
115:138-141.
10. Liu G, Crump M, Goss PE, Dancey J, Shepherd FA. Prospective comparison of the sclerosing agents
doxycycline and bleomycin for the primary management of malignant pericardial effusion and cardiac
tamponade. J Clin.Oncol. 1996; 14(12):3141-47.
11. Yano T, Yokoyama H, Inoue T, et al. A simple technique to manage malignant pericardial effusion with a local
instillation of bleomycin in non-small cell carcinoma of the lung. Oncology. 1994; 51:507-509.
12. van Belle SJ, Volckaert A, Taeymans Y, Spapen H, Block P. Treatment of malignant pericardial tamponade
with sclerosis induced by instillation of bleomycin. Int.J.Cardiol. 1987; 16(2):155-160.
13. Galli M, Politi A, Pedretti F, Castiglioni B, Zerboni S. Percutaneous balloon pericardiotomy for malignant
pericardial tamponade. Chest. 1995; 108(6):1499-1501.
14. Palacios IF, Tuzcu EM, Ziskind AA, Younger J, Block PC. Percutaneous balloon pericardial window for
patients with malignant pericardial effusion and tamponade. Cathet.Cardiovasc.Diagn. 1999; 22(4):244-49.
15. Ziskind AA, Pearce AC, Lemmon CC, et al. Percutaneous balloon pericardiotomy for the treatment of cardiac
tamponade and large pericardial effusions: description of technique and report of the first 50 cases.
J.Am.Coll.Cardiol. 1993; 21(1):1-5.
Author Affiliation: University of Alberta, Edmonton, Alberta.

Version History: Originally published October 2008; copy-edited July 2015.
!15
MANAGEMENT OF SPINAL CORD COMPRESSION
Rohtesh S Mehta MD, MPH and Robert Arnold MD
Background Metastatic spinal cord compression (SCC) is a medical emergency; early treatment is
associated with less functional disability. Treatment options include corticosteroids, radiotherapy and
surgery. This Fast Fact discusses management of SCC in adults. Fast Fact #237 discusses its diagnosis.
Corticosteroids Dexamethasone is the most tested steroid in clinical trials. Studies have shown that
steroids provide analgesia and reduce vasogenic edema which may lead to better neurological outcomes.
Treatment should be started as soon as diagnosis is made; studies in acute spinal cord injury suggest
significant neurological improvement when used within 8 hours of injury. Historically, debate existed
between using high dose dexamethasone (100 mg loading, then 96 mg daily) versus moderate dose (10
mg loading, then 16 mg daily). A randomized controlled trial comparing the two doses found no
differences in efficacy and thus most give the lower dose. (1) Many studies give the steroids divided 4
times a day (total 16 mg daily), tapered over 10-14 days. Most generally start IV and then switch to PO
when patients are “clinically stable” and more definitive therapy (radiation or surgery) has been initiated.
Steroids should be tapered as soon as possible to prevent long term toxicities (2). Common short term
side effects include hyperglycemia, insomnia and gastric distress. Serious acute adverse effects such as
gastrointestinal perforation or bleeding, psychosis, risk of infections and death are associated with high
doses only (17%) (3).
Radiotherapy (RT) In the absence of bony instability, RT has historically been the treatment of choice,
preferably started within 24 hours of diagnosis. Dose schedule for RT ranges from single fraction 8 Gy to
20 fractions of 40 Gy. One or two fractions of 8 Gy may be preferable in patients with short prognoses
and, in one study, had a similar outcome to more prolonged treatment (4). RT results in pain relief in
40-80% of patients and sphincter control in 45-90% of cases (3, 4) when instituted in time. About 90% of
ambulatory patients retain ambulation with RT alone, but less than 30% of patients who have lost the
ability to walk by the time RT is initiated regain ambulation (3).
Surgery Until recently, surgery was reserved for cases with SCC in a previously irradiated area,
neurologic deterioration during RT, spinal instability, or bony compression. However a recent meta-
analysis (5) and a randomized controlled trial (6) found better functional outcomes with surgery plus post-
operative RT as compared to RT alone. This trial used a newer surgical technique (circumferential
decompression, reconstruction and immediate stabilization). 84% of the patients in the surgery group
were ambulatory and retained ambulation for a longer time (a median of122 days) after treatment
compared to 57% in the RT group (median 13 days). 62% of the non-ambulatory patients regained the
ability to walk after the surgery compared to 19% in the RT groups. The surgery group also maintained
continence for a significantly longer time (median 156 days vs. 17 days). A more recent retrospective
matched pair analysis of cancer patients with SCC comparing RT alone to surgery plus RT did not find
any significant differences in outcome between the two treatments (7). Prompt, interdisciplinary evaluation
by radiation oncologists and spine surgeons is indicated in order to identify the best treatment course.
Other treatments Spinal Stereotactic Radiosurgery (SRS) has an investigational role in adult non-
surgical patients with radio-resistant tumor or those with previously irradiated areas. Studies suggest
more than 80% improvement in overall neurological function (8). Transarterial embolization is another
novel investigational treatment. It is generally used preoperatively for hypervascular spinal tumors
causing compression, is safe and effective, and can make radical tumor resection possible at times (9). In
adults, chemotherapy has no role in acute management even in chemo-sensitive cancers because of its
slow effect. Although bisphosphonates reduce the incidence of skeletal complications of cancer, there
are no data to suggest a benefit in treating SCC.
Prognosis Median survival after developing SCC is between 3-6 months in adults. Poor prognostic
factors for survival include non-ambulatory status, SCC within 15 months of original cancer diagnosis,
presence of visceral or other bone metastases, cancer type (survival is worse for lung cancer and better
for myeloma/lymphoma), and rapidity of developing motor symptom (worst if <7 days and better if more
than 2 weeks after the onset of symptoms).
!16
Conclusion A loading dose of dexamethasone 10 mg IV should be given as soon as possible after
diagnosis, followed by maintenance dose of 4 to 6 mg every 6-8 hours, and referral made for primary
surgery (if feasible) with adjuvant RT. If surgery is contraindicated, palliative RT alone is indicated.
References
1. Vecht CJ, et al. Initial bolus of conventional versus high-dose dexamethasone in metastatic spinal
cord compression. Neurology. 1989; 39(9):1255-7.
2. Weissman DE, Dufer D, Vogel V, Abeloff MD. Corticosteroid toxicity in neuro-oncology patients. J
Neurooncol. 1987;5(2):125-8
3. George R, Jeba J, Ramkumar G, Chacko AG, Leng M, Tharyan P. Interventions for the treatment of
metastatic extradural spinal cord compression in adults. Cochrane Database of Systematic
Reviews 2008, Issue 4. Art. No.: CD006716. DOI: 10.1002/14651858.CD006716.pub2
4. Maranzano E, et al. Short-course versus split course radiotherapy in metastatic spinal cord
compression: results of a phase III, randomized, multicenter trial. J Clin Oncol. 2005; 23:3358–65
5. Klimo P, et al. A meta-analysis of surgery versus conventional radiotherapy for the treatment of
metastatic spinal epidural disease. Neuro Oncol. 2005; 7(1):64-76.
6. Rades D, et al. Validation and simplification of a score predicting survival in patients irradiated for
metastatic spinal cord compression. Cancer. 2010; 116:3670-3.
7. Rades D, Huttenlocher S. Matched pair analysis comparing surgery followed by radiotherapy and
radiotherapy alone for metastatic spinal cord compression. J Clin Oncol. 2010; 28(22):3597-3604.
8. Ryu S, Rock J, Jain R, et al. Radiosurgical decompression of metastatic epidural compression.
Cancer. 2010; 116(9):2250-7
9. Kato S, et al. Surgical management of aggressive vertebral hemangiomas causing spinal cord
compression: long-term clinical follow-up of five cases. J Orthop Sci. 2010; 15(3):350-6.
10. Rades D, et al. Validation and simplification of a score predicting survival in patients irradiated for
metastatic spinal cord compression. Cancer. 2010; 116:3670-3.
Author Affiliations: University of Pittsburgh Medical Center, Pittsburgh, PA.
Version History: Originally published December 2010; Copy-re-edited November 2015.

Fast Facts and Concepts are edited by Sean Marks MD (Medical College of Wisconsin) and associate editor Drew
A Rosielle MD (University of Minnesota Medical School), with the generous support of a volunteer peer-review
editorial board, and are made available online by the Palliative Care Network of Wisconsin (PCNOW); the authors of
each individual Fast Fact are solely responsible for that Fast Fact’s content. The full set of Fast Facts are available at
Palliative Care Network of Wisconsin with contact information, and how to reference Fast Facts.
Copyright: All Fast Facts and Concepts are published under a Creative Commons Attribution-NonCommercial 4.0
International Copyright (http://creativecommons.org/licenses/by-nc/4.0/). Fast Facts can only be copied and
distributed for non-commercial, educational purposes. If you adapt or distribute a Fast Fact, let us know!
information should be consulted before any such product is used.
!17
!
Communication
#6 Delivering Bad New – Part
I . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3-4
#11 Delivering Bad News – Part II . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . .

. . . . . . . . . .5-6
#19 Taking a Spiritual History

3rd . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .7-8
#21 Hope and Truth

Telling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
9-10
#22 Writing a Condolence Letter . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . 11-12
#23 Discussing DNR Orders – Part I . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . 13-14
#24 Discussing DNR Orders – Part

2 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .15-16
#47 What Do I Tell the Children? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . 17-18
#64 Informing Significant Others of a Patient’s Death . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . 19-20
#76 Telephone Notification of Death – Part

I . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .21-22
#77 Telephone Notification of Death – Part II . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . 23-24
#155 Completing a Death Certificate . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . .25-27
#162 Advance Care Planning in Chronic Illness . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . .28-29
!1
#183 Conflict Resolution I: Careful
Communication . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .30-31
#184 Conflict Resolution II: Principled Negotiation . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . .32-33
#222 Preparing for the Family Meeting . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . 34-35
#223 The Family Meeting: Starting the Conversation . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . 36-38
#224 Responding to Emotion in Family

Meetings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39-40
#225 The Family Meeting: Causes of Conflict . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . .41-42
#226 Helping Surrogates Make Decisions Meeting . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . 43-44
#227 The Family Meeting: End of Life Goal Setting and Future Planning . . . . . . . . . . .
. . . . . .45-46
#274 The Fica Spiritual History Tool

2 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47-49
!2
!
FAST FACT AND CONCEPT #6

DELIVERING BAD NEWS – PART 1
Bruce Ambuel PhD and David E Weissman MD
Case Scenario: You are caring for a previously healthy 52 year old man with new abdominal
pain. After conservative treatments fail, a diagnostic abdominal CT scan is done showing a focal
mass with ulceration in the body of the stomach and numerous densities in the liver compatible
with liver metastases. The radiologist feels that the findings are absolutely typical of metastatic
stomach cancer. How do you prepare to discuss these test results with the patient?
Preparing to Deliver Bad News

1. Create an appropriate physical setting: a quiet, comfortable room, turn off beeper, check
personal appearance, have participants – including yourself – sitting down.
2. Determine who should be present. Ask the patient who they want to participate and
clarify their relationships to the patient. Decide if you want others present (e.g. nurse,
consultant, chaplain, social worker) and obtain patient/family permission.
3. Make sure you know basic information about the patient’s disease: prognosis, treatment
options, next steps.
4. Special circumstances: If the patient lacks decision-making capacity (e.g.
developmentally delayed, demented, delirious, etc.), make sure the legal decision-maker
is present. See Fast Fact # 226 Helping Surrogates Make Decisions.
5. Special circumstances: If the patient or family does not speak English, obtain a skilled
medical interpreter. Use phone translation services if necessary. See Fast Fact #154
6. Special circumstances: If the patient or family is of anther cultural background, see Fast
Fact # 216 Asking About Cultural Beliefs in Palliative Care.
Precepting self-reflection Residents will invariably have strong emotions when they have to
give bad news. This emotional response can be heightened by various factors—a young patient,
an unexpected diagnosis, a patient with whom the physician has a long-standing relationship, etc.
Preceptors need to support the resident. Key teaching points:
1. Residents may not spontaneously discuss their own emotional reaction with a preceptor,
therefore preceptors need to introduce this topic. “This is a really hard case, how are you
doing?”
!3
2. Physicians often have strong emotional reactions when a patient encounters bad news.
Normalize the experience for the resident. “It’s normal to have strong feelings”.
3. Three methods for coping with these feelings are: Identify your feelings (anger, sadness,
fear, guilt); Talk with a colleague; Keep a personal journal.
4. Role play the discussion with the resident before you go into the room; ask them to reflect
on how it “feels”…what is hard…what is easy. Encourage continued self-reflection.
See related Fast Facts: Delivering Bad News Part 2 (#11); Death Pronouncement (#4);
Moderating a Family Conference (#16, #222, 223, 224, 225, 227); Responding to Patient Emotion
(#29); Dealing with Anger (#59).
References
1. Buckman R. How to break bad news: A guide for health care professionals. Baltimore,
MD: Johns Hopkins University Press; 1992.
2. Faulkner A. Breaking bad news – a flow diagram. Palliative Medicine. 1994: 8;145-151.
3. Iverson, VK. Pocket protocols—Notifying Survivors About Sudden, Unexpected Deaths.
Tuscon, AZ: Galen Press; 1999.
4. Ptacek, JT, Eberhardt, TL. Breaking bad news: A review of the literature. JAMA. 1996;
276(6): 496-502.
5. Quill TE. Bad news: delivery, dialogue and dilemmas. Arch Intern Med. 1991;
151:463-468.
6. Girgis A, Sanson-Fischer RW. Breaking bad news: consensus guidelines for medical
practitioners. J Clin Onc. 1995; 13:2449-2456.
7. Von Gunten CF, Ferris FD and Emanuel LL. Ensuring competency in end-of-life care:
Communication and Relational Skills. JAMA. 2000; 284:3051-3057.
Version History: This Fast Fact was originally edited by David E Weissman MD. 2nd Edition
published July 2005; 3rd Edition May 2015. Current version re-copy-edited May 2015.
Fast Facts and Concepts are edited by Sean Marks MD (Medical College of Wisconsin) and
associate editor Drew A Rosielle MD (University of Minnesota Medical School), with the generous
support of a volunteer peer-review editorial board, and are made available online by the Palliative
Care Network of Wisconsin (PCNOW); the authors of each individual Fast Fact are solely
responsible for that Fast Fact’s content. The full set of Fast Facts are available at Palliative Care
Network of Wisconsin with contact information, and how to reference Fast Facts.
Fast Facts can only be copied and distributed for non-commercial, educational purposes. If you
adapt or distribute a Fast Fact, let us know!
Disclaimer: Fast Facts and Concepts provide educational information for health care
professionals. This information is not medical advice. Fast Facts are not continually updated, and
new safety information may emerge after a Fast Fact is published. Health care providers should
always exercise their own independent clinical judgment and consult other relevant and up-to-
date experts and resources. Some Fast Facts cite the use of a product in a dosage, for an
indication, or in a manner other than that recommended in the product labeling. Accordingly, the
official prescribing information should be consulted before any such product is used.
!4
!

DELIVERING BAD NEWS – PART 2
Bruce Ambuel PhD and David E Weissman MD
Case Scenario: You are caring for a previously healthy 52 year old man with a one-month of
abdominal pain and weight loss. On exam he had a 2 cm hard left supraclavicular lymph node. A
CT scan showed a focal mass with ulceration in the body of the stomach and numerous densities
in the liver compatible with liver metastases. The radiologist feels that the findings are consistent
with metastatic stomach cancer. How do you discuss these test results with the patient?
Steps in Delivering Bad News

1. Determine what the patient & family knows; make no assumptions. Examples: What is
your understanding of your present condition? What have the doctors told you?
2. Before presenting bad news, consider providing a brief overview of the patient’s course
so that every one has a common source of information.
3. Speak slowly, deliberately and clearly. Provide information in small chunks. Check
reception frequently.
4. Give fair warning – I am afraid I have some bad news – then pause for a moment.
5. Present bad news in a succinct and direct manner. Be prepared to repeat information
and present additional information in response to patient and family needs.
6. Sit quietly. Allow the news to sink in. Wait for the patient to respond.
7. Listen carefully and acknowledge patient’s and family’s emotions, for example by
reflecting both the meaning and emotion of their response.
8. Normalize and validate emotional responses: feeling numb, angry, sad, and fearful.
9. Give an early opportunity for questions, comments.
10. Present information at the patient’s or family’s pace; do not overwhelm with detail. The
discussion is like pealing an onion. Provide an initial overview. Assess understanding.
Answer questions. Provide the next level of detail or repeat more general information
depending upon the patient’s and family’s needs.
11. Assess thoughts of self-harm
12. Agree on a specific follow-up plan (I will return later today, write down any questions.).
Make sure this plan meets the patient’s needs. Involve other team members in follow-up.
Precepting Points
Residents often feel strong emotions when they have to give bad news to a patient. This
emotional response can be heightened by various factors—a young patient, an unexpected
diagnosis, a patient with whom the physician has a long-standing relationship, etc. As a
preceptor, you will want to support the resident. Key teaching points:
• Residents may not spontaneously discuss their own emotional reaction with a preceptor,
therefore you will want to introduce this topic.
• Physicians often have strong emotional reactions when a patient encounters bad news.
This is normal and OK.
• Three methods for coping with these feelings: Identify your feelings (anger, sadness, fear,
guilt); Talk with a colleague; Keep a personal journal.
!5
See related Fast Facts: Delivering Bad News – Part 1 (#6); Death Pronouncement (#4);
Responding to Patient Emotion (#29); Dealing with Anger (#59); Family Conferences (#222, 223,
224, 225, 227).
Resources
1. Buckman R. How to break bad news: A guide for health care professionals. Baltimore,
Johns Hopkins University Press: 1992.
2. Faulkner A. Breaking bad news – a flow diagram. Palliative Medicine. 1994: 8;145-151.
3. Iverson, VK. Pocket protocols—Notifying survivors about sudden, unexpected deaths.
Tuscon, Arizona, Galen Press: 1999.
4. Ptacek, JT, Eberhardt, TL. Breaking bad news: A review of the literature. JAMA. 1996;
276(6): 496-502.
5. Quill TE. Bad news: delivery, dialogue and dilemmas. Arch Intern Med. 1991;
151:463-468.
6. Girgis A, Sanson-Fischer RW. Breaking bad news: consensus guidelines for medical
practitioners. J Clin Onc. 1995; 13:2449-2456.
7. Von Gunten CF, Ferris FD and Emanuel LL. Ensuring competency in end-of-life care:
Communication and Relational Skills. JAMA. 2000; 284:3051-3057.
Version History: 2nd Edition published September 2005. 3rd Edition May 2015. Current version
re-copy-edited May 2015.
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!

TAKING A SPIRITUAL HISTORY 3rd
Bruce Ambuel PhD
Background Illness raises fundamental questions – For what may I hope? Why do I suffer?
Does my suffering have meaning? What happens after I die? When a physician stands with a
patient as they face death, the physician inevitably plays a role in supporting the patient’s inquiry
into these spiritual questions (see Fast Fact #31 Confronting Personal Mortality). In addition
some patients have specific preferences regarding medical care, death and dying that are based
upon their religious beliefs. The physician often plays an important role in supporting a patient’s
exploration of these issues. Taking a spiritual history is one way to support the patient in this
exploration. Maugans (1997) presents a framework for taking a spiritual history; the interview
below comes primarily from Maugans’ article with some modification based upon the other
sources cited. See Fast Fact #274 for information on the FICA Spirituality History Tool.
Taking a Spiritual History
S—Spiritual belief system
• Do you have a formal religious affiliation? Can you describe this?
• Do you have a spiritual life that is important to you?
• What is your clearest sense of the meaning of your life at this time?
P—Personal spirituality
• Describe the beliefs and practices of your religion that you personally accept.
• Describe those beliefs and practices that you do not accept or follow.
• In what ways is your spirituality/religion meaningful for you?
• How is your spirituality/religion important to you in daily life?
I—Integration with a spiritual community
• Do you belong to any religious or spiritual groups or communities?
• How do you participate in this group/community? What is your role?
• What importance does this group have for you?
• In what ways is this group a source of support for you?
• What types of support and help does or could this group provide for you in dealing
with health issues?
R—Ritualized practices and restrictions
• What specific practices do you carry out as part of your religious and spiritual life
(e.g. prayer, meditation, services, etc.)
• What lifestyle activities or practices do your religion encourage, discourage or
forbid?
• What meaning do these practices and restrictions have for you? To what extent have
you followed these guidelines?
I—Implications for medical care
• Are there specific elements of medical care that your religion discourages or
forbids? To what extent have you followed these guidelines?
• What aspects of your religion/spirituality would you like to keep in mind as I care for
you?
• What knowledge or understanding would strengthen our relationship as physician
and patient?
• Are there barriers to our relationship based upon religious or spiritual issues?
• Would you like to discuss religious or spiritual implications of health care?
T—Terminal events planning
• Are there particular aspects of medical care that you wish to forgo or have withheld
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because of your religion/spirituality?
• Are there religious or spiritual practices or rituals that you would like to have
available in the hospital or at home?
• Are there religious or spiritual practices that you wish to plan for at the time of death,
or following death?
• From what sources do you draw strength in order to cope with this illness?
• For what in your life do you still feel gratitude even though ill?
• When you are afraid or in pain, how do you find comfort?
• As we plan for your medical care near the end of life, in what ways will your religion
and spirituality influence your decisions?
References:
1. Maugans TA. The SPIRITual History. Arch Fam Med. 1997; 5:11-16.
2. Ambuel B, Weissman DE. Discussing spiritual issues and maintaining hope. In:
Weissman DE, Ambuel B, eds. Improving End-of-Life Care: A Resource Guide for
Physician Education, 2nd Edition. Milwaukee, WI: Medical College of Wisconsin; 1999.
3. Griffith JL, Griffith ME. Hope in suffering/pain in health: Talking with patients about
spiritual issues. Presented at The 18th Forum for the Behavioral Sciences in Family
Medicine, Chicago, Illinois, October 1997.
published August 2005; 3rd Edition May 2015. Current version re-copy-edited May 2015.
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!

HOPE AND TRUTH TELLING
Eric Warm MD and David E Weissman MD
‘The miserable have no other medicine; But only hope.’ Claudio, in Measure for Measure Act 3,
Sc.1, by William Shakespeare (1564-1616).  
This Fast Fact discusses the difficult balance between maintaining hope and truth telling,
especially as it applies to giving bad news. One of the most difficult things physicians do is give
bad news. Medical students and residents are often afraid that by telling someone the truth about
his/her diagnosis, they will be responsible for taking away hope. And yet, are physicians really
that powerful? Isn't it possible that our fear of causing the loss of hope is just another way we can
avoid the harsh reality of impending death? This conflict, between truth-telling and fear of
destroying hope, is commonly noted by patients and families who feel that "the doctor is not really
telling me everything,” a feeling that is highly corrosive to the doctor-patient relationship.
 
Brody (1981) writes, ‘Hope means different things to different people, and different things to the
same person as he/she moves through stages of illness.’ The physician can play a valuable role
in helping the individual patient define her or his hopes and fears. When close to death, hope
often becomes refocused away from long-term goals and towards short-term or spiritual goals.
Hope may mean a pain-free day, a sense of security, love and non-abandonment, or a wedding to
attend in the near future. ‘When we talk to patients and find out what is really worrying them, we
can almost always give them realistic assurances’ (Brody 1981).Factors that often increase hope
in the terminally ill include feeling valued, meaningful relationships, reminiscence, humor, realistic
goals, and pain and symptom relief. Factors that often decrease hope include feeling devalued,
abandoned or isolated ("there is nothing more that can be done"), lack of direction and goals, and
unrelieved pain and discomfort.
Some strategies for beginning a dialogue about hope and goals include:
• Ask the patient, "Do you have long term hopes and dreams that have been threatened by
this illness?" Support the patient in recognizing and grieving their possible losses.
• Ask the person if there are particular upcoming events they wish to participate in –
a wedding, birth, trip, etc.
• Ask "What are your hopes for the future?" and "Do you have specific concerns or fears?"
• Encourage the patient to make short, medium, and long range goals with an
understanding that the course of terminal illness is always unpredictable.
• Utilize “I wish…” statements when conveying bad clinical news in order to convey an
appropriate degree of humility – “I wish there was more we could do for your cancer but
I’m afraid time may be getting short.”
Teaching Tips
• Use the Brody article as a starting point for discussion with trainees
• When faced with the need to give bad news, ask trainees how they feel before they give
the news; are they worried about causing a loss of hope? Ask them to reflect further – do
they feel hopeless because of the situation? Whose feelings are they trying to protect,
their own or the patient’s?
• Ask trainees to make a list of risks and benefits of truth telling. Use the list as a starting
point for group discussion of the hope-truth telling conflict.
References
1. Brody H. Hope. JAMA. 1981; 246:1411-1412.
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2. Ambuel, B. Spirituality. In: Weissman D, Ambuel B, Hallenbeck J, eds. Improving End of
Life Care: A Resource Guide for Physician Education. 3rd Edition. Milwaukee, WI:
Medical College of Wisconsin; 2001.
3. Twycross R, Lichter I. The terminal phase. In: Doyle D, et al, eds. Oxford Textbook of
Palliative Medicine. 2nd Edition. New York, NY: Oxford University Press; 1998: pp. 977-78.
4. Remen RN. Kitchen Table Wisdom: Stories That Heal. New York, NY: Riverhead Books;
1997.
published July 2005. 3rd Edition published May 2015. Current version re-copy-edited May 2015.
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!

WRITING A CONDOLENCE LETTER
Ron Wolfson PhD and Elizabeth Menkin MD
Introduction One of the most meaningful acts of kindness you can do for a mourner is to write
a letter of condolence. The words of sympathy and memory are comforting to the bereaved.
More importantly, mourners are very appreciative that you took the time to sit and compose a
personal message to them or share a memory of the deceased. For professionals who work with
dying patients, writing a condolence letter is an opportunity to reflect on both the pain and the
rewards of our work. When we can appreciate the privilege it is to bear witness to the courage,
kindness, caring and dignity that our patients and their families exhibit under duress, it gives us
strength to continue this work.
A good condolence letter has two goals: to offer tribute to the deceased and to be a source of
comfort to the survivors. The best letters are like conversations, as if you were talking during a
visit. Most often, they are written to the bereaved person to whom you feel closest, although it
could be a general letter to the family. It should be written and sent promptly, generally within two
weeks after the death. Use any standard stationery and write it by hand. Here are some specific
guidelines for writing a good condolence letter:
• Acknowledge the loss and name the deceased. This sets the purpose and tone of the
letter. Let the bereaved know how you learned of the death and how you felt upon
hearing the news. Using the name of the deceased is a tribute that comforts most
mourners.
• Express your sympathy. Use words of sympathy that remind the bereaved that they are
not alone in their feelings of sadness and loss.
• Note special qualities of the deceased. Acknowledge those characteristics that you
cherished most about the person who has died. These might be qualities of personality
(courage, sensitivity), or attributes (funny, affable), or ways the person related to the
world (religious, devoted to community welfare).
• Recall a memory about the deceased. Talk about how the deceased touched your life.
Try to capture what it was about the person in the story that you admired, appreciated or
respected. You may use humor – the funny stories are often the most appreciated by the
bereaved.
• Remind the bereaved of their personal strengths. Bereavement often brings with it
self-doubt and anxiety about one's own personal worth. By reminding the bereaved of the
qualities they possess that will help them through this period, you reinforce their ability to
cope. Qualities to mention might be patience, optimism, religious belief, resilience, and
competence. If you can recall something the deceased used to say about the mourner in
this regard, you will really be giving the bereaved a gift. An example: “I was (impressed,
inspired, awed, strengthened) by the devotion you and your family evidenced during the
period of Mort's illness. Your presence (concern, care, attentiveness) was only one
indication of your love for him.”
• Offer help, but be specific. “If there is anything I can do, please call” actually puts a
burden on those in grief who may be totally at a loss about what needs to be done. A
definite offer of help is more appreciated. Whatever you offer, do it – don't make an offer
you cannot fulfill.
• End with a word or phrase of sympathy. Somehow, “sincerely,” “love,” or “fondly,” don't
quite make it. Try one of these: “You are in my thoughts and prayers.” Or, “My fond
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respects to you and yours.”
If you don't have enough to say for a formal condolence letter, you may prefer to send a
sympathy note. These are shorter communications that can be written on personal stationery or
added to a commercially available card. As with a condolence letter, the major goal is to offer a
tribute to the deceased and to offer comfort to the bereaved.
Reference
Wolfson, R. A Time to Mourn, A Time to Comfort. Woodstock, VT: Jewish Lights Publishing; 1993:
pp 223-226.
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!

DISCUSSING DNR ORDERS – PART 1
Charles F von Gunten MD, PhD and David E Weissman MD
Background ‘Code status’ discussions with seriously ill patients should always take place in the
context of the larger goals of care, using a step-wise approach. This Fast Fact introduces an
approach to having these discussions; Fast Fact #24 discusses disagreements about ‘code
status.’ Prior to any discussion of a do-not-resuscitate (DNR) order, physicians must know the
data defining outcomes and morbidity of cardiopulmonary resuscitation in different patient
populations (see Fast Fact #179) and care settings (see Fast Fact #292 regarding DNR orders in
the Operating Room).
1. Establish the setting. Ensure comfort and privacy; sit down next to the patient. Ask if family
members or others should be present. Introduce the subject with a phrase such as: I’d like to talk
with you about possible health care decisions in the future.
2. What does the patient understand? An informed decision about DNR status is only possible
if the patient has a clear understanding of their illness and prognosis. Ask an open-ended
question to elicit patient understanding about their current health situation. It is important to get
the patient talking – if the doctor is doing all the talking, it is unlikely that the rest of the
conversation will go well. Consider starting with phrases such as: What do you understand about
your current health situation? What have the doctors told you about your condition? If the patient
does not know/appreciate their current status this is time to review that information.
3. What does the patient expect? Ask the patient to consider the future. Examples of ways to
start this discussion are What do you expect in the future? or What goals do you have for the time
you have left—what is important to you? This step allows you to listen while the patient describes
a real or imagined future. Many patients with advanced disease use this opening to voice their
thoughts about dying—typically mentioning comfort, family, and home, as their goals of care. If
there is a sharp discontinuity between what you expect and what the patient expects, this is the
time to clarify.
Listen carefully to the patient’s responses; most patients have thought a lot about dying, and only
need permission to talk about what they have been thinking. Setting up the conversation in this
way permits the physician to respond with clarifying and confirming comments such as:
So what you’re saying is – you want to be as comfortable as possible when the time comes? Or –
What you’ve said is – you want us to do everything we can to fight, but when the time comes, you
want to die peacefully? Whenever possible, ask patients to explain the values that underlie their
decisions: Can you explain why you feel that way?
4. Discuss a DNR order. Use language that the patient will understand; give information in small
pieces. Don’t introduce CPR in mechanistic terms (e.g. “starting the heart” or “putting on a
breathing machine”). Never say Do you want us to do everything? “Everything” is euphemistic
and easily misinterpreted. Using the word “die” helps to clarify that CPR is a treatment that tries
to reverse death. To most lay-people, when the heart and/or lungs stop, the patient dies.
If the patient and doctor mutually recognize that death is approaching and the goals of care are
comfort, then CPR is not an appropriate medical intervention and a clear recommendation
against CPR should be made. You can say: We have agreed that the goals of care are to keep
you comfortable and get you home. With this in mind, I do not recommend the use of artificial or
heroic means to keep you alive. If you agree with this, I will write an order in the chart that if you
die, no attempt to resuscitate you will be made.
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If the clinical situation is more ambiguous in terms of prognosis and goals of care, and you have
no clear recommendation, the issue of DNR can be raised by asking: If you should die in spite of
all of our efforts, do you want us to use heroic measures to attempt to bring you back? Or, How
do you want things to be when you die? If you are asked to explain “heroic measures”, then
describe the purpose, risks and benefits of CPR in greater detail. The clinical pearl here is to start
general and become specific later in the conversation.
5. Respond to emotions. Strong emotions are common when discussing death. Typically the
emotional response is brief. The most profound initial response a physician can make may be
silence, providing a reassuring touch, and offering facial tissues (see Fast Fact #29).
6. Establish a plan. Clarify the orders and plans that will accomplish the overall goals you have
discussed, not just the DNR order. A DNR order does not address any aspect of care other than
preventing the use of CPR. It is unwise and poor practice to use DNR status as a proxy for other
life-sustaining therapies. Consider using words: We will continue maximal medical therapy to
meet your goals. However, if you die, we won’t use CPR to bring you back. Or, It sounds like we
should move to a plan that maximizes your comfort. Therefore, in addition to a DNR order, I’d like
to talk further with you how we can best do that.
References
1. Quill TE and Brody H. Physician recommendations and patient autonomy: finding a
balance between physician power and patient choice. Ann Int Med. 1996; 125:763-769.
2. Buckman R. How to break bad news: a guide for health care professionals. Baltimore,
MD: Johns Hopkins University Press; 1992.
3. Junkerman C, Schiedermayer D. Practical Ethics for Students, Interns and Residents.
2nd Edition. Hagerstown, MD: University Publishing Group; 1998.
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!

Introduction The basic steps in the DNR discussion for seriously ill hospitalized patients were
described In Fast Fact # 23. If you have followed those steps, what do you do if the patient or
family/surrogate continues to want CPR and you think it is not in the patient's best interest? The
seemingly unreasonable request for CPR typically stems from one of several themes:
1. Inaccurate information about CPR. The general public has an inflated perception of CPR
success. While most people believe that CPR works 60-85% of the time, in fact the actual
survival to hospital discharge is more like 10-15% for all patients, and less than 5% for the elderly
and those with serious illnesses. This is a time to review/clarify the indications, contraindications,
potential outcomes and morbidity of CPR. Start the discussion by asking, “What do you know
about CPR?”
2. Hopes, fears, and guilt. Be aware that guilt (I haven't lived nearby to care for my dying
mother) and fear (I am afraid to make a decision that could lead to my wife's death) are common
motivating emotions for a persistent CPR request. Some patients or families need to be given an
explicit recommendation, or permission from the physician, to stop all efforts to prolong life, to be
told that that death is coming and that they no longer have to continue "fighting". Whenever
possible, try to identify the underlying emotions and offer empathic comments that open the door
to further conversation. This decision seems very hard for you. I want to give you the best
medical care possible; I know you still want CPR, can you tell me more about your decision?
Agreeing to a DNR order for many patients feels equivalent to them "choosing" to die.
Acceptance of impending death occurs over a vastly different time course for different patients/
families; for some, it never occurs. Some patients see CPR as a "last chance" for continued life.
Probe with open-ended questions: What do you expect to happen? What do you think would be
done differently, after the resuscitation, that wasn't being done before? Many patients describe
hope for a new treatment. Use the opportunity to respond by describing that you are doing
everything in your power to prolong their life before a cardiopulmonary arrest – you wouldn't be
"saving something" to do after they had died. If patients are not ready for a DNR order, don't let it
distract you from other important end-of-life care needs; emphasize the goals that you are trying
to achieve; save a repeat discussion for a future time; good care, relationship building and time
will help resolve most conflicts.
3. Distrust of the medical care system. Patients or families may give you a clue that there is
a fundamental distrust of doctors or the medical system; this should be addressed openly. What
you said makes me wonder if you may not have full trust in the doctors and nurses to do what is
best for you? Can you tell me about your concerns?
4. Managing persistent requests for CPR. Decide if you believe that CPR represents a futile
medical treatment—that is, CPR cannot be expected to either restore cardiopulmonary
function or to achieve the expressed goals of the patient (see Fast Fact #136). Physicians
are not legally or ethically obligated to participate in a futile medical treatment, and some
facilities have a policy that a physician may enter a DNR order in the chart against patient
wishes. Aside from writing a DNR order without patient or family agreement, other options
at this time include:
• Transfer care to another physician chosen by the patient/family.
• Plan to perform CPR at the time of death – but don't end the discussion. Engage the
patient about her or his wishes if she or he survive the resuscitation attempt. Tell the
patient that you need guidance because it is very likely that if she or he survives CPR,
!15
they will be on life support in the ICU, and they may not be able to make decisions for
themselves; ask them (or the family) to help you determine guidelines for deciding
whether to continue life-support measures. If not already done, clarify if there is a legal
surrogate decision-maker.
References
1. Cantor MD, et al. Do-Not-Resuscitate orders and medical futility. Arch Int Med. 2003;
163:2689-2694.
2. Layson RT, OcConnell T. Must consent always be obtained for a Do-Not-Resuscitate
order? Arch Int Med. 1996; 156:2617-2620..
3. Diem SJ, Lantos JD, Tulsky JA. Cardiopulmonary resuscitation on television. Miracles
and misinformation. NEJM.1996; 334(24):1578-82.
4. Council on Ethical and Judicial Affairs. Medical futility in end-of-life care: Report of the
Council on Ethical and Judicial Affairs of the AMA. JAMA. 1999; 281:937-941. .
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!

WHAT DO I TELL THE CHILDREN?
Paula Rauch and Robert Arnold MD
Background The death of a young adult is always difficult, even more so when there are young
children survivors. A common question asked by dying adults or their family members is What
do I tell the children? Physicians and other health care providers can provide leadership and
guidance to help young families through this crisis.
I. Screening and awareness

• Ask if the ill person has children at home. Ask about their age, personality, and coping
style.
• Ask what the ill person has told the children about the illness.
• Ask if they have a specific worry about the child.
• Ask if the child has had recent problems in school, at home or with relationships.
• Ask who they would like to talk to if they have concerns?
II. Give them some words.

• Often a parent’s biggest worry is what to say if the child asks if he or she is dying. Here
are two examples of words a parent might use. Asking a parent if these words would feel
comfortable to say can begin a dialogue between patient and clinician to arrive at
language that is honest, and life affirming.
• “X” can kill people, but I am taking the best care of myself I can. I am following the
doctor’s plan so that I can live as long as possible.
• Even with trying my hardest and getting the best possible care, my ____ is getting worse;
still I plan to live every day.
III. Give adults concrete examples to guide their interactions.

• Express interest in the child’s day.
• Work to maintain normal routines (e.g. maintain family rituals: Friday night supper,
Monday night pizza, watching television together).
• Welcome all questions but do not force discussions. Make sure you understand the real
question before answering. Take your time to think about how you want to answer.
• Overhearing bad news is the worst way to hear it. Talk with children from diagnosis
onward, being sure to give updates when there are changes in prognosis or treatment.
• Avoid euphemisms (e.g. lump, boo-boo, or sickness) that may confuse children.
• Ask children to share what they are thinking, or hear from others, so they do not worry
alone.
• Prepare children for visits with the sick person. Describe what they are likely to see.
Bring along another adult who is comfortable to stay only as long as the child wants.
Bring along markers and paper, so children can leave the parent with a picture or
message.
• Talk to the child's teacher or guidance counselor to alert the teachers. Ask teachers and
the child's friends' parents to let the parent know if the child talks about worries.
IV. Refer adults to one of the popular books on the subject (Kroen, McCue)
V. Know the resources for parents and children in your hospital and community
VI. Consider referral to a child life specialist or mental health professional when any of the
following occur:
• Symptoms of depression or anxiety that interfere with school, home or with peers
• Risk taking behavior
!17
• Significant discord between the child and the surviving parent
• Significant discord between the parents
• The child says he or she wants to talk to someone outside of the family.
References:
1. Rauch P. Comment: Supporting the Child Within the Family. J Clin Ethics. 2000;
11:169-170.
2. Harpham,W. When a Parent Has Cancer. A Guide to Caring for Your Children. San
Francisco, CA: HarperCollins; 1997.
3. Keeley D. Telling Children About a Parent's Cancer. BMJ. 2000; 321:462-463.
4. Krementz J. How It Feels When a Parent Dies. New York, NY: Alfred Knopf; 1988.
5. Kroen WC. Helping Children Cope with the Loss of a Loved One. Minneapolis, MN: Free
Spirit Publishing; 1996.
6. McCue K. How to Help Children Through a Parent's Serious Illness. New York, NY: St.
Martins Griffin; 1994.
7. Rauch PK, Muriel AC. Raising an Emotionally Healthy Child When a Parent is Sick. New
York, NY: McGraw-Hill; 2005.
published August 2005; 3rd Edition May 2015. Current version re-copy-edited April 2009; then
again May 2015.
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!

INFORMING SIGNIFICANT OTHERS OF A PATIENT'S DEATH
Diane Midland BSW, MS
Introduction This Fast Fact reviews the components of a sensitive notification of loved ones
when a patient dies. The physician is a key figure in the death notification process. Family and
friends who are present at the time of death look to the physician for information, reassurance
and direction regarding the weeks and months ahead. The lasting impression and memories that
family members have regarding the manner in which they received word that their loved one died
may affect the grief process and eventual integration of the loss within the survivors' world.
Research has demonstrated that the skills of compassion and sensitivity can be learned and must
be incorporated into the practice of all physicians.
A. Preparation
1. Confer with nursing and other staff working with the family/significant others. Review the
medical record (including any advance directive).
2. Examine the patient; confirm death (see Fast Fact #4).
3. Find a private place to meet with family/significant others.
4. Involve other members of the interdisciplinary team (e.g. nurse or chaplain) in the
notification process.
5. If possible, learn the names of those you will be talking with and their relationship to the
deceased.
B. Meeting with the Family/Significant Others
1. Introduce yourself and identify those present. In situations where there are family and
friends present, ask the next-of-kin who they would like with them during the
conversation.
2. Identify and respect ethnic, cultural or religious traditions (see Fast Fact #26).
3. Invite those present to sit down with you. Use body language, eye contact and touch
(introductory hand shake or clasp), if appropriate and accepted by family/significant
others.
4. Express your condolence (e.g. I’m sorry for your loss; My condolences to you and your
family.)
5. Talk openly about the death. Use "died" or "dead" during the initial conversation. Listen
for the words used by the family/significant others to describe death and use their term(s)
throughout the remaining discussion. Refer to the deceased by name.
6. If requested, explain the cause of death in non-medical terms. Allow time for questions;
be open to acknowledging that there may be things you don't know. Offer assurance that
everything possible was done to keep the patient comfortable.
7. Be prepared for a range of emotional expression. Do not offer sedation as a way to deal
with expressions of emotion. (Mild sedation for a brief time period may be considered to
assist with insomnia.)
8. Offer the opportunity to view the deceased. Prepare family/significant others for how the
deceased will appear; model touching and talking to the deceased. Offer time alone with
the deceased and assurance that survivors will not be rushed.
9. Provide time for the family/significant others to process the reality of the death before
discussing autopsy or tissue/organ donation.
10. Let family/significant others know that you will return, should questions arise or
they desire additional information. Provide information about how the family can
reach you after they leave the facility.
C. Follow-up
1. Personalize and sign a sympathy card to the bereaved (see Fast Fact #22).
2. Consider attending the wake, funeral, or memorial service.
!19
3. Consider referral to a bereavement support service or agency, particularly if children are
involved.
4. Encourage the bereaved to schedule a physical exam four to six months after the death.
5. Invite the bereaved to meet with you regarding autopsy results or to discuss unresolved
questions.
References
1. Schaefer C, Quesenbery CP Jr, Wi S. (1995). Mortality following conjugal bereavement
and the effects of a shared environment. Am J Epidemiology. 1995; 144(12):1142-52.
2. Shively P, Midland D, eds. The Art of Compassionate Death Notification. La Crosse, WI:
Gundersen Lutheran Medical Foundation; 1999.
3. Tolle SW, Bascom PB, Hickman DH, Benson JA. Communication between physician and
surviving spouses following patient deaths. J Gen Int Med. 1986; 1:309- 314.
4. Witter DM, Tolle SW, Moseley JR. A bereavement program: good care, quality assurance,
and risk management. Hosp Health Services Admin. 1990; 35(2):263-275.
5. Zunin HS, Zunin LM. The Art of Condolence, What to Write, What to Say, What to do at a
Time of Loss. New York, NY: Harpers Collins; 1991.
published July 2006; 3rd Edition May 2015. Current version re-copy-edited April 2009; then again
May 2015.
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!

TELEPHONE NOTIFICATION OF DEATH – Part I
Rosalia R Osias MD, Daniel H Pomerantz MD, Jeffrey M Brensilver MD, FACP
Background Telephone notification to family members about a death is one of the most
challenging and stressful communication skills, especially for cross-covering housestaff who may
have had no direct interactions with the patient or family. Unpredictable variables are involved;
telephone notification does not allow the same level of interaction possible with direct personal
contact. This Fast Fact offers some guidelines when telephone notification is unavoidable; Fast
Fact #77 discusses issues surrounding whether or not to delay notification of death until loved
ones arrive at the hospital.
I. Preparing for the Call
1. Review death pronouncement protocol (See Fast Facts # 4 and 64).
2. Positively identify the patient (hospital ID tag) and confirm death.
3. Obtain relevant information; e.g. patient's name, age, gender, identification numbers.
4. Obtain the full name, address, phone number(s) of the person/s you are calling. Try to
establish from the chart and nursing staff the relationship of the contact to the deceased
patient.
5. Establish the circumstances of death; expected or sudden. Write down the key
information you need and thoroughly review what you will say.
6. Find a quiet or private area with a phone.
II. Timing
The call should be made as soon as possible following the death. Whenever possible, inform
the family of a grave turn of events prior to the patient dying. When substantial delay is likely,
the responsibility for informing the family should be taken by the covering doctor (or the
resident).
III. The Actual Notification
1. Identify yourself. Ask the identity of the person you are talking to and their relationship to
the patient. Ask to speak to the person closest to the patient (ideally, the health care
proxy or the contact person indicated in the chart). Avoid responding to any direct
question until you have verified the identity of the person to whom you are speaking. Ask
if the contact person is alone. Do not give death notification to minor children.
2. If you do not have a prior relationship with the person you are speaking to, ask what they
know about the patient’s condition: What have the doctors told you about _____’s
condition?
3. Provide a warning shot: I’m afraid I have some bad news.
4. Use clear and direct language, no medical jargon: I’m sorry, _____ has just died. Words
like "dead" or "died" should be used. “Expired”, “passed away” or "didn't make it" can be
misinterpreted.
5. Speak clearly and slowly, allow time for questions. Be empathetic. A perceptive family
can easily tell whether the notifier cares or is merely "going through the motions.”
6. If the family chooses to come to see the body, arrange to meet them personally.
7. Provide contact information for the physician or hospital official who can meet with them
and answer questions about the patient's death and other administrative issues.
8. Ask if you can contact anyone for them. Assess their emotional reaction (see Fast Fact
#77).
9. If you feel uncomfortable about telephone notification, ask for help.
10. Never deliver the news of death to an answering machine or voice mail. Instead, leave
specific contact information. If you are unable to make contact within 1-2 hours, contact a
hospital representative (e.g. social worker) to assist you in locating family or others.
References:
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1. Iserson KV. The gravest words: sudden-death notification and emergency care. Ann
Emerg Med. 2000; 36:75-77.
2. Iserson KV. The gravest words: notifying survivors about sudden, unexpected deaths.
Resident and Staff Physician. 2001; 47:66-72.
published October 2006; 3rd Edition June 2015. Current version re-copy-edited April 2009; then
again May 2015.
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!

TELEPHONE NOTIFICATION OF DEATH – PART II
Introduction In Part I (Fast Fact # 76), the basic steps and precautions of telephone notication
of death were outlined. This Fast Fact discusses the dilemma of whether to provide telephone
information versus asking family members to first come to hospital before telling them that death
has occurred.
Delay vs. Disclose Immediately Few would disagree that it is always preferable to present
death notification in person. However, when families live at a great distance, or are physically
unable to travel, telephone discussion will be necessary. In other situations, clinicians must
weigh the benefits of truthfulness against the risk of potential harm resulting from abrupt
disclosure of the bad news. Factors to consider in making this decision include:
• Whether death was expected or not, including the nature and chronicity of the illness.
• How well the death notifier knows the patient and the patient’s family.
• The relationship of the contact person to the patient.
• The anticipated emotional reaction of the contact person based on prior information.
• Whether the contact person will be alone when receiving the information
• The contact person's level of understanding.
• Distance, availability of transport, and time of day.
For example, when death is expected due to progressive cancer and the notifier knows both the
patient and the contact person, telephone notification is very acceptable. In fact, you should have
prepared for this moment ahead of time by asking the contact how he or she wishes to be
contacted at the time of death. In contrast, if the death is sudden, especially of a minor,
notification in person is always preferred, although time and distance issues may make this
impractical.
The notifier must be prepared to quickly integrate all these factors to decide whether to reveal
that the patient is dead, or whether to describe the patient as gravely ill and request that the
contact person come to the hospital immediately. If you decide to delay disclosure of the death,
be prepared to make immediate admission of such nondisclosure as soon as you meet the family
(e.g. I'm sorry for not telling you the whole thing right away over the phone; then give your
reason for doing so).
Responding to Emotions Whether in person or by telephone, you should expect an

emotional reaction to the death notification (see Fast Fact #29). Responding to emotions via
telephone is especially difficult. Some tips include:
• Ensure that the contact has someone else with them. Offer to contact family members,
friends, clergy or others.
• Offer to meet with the contact in person.
• Contact your hospital social worker for advice on contacting other local resources such
as the Red Cross, local police, or other service agencies.
References:
Emerg Med. 2000; 36:75-77.
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again June 2015.
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!

COMPLETING A DEATH CERTIFICATE
Nikkisha Prentice and Robert Arnold MD
Background Physicians are responsible for providing proper documentation of death. This
Fast Fact reviews key steps in the completion of a death certificate.
Importance of Proper Completion Death certificate information is a permanent record of
death. It is usually necessary for burial and settlement of the deceased’s estate. Documentation
of the cause of death, in addition to direct communication, may provide family members with
closure and peace of mind. Death certificates are also used to 1) evaluate the general health of
the population, 2) assess the prevalence of medical problems among specific groups, 3) triage
medical research needs, and 4) apportion health services, grants, and other resources to
common illnesses.
Basic Guidelines Death certificates are governed by state statutes; variations exist in who can
complete a death certificate and how they should be filled out. Certification and completion of
death certificates is usually the primary responsibility of the attending physician. However, in
some states, death may be certified by the attending advanced practice nurse.
• Verify the correct spelling of names.

• Personally sign the death certificate; stamps are unacceptable.
• Complete all required items. If necessary, write “unknown” or “pending further study.”
• Common Errors
o Do not delay completion of the certificate. Some states have specific time periods
and civil and/or criminal penalties for non-completion. Moreover, funeral homes will
typically not proceed with burial without the death certificate.
o Do not use abbreviations.
o Some state forms require you spell out the month.
o Use 24 hour clock rather than 12:00 midnight.
o Some state forms do not allow alteration of the document; avoid erasing or using
white-out.
o Avoid cursive writing; print clearly or type using black ink.
Causality of Death This section of the certificate often consists of two parts. The first part asks
for a sequential chain of events that led to death and the time interval between onset of a
condition and death. The most immediate cause of death is stated on line a and the underlying
causes follow on lines b, and so on. In assessing the approximate interval between onset and
time of death, terms such as “unknown” or “approximately” may be used and general terms such
as “minutes,” “hours,” and “days” are acceptable. The second part asks about other significant
conditions that contributed to death, but that did not result in the underlying cause stated
previously.
Mechanism vs. Cause of Death It is important not to write the mechanism of death (i.e.
cardiac arrest, respiratory arrest) as the cause of death. The mechanism of death is the
physiologic derangement or biochemical disturbance by which the cause of death exerts its lethal
effect. For accurate public health records, the cause of death (e.g. chronic obstructive pulmonary
disease) is more helpful than the mechanism of death (e.g. respiratory failure). When there is
doubt as to the cause of death, it is acceptable to enter “unknown” or “pending further study.” In
some states, a condition may also be listed as “probable.” As additional medical information,
such as an autopsy report, becomes available, the certifying physician should report amendments
to the state vital records office or local registrar.
Note: Listed below are common terms and definitions that are generally interchangeable
between states. The table presents some examples.
• Immediate (or Principle) Cause = Final complication resulting in death.
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• Intermediate (or Antecedent or Underlying) Cause = Disease or condition causing the
immediate cause of death.
• Underlying (or Contributory) Cause = The condition present before and leading to the
intermediate or immediate cause of death.
Example 1 Example 2 Example 3 Example 4

D. Line A Acute Myocardial Acute Pulmonary Pneumocystis
Infarction Exacerbation of Embolism jiroveci
Obstructive pneumonia
Airway Disease
Line B Coronary Artery Chronic Deep Venous Acquired
Disease Bronchitis Thrombosis Immunodeficienc
y Syndrome
Line C Chronic Ischemic Metastatic Non- Human

Heart Disease Small Cell Lung Immunodeficienc
Cancer y Virus
Mechanism Cardiac Arrest Respiratory Respiratory Arrest Septic Shock
of death Arrest
Other Diabetes Smoking Stroke,
Significant Hemiparesis
Conditions
References
1. Campos-Outcalt D. Cause-of-death certification: Not as easy as it seems. J Fam
Practice. 2005. 54(2):134-138
2. Herring ME. The Death Certificate. AAHPM Bulletin (reprinted with permission of the
Camden Medical Society). Winter 2005; 8-9.
3. Lakkireddy DR, Gowda MS, Murray CW, Basarakodu KR, Vacek JL. Death Certificate
Completion: How well are physicians trained and are cardiovascular causes overstated?
Am J Med. 2004; 117:492-498.
4. Magrane BP, Gilliland MG, King DE. Certification of death by family physicians. Am Fam
Physician. 1997; 56:1433-8.
5. Myers KA, Farquhar DE. Improving the accuracy of death certification. CMAJ. 1998;
158:1317-23.
6. Nowels D. Curbside consultation: completing and signing the Death Certificate. Am Fam
Physician. 2004; 70(9):1873.
7. Physicians’ Handbook on Certification of Death. Department of Health and Human
Resources, Centers for Disease Control and Prevention, National Center for Health
Statistics; April 2003. DHHS Publication No. (PHS) 2003-1108.
Version History: This Fast Fact was originally edited by David E Weissman MD and published
in May 2006. Version copy-edited in April 2009; then again July 2015.
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ADVANCE CARE PLANNING IN CHRONIC ILLNESS
Sara N Davison MD
Background A cornerstone of excellent medical care is helping patients decide how future
medical interventions match their personal goals and values for care near the end-of-life. This
Fast Fact reviews key concepts of the Advance Care Planning (ACP) process.
Advance Care Planning is a process of communication between the patient, the family/health
care proxy, and staff for the purpose of prospectively identifying a surrogate, clarifying treatment
preferences, and developing individualized goals of care near the end of life. Advance Directives
(e.g. living wills, durable powers of attorney for health care) are legal documents with capabilities
and requirements that vary between jurisdictions.
Primary Goals of ACP
• Enhance patient and family education about their illness, including prognosis and likely
outcomes of alternative care plans.
• Define the key priorities in end-of-life care and develop a care plan that addresses these
issues.
• Shape future clinical care to fit the patient's preferences and values.
Other Potential Benefits of the ACP process
• Help patients find hope and meaning in life, and help them achieve a sense of spiritual
peace.
• Strengthen relationships with loved ones.
Timing At a minimum, ACP should be considered whenever the health care provider would not
be surprised if that patient died within the next 12 months.
Facilitating ACP
• Take the lead in starting the discussion. Many patients are reluctant to initiate an ACP
discussion; physicians and nurses can “open the door” to such discussions by asking,
How do feel things are going? Have you given any thought to how you wish to be cared
for should your illness worse?
• Explain the rationale for ACP. Patients identify ACP as an important part of medical
care if they have a clear idea of how the process will benefit them: I’d like to spend some
time talking to you about the future course of your illness so that I have a clear
understanding of your wishes.
• Use good communication skills. Do not use medical jargon (e.g. ‘ventilator’);
language used should be positive (I want to ensure you receive the kind of treatment you
want). Use empathetic listening skills (using words, posture and appropriate touch to
convey sense of caring) to help build a trusting relationship. Ensure privacy and allow
sufficient time for the discussion.
• Provide information. Patients require realistic information on prognosis and treatment
options with an emphasis on how you expect their illness will impact their daily function.
• Identify a surrogate. Patients should be encouraged to both identify a surrogate
decision-maker and, most importantly, discuss their wishes with this individual. The
power of the ACP discussion is the sharing of information between patient and the
patient’s surrogate decision maker and other family members, and the health care team.
The surrogate should have the greatest knowledge of the patient’s preferences and
values. If desired, offer to facilitate a discussion between the patient and their surrogate
or other family members.
• Identify how future decision-making will occur. A patient may have specific desires
for how information is shared among family members – this needs to be explicitly
discussed.
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• Determine goals of care. If decisions need to be made at the same time as an ACP
discussion, this is an appropriate venue to establish the goals of care (see Fast Fact #16,
65).
Cautions
• The ACP process must be sensitive to disease, gender, age, social and cultural contexts.
• Providing opportunities to discuss end-of-life issues does not mean everyone will want or
be able to do so at that moment. ACP is an evolving process that requires varying
amounts of time to be effective. Patients often need time to reflect on information and
how it impacts their lives.
References
1. Martin DK, Thiel EC, Singer PA. A new model of advance care planning.
Observations from people with HIV. Arch Intern Med. 1999; 159: 86-92.
2. Briggs L. Shifting the focus of advance care planning: using an in-depth
interview to build and strengthen relationships. Innovations in End-of-Life Care.
2003; 5(2). Available at: http://www2.edc.org/lastacts/archives/
archivesMarch03/default.asp.
3. Johnstone SC, Pfeifer MP, McNutt R. The discussion about advance directives.
Arch Intern Med. 1995; 155:1025-1030.
in September 2006. Version copy-edited in April 2009; then again July 2015.
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CONFLICT RESOLUTION I: CAREFUL COMMUNICATION
Adam Kendall MD, MPH and Robert Arnold MD
Background Conflicts about medical care occur frequently at the end of life. These conflicts
threaten therapeutic relationships and lead to patient, healthcare provider, and family
dissatisfaction. Conflict between the patient/family and physician may arise from simple factual
misunderstandings about medical care. Frequently, however, conflict is driven by a patient’s or
family’s emotions such as feeling unheard or ignored, as well as having goals that conflict those
of the medical team. In these instances, attempting to convince a patient or family through
providing additional medical information will not work. This Fast Fact provides an alternative
approach to conflict resolution based on understanding a patient’s or family’s story, attending to
their emotions, and establishing shared goals. A subsequent Fast Fact (#184) will focus on
conflict resolution employing the techniques of Principled Negotiation.
1. Learn the patient’s and family’s story

• Begin discussions with a genuine curiosity to learn what they perceive to be the course of
events during the illness.
• Explore the context of the patient’s illness narrative with attention paid to their
relationships with doctors, their sources of medical information, and their life goals (see
Fast Fact #26)
• Avoid presenting agenda items for a meeting that are defined by the medical team’s
priorities. Instead, focus on the patient’s and family’s concerns.
• If a patient or family is asking for treatment against the recommendation of the medical
team, focus on the context of the request. Have they been let down by the medical
system in the past? Have they found that others in their family have benefited from the
treatment they request?
• Find out how they want information presented to them. Do they want specific benefits
and risks? Do they want written information?
2. Attend to emotions
• Conflict can cause strong emotions in healthcare providers including guilt, anger, and
resentment. Acknowledge these emotions to yourself and other professionals, but strive
to prevent them from interfering with your interactions with the patient and family.
• Patient and family emotions such as grief, disappointment, and anger are to be expected
in these situations. Compassionately acknowledge and address these emotions as they
arise, and allow the patient and family to express what is making a situation frustrating for
them (see Fast Facts #29, #59). When people are emotionally stressed, they may have
trouble cognitively processing information. Empathically attending to emotions often
allows a patient or family to move on to understanding medical information.
• If a family is focusing on what they believe was an error in care, be transparent about
where a mistake may have been made (see Fast Facts #194, 195). Apologize. Even if it
was not an error, one can acknowledge how frustrating the situation is. Saying “I can tell
that this situation is frustrating for you,” is not an admission of error—it is empathic.
3. Establish shared goals for treatment

• Use the patient’s core values as a foundation for developing a treatment plan. “I would
like to know more about your mother and what her values have been during her life.”
• Ask about a patient’s goals including what they would want if they were dying or if there
were no curative treatments available for their condition.
• When there are requests for ineffectual treatment, describe instead where the medical
team can make a difference for the patient, in relation to their goals. “Please correct me
if I’m wrong, but it sounds like your mother really values her independence and freedom
from being in pain. Let’s try to figure out how we can best help her achieve these goals.”
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Summary Providing medical information to patients and families may seem at first to be the
most natural approach to resolving conflict. Addressing the underlying roots of conflict will have a
longer lasting effect. The above approach emphasizes resolving conflict through finding mutual
trust and shared goals between physicians, patients, and families.
Reference
Stone D, Patton B, Heen S. Difficult Conversations: How to Discuss What Matters Most. New
York, NY: Penguin Books; 1999.
Version History: Originally published July 2007. Version re-copy-edited in May 2009; then
again July 2015.
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!

CONFLICT RESOLUTION II: PRINCIPLED NEGOTIATION
Adam Kendall MD, MPH and Robert Arnold MD
Background When conflicts about medical care persist despite gaining mutual trust and a
deep understanding of goals (see Fast Fact #183), it may be effective to use principled
negotiation. Principled negotiation is an approach to resolving conflict that avoids power
struggles and unwanted compromises. The following is an illustration of the steps that are
involved. Within each step, we will refer to a case example: a family who is requesting artificial
feeding against medical advice for their father who is dying from end-stage dementia.
1. Separate people from the problem. Identify the fundamental problem, separating that from
individuals’—on both sides—intentions and culpability.
• The problem is not that the family members are “in denial” that their loved one is dying or
“uneducated” when they do not hear the medical team’s recommendations.
• The problem is not that the family is acting out their frustration by making unreasonable
demands.
• Nor is the problem that the medical team and hospital are trying to withhold treatment
from the patient or “giving up” on him.
• The problem is that the patient is dying, no longer able to eat properly, and that artificial
nutrition does not improve quality or quantity of life in this situation.
2. Focus on interests. Listen to requests and demands but try to look into underlying interests.
In addition, express the intentions and goals of the medical team.
• The family wants what is best for the patient. Their intent may be to provide comfort and
to build up the patient’s strength, and to prevent a painful starvation.
• The medical team wants to provide the best medical care for the patient. Their intent
may be to avoid an intervention that has no clear benefit for the patient, may cause harm,
and may not have been desired by the patient.
3. Invent solutions. Avoid contrasting different philosophies of medical care. Instead, propose
a plan of care that meets a family’s expectations without detracting from good medical care.
Consideration could be given to:
• Meeting the family’s goals of providing food by allowing for the patient to taste home
cooked meals.
• A short trial of tube-feeding with the plan to continue only if the overall quality of life for
the patient improves.
• A trial of attentive oral feeding with a plan to reconsider tube feeding if the patient
appears to be hungry or otherwise suffering.
• Solutions that do not promote mutual interests are: placing a feeding tube without a plan
to measure its success or failure at meeting a goal, arranging for another medical team to
take over the patient’s care, or referring the case to an ethics committee.
4. Outline objective criteria. If a time trial is being pursued, agree upon what the deciding
factors would be in determining a trial’s success. Provide objective information to substantiate
medical recommendations.
• Establish signs of improvement or worsening such as functional ability, weight, ability to
interact, and level of consciousness.
• Establish criteria for harm such as infections, restraint or sedative use, hospitalizations or
emergency department visits.
• Consider providing publications from organizations that advocate for patients and
families, and are not associated with physicians or hospitals.
• Provide opinions or guidance from individuals outside of the conflict. These could include
social workers, case managers, chaplains, or therapists.
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References
1. Fisher R, Ury W. Getting to Yes: Negotiating Agreement Without Giving In. New York,
NY: Penguin Books; 1992.
2. King DA, Quill T. Working with families in palliative care: one size does not fit all. J Pall
Med. 2006; 9(3):704-715.
Version History: Originally published July 2007. Version re-copy-edited in May 2009; then
copy-edited again in July 2015.
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!

PREPARING FOR THE FAMILY MEETING
David E Weissman MD, Timothy E Quill MD, and Robert M Arnold MD
Background A cornerstone procedure in Palliative Medicine is leadership of family meetings to

establish goals of care, typically completed at a time of patient change in status, where the value
of current treatments needs to be re-evaluated. As with any procedure, preparation is essential to
ensure the best outcome. This Fast Fact reviews how to prepare for a Family Meeting. See also
Fast Fact #16 for a concise overview of family meetings, as well as Fast Facts 223-227 for
discussion of additional aspects of family conferences.
Data Review
• Review the medical history relevant to the current medical situation (e.g. history of disease
progression, symptom burden, past treatments, treatment-related toxicity, and prognosis).
• Review all current treatments (e.g. renal dialysis, artificial nutrition, antibiotics) and any
positive and/or negative treatment effects.
• Review all treatment options being proposed.
• Determine the prognosis with and without continued disease-directed treatments. Prognostic
information includes data concerning future patient function (physical/cognitive), symptom
burden, and time (longevity).
• Solicit and coordinate medical opinions about the utility of current treatments among
consultants and the primary physician. If possible, families need to hear a single medical
consensus—all relevant clinicians should be contacted and consensus reached prior to the
meeting. If the consultants do not agree, then prior to the family meeting they should meet to
negotiate these differences and attempt to reach consensus regarding the plan. If there is no
consensus, a plan should be developed for how to describe these differences to families.
• If the patient lacks capacity, review any Advance Directive(s), with special attention to
discover if the patient has named a surrogate decision maker, and if the patient has indicated
any specific wishes (e.g. DNR status, ‘no feeding tubes’).
• Seek out patient/family psychosocial data. Focus on psychological issues and family
dynamics (e.g. anger, guilt, fear) potentially impacting decision making. These issues may be
long-standing, or due to the current illness. Note: talking to the patient’s social worker,
bedside nurses, and primary and consulting physicians can help you get a better sense of the
family and how they make decisions.
o Review what transpired in prior family meetings.
o Learn about particular cultural/religious values and/or or social/financial issues that may
impact decision making.
Information Synthesis Based on your review of the medical and prognostic data, make an
independent determination of which current and potential tests/treatments will improve, worsen,
or have no impact on the patient’s function/quality of life (physical/cognitive) and time (longevity).
Meeting Leadership Leading a family meeting requires considerable flexibility to ensure that
all relevant participants have the opportunity to have their points of view expressed. Though it is
useful to have one person designated as the main orchestrator and coordinator of the meeting,
the essential skills for making a family meeting successful can come from more than one
participant. These skills include:
• Group facilitation skills.
• Counseling skills.
• Knowledge of medical and prognostic information.
• Willingness to provide leadership/guidance in decision making.
Invitations A decisional patient can be asked who he/she wants to participate from his/her
family/community, including faith leaders; in general it is wise not to set any arbitrary limits on the
number of attendees. The medical care team should likewise decide who they want to
!34
participate. Note: it is important not to overwhelm a family with too many health professionals.
On the other hand, a physician from the primary team as well as a nurse and social worker
should attend when possible; these individuals can help ensure the consistency of information as
well as help deal with complicated dynamics. If the patient has a long-time treating physician
whom he/she trusts, this person should ideally be present.
Setting The ideal setting is private and quiet, with chairs arranged in a circle or around a table.
Everyone should be able to sit down if they wish. For non-decisional patients, the clinical team
should negotiate with the surrogate whether or not to have the meeting in the presence of the
patient.
The Pre-Meeting Meeting The participating health care members should meet beforehand to
confirm: a) the goals for the meeting (e.g. information sharing, specific decisions sought), b) who
will be the meeting leader to start the meeting, and c) likely sources of conflict and initial
management strategies.
References
1. Back A, Arnold R, Tulsky J. Mastering communication with seriously ill patients:
balancing honesty with empathy and hope. New York, NY: Cambridge University Press;
2009.
2. Curtis JR, Patrick DL, Shannon SE, et al. The family conference as a focus to improve
communication about end-of-life care in the intensive care unit: opportunities for
improvement. Crit Care Med. 2001; 29(2 Suppl):N26-33.
3. Lautrette A, Ciroldi M, Ksibi H, Azoulay E. End-of-life family conferences: rooted in the
evidence. Crit Care Med. 2006; 34(11):S364-S372.
Med. 2006; 9:704-715.
5. Weiner JS, Roth J. Avoiding iatrogenic harm to patient and family while discussing goals
of care near the end of life. J Pall Med. 2006; 9:451-463.
6. Weissman DE. Decision making at a time of crisis near the end of life. JAMA. 2004;
292:1738-1743.
Author Affiliations: Medical College of Wisconsin, Milwaukee, WI (DEW); University of

Rochester Medical Center, Rochester, NY (TEQ); University of Pittsburgh School of Medicine,
UPMC Health System, Pittsburgh, PA (RMA).
Version History: Originally published October 2009; copy-edited August 2015.
emerge after a Fast Fact is published. Health care providers should always exercise their own independent
clinical judgment and consult other relevant and up-to-date experts and resources. Some Fast Facts cite the
use of a product in a dosage, for an indication, or in a manner other than that recommended in the product
labeling. Accordingly, the official prescribing information should be consulted before any such product is
used. 
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!

THE FAMILY MEETING: STARTING THE CONVERSATION
David E Weissman MD, Timothy Quill MD, and Robert M Arnold MD
Background Fast Fact #16 gives a concise overview of running a family meeting. Fast Fact
#222 provides a list of preparatory steps in planning for a family meeting to discuss end-of-life
goals; this Fast Fact reviews the early steps of the actual meeting.
1. Introductions & setting goals for the meeting

• The meeting leader begins the meeting by introducing him or herself, and suggesting that
each person present (medical team and family/community) introduce themselves
including their relationship to the patient.
• The meeting leader should summarize the meeting goals (e.g. We are here to discuss
next steps in the care of Mr. Jones) and ask the family to confirm these goals and/or add
other agenda items.
• Note: if you do not know the patient or family well, take a moment to build relationship.
Ask a non-medical question such as I am just getting to know you. I had a chance to look
at your chart and learn about your medical condition but it does not say much about your
life before you got sick. Can you tell us about the things you liked to do before you got
sick? Similarly, if the patient is not able to participate in the meeting, ask family to
describe the patient prior to his becoming ill: As we get started, can you describe what
Mr. Jones was like before he became ill?
2. Determine what the patient/family already knows This step is essential as it guides you in
providing a synthesis of the medical information (see below). Always invite the patient and all
family members to provide their understanding of the medical information. Examples of opening
lines:
• Tell me what the doctors have told you about your condition?
• Can you describe for me your sense of how things are going?
• For patients who have been declining from a chronic illness, you can ask: Tell me about
the past 3-6 months: what types of changes have you noted? The patient or family will
typically describe changes in terms of function (physical or cognitive) and quality of life.
3. The Medical Review Once you know what the patient/family understands, you are in a good
position to confirm their understanding, or provide new information/correct misunderstandings.
First, ask if you can bring them up-to-date about what is going on; asking shows politeness and
also signals that they should attend to what you are trying to say. The clinician most closely
aligned with the patient’s ongoing treatment should begin this discussion, supplemented with
information from consulting services if relevant. Do not provide information using medical jargon
or in an organ system approach (e.g. The creatinine is improving, but there is a new pleural
effusion and the heart rate has become irregular). A more patient-centered approach is to
provide a succinct summary of the current condition, without any medical jargon, focusing on the
issues of most importance, which are usually function/quality/time. Give a ‘bottom-line’
statement: ‘getting worse,’ ‘not going to improve,’ ‘dying and time is likely very short.’
• The worsening weakness and pain you describe is from the cancer which is growing
despite the chemotherapy.
• You are telling me that despite the recent hospitalization, you are not able to do as much
around the house; unfortunately your lung disease is getting worse despite all our best
treatments.
• Despite our best efforts, your wife’s brain injury from the car crash is getting worse. She
can no longer stay awake or move her arms/legs.
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Using the ‘D word’ if relevant: when a patient is clearly deteriorating and death is likely within
the next days to weeks, or even a few months, it is appropriate to use the word dying in the
conversation. Both patients and surrogates find that saying the word dying, if done
compassionately, is helpful in clearing what is often a confusing and frightening situation. I’m
afraid we have run out of options to shrink the cancer. Based on your declining function, I believe
you are dying.
4. Silence Whether or not you use the word dying, when you have presented bad news (such
as information about disease progression), the next step is for you to allow silence, and let the
family/patient respond. In truth, no matter what you might imagine the response from the patient/
family to be once the bad news is delivered, you really cannot predict their emotional reaction
(e.g. relief, anxiety, anger, regret, fear). This silence can be uncomfortable; resist the urge to fill it
with more facts as they will not be heard. Not all patients/families express emotions at this point
and instead respond practically (Well, what happens next then?). This is fine, but you need to
wait, silently, to see what response the patient/family demonstrates. In addition, even practical
questions have underlying emotions (Are you sure? Or – There must be something you can do?).
It is important to respond to both the factual aspect of the question (Yes I am sure. Or – There are
no more effective treatments available.), as well as the emotional level (I wish I had better news
for you. Or – I wish our treatments worked better than they do.).
When the patient/surrogates openly acknowledge that current treatments are no longer effective,
that death is coming, they will generally ask one or all of the following questions: How long?
What will happen? Will there be suffering? What do we do now? Your response at this point
should be to address prognosis in terms of time, function, and symptoms, as best you can (see
Fast Facts #13,141,143,149,150). This will answer the first two questions; the last questions will
require more discussion of patient-centered goals (see Fast Fact #227).
References
2009.
2. Quill TE, Townsend P. Bad news: delivery, dialogue and dilemmas. Arch Intern Med.
1991; 151:463-468.
Med. 2006; 9:704-715.
6. Quill TE, Arnold RM, Platt FW. "I wish things were different": Expressing wishes in
response to loss, futility, and unrealistic hopes. Ann Intern Med. 2001; 135:551-555.

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RESPONDING TO EMOTION IN FAMILY MEETINGS
Background Family meetings are stressful events, often provoking strong emotional reactions.
Fast Fact #29 presents a general outline on the topic of how clinicians can respond to emotions.
The Fast Fact will provide a more detailed approach to emotions that arise during family
meetings.
Consider your role. It is important to reflect on the role of clinicians in responding to patient/
family emotions at the time life-altering information is shared. The goal is not to prevent a patient/
family from having those emotions. Sadness, fear, anger, and loss are normal responses to
unwelcome news. Instead your role is: 1) to maintain a trusting therapeutic relationship and safe/
supportive environment that allows emotions to be expressed in a way that meets the patient’s/
family’s needs; and 2) not to worsen the experience for the patient/family by ignoring or
delegitimizing their responses, or confusing them with medical information when they are not
ready to hear it. Recognize that most families find clinicians’ expressions of empathy
tremendously supportive and these are associated with family satisfaction.
Acknowledge that emotion is being expressed. If you have a good sense of what the emotion
is, then it is useful to name it. If not, using more general language is preferable.
• I can see this is really affecting you.
• This information is very upsetting.
Legitimize the appropriateness and normalcy of the reaction. Medical professionals are in a
powerful position to help patients and families feel that strong emotions under these
circumstances are normal and to be expected.
• Anyone receiving this news would feel devastated.
• It is completely expected to be very distressed by this kind of news.
Explore more about what is underneath the emotion. It is tempting to try to limit the emotion,
and be prematurely reassuring. But it is generally more helpful and ultimately more time-efficient
to allow the patient and family to more deeply explore their feelings and reactions.
• Tell me what is the scariest (most difficult) part for you.
• Tell me more about that…. (Keep the exploration going until it is fully expressed and
understood.)
Empathize (if you genuinely feel it). Empathy means being able to emotionally imagine what
the patient is going through. Clinicians can initiate the prior responses (acknowledge, legitimize,
explore) without having a clear feeling for the patient’s experience. These responses can be
adequate in themselves. If the clinician cannot imagine the patient’s experience, he or she can
still sensitively explore the experience and provide caring and support. But if you have a strong
sense of what the patient is experiencing, it can be very therapeutic to express it.
• This seems really unfair.
• I can imagine that you might feel very disappointed.
Explore strengths/coping strategies. This may occur at this phase of the interview, or it may
be postponed to a later phase when planning for next steps begins.
• In past circumstances, what has helped?
• How have you adapted to difficult circumstances in the past?
• What are you hoping for now?
References
1. Back A, Arnold R, Tulsky J. Mastering communication with seriously ill patients: balancing
honesty with empathy and hope. New York, NY: Cambridge University Press; 2009.
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2. Suchman AL, Markakis K, Beckman HB, Frankel R. A model of empathic communication
in the medical interview. JAMA. 1997; 277:678-682.
3. Hardee JT. An overview of empathy. The Permanente Journal. 2003; 7(online). Available
at: http://xnet.kp.org/permanentejournal/fall03/cpc.html. Accessed August 5, 2009.

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THE FAMILY MEETING: CAUSES OF CONFLICT
Background When family meetings are conducted with the goal of helping a patient/family cope
with a shift in goals from life-sustaining treatments to a more comfort focused approach,
communication can break down. This Fast Fact reviews the common causes of conflict.
Recognizing Conflict When the patient/surrogates are not psychologically ready to accept the
limits of medical interventions or the finality of the impending death, you will hear comments such
as these: There must be some mistake; I know there are other treatments available; We want a
second opinion; We believe in miracles; She is fighter, she will never give up; There must be
something (medically) you can do. Health professionals may interpret these statements as
‘denial.’ But the term denial, by itself, is insufficient to help the clinician understand what is
causing the impasse. Understanding the cause is essential in planning an effective strategy to
move beyond the conflict to meet the needs of the patient and surrogates.
Information Gaps
• Inaccurate understanding of the patient’s medical condition (e.g. overly optimistic/
pessimistic prognosis).
• Inconsistent information (One doctor tells us one thing and another something else.).
• Confusing information (e.g. use of medical jargon, multiple treatment options presented
without a clear recommendation).
• Excessive information (well-meaning family/friends/clinicians providing information
without full awareness of the problems).
• Genuine uncertainty (e.g., predicting functional outcome from a brain injury in its
immediate aftermath may be impossible).
• Language/translation/cultural issues (We never tell someone they are dying in our
culture.).
Treatment Goal Confusion
• Inconsistent treatments and unclear goals, often due to physician/patient/surrogate
emotional issues (see below):
o Clinician initiated: We will keep your husband on blood pressure raising medicine
but stop antibiotics.
o Family initiated: We want you to do CPR, but not intubate her.
• Differing priorities about disease-directed treatment and comfort-oriented treatment
between clinicians and patient/family.
• Lack of clarity about goals when several things are going on simultaneously (advanced
cancer, severe infection, respiratory failure – Isn’t the pneumonia potentially treatable?)
Emotions
• Grief (I don't know how I will live without him.)
• Fear/anxiety (I don't want to be responsible for ending my father's life. My family will be
angry at me for doing this.)
• Guilt (I haven't visited my sister in 20 years. I should have been here for her.)
• Anger (My mother was very abusive, I've never forgiven her; you are just giving up on
her.)
• Hope (I’m still hoping and praying she can pull through this.)
Family/Team dynamics
• Patient/family conflicted within themselves; may want different things at different times
• Dysfunctional family system (family members unable to put the patient's needs/values/
priorities above their own).
• Surrogate lack of ability (cognitive deficit, psychological/psychiatric trait/illness). In
pediatrics, this can be conflict between what is in the best interest of a child vs. a
caregiver or family.
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• Consulting teams disagree about the optimal approach, putting the patient/family in the
middle of the dispute.
Relationship between the Clinician and the Patient/Surrogate

• Lack of trust in the health care team/health care system.
• Past experiences where the patient has had a better outcome than predicted.
• Genuine value differences:
o Cultural/religious values concerning life, dying, and death.
o Clinician value to protect the patient from invasive, non-beneficial treatment while
the family values wanting to prolong life no matter how much suffering it might
entail.
All of these issues represent a degree of conflict and will need to be addressed before proceeding
to set end-of-life goals. See Fast Facts #183,184 for additional discussion on managing conflict.
Debriefing Conflicts are stressful for all involved health professionals. It is helpful to debrief the
process – what went well, what could have been improved, and – most importantly – addressing
the emotional reaction and needs of the care team. See Fast Fact # 203 on managing clinician
emotions.
References
1. Back AL, Arnold RM. Dealing with conflict in caring for the seriously ill. JAMA. 2005;
293:1374-1381.
2. Lazare A, Eisenthal S, Frank A. Clinician/Patient Relations II: Conflict and Negotiation.
In: Lazare A, ed. Outpatient Psychiatry. Baltimore, MD: Williams and Wilkins; 1989.
3. Fisher R, Ury W. Getting to Yes: Negotiating Agreement Without Giving In. Boston, MA:
Houghton-Mifflin; 1981.
4. Quill TE. Recognizing and adjusting to barriers in doctor-patient communication. Ann
Intern Med. 1989; 111:51-57.
2009.
Author Affiliations: Medical College of Wisconsin, Milwaukee, WI (DEW); University of Rochester Medical
Center, Rochester, NY (TEQ); University of Pittsburgh School of Medicine, UPMC Health System,
Pittsburgh, PA (RMA).

used. 
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HELPING SURROGATES MAKE DECISIONS
Background Surrogate decision makers are often placed in the difficult position of making
what feels to them as life or death decisions. This Fast Fact reviews an approach to help
surrogates through the decision process when patients cannot participate in decision-making
themselves.
Surrogate decision making The surrogate’s role is clearly to exercise “substituted judgment” –
that is, to make decisions as the patient would make them using the patient’s values and
preferences as previously expressed. The challenge was clearly expressed by the New Jersey
Supreme Court in the Quinlan case: if (the patient) could wake up for 15 minutes, understand his
current medical situation completely, and then had to go back into it, what would he tell us to do?
In the case of children, surrogate decision makers (usually parents) are expected to make
decisions that represent the child’s ‘best interests’; depending on the age and capacity of the
child to participate in his/her own healthcare decision making, the applied ‘best interest’ judgment
by the surrogate and healthcare providers may incorporate the patient’s values and preferences
to the extent possible, or may be solely based on the decision maker’s interpretation of best
interest. If there is conflict about what is in a child’s best interest, or in cases of developmentally
disabled adults who have never had capacity, consultation from ethics and law may be
appropriate, as the rules governing decision-making vary considerably.
Helping surrogates
1. Before making a recommendation, make sure there is a common understanding of the
patient’s condition and prognosis. Following this, the next step is to try to understand the
patient’s goals in light of these medical facts.
2. Bring the patient’s “voice” into the decision process even if he/she cannot participate directly:
If your father were sitting here with us, what would he say? If available, share a copy of any
advance care planning document with the surrogate. Realize that it is common for the
surrogate never to have seen the document.
3. Whenever possible, frame the decision around the treatment goals (e.g. life prolongation,
allowing a peaceful death) in light of the patient’s current condition, rather than focusing on
very specific treatments (e.g. thoracentesis, antibiotics). The details of the medical plan
should flow from the overall goals of care.
4. Do not make the surrogate feel that they are taking full responsibility for medical decisions,
especially those which may result in the death of their loved one (We can do option a or b;
what would like me to do?). Once you have a sense of the patient’s goals in light of his/her
medical condition, offer to make a recommendation that reflects those goals. Note: Many
families are looking for support and guidance from medical professionals, especially the
physician. Given what you have told me about your mother, and what we know about her
medical condition, I would recommend…. Start with what you are going to do to achieve the
patient’s goals and then talk about what does not make sense given those goals. Remember,
however, that some families may want information but not your recommendation. It is
therefore important to offer your recommendation (Would it be helpful for me to say what
medically makes the most sense, given what you’ve told me about your Dad?).
5. Remember that we are talking about the potential death of the surrogate’s loved one.
Emotions – sadness, frustration and guilt – are appropriate and to be expected. Use
previously discussed emotion management skills to acknowledge, legitimize, empathize and
support the family’s emotional response (see Fast Facts #29 and #224).
6. Do not argue over the facts; repeating the facts over and over again is not likely to be
effective. When the surrogate says He is a fighter, acknowledge that he is and has really
fought hard. The surrogate saying I want you to do everything is as much a sign of emotional
desperation as it is a factual request. Respond with empathy: It seems this is really hard for
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you. If hope for a miracle is expressed, it is appropriate to acknowledge that you hope for an
un-anticipated recovery as well, but that a miracle is truly what it would take at this point.
7. Rather than reiterating what medicine cannot do, consider using “I wish” statements to keep
you in touch with the surrogate’s feelings, while simultaneously expressing medicine’s
limitations (I wish our medicines were more effective; I wish we had more medical treatment
to offer than we do…).
8. Recognize the importance of time and support for surrogates to do their necessary grief-
work. Offer counseling services, either informal through the work of a palliative care team, or
more formal resources available at your institution. Bring together your clinical care team and
strategize potential resources for support such as chaplaincy, social services, psychology,
palliative care or ethics consultation.
Remember that time is your ally. The surrogate needs to process that their loved one is dying
and conceptualize what life will be like without him or her. This grief work takes time and
psychological support. Often, letting people think about what you have said and talking again
over subsequent days provides them the space to do grief work. It also allows them to see for
themselves that what you have advised is coming true (e.g. the patient is not getting better).
References
1. Quill TE, Brody H. Physician recommendations and patient autonomy: Finding a balance
between physician power and patient choice. Ann Intern Med. 1996; 125:763-769.
4. Quill TE, Arnold RM, Back A. Discussing treatment preferences in patients who want
"everything". Ann Intern Med. 2009; 151:345-349.


THE FAMILY MEETING: END OF LIFE GOAL SETTING AND FUTURE PLANNING
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Background End-of-life goal setting is a key palliative care skill, typically occurring as part of a
family meeting (see Fast Facts #16, 65, 222-226). This Fast Fact discusses an approach to goal
setting when the expected length of life is short.
Establishing patient-centered goals Here is an example of how to start the conversation (the
patient should be given sufficient time to respond to each of these questions):
I/we have discussed your current condition and that time may be short. With that in mind –
• What is important to you?
• What do you need to accomplish?
• Who do you need to see in the time that is left?
Common responses invoke family, home, and comfort; often surviving until a specific future family
event/date or visit with a key family member is described as an important goal. Re-state your
understanding: What I hear you saying is that you want to be home, comfortable, and survive
until your daughter gives birth – you hope to meet your next grandchild. Note: if you believe the
patient’s goal of survival to a specific event/date is not practical, it is important to say so and
discuss alternative plans.
Recommend a care plan based on the goals Once the goal(s) is/are established, you can
then review the patient’s current treatments (e.g. antibiotics, chemotherapy), monitoring (e.g.
pulse oximetry), planned tests (e.g. colonoscopy), and medications (e.g. anti-hypertensives), and
decide which will help meet, or not, the patient’s goals. Anything that will not help meet the goals
should be discussed for potential discontinuation. Depending on the specific disease/patient
condition, other issues that are naturally discussed at this point include:
• Future hospitalizations, ICU admissions, laboratory and radiology tests.
• Resuscitation orders/code status (see Fast Facts #23-24).
• Current/future use of blood products, antibiotics, artificial hydration/nutrition.
• If present, the potential continuation or stopping of dialysis or cardiac devices.
• Role of a second (or third) opinion.
• Exploration of experimental therapy.
• Exploration of treatment options the patient or family may bring into the conversation.
• Disposition options to best meet the goals (e.g. home hospice referral).
Note: There is no need to ask about each option as a yes/no question (Do you want blood
products?). Based on what you know about the patient’s goals, make a recommendation about
what should and should not be done in light of the patient’s goals, condition and prognosis. If you
are unsure, you can explore the issue with the patient/family (Given that your dad wanted to get
home as soon as possible and yet he was also willing to do easy things that might help him live
longer, I am unsure whether it makes sense to stay in the hospital an extra day or two to finish the
antibiotics. What do you think he would say?).
‘Long-shot’ goals If patients are going to pursue ‘long-shot’ or experimental therapy, perhaps
even against the recommendation of the treating team, it is useful to ensure the following:
• Reinforce the team’s respect for the decision, and desire to make sure the treatment has
the best possible chance of working.
• Simultaneously try to maximize quality of life in the present, including the best possible
pain and symptom management and support.
• Encourage the patient and family to prepare in case treatment is not successful and the
patient dies sooner rather than later. Useful language is to say, I’d encourage us all to
hope for the best, but prepare for the worst.
• Reinforce that the team will not abandon the patient and family even if the decision is not
what is being recommended.
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Close the meeting Following this discussion, restate your understanding of the patient’s goals
and agreed-upon next steps to meet those goals, invite and answer questions, and close the
meeting.
Discussion & documentation Discuss the goals with key staff not in attendance (e.g.
consulting physicians, patient’s nurse, discharge planner, primary care provider). Document the
goals, preferably using a templated family meeting note (see Reference 1): who was present,
what was discussed (e.g. treatment options, prognosis), what was decided, next steps.
Debriefing A useful step after every family meeting is to debrief the process – what went well,
what could have been improved and, most importantly, addressing the emotional reaction and
needs of the care team.
References
1. Clinical Tools. Center to Advance Palliative Care. Available at: http://www.capc.org/tools-
for-palliative-care-programs/clinical-tools/. Accessed August 4, 2009. Free registration
required.
2009.

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THE FICA SPIRITUAL HISTORY TOOL
Christina Puchalski MD
Background Spirituality is defined as “the aspect of humanity that refers to the way individuals
seek and express meaning and purpose and the way they experience their connectedness to the
moment, to self, to others, to nature, and to the significant or sacred” (1). Taking a spiritual history
is an important patient assessment skill, and most American patients report they want medical
professionals to be aware of the importance of religion or spirituality to them (2). Fast Fact #19
presents one approach to taking a spiritual history. This Fast Fact discusses the FICA Spiritual
History Tool© (Faith, Importance/Influence, Community, Action/Address in care).
Spirituality & Health There is a large body of evidence that demonstrates a relationship
between spirituality, religion and healthcare outcomes (3-9). Spirituality and religion are strong
contributors to how people cope with illness and suffering (10-12). Providing for spiritual and
religious needs benefits both patients and the health care system (13).
Spiritual History & the Healthcare Team A National Consensus Conference (NCC) developed
models and guidelines for interprofessional spiritual care (1). While the conference highlighted the
importance of board-certified or board-eligible chaplains as the spiritual care experts and
essential members of palliative care and other care teams, it recommended that all members of
the health care team be responsible for addressing patients’ spiritual issues within the
biopsychosocialspiritual framework (14). The NCC recommended that all patients should have a
spiritual screening or history, that spiritual distress should be diagnosed and attended to, and that
validated assessment tools should be used.
Taking a Spiritual History – Key Principles

1. Consider spirituality as a potentiality important component of every patient's life.
Spirituality can impact a patient’s quality of life; it is an inherent part of most people’s
wellbeing.
2. Address spirituality at each new visit, at annual examinations, and at follow-up visits if
appropriate.
3. Respect a patient's privacy regarding spiritual beliefs.
4. Be aware of your own beliefs; don't impose your spiritual/religious beliefs on others.
5. Make referrals to chaplains, spiritual directors, or community resources as appropriate.
FICA The FICA Spiritual History Tool© was developed to help healthcare professionals
address spiritual issues with patients. FICA serves as a guide for conversations in the clinical
setting. It is also used to help identify spiritual issues patients face, spiritual distress, and patients’
spiritual resources of strength. The FICA tool has been evaluated in cancer patients (15). This
study suggests FICA is a feasible tool for the clinical assessment of spirituality, and responses to
the FICA were correlated to many aspects of quality of life. Healthcare professionals are
encouraged not to use the FICA tool as a checklist, but rather to rely on it as a guide to aid and
open the discussion to spiritual issues.
F - Faith, Belief, Meaning Do you consider yourself spiritual or religious? Do you have
spiritual beliefs that help you cope with stress? If the patient responds No, the health care
provider might ask, What gives your life meaning? It is important to contextualize these questions
to the reason for the visit – e.g., wellness, stress management, breaking bad news, the end of
life. Meaning might be found in family, career, nature, arts, humanities or other spiritual, cultural
or religious beliefs and practices.
I - Importance and Influence What importance does your faith or belief have in your life?
Have your beliefs influenced you in how you handle stress? Do you have specific beliefs that
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might influence your health care decisions? If so, are you willing to share those with your
healthcare team?
C – Community Are you part of a spiritual or religious community? Is this of support to you
and how? Is there a group of people you really love or who are important to you?
A - Address/Action in Care How should I address these issues in your healthcare? This is
also to remind clinicians to develop a plan to address patient spiritual distress or other spiritual
issues.
Further Resources More information and educational materials about FICA are available at
http://www.gwish.org/.
References
1. Puchalski CM, Ferrell B, Viriani R, et al. Improving the quality of spiritual care as a
dimension of palliative care: Consensus conference report. J Palliat Med. 2009;12(10):
885-903.
2. Puchalski CM, Romer AL. Taking a spiritual history allows clinicians to understand
patients more fully. J Palliat Med. 2000; 3:129-37.
3. Cohen SR, Mount BM, Tomas JJ, Mount LF. Existential well-being is an important
determinant of quality of life. Evidence from the McGill quality of life questionnaire.
Cancer. 1996; 77:576-586.
4. Gall TL and Comblatt MW. Breast cancer survivors give voice: a qualitative analysis of
spiritual factors in long-term adjustment. Psycooncol. 2002; 11:524-535
5. George LK, Larson DB, Koenig HG, McCullough ME. Spirituality and health: what we
know, what we need to know. J Soc Clin Psychol. 2000; 19:102-116.
6. Jenkins RA, Pargament KI. (1995). Religion and spirituality as resources for coping with
cancer. J Psychosocial Oncol. 1995; 13: 51-74.
7. Koenig HG. A commentary. The role of religion and spirituality at the end of life.
Gerontologist. 2002; 42(suppl 3):20-23.
8. Puchalski CM. Addressing the spiritual needs of patients. Ethical issues in cancer patient
care, 2nd edition. Can Treat Research. 2008; 140:79-91.
9. Tsevat J, Sherman SN, McElwee JA, et al. The will to live among HIV-infected patients.
Ann Int Med. 1999;131(3):194–198.
10. Balboni TA, Vanderwerker LC, Block SD, et al. Religiousness and spiritual support among
Advanced cancer patients and associations with end-of-life treatment preferences and
quality of life. J Clin Oncol. 2007;25:555-560.
11. Delgado-Guay MO, Hui D, Parsons HA, et al. Spirituality, religiosity, and spiritual pain in
advanced cancer patients. J Pain Symptom Manage. 2011; 41:986-994.
12. Pargament KI. The Psychology of Religion and Coping. New York: Guilford Press; 1997.
13. Balboni T, Balboni M, Paulk, ME, et al. Support of cancer patients' spiritual needs and
associations with medical care costs at the end of life. Cancer. 2011; 117: 5383–5391.
14. Sulmasy DP. A biopsychosocial-spiritual model for the care of patients at the end of life.
Gerontologist. 2002; 42(Spec No 3): 24-33.
15. Borneman T, Ferrell B, Puchalski CM. Evaluation of the FICA Tool for Spiritual
Assessment. J Pain Symptom Manage. 2010; 40:163-173.
Author’s Affiliation: George Washing Institute for Spirituality and Health, George Washington
University Medical Center, Washington, DC.
Conflict of Interest Statement: The author has disclosed no relevant conflicts of interest.
Version History: First published November 2013. Re-copy-edited in September 2015.
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Ethics
#8 Morphine and Hastened
Death . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2-3
#55 Decision Making Capacity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . 4-5
#115 Declaring Brain Death: The Neurologic

Criteria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .6-7
#164 Informed Consent in Palliative Care – Part I . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . 8-9
#165 Informed Consent in Palliative Care – Part

II. . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . .10-11
#178 The National Polst Paradigm

Initiative . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .12-13
#219 Responding to Requests for Non-Disclosure of Medical Information . . . . . . . . . . .

. . . 14-15
#242 Organ Donation After Cardiac

Death . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16-18
#292 Do Not Resuscitate Orders in an Operating Room

Setting . . . . . . . . . . . . . . . . . . . . . . . 19-21
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!

MORPHINE AND HASTENED DEATH
Charles F von Gunten MD
Question: What is the distinction between the use of morphine at the end of life to control
symptoms and euthanasia/assisted suicide?
Case Scenario: An 83 year old former industrial worker has been hospitalized because of
severe pain. He has pancreatic cancer with metastases to liver and lung. He has severe
abdominal pain, and opioid therapy with morphine is recommended for pain relief.
Main Teaching Points

1. Many physicians inaccurately believe that morphine has an unusually or unacceptably
high risk of an adverse event that may cause death, particularly when the patient is frail
or close to the end of his or her life. In fact, a large study of opioid use at the end of life
from the US National Hospice Outcomes Project, as well as a systematic review of
various other countries, found no difference in survival with absolute opioid dose or
change in opioid dose. Furthermore, morphine-related toxicity will be evident in
sequential development of drowsiness, confusion, then loss of consciousness before
respiratory drive is significantly compromised.
2. Many physicians inappropriately call this risk of a potentially adverse event, a double
effect, when it is in fact a secondary, unintended consequence. The principle of double
effect refers to the ethical construct where a physician uses a treatment, or gives
medication, for an ethical intended effect where the potential outcome is good (eg, relief
of a symptom), knowing that there will certainly be an undesired secondary effect (such
as death). An example might be the separation of conjoined twins knowing that one twin
will die so that the other will live. Although this principle of “double effect” is commonly
cited with morphine, in fact, it does not apply, as the secondary adverse consequences
are unlikely.
3. When offering a therapy, it is the intent in offering a treatment that dictates whether it is
ethical medical practice:
a. if the intent in offering a treatment is desirable or helpful to the patient and the
potential outcome good (such as relief of pain), but a potentially adverse
secondary effect is undesired and the potential outcome bad (such as death),
then the treatment is considered ethical
b. If the intent is not desirable or will harm the patient and the potential outcome
bad, the treatment is considered unethical
4. All medical treatments have both intended effects and the risk of unintended, potentially
adverse, secondary consequences, including death. Some examples are total parenteral
nutrition, chemotherapy, surgery, amiodarone, etc.
5. Assisted suicide and euthanasia are not examples of “double effect.” The intention in
offering the treatment in assisted suicide and euthanasia is to end the patient’s life.
6. If the intent for using morphine in the scenario is to relieve pain and not to cause death,
and accepted dosing guidelines are followed:
a. the treatment is considered ethical,
b. the risk of a potentially dangerous adverse secondary effects particularly
hastening death is minimal, and
c. the risk of respiratory depression is vastly over-estimated.
References
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1. Emanuel LL, von Gunten CF, Ferris FD. The Education for Physicians on End-of-Life
Care (EPEC) curriculum. Chicago, IL: American Medical Association, Chicago; 1999.
http://www.epec.net.
2. Morita T, et al. Effects of high dose opioids and sedatives on survival in terminally ill
cancer patients. J Pain Sympt Manage. 2001; 21:282-9.
3. Regnard D. Double effect is a myth leading a double life [letter]. BMJ. 2007; 334:440.
4. Portenoy R, Sibirceva U, et al. Opioid use and survival at the end of life: a survey of a
hospice population. J Pain Sympt Manage 2006; 32:532-40
5. Sykes N, Thorns A. The use of opioids and sedatives at the end of life. Lancet Oncol
2003; 4:312-8.
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!

DECISION MAKING CAPACITY
Robert Arnold MD
Background Informed consent is based on the principle that patients should be allowed to
make decisions for themselves. Decision making capacity thus serves as a gatekeeper concept.
Patients who have it can make decisions for themselves; conversely, a surrogate is needed for
patients who lack decision-making capacity. Competency is a legal term referring to a decision
made by judge, although a physician’s opinion carries considerable weight in a competency
hearing. In contrast, decision making capacity (‘decisionality’) refers to a physician’s
determination, based on clinical examination, that a patient is able to make medical decisions for
him- or herself. Most state Power of Attorney for Health Care documents require a physician (or
similarly qualified individual such as a psychologist) to document that a patient has lost decision
making capacity for the surrogate to become the legal agent for medical decisions.
Assessing decision making capacity

• To be deemed ‘decisional,’ a physician must be satisfied that a patient is able to do three
tasks:
o Receive information (e.g. must be awake, but not necessarily oriented x 4),
o Evaluate, deliberate, and mentally manipulate information, and
o Communicate a treatment preference (e.g. the comatose patient by definition is not
decisional).
• Physicians should look for:
o Understanding. Does the patient adequately understand the information about the
risks, benefits, and alternatives of what is being proposed? The patient does not
have to agree with your interpretation, but should be able to repeat what you have
said. Ask, Can you repeat to me the options for treating X I have just discussed with
you? Can you explain to me why you feel that way? What is your understanding of
what will happen if we don’t do Y?
o Logic. Is the logic the patient uses to arrive at the decision “not-irrational”? One
wants, as much as possible to make sure the patient’s values are speaking, rather
than an underlying mental or physical illness. Note: Severe depression or
hopelessness will make it difficult to interpret decisionality; consult psychiatry for
assistance with this or other complex cases.
o Consistency. Is the patient able to make a decision with some consistency? This
means not changing one’s mind every time one is asked. Is the decision consistent
with the patient’s values? If there is a change in the patient values, can the patient
explain the change?
Decision making capacity is contingent
• Task specific. Deciding if the patient is decisional means weighing the degree to which
the patient has decision making capacity against the objective risks and benefits to the
patient. Some decisions are more complex than others, requiring a higher level of
decision-making capacity. Thus a moderately demented patient may be able to make
some decisions (e.g. antibiotics for pneumonia) but not others (e.g. chemotherapy for
metastatic lung cancer). This sliding scale view of decisionality holds that it is proper to
require a higher level of certainty when the decision poses great harm.
• Time specific. When encephalopathic a patient may not be decisional; after treatment
decisionality may be regained.
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References
1. Drane JF. The Many Faces of Competency. Hasting Center Report. 1985; 15(2):17-21.
2. Junkerman C, Schiedermayer D. Practical Ethics for Students, Interns and Residents. A
Short Reference Manual. 2nd Edition. University Publishing Group; 1998.
3. Jones RC, Holden T. A guide to assessing decision-making capacity. Cleve Clin J Med.
2004; 71:971-5.
Version History: 2nd Edition published July 2006; 3rd Edition published May 2015. Current
version re-copy-edited April 2009; references updated; then copy-edited again May 2015.
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!

DECLARING BRAIN DEATH: THE NEUROLOGIC CRITERIA
Amal Puswella, Mike DeVita, Robert M Arnold MD
Background This Fast Fact reviews the details of declaring death based on neurological
criteria. In 1980, the Uniform Determination of Death Act (UDDA) was created which stated that
“An individual who has sustained either 1) irreversible cessation of circulatory and respiratory
function, or 2) irreversible cessation of all functions of the entire brain, including the brainstem, is
dead. A determination of death must be made with accepted medical standards.” The UDDA did
not define “accepted medical standards,” and so the American Academy of Neurology published
guidelines in 1995, and updated them in 2010. Despite these national guidelines, there is still
considerable variability in local institutional guidelines.
Determining death by neurologic criteria involves two steps:
• Step 1: Rule out reversible causes of unconsciousness: sedative medication,
neuromuscular blocking agents or hypothermia.
• Step 2: Rule out the presence of cortical activity and brainstem reflexes using clinical
exams/tests. The exact tests done may vary by institution and one should check with their
own institution’s policies. Brain death exams are typically completed by neurologists,
neurosurgeons, and critical care physicians. For a person to be dead by brain death,
typically all of the following tests must show lack of brain function:
o No spontaneous movement and no movement in response to painful stimuli (movement
due to spinal reflexes are acceptable).
o No seizures, decerebrate or decorticate posturing, or dyskinetic movements.
o Absent cranial nerve reflexes including pupillary response to light, corneal reflexes,
oculocephalic reflex, caloric response, facial movement to a noxious stimulus, and
gagging and cough with suctioning.
o Caloric testing is done by first ensuring the auditory canal is clear and the tympanic
membranes are intact. The head is elevated to 300, 50 ml of ice water is slowly infused
into the canals, and the eyes are observed for one minute. The normal response in an
awake patient is tonic deviation of the eyes toward the cold stimulus followed by
nystagmus back to the midline; the normal response in a comatose patient with an intact
brainstem is tonic deviation of the eyes toward the cold stimulus without nystagmus; in
brain death, the eyes do not move. Both ears must be tested with an interval of several
minutes in between.
o Note: At some institutions other clinical tests are done before a formal apnea test (see
below). For example, some require documentation of no vagal nerve activity – an
atropine test is used. The patient is given 2 mg IV atropine. In the dead patient, the
parasympathetic outflow is non-functioning and the heart rate will not change (<10 beats/
minute).
o Absence of central respiratory drive is assessed using the apnea test to see if a rise of
CO2 provides a stimulus to breathe. The patient is ventilated with 100% oxygen for 10-20
minutes and a baseline blood gas is obtained. The ventilator is then removed while
100% oxygen is delivered; O2 saturation is continuously assessed. A follow-up ABG is
done after 5-10 minutes. If the PaCO2 rises past 60mm Hg (or >20 mm Hg above
baseline), and no breathing efforts are observed, the respiratory center is not functioning.
The test should be aborted if the patient develops hypoxemia (also indicates no
respiratory drive), hypotension, or arrhythmias.
Adjunctive or confirmatory tests are needed in complex clinical situations such as uremia or
hepatic encephalopathy, when apnea testing cannot be performed, when the primary brain insult
is infratentorial, or if required by the local institutional brain death policy.
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• Electroencephalogram: must be isoelectric, which is difficult in the ICU due to electrical
artifact).
• Transcranial Doppler: intracranial arteries demonstrate either absence of diastolic flow,
or small systolic peaks.
• Somatosensory Evoked Potentials: bilateral median nerve stimulation demonstrates an
absence of the N20-P22 response.
• Intracranial Pressure: sustained, elevated ICP within 10 mmHg of mean arterial
pressure.
• Tests of cerebral blood flow: if there is no cerebral blood flow then there is no brain
function and death may be determined based on this test alone. Specific tests include
cranial radionuclide angiography and conventional contrast angiography.
References
1. Wijdicks E, Varelas P, Gronseth G, et al. Evidence-Based guideline update: Determining
brain death in adults. Report of the quality standards subcommittee of the American
Academy of Neurology. Neurology 2010; 74;1911-1918.
2. Greer D, Varelas P, Haque S, et al. Variability of brain death determination guidelines in
leading US neurologic institutions. Neurology 2008; 70:284-289.
3. Plum F, Posner J. The Diagnosis of Stupor and Coma. 3rd Edition. New York, NY: Oxford
University Press; 1982: pp57-61, 313-320.
4. Van Norman G. A matter of life and death: what every anesthesiologist should know
about the medical, legal, and ethical aspects of declaring brain death. Anesthesiology.
1999; 91(1):275-287.
5. Certification of Death in Adults Policy: 5108. University of Pittsburgh Medical Center,
Pittsburgh, PA; 2000.
in May 2004. Re-copy-edited in April 2009; then it was copy-edited again by Sam Maiser MD in
June 2015 in which references 1 and 2 were added and incorporated into the text.
in June 2004. Re-copy-edited in April 2009; web-sites updated; revised again in July 2015 by
Sarah Friebert MD.
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INFORMED CONSENT IN PALLIATIVE CARE – PART I
David E Weissman MD and Arthur Derse MD, JD
Background Informed consent is frequently misunderstood as something that only applies to
research trials or a form that a patient signs to indicate understanding and agreement when
undergoing an invasive procedure. This Fast Fact reviews the legal basis for informed consent.
Fast Fact #165 will discuss common myths about informed consent in the care of seriously ill and
dying patients.
Definition Informed consent is a process, not a signature, whereby a physician discloses key
information to help patients make a choice among healthcare options. The informed consent
process requires that three conditions be met: a) the patient is able to make a voluntary choice, b)
the patient is informed (see below), and c) the patient has the capacity to make medical
decisions.
Legal Standard The legal standard of informed consent varies between states. Some use:
what a reasonable patient would want to know; in other states the standard is, what a reasonable
physician should provide. A failure to meet the legal standard may meet the threshold for liability.
Information No matter which legal standard is operational, the consensus among national
medical and ethical organizations is that following information should be provided to meet the
spirit of the informed consent doctrine:
• The patient's diagnosis, if known;
• The nature, purpose, risks and benefits of a proposed treatment or procedure;
• The nature, purpose, risks and benefits of alternative treatments or procedures;
• The risks and benefits of not receiving or undergoing a treatment or procedure.
Emergency Exception to Informed Consent—physicians may proceed with treatment in
emergency situations when all of the following criteria are met:
• Life threatening emergency and time is of the essence.
• Patient is not decisional and no legal surrogate decision maker is available.
• Reasonable person would consent to the emergency treatment.
Therapeutic Privilege A long-standing legal principle is that physicians may withhold

information if they believe the information would harm the patient. The use of this privilege
should be restricted to rare instances when there is good evidence that providing information will
upset a patient so he/she “could not rationally engage in a conversation about therapeutic options
and consequences” (Meisel 1996). Physicians should not use the privilege out of concern that
with information, the patient will refuse a recommended treatment, nor out of fear of provoking
normal emotional reactions to bad news.
Summary The purpose of the informed consent doctrine is to promote autonomy of the
individual in medical decision making (Meisel 1996). However, the informed consent process is
often viewed by physicians as being counter to an equally desirable social goal – a physician’s
responsibility for a patient’s well-being and promotion of health. The point of balance between
these two social goals is frequently misunderstood, and will be discussed in the next Fast Fact.
References
1. American Medical Association. Informed Consent. Available at: http://www.ama-assn.org/
ama/pub/physician-resources/medical-ethics/code-medical-ethics/opinion808.page.
2. American Medical Association. AMA Position on Provision of Life-Sustaining Medical
Treatment. Available at: http://www.ama-assn.org/ama/pub/physician-resources/
medical-ethics/about-ethics-group/ethics-resource-center/end-of-life-care/ama-policy-
provision-life-sustaining-medical.page
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3. Meisel A and Kuczewski. Legal and ethical myths about informed consent. Arch Int Med.
1996; 156:2521-2526.
292:1738-1743.
in September 2006. Version re-copy-edited in April 2009; then again July 2015: web-links
updated.
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!

INFORMED CONSENT IN PALLIATIVE CARE – PART II
David E Weissman MD and Arthur Derse MD, JD
Background In Fast Fact #164, the legal basis for the informed consent process was
reviewed; this Fast Fact discusses common myths about informed consent that arise in palliative
care. Readers wishing more information should read the excellent review by Meisel and
Kuczewski.
Myths:
1. Use of Signed Consent Forms—Myth: Federal or state laws require written informed
consent (patient signature) for invasive procedures. FALSE: The use of signed consent
forms are used per local hospital or institutional or accrediting organization policies. They are
generally not mandated by law or federal/state regulation. Note: state law may mandate
written consent for certain tests or high risk treatment (e.g. HIV, genetic testing, or
electroconvulsive therapy) and federal law may require written consent in some
circumstances (e.g. transfers from emergency departments). Signed consent forms may not
shield the physician from claims of negligence due to failure to provide informed consent if
the physician did not fulfill the informed consent process (see Fast Fact #164).
2. Emergency Transport to a Medical Facility—Myth: No informed consent is necessary for
patients admitted to a hospital in transfer from a nursing home, of for patients transported to
the hospital following a 911 call. FALSE: There is no “implied consent” just because 911 or a
transport ambulance was called; such patients require the same level of informed consent
discussions for medical care decisions as any other patient, unless the medical situation
satisfies the criteria for the emergency exception (see Fast Fact #164).
3. Low Risk Treatments—Myth: No informed consent is necessary when starting “low risk” life
sustaining treatments such as IV antibiotics, intravenous hydration, feeding-tube placement,
or blood products. FALSE: All these treatments represent interventions with risks and
alternatives. An informed consent discussion is especially necessary in seriously ill or dying
patients where the option of no intervention is a reasonable choice; the failure to discuss not
using life sustaining intervention represents a failure to provide full informed consent. Also,
patients should be informed that if a life sustaining treatment becomes too burdensome (a
risk of any treatment), the patient may withdraw his or her consent and the treatment will be
withdrawn.
4. Present options but not a recommendation—Myth: Informed consent means that patients
should choose among medical option without physicians introducing their bias toward one
specific option. FALSE: The physician’s obligation is to present medical information
accurately to the patient or to the individual responsible for the patient’s care and to make
recommendations for management in accordance with good medical practice. The physician
has an ethical obligation to help the patient make choices from among the therapeutic
alternatives.
5. Documentation—Myth: An informed consent discussion needs no special documentation
except in cases of invasive procedures. FALSE: Even if not legally required, the content and
outcome of an informed consent discussion should always be documented in the medical
record and include the elements noted in Fast Fact #164 as an indication that the ethical and
legal requirements of the process of informed consent have been fulfilled.
References
1. Meisel A, Kuczewski. Legal and ethical myths about Informed Consent. Arch Int Med.
1996; 156:2521-2526.
2. Brett A, Rosenberg JC. The adequacy of informed consent for placement of gastrostomy
tubes. Arch Intern Med. 2001; 161:745-748.
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3. American Medical Association. Informed Consent. Available at: http://www.ama-assn.org/
ama/pub/physician-resources/medical-ethics/code-medical-ethics/opinion808.page.
4. American Medical Association. AMA Position on Provision of Life-Sustaining Medical
Treatment. Available at: http://www.ama-assn.org/ama/pub/physician-resources/
medical-ethics/about-ethics-group/ethics-resource-center/end-of-life-care/ama-policy-
provision-life-sustaining-medical.shtml.
in October 2006. Version re-copy-edited in April 2009; then again July 2015: web-links updated.
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!
FAST FACTS AND CONCEPTS #178 

THE NATIONAL POLST PARADIGM INITIATIVE
Judy Citko JD, Alvin H Moss MD, Margaret Carley RN, JD, and Susan Tolle MD 
Background One barrier in the treatment of seriously-ill and dying patients has been the
inability to develop a system by which a patient’s preferences for life-sustaining treatment are
both documented and honored across different care sites. Regional and statewide programs
have tackled this problem with variable success. Originally started in Oregon in 1991, the
Physician Orders for Life Sustaining Treatment (POLST) Program creates a coordinated
system for eliciting, documenting, and communicating the life-sustaining treatment wishes of
seriously-ill patients. Programs with the essential core elements of POLST are developing in
the majority of states. Although different states may use different names, the program is
universally referred to as the POLST Paradigm Program. This Fast Fact will review key
elements of the POLST Paradigm Program.
The Paradigm The POLST Paradigm was developed as a standardized, advance care planning
document to be completed by health care professionals, together with a patient or surrogate
decision-maker. The POLST form translates the values expressed in an advance directive into
immediately active medical orders which do not require interpretation or further activation. POLST
aims to provide continuity of care for patients according to their preferences across all care
settings (e.g. hospitals, hospice, long-term care and home), and is transferred with the patient
throughout the health care system. In each region or state, local leaders have presented
widespread education to support its application across the spectrum of health care settings.
The Form The form is brightly colored to facilitate identification and is divided into several
sections:
• CPR decision: Resuscitate or Do Not Resuscitate (DNR).
• Scope of treatment: comfort measures vs. limited additional interventions vs. full
treatment.
• Medically administered nutrition: none vs. defined trial period vs long-term use.
• Health care professional signature: in some states or regions, patient/surrogate
signature is strongly recommended or required.
How It Works POLST is designed for seriously-ill adults or those who are medically frail.
Completion of the form is voluntary. The health care professional turns the patient's values
(expressed personally through conversation, and/or an advance directive, or by the patient's
legal representative if the patient lacks decision-making capacity) into actionable medical orders.
The orders are valid when signed by a physician (or NP/PA depending on state regulations).
Many state/regional POLST programs also require the patient’s or legal agent’s signature to
make the form valid. A copy of the POLST form is included in the medical record while the
original remains with the patient as they move across care settings.
Effectiveness Data from completed research projects related to POLST are available on the
POLST website (www.polst.org). Key findings indicate that patients’ values are accurately
reflected in the orders, that the orders are followed by first responders, that life-sustaining
treatment orders beyond CPR (e.g. artificial nutrition) are useful to guide care consistent with
the patient’s wishes, and that implementation can evolve to become a standard of care in a
community, region, or state.
State/Regional Initiatives Numerous communities and states are developing or have
implemented programs similar to Oregon’s with the guidance of the National POLST Paradigm
Task Force. The names of endorsed programs include: Medical Orders for Life Sustaining
Treatment or MOLST (New York); Medical Orders for Scope of Treatment or MOST (North
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Carolina); POLST (California, Hawaii, Oregon, Wisconsin, Washington state); and Physician
Orders for Scope of Treatment or POST (West Virginia, Tennessee).
Resources The POLST website has sample downloadable forms, educational materials and
videos; a map of states and regions using the form, contact information; a description of the core
elements of a POLST Paradigm Program; and information on how to build a coalition to start a
POLST Paradigm Program available at no cost. There may be a low cost for larger orders to help
cover expenses of a state or regional program’s coordinating center. The Center for Ethics in
Health Care at Oregon Health & Science University coordinates the national initiative.
References
1. Physician Orders for Life-Sustaining Treatment Paradigm. Available at: http://
www.polst.org.
2. Tolle SW, Tilden VP, Dunn P, Nelson C. A prospective study of the efficacy of the
physician orders for life sustaining treatment. J Amer Ger Soc. 1998; 46:1097-1102.
3. Hickman SE, Hammes BJ, Moss AH, & Tolle SW. Hope for the future: achieving the
original intent of advance directives. The Hastings Center Report Special Report. 2005;
35(6—Suppl):S26-S30.
4. Hickman SE, Nelson CA, Perrin NA, Moss AH, Hammes BJ, Tolle SW. A comparison of
methods to communicate treatment preferences in nursing facilities: traditional practices
versus the physician orders for life-sustaining treatment program. J Amer Ger Soc.
2010; 58:1241-1248.
Author Affiliations: Coalition for Compassionate Care, Sacramento CA (JC); West Virginia
University, Morgantown, WV (AHM); Oregon Health & Science University, Portland, OR (MC, ST).
Version History: 1st edition published April 2007. Revised 2nd edition published September
2010. Copy-edited again in July 2015.
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!

RESPONDING TO REQUESTS FOR NON-DISCLOSURE OF MEDICAL INFORMATION
Elizabeth Chaitin DHCE and Drew A Rosielle MD
Background What do you do when a family member asks you not to tell your patient important
medical information such as a diagnosis or prognosis? Requests for non-disclosure can
represent a loving family’s efforts to protect a patient from emotional harm, an inaccurate
assessment by the family about a patient’s preferences or emotional resilience, or an accurate
reflection of how the patient would prefer to make decisions. This Fast Fact will introduce readers
to a practical approach to these clinical dilemmas.
The Problem Contemporary medical ethics and professional standards dictate that patients
have the right to choose the medical care that best allows them to meet their life goals. To make
such choices requires they be fully informed of their condition, prognosis, and reasonable
treatment options (see Fast Facts #164, 165). One needs to differentiate the right to such
information from the duty to hear the information, however. Patients have different preferences
for medical decision-making, ranging from individualistic, to paternalistic (doing whatever the
physician recommends), to communal (sharing, or deferring, important medical decisions to
family members or religious/community leaders). Truly respecting patient autonomy requires
clinicians to identify and respect patient wishes to share or defer decision-making, including a
patient’s preference to not be informed of key medical information.
Prevention Negotiate with the patient before the results of testing arrive as to how much
information they would like and who they would like to have present for information sharing. Are
you the kind of person who wants to know the results of the test or would you rather I talk to your
children?
Managing Requests for Non-Disclosure (adapted from Hallenbeck and Arnold, 2007):
• Stay Calm. These situations can be confusing and emotional for clinicians. The calmer
you remain the more information you will gain from the family as to why they do not want
their loved one to be informed of the bad news. Demonstrating frustration or implying that
the request is inappropriate can break trust and derail your efforts to resolve the situation.
• Try to understand the family’s viewpoint. They know the patient best and can provide
insight into the cause of the request. Politely ask questions to understand the nature of
the request. Can you tell me more about why you feel this way? How does your family
typically handle difficult information? How are important decisions made by your family?
Ask about how the patient has responded in the past to bad news and if they have made
specific statements to others about what they want to know. Is the family more worried
more about how the information is given rather than the information itself (e.g. given to
the patient when alone, use of ‘death’ or ‘dying,’ the disclosure of specific prognostic
time-frames)?
• Clarify what the patient already knows. Politely ask questions to understand what the
family believes the patient already knows. Does the family think the patient already
knows or strongly suspects what is going on and would rather not talk further about it, or
is the patient completely in the dark? Have other clinicians already told or implied to the
patient what is going on? How did the patient respond to that? Is the patient talking with
the family about their concerns? A patient’s reluctance to talk with family members may
represent an attempt to protect them.
• Respond empathically. A family’s request to not tell their loved ones usually comes from
a kind and loving place; they are often frightened for themselves and the patient.
Responding empathically (see Fast Fact #29) allows them to recognize that you care
about them. It may allow them to see your ability to give information to their loved one in
a compassionate way.
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• State your views openly, but as your own views. Disclose any discomfort you have with
the family’s request; explain your professional obligation to ensure the patient is able to
make informed decisions in the manner they prefer. Disclose this specifically in the
context of you wanting what is best for the patient, including respecting how she or he
would like to hear information.
• Be willing to brainstorm possible solutions. Rigidly informing the family that you must tell
the patient breaks trust and is inaccurate. There is no ‘one-size-fits-all’ solution to these
scenarios. Often, there are solutions neither of you have thought about that will meet
everyone’s goals. In other cases, the family may not have thought about the implications
of the request (e.g. giving Mom chemotherapy but not telling her she has cancer).
• Negotiate a solution. Recommend to the family that you, in their presence, share with the
patient a limited amount of information, and then specifically ask the patient if they would
like to hear more. Tell the family what you plan on saying, i.e. – You came to the hospital
because you were not eating well and became dehydrated. We have been trying to figure
out what is going on. Some people want to know everything about their medical
condition, others prefer the doctors talk with family members about what is happening
and the best way to help a patient. What would you prefer? Contract with the family that
they, and you, will respect the patient’s decision.
References
1. Bok S. Lying: Moral Choice in Public and Private Life. New York, NY: Vintage Books;
1989.
2. Hallenbeck J, Arnold R. A request for nondisclosure: don’t tell mother. J Clin Oncol.
2007; 25(31):5030-34.
3. Lagarde SM, Franssen SJ, van Werven JR, et al. Patient preferences for the disclosure
of prognosis after esophagectomy for cancer with curative intent. Ann Surg Oncol. 2008;
15(11):3289-3298.
Author Affiliations: University of Pittsburgh Medical Center, Pittsburgh, PA (EC); Medical

College of Wisconsin, Milwaukee, WI (DAR).
Version History: Originally published September 2009; copy-edited August 2015.
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!

ORGAN DONATION AFTER CARDIAC DEATH
Dana Lustbader MD, FCCM, FCCP and Michael J Goldstein MD
Background Organ donation after cardiac death (DCD) refers to organ donation from a
deceased donor who has been declared dead on the basis of cardio-pulmonary criteria
(permanent cessation of circulatory and respiratory function) rather than on neurological “brain
death” criteria (permanent cessation of brain function – see Fast Fact #115). This Fast Fact
reviews key elements of the DCD process.
Two Types of Organ Donation

1. Donation after death by neurologic criteria occurs when a comatose patient meets
brain death criteria. After obtaining consent from the family, the donor is brought to the
operating room on the ventilator. Organ procurement occurs in the operating room while
the patient remains intubated with a beating heart.
2. Donation after cardiac death occurs when a decision is made to discontinue
mechanical ventilation/other life-sustaining treatments in a comatose or gravely ill patient
who is expected to die quickly after cessation of life-support. Depending on hospital
policy, the patient may be extubated in the operating room (OR) to minimize the time
between death and organ procurement and thereby optimize donor organ viability for
transplantation. Most organ procurement organizations (OPO) have guidelines governing
the amount of time between extubation and death during which the organs are
considered viable for transplantation. This is generally 60 minutes. If the patient survives
longer than that, excessive organ ischemia occurs rendering the patient an unsuitable
donor. The patient is then returned to the ICU or other appropriate location for end-of-life
care.
Selecting Patients for DCD Appropriate patients are generally comatose patients for whom a
decision has been made to discontinue life-sustaining treatments with the expectation of
imminent death. The decision to discontinue life-sustaining treatments is made prior to any
discussions of organ donation. Most institutions have policies and procedures which alert the
OPO of potential donors. After discussion with their medical director and recipient transplant
centers, the OPO determines donor suitability. Trained professionals – usually OPO
representatives – approach the family about organ donation, and consent the family/patient
decision makers for organ donation. Potential donors are generally between 0 and 60 years of
age. Patients should not meet the criteria for death by neurologic criteria (they are candidates for
organ donation via brain death protocols). The OPO staff prognosticate whether the patient is
sufficiently likely to die within the 60 minute window after cessation of life-prolonging treatments.
This estimate is based on physiologic parameters including spontaneous respiratory rate,
negative inspiratory force, age, oxygen saturation, level of hemodynamic instability, and body
mass index (BMI).
Procedure
1. Families are counseled about what to expect during the discontinuation of life-sustaining
treatments and what to expect as the patient receives comfort care. Hospitals may have
policies requiring the patient to have a DNR order while awaiting the DCD procedure; in
others the decision to resuscitate a patient or not in order to attempt to maintain the
patient as a viable organ donor is a negotiated decision. Families should be prepared for
the possibility that the patient may not die quickly after the ventilator is withdrawn and
that the patient may become an unsuitable donor. This occurs in about 20-30% of DCD
cases nationally. This can cause added emotional trauma to grieving families who may
want both a swift and comfortable death for their loved one as well as the opportunity to
help others through organ donation. Families should be reassured that the patient will
!16
continue to receive careful symptom management until she or he die no matter how long
that takes.
2. In order to prevent conflicts of interest, members of the OPO and organ recovery teams
should not be involved in the decision to discontinue life-support, or in directing the
medical care of the patient prior to the declaration of death. Because of this, intensivists,
palliative care physicians, or other clinicians may be asked to direct the care of the dying
donor after extubation.
3. Once consent is obtained from a legal surrogate and appropriate teams are ready,
discontinuation of life-sustaining treatments begins. Extubation generally occurs in the
operating room but may occur in a nearby ICU or recovery area based upon local
hospital practice. Many hospital policies allow family members to be present in the
operating room until the patient dies.
4. The patient may be given pre-extubation medications to relieve anticipated distress.
These medications, as well as symptom medications given after cessation of life-support,
should be given in the exact same way as in non-DCD situations to alleviate signs of
pain, labored breathing, and other symptoms (see Fast Facts 33-35).
5. The patient is extubated to room air. Other lines and tubes are discontinued as deemed
appropriate to maximize patient comfort.
6. All non-comfort medications are discontinued including vasoactive agents.
7. Declaration of death is based on hospital policy. Usually policies require apnea and 2 to
5 minutes of asystole or pulseless electrical activity. The hospital’s DCD policy will
outline the exact criteria for declaring cardiac death.
8. Following death pronouncement the patient is taken to the OR, or the organ recovery
team enters the OR where the patient died and procurement begins. The organ recovery
team never encounters the patient’s family during the DCD process.
9. If the patient does not die in a reasonable amount of time as determined by the organ
procurement organization, the patient is returned to a location in the hospital for ongoing
symptomatic treatment until death occurs. Ongoing emotional and bereavement support
should occur for family members throughout the process.
References
1. Ethics Committee, American College of Critical Care Medicine, Society of Critical Care
Medicine. Recommendations for nonheartbeating organ donation. Crit Care Med. 2001;
29(9):1826-1831.
2. Truog RD, Miller FG. The dead donor rule and organ transplantation. N Engl J Med.
2008; 359:674-5.
3. Steinbrook R. Organ donation after cardiac death. N Engl J Med. 2007; 357:209-213.
4. Abt P, Fisher CA, Singhal AK. Donation after cardiac death in the US: history and use. J
Am Coll Surg. 2006; 203(2):208-225.
5. Kolovos NS, Webster P, Bratton SL. Donation after cardiac death in pediatric critical
care. Ped Crit Care Med. 2007; 8(1):76-77.
Author Affiliations: Hofstra North Shore – Long Island Jewish School of Medicine, Manhasset,
NY (DL); Mount Sinai Medical Center, New York, NY (MJG).
Version History: Originally published June 2011; Copy-re-edited August 2015.
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!
FAST FACTS AND CONCEPTS # 292

DO NOT RESUSCITATE ORDERS IN AN OPERATING ROOM SETTING
David Dugan MD and Jay Riseman, MD, FACS
Background Because of the rapid physiologic changes that may occur inside of an operating
room (OR), patients and families may be unaware of the resuscitative efforts and management
plans that may happen inside of them. Many health care institutions have practices and policies
which automatically suspend do-not-resuscitate (DNR) orders when patients go to the OR. This
Fast Fact will review ethical considerations and positions of major medical organizations
regarding such policies and DNR orders in the OR in general.
Policies The Association of Perioperative Registered Nurses (1), the American College of
Surgeons (ACS) (2), and the American Society of Anesthesiology (ASA) (3) all have position
statements on the status of DNR orders in ORs. There is firm agreement among them that health
care institutions should promote opportunities for a careful, informed discussion about potential
resuscitative measures between the patient (or surrogate), surgical, and anesthesia teams,
before a planned procedure in order that a treatment approach best matches the patient’s goals
of care and medical situation. There also is agreement that policies which automatically suspend
DNR orders in the OR are inappropriate if the policy does not mandate an informed consent
discussion with the patient/surrogate, or factor in the risk/benefit profile of the intervention.
Causes and Outcomes of Cardiac Arrest in the OR National in-hospital resuscitation registry
data suggests that survival from CPR is higher in the perioperative setting versus other in-hospital
setting: asystole 30.5% vs. 10%; pulseless electrical activity 26.4% vs 10%; pulseless VT/VF
41.9% vs approximately 34% (4,5). The overall frequency of major perioperative cardiac events
in patients undergoing non-cardiac surgery is likely between 2-6% depending on the study (6).
Cardiac arrest rates attributable to anesthesia is likely much lower -- approximately 0.5 per
10,000 (7). In a single center study, 35% of cardiac arrests in the OR were due to bleeding,
43.9% were related to cardiac causes, and 21.1% were attributable to other causes, with
hemorrhage having the poorest outcome (7).
Balancing Ethical Precepts Patient autonomy is paramount to ethical decision-making.

Indeed, concerns about differential treatment once a DNR order is in place may make a patient
hesitant to pursue such a directive (8). Still, there are considerations that may lead surgical
teams and anesthesiologists to hesitate when adopting “no resuscitation efforts” especially for
risky surgeries. Anesthesiologists are often resuscitating patients in an ongoing fashion via
titration of vasopressors and other life sustaining therapies; hence there may not be a clear line
between normal anesthesia management and intra-operative resuscitation. Surgical teams may
view their primary objective in the OR as to provide care that sustains survival during the
procedure. Thus, intra-operative deaths in the setting of a DNR order may not only contribute to
feelings of guilt, but may also lead to quality reviews and a negative impact on quality metrics
such as 30 day mortality rates. Regardless, most important to achieving balance among these
concerns is an open discussion among relevant parties that allows patients to negotiate their
treatment preferences whilst attaining the input of the anesthesia and surgical teams with regards
to how specific treatment preferences may affect their care during the proposed procedure.
Required Reconsideration of DNR Orders Instead of a policy that leads either to the
automatic enforcement or cancellation of a DNR order in the OR, the American College of
Surgeons (ACS) recommends that a “required reconsideration of DNR orders” discussion be
incorporated systematically prior to a proposed procedure (2). During such a discussion, the
surgical/anesthesia team should clearly delineate to the patient or surrogate which resuscitative
efforts are felt to be essential to the success of the proposed procedure and which are not. They
should also describe the challenges in discerning routine anesthesia management in the OR from
resuscitative efforts as well as the more favorable outcomes of cardiac arrests in the OR. Based
upon the patient/surrogate’s goals of treatment and the nature of the surgical procedure, the
!19
intent of such a discussion is to achieve a mutually agreeable operative and peri-operative
management approach. Potential outcomes could include (3):
a. The DNR order is rescinded during surgery and the perioperative period and the patient
consents to the use of any resuscitation procedure needed to treat the clinical events that
occur.
b. The original DNR order is maintained and prior treatment limitations are upheld.
c. The DNR order is modified such that limited attempts at resuscitation are clearly defined
with regards to specific procedures.
d. The patient and surrogate allow the anesthesiologist and surgical team to use clinical
judgment in determining which resuscitation procedures are appropriate in the context of
the situation and the patient’s stated goals of care.
Changes or clarifications should be documented in the medical records and discussed with the
members of the operating room staff.
Ethical or Professional Conflict When any member of the team disagrees with the
management approach established, he or she may withdraw from the patient’s care in a
nonjudgmental fashion. If agreement on a surgical care strategy cannot be achieved, the
surgeon should consider a referral to another surgeon or institution, and/or provide an alternative
for care. In such scenarios, assistance from palliative care and/or bioethics consult teams may
be of assistance to patients and clinicians.
Authors’ Affiliations: University of Kansas Medical Center, Kansas City, KS; Kansas City
Hospice and Palliative Care, Kansas City, MO
References
1. AORN Position Statement on Perioperative Care of Patients with Do-Not-Resuscitate or

Allow-Natural-Death Orders. Available at: https://www.aorn.org/Clinical_Practice/
Position_Statements/Position_Statements.aspx. Accessed 11/6/2014.
2. American College of Surgeons. Statement on Advance Directives by Patients: “Do Not
Resuscitate” in the Operating room. Bulletin of the American College of Surgeons.
2014;99(1):42-43.
3. Ethical Guidelines for the Anesthesia Care of Patients with Do-Not-Resuscitate Orders or
Other Directives that Limit Treatment. American Society of Anesthesiologists. Last
amended on October 16, 2013 Available at: https://www.asahq.org/coveo.aspx?
q=ethical%20guidelines%20DNR. Accessed 11/2/2014.
4. Ramachandran SK, Mhyre J, Kheterpal S, Christensen RE, Tallman K, Morris M, Chan
PS. Predictors of survival from perioperative cardiopulmonary arrests: a retrospective
analysis of 2,524 events from the get with the guidelines-resucitation registry.
Anesthesiology. 2013; 119:1322-39.
5. Peberdy MA, Kaye W, Ornato JP, Larkin GL, Nadkarni V, Mancini ME, Berg RA, Nichol G,
Lane-Trultt T. Cardiopulmonary resuscitation of adults in the hospital: a report of 14,720
cardiac arrests from the National Registry of Cardiopulmonary Resucitation.
Resucitation. 2003; 58: 297-308.
6. Devereaux PJ, Gold man L, et al. Perioperative cardiac events in patients undergoing
noncardiac surgery: a review of the magnitude of the problem, the pathophysiology of the
events and methods to estimate and communicate risk. CMAJ 2005; 173(6):627-34.
7. Sprung, J., Warner, M.E., Contreras, M.G., Schroeder, D.R., Beighley, C.M., Wilson,
G.A., Warner, D.O. "Predictors of survival following cardiac arrest in patients undergoing
noncardiac surgery: a study of 518,294 patients at a tertiary referral center."
Anesthesiology. 2003; 99:259-69
8. Ewanchuk M, Brindley PG. Perioperative do-not-resuscitate orders – doing ‘nothing’
when ‘something’ can be done. Critical Care. 2006;10(4):219.
Conflict of Interest: The authors have disclosed no relevant conflicts of interest.
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Version History: First published electronically February 2015; the Causes and Outcomes of
Cardiac Arrest in the OR section was updated in November 2018 in response to an attentive
reader who noticed a factual error.
support of a volunteer peer-review editorial board, and are made available online by the Center to
Advance Palliative Care (www.capc.org). Fast Facts and Concepts are editorially independent of
the Center to Advance Palliative Care, and the authors of each individual Fast Fact are solely
responsible for that Fast Fact’s content. The full set of Fast Facts are available at http://
www.capc.org/fast-facts/ along with contact information, and how to reference Fast Facts.
!21
!
Hospice
#38 Discussing
Hospice . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . 2-3
#82 Medicare Hospice Benefit – Part I: Eligibility and Treatment

Plan. . . . . . . . . . . . 4-5
#87 Medicare Hospice Benefit – Part II: Places of Care and

Funding. . . . . . . . . . . . . . 6-7
#90 Medicare Hospice Benefit - Part III: Special

Interventions . . . . . . . . . . . . . . . . . . 8-9
#138 Hospice Referral: Moving From Hospital to

Home . . . . . . . . . . . . . . . . . . . . . . . 10-11
#140 Medicare Hospice Benefit: Levels of Hospice Care . . . . . . . . . . . . . . . . .

. . . . . . 12-13
#246 Emergency Department Management of Hospice Patients . . . . . . . . . . . .

. . . . 14-15
#247 Initiating a Hospice Referral from the Emergency Department. . . . . . . . .

. . . . .16-18
#286 Medication Disposal . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . .19-21
#341 Bleeding in Hospice Care Settings. . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . 22-24
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!

DISCUSSING HOSPICE
Charles F von Gunten MD, PhD, FACP
Introduction Hospice discussions with seriously ill patients should always take place in the
context of the larger goals of care, using a step-wise approach. Fast Facts #82, 87, and 90
discuss the hospice benefit and regulations in more detail.
1. Establish the setting

Ensure comfort and privacy; sit down next to the patient. Ask if family members or others
should be present. Introduce the subject: I’d like to talk with you about the overall goals for
your care.
2. What does the patient understand?
Ask an open-ended question to elicit patient understanding about their current health
situation. It is important to get the patient talking – if the doctor is doing all the talking, it is
unlikely that the rest of the conversation will go well. Consider starting with phrases such as:
What do you understand about your current health situation? Or, What have the doctors told
you about your condition?
If the patient does not know/appreciate their current status this is time to review that
information. An informed decision about hospice is only possible if the patient has a clear
understanding of her or his illness and prognosis.
3. What does the patient expect?
Next, ask the patient to consider the future. What do you expect in the future? What goals do
you have for the time you have left—what is important to you? This step allows you to listen
while the patient describes a real or imagined future. Most patients with advanced disease
use this opening to voice their thoughts about dying—typically mentioning comfort, family,
and home, as their goals of care. If there is a sharp discontinuity between what you expect
and what the patient expects, this is the time to clarify. Listen carefully to the patient’s
responses; most patients have thought a lot about dying, they only need permission to talk
about what they have been thinking. Setting up the conversation in this way permits the
physician to respond with clarifying and confirming comments such as: So what you’re saying
is, you want to be as independent as possible and stay out of the hospital. Or, What you’ve
said is, you don’t want to be a burden on your family.
4. Discuss Hospice Care
Use language that the patient will understand; give information in small pieces. Never say,
There’s nothing more we can do. “Nothing” is euphemistic and easily misinterpreted; to a
patient “nothing” means abandonment. Summarize the patient’s goals as part of your
!2
introducing a discussion of hospice care: You’ve told me you want to be as independent and
comfortable as possible. Hospice care is the best way I know to help you achieve those
goals. Listen carefully to the response; patients often have a distorted view of hospice care,
others have never heard the term. Ask what the term means to them; patients frequently
describe hospice as a place to go to die or what you do when you give up. Probe for
previous experiences or how they developed their point of view. Respond by describing
hospice as A program that helps the patient and family achieve the goals you’ve just
described; it’s a team of people that help meet the patient’s and family’s physical,
psychological, social and spiritual needs. Offer to ask someone from the hospice program to
meet with them to give information.
5. Offer your recommendation
From what you’ve told me, I would recommend that hospice care begin so that I can do the
best possible job in meeting the goals we discussed today. I think it would be best if we got
hospice involved. Normalize your recommendation: I always ask hospice to get involved for
my patients at this stage of their illness. Reinforce that entering hospice care does not mean
that the patient can never return to the office or hospital for care, that the decision is
revocable, and that the patient can continue seeing their current physicians.
6. Respond to emotions
Strong emotions are common when discussing death. Typically the acute emotional response
is brief. The most profound initial response a physician can make may be silence, providing a
reassuring touch, and offering facial tissues (see Fast Fact #29).
7. Establish a plan
Summarize the plan: I’ll ask hospice representatives to come by to give information, then you
and I can discuss it.
References
1. von Gunten CF. Discussing Hospice Care. J Clin Oncol. 2002; 20:1419-1424.
2. Casarett DJ, Quill TE. “I’m not ready for hospice”: Strategies for timely hospice
discussions. Ann Int Med. 2007; 146:443-449.
published July 2005; 3rd edition May 2015. Current version re-copy-edited March 2009;
references updated; re-edited again May 2015.
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!
MEDICARE HOSPICE BENEFIT – PART I: ELIGIBILITY AND TREATMENT PLAN
Robin Turner MD and Drew A Rosielle MD
Background In the United States, the Medicare Hospice Benefit (MHB) pays for 80% of all
hospice care. Established in 1983, the MHB pays for medical, nursing, counseling, and
bereavement services to terminally ill patients and their families. The original goal of the MHB
was to support families caring for a dying relative at home. Under certain circumstances, hospice
services under the MHB can also be provided in a nursing home or the acute care hospital.
Referral for hospice care is appropriate when the overall plan of care is directed toward comfort
rather than reversing the underlying disease process. Fast Facts #87, 90, 139, and 140 further
discuss the MHB.
Eligibility—Medicare Hospice Benefit
1. The patient must be entitled to Medicare Part A (hospital payments); once the patient decides
to enter hospice care, they sign off Part A and sign on (elect) the MHB. Note: this process is
reversible—patients may at a future time elect to return to Medicare Part A.
2. The patient must be certified by the Hospice Medical Director and primary physician to have
a life expectancy < 6 months “if the patient's disease runs its natural course.” Patients can
continue to be eligible if they live beyond 6 months as long as the physicians believe death is
likely within 6 months.
3. Under the MHB, DNR status cannot be used as a requirement for admission.
Covered Services (100% coverage with no co-pay)
• Case oversight by the physician Hospice Medical Director
• Nursing care: symptom assessment, skilled services/treatments and case management.
The nurse visits routinely; 24-hour/7-day per week emergency contact is also provided.
• Social work: counseling and planning (living will, DPOA).
• Counseling services including chaplaincy.
• All medications and supplies related to the terminal illness. The hospice can charge a $5
copay per medication, but most choose not to charge this. Medications for conditions not
related to the terminal condition are not covered.
• Durable medical equipment: hospital bed, commode, wheelchair, etc.
• Home health aid and homemaker services.
• Speech, nutrition, physical, and occupational therapy services as determined by the plan
of care (see below).
• Bereavement support to the family after the death of the patient.
• Short term General Inpatient Care for problems that cannot be managed at home—most
commonly intractable pain, delirium, or caregiver breakdown.
• Short term Respite Care—up to 5 days to permit family caregivers to take a break.
• Continuous care at home for short episodes of acute need.
Not Covered: Continuous nursing assistance (i.e. extended supervisory care) or nursing home
room and board charges.
Plan of Care (POC): The hospice team and the patient’s physician work together to maximize
quality of life by jointly developing the Plan of Care. The POC is based on the patient's diagnosis,
symptoms, and other needs. The hospice program and the patient’s physician must together
approve any proposed tests, treatments, and services. In general, only those treatments that are
necessary for palliation and/or management of the terminal illness will be approved.
Physician Role: At the time of enrollment the patient indicates the primary physician who will
direct care; the patient may select a hospice physician for this role or may select their usual
primary doctor. The primary physician is responsible for working with the hospice team to
determine appropriate care.
!4
Non-Medicare Hospice Plans: Medicaid hospice benefits closely mirror the MHB. Private
insurance plans generally emulate the MHB but occasionally depart from it dramatically (e.g.
capping the total number of days a patient may receive hospice care).
References:
1. The Hospice Manual. Centers for Medicare & Medicaid Services. Available at: http://
www.cms.hhs.gov/manuals/downloads/pub_21.zip. Accessed November 1, 2007.
2. Herbst L. Hospice care at the end of life. Clin Geriatr Med. 2004; 20: 753-65.
3. Gazelle G. Understanding hospice – an underutilized option for life’s final chapter.
NEJM. 2007; 357: 321-324.
Version History: This Fast Fact was originally edited by David E Weissman MD. 2nd Edition was
edited by Drew A Rosielle and published November 2007; 3rd Edition June 2015. Current version
re-copy-edited April 2009; then again June 2015.
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!
FAST FACT AND CONCEPT # 87

MEDICARE HOSPICE BENEFIT – PART II: PLACES OF CARE AND FUNDING
Introduction Fast Fact #82 described eligibility for the Medicare Hospice Benefit (MHB) and the
services it covers. This Fast Fact will review where services are provided and the reimbursement
system for hospice care. Fast Fact #90 reviews special interventions under the MHB, and #140
further discusses levels of care.
Places of Care
• Home: The majority (~95%) of hospice care takes place in the home. Hospice team
members visit the patient and family on an intermittent basis determined by the Plan of Care
(see Fast Fact #82), which changes based on the patient’s needs. Medicare rules do not
require a primary caregiver in the home, but as death nears, it becomes increasingly difficult
to provide care for a patient who does not have someone (family, friends, hired caregivers)
who can be present 24 hours a day in the home.
• Long-term care facility: 25% of patients in the US die in nursing homes. Medicare
recognizes that this can be the resident’s ‘home’ and that the patient’s ‘family’ frequently
includes the nursing home staff. Hospice care under the MHB can be provided to residents
in addition to usual care provided by the facility. Individual hospice programs must establish
a contract with the facility to provide hospice care. The MHB does not pay for nursing home
• Hospice inpatient unit: Dedicated units, either free-standing or within other facilities (such
as nursing homes or hospitals) are available in some regions. Patient eligibility (e.g,
whether or not a patient requires general inpatient care or not), permitted length-of-stay, and
fees for room and board vary between facilities.
• Hospital: When pain or other symptoms related to the terminal illness cannot be managed
at home, the patient may be admitted to a hospital for more intensive management, still
under the MHB. The inpatient facility must have a contract with the hospice program to
provide this service.
Payment Medicare pays for covered services using a per diem capitated arrangement in one
of four categories (see Fast Fact #140). The rates below reflect 2015 Medicare and Medicaid
reimbursements.
• Routine Home Care: care at home or nursing home (~$159/day).
• Respite Care: care in an inpatient setting (nursing home, hospice facility, or hospital) for up
to 5 days to give caregivers a rest (~$164/day).
• General Inpatient Care: acute inpatient care (at a hospital or hospice facility) for conditions
related to the terminal illness such as pain and symptom control, caregiver breakdown, or
impending death that requires inpatient-level interventions (~$709/day).
• Continuous Home Care: provides acute care at home with around-the-clock nursing for a
crisis that might otherwise lead to inpatient care (~$930/day).
The rates of reimbursement are fixed for each category of care on an annual basis, but they vary
by geographical location. Cited rates are approximate and are intended to convey general orders
of magnitude of payment. Payment is made from Medicare to the hospice agency, which then
pays the hospital or nursing home (for respite or acute care), depending on the specifics of the
contractual arrangement between the hospice agency and the facility.
Physician Services Direct patient care services by physicians, for care related to the terminal
illness, are reimbursed by Medicare, and are not included in the per diem. If the attending
physician is not associated with the hospice program via employment or similar contract, the
physician bills Medicare Part B in the usual fashion. The bill must indicate that the physician is not
associated with the hospice program or the claim may be denied. If the attending is associated
!6
with the hospice program (e.g. as a medical director) the physician submits the bill to the hospice
program, which in turn submits the claim to Medicare under Part A. The physician is then
reimbursed based on a contract with the hospice program. Patients can see consulting physicians
under the MHB if the hospice agency contracts with the consultant to do so. The hospice agency
submits the claim under Medicare Part A and reimburses the consultant per their contract.
References
1. von Gunten CF, et al. Coding and reimbursement mechanisms for physician services in
hospice and palliative care. J Pall Med. 2000; 3:157-164.
NEJM. 2007; 357:321-324.
3. Hospice Center. Centers for Medicare and Medicaid Services. Available at: http://
www.cms.hhs.gov/center/hospice.asp. Accessed November 1, 2007.
4. National Hospice and Palliative Care Organization. “The Medicare Hospice Benefit.”
January 2015. Available at: http://www.nhpco.org/sites/default/files/public/
communications/Outreach/The_Medicare_Hospice_Benefit.pdf. Accessed July 9 2015.
5. CGS Medicare. “Hospice Payment Rates.” Available at: http://www.cgsmedicare.com/
hhh/claims/fees/hospice_rates.html. Accessed July 9 2015.
edited by Drew A Rosielle MD and published November 2007. It was re-copy-edited April 2009
and then again in February 2016.
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!

MEDICARE HOSPICE BENEFIT – PART III: SPECIAL INTERVENTIONS
Introduction This Fast Fact will discuss the use of interventions in hospice care that can be
controversial due to high cost and/or uncertainty whether they constitute ‘palliative’ interventions.
When a patient elects the Medicare Hospice Benefit (MHB), the patient, the doctor, and the
hospice team develop a Plan of Care (POC) that lists a) the patient’s goals for care and b) the
services needed to achieve these goals. A hospice program is fiscally responsible for all services
outlined in the POC, and these services are paid for from the pool of money the hospice program
gets from per diem payments (physician fees are billed separately – see Fast Fact #87).
Note: since there is no Medicare regulation that specifies what treatments are deemed ’palliative,’
it is up to the individual hospice agency to determine whether or not they can financially and
philosophically provide the interventions listed below. Most hospice agencies are not able to
provide high-cost interventions due to financial limitations; patients may elect to be discharged
from hospice care if they wish to pursue these options. Hospices with a large number of enrolled
patients have greater financial resources and thus are better able to provide high-cost treatments.
Recently, some hospices have introduced ‘open-access’ programs which more freely provide
costly and even life-prolonging therapies to dying patients who would otherwise benefit from
hospice services. The hope is that the increased costs will be covered by increased revenue from
enrolling more patients earlier in the course of their illness.
Indications for use in Hospice Care In general, the interventions listed below are potentially
indicated in patients with a) a good functional status (up, out of bed > 50% of the time; Karnofsky
Performance Status >50; ECOG ≤2 – see Fast Facts #13, 124), or b) a clear goal to be met (e.g.
wedding anniversary in two weeks). These interventions are not indicated solely to assist
patients or families psychologically cope with impending death – to give the impression that
’something is being done.’
• Parenteral Fluids. Indication: symptomatic dehydration where there is a patient-defined
goal (e.g. upcoming family event). Fluids are not indicated to treat dry mouth or solely to
reverse dehydration occurring as a normal aspect of the dying process; fluids may be of
benefit to treat delirium in selected patients (see Fast Fact #133).
• Enteral feeding. Indication: patient is hungry and there is a reason oral nutrition cannot be
given (e.g. upper GI obstruction from esophageal cancer). See Fast Facts #10 and 84 for a
complete review of the indications/contraindications for tube feeding.
• Total Parenteral Nutrition. Indication: patient has short-gut syndrome or bowel obstruction
and good functional status and a functional goal. See Fast Fact #190 for further discussion.
• Radiation Therapy. Indication: symptoms of pain, bleeding, or neurological catastrophe (e.g.
acute spinal cord compression) and the patient is expected to live long enough to experience
benefit (> 4 weeks) and the potential benefits outweigh logistic burdens (e.g. travel to the
radiotherapy site, getting on and off the treatment table). See Fast Facts # 66, 67.
• Red Blood Cell Transfusions or Erythropoietin. Indication: Symptomatic anemia
(dyspnea or fatigue) in ambulatory patients who demonstrate continued functional benefit
from treatment.
• Platelet Transfusions. Indication: active bleeding and severe thrombocytopenia (Platelet
count < 10,000).
• Chemotherapy. Indication: symptoms from the cancer are causing distress; the likelihood of
effectiveness is high (expected Response Rate greater than 25% - see Fast Facts #14, 99);
patient will live long enough to benefit (> 4-8 weeks, ECOG 0-2); and benefits outweigh
burdens.
• Antibiotics. Indication: oral antibiotics are appropriate to treat simple symptomatic
infections (e.g. UTI). Parenteral antibiotics are not indicated unless there is an identified
!8
susceptible organism, there is a clear functional goal to be met, the likelihood of successful
treatment is high, and the patient is expected to live long enough to achieve benefit.
• Laboratory/Diagnostic services. Indication: to monitor aspects of POC (e.g. warfarin
monitoring) or as part of a diagnostic evaluation for a new symptom for which the testing is
likely to substantially alter patient management. Note: diagnosis of a new problem that does
not relate to the terminal illness can be evaluated and treated by the patient’s primary care
provider under usual Medicare billing (e.g. acute myocardial infarction).
References
2. Wright AA, Katz IT. Letting go of the rope – aggressive treatment, hospice care, and
open access. NEJM. 2007; 357:324-327.
3. Marantz Henig R. Will we ever arrive at the good death? New York Times. August 7,
2005. Available at: http://www.nytimes.com/2005/08/07/magazine/07DYINGL.html.
Accessed November 2, 2007.
edited by Drew A Rosielle MD and published November 2007; 3rd Edition June 2015. Current
version re-copy-edited April 2009; then again in June 2015.
!9
!
HOSPICE REFERRAL: MOVING FROM HOSPITAL TO HOME
Tara C Friedman MD
Background The transition from hospital to home for the patient about to be enrolled in home
hospice care is complex. Miscommunication between hospital staff and hospice care providers
regarding goals of care and medications occurs commonly and only heightens existing stress and
fear among patients and their caregivers. This Fast Fact reviews key steps in the transition from
the acute care hospital setting to home hospice care.
Clarify goals Fast Fact #38 reviews key do’s and don’ts of the initial hospice discussion with
patients and families. Prior to discharge additional steps to clarify the goals of care include:
• Confirm in the records that you believe the patient meets hospice eligibility requirements
(see Fast Fact #82): “In my medical judgement, the patient has a prognosis of less than
6 months if the disease follows its usual course.”
• Review all medications and interventions (e.g. tube feedings, oral antibiotics). Any
medications and interventions that do not help the patient and family meet their goals of
care or enhance quality/comfort should be discussed with patients/families, and a
recommendation made to discontinue them.
• Project ahead to the coming days to weeks: what symptoms/problems do you anticipate
will likely occur (e.g. dyspnea in a lung cancer patient)? Ask yourself if the current
medications/interventions will likely meet these needs or do additional medications/
interventions need to be made available in the home?
Contact the Hospice Agency Whoever makes the initial contact with a hospice agency
(physician, discharge planner, palliative care nurse, etc.) should have the following information in
hand:
• Patient’s address – confirm the patient lives within the hospice’s catchment area.
• Birth date and medical insurance information.
• Terminal diagnosis (e.g. dementia, cancer).
• Name of physician who will be physician of record for hospice care.
• Overall goals of care and special issues (e.g. family needs special bereavement support
for children who live in the home or patient has two days of palliative radiation left).
• Medical equipment needs (e.g. hospital bed, oxygen).
• Anticipated discharge date/time.
Coordinated Discharge
• Whenever possible, have someone from the hospice program meet the patient and their
caregiver in the hospital prior to discharge to review hospice eligibility and covered
services. If not feasible, arrange for the initial hospice referral visit to occur when the
patient arrives home, or within 24 hours of hospital discharge at the outside.
• Include the hospice staff in the discharge plan.
• Inquire if the home hospice team can offer continuous care for patients with acute
symptom management needs or in patients in whom discontinuation of life supporting
therapies will be occurring during the transition to home. There is some published
evidence that continuous care can significantly improve the chances that the patient can
die at home.
• Review symptoms and confirm treatments for the terminal illness with hospice staff.
• Review symptoms and confirm treatments for diseases unrelated to the terminal illness.
• Plan to have durable medical equipment and medications available when the patient
arrives at home; coordinate this with your hospice agency provider. Most hospice
agencies need at least 24 hours to coordinate the delivery of these items to the home.
With careful planning, the stress of transitioning to home hospice care will be minimized, allowing
your patients, their families and yourself the opportunity to focus on important issues near the end
of life.
!10
References
1. Turner R, Rosielle D. Medicare Hospice Benefit – Part I: Eligibility and Treatment Plan,
2nd Edition. Fast Facts and Concepts. November 2007; 82. Available at: http://
www.eperc.mcw.edu/fastfact/ff_082.htm.
2. von Gunten CF. Discussing Hospice, 2nd Edition. Fast Facts and Concepts. July 2005;
38. Available at: http://www.eperc.mcw.edu/fastfact/ff_038.htm.
3. Barclay JS, Kuchibhalta M, et al. Association of hospice patients' income and care level
with place of death. JAMA Intern Med. 2013; 173(6):450-456
in June 2005. Version re-copy-edited in April 2009; revised again July 2015 by Sean Marks MD.
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!

MEDICARE HOSPICE BENEFIT: LEVELS OF HOSPICE CARE
Tara C Friedman MD
Background In the United States, modern hospice care is guided by the Medicare Hospice
Benefit (MHB), which pays for 80% of all hospice care (see Fast Facts #82, 87, 90). Because
most of hospice care is in the form of routine home care, clinicians may not be aware that the
MHB specifies four different levels of hospice services to meet the diverse needs of dying
patients and their family.
1. Routine Home Care:

• The most common type of hospice services in the United States.
• Hospice interdisciplinary team provides core services (see Fast Fact #82) in the patient’s
home.
• The patient’s home may be a private home, an assisted living facility, a boarding home, or
a long-term care facility – wherever the patient lives.
2. Respite Care:
• Respite care is short-term inpatient care to relieve the family/primary caregiver.
Caregivers often schedule respite in order to travel or tend to their own healthcare needs.
• Respite is limited to 5 consecutive days.
• The hospice agency may provide respite in a variety of contracted settings (e.g. inpatient
facility, local nursing home, etc.).
3. General Inpatient Hospice Care (GIHC): The MHB provides for care to be provided in an
acute care hospital or other setting where intensive nursing and other support is available outside
of the home. Criteria for this level of care include:
• Uncontrolled distressing physical symptoms (e.g. uncontrolled pain, intractable nausea,
respiratory distress, severe wounds, etc.).
• Psychosocial problems (e.g. unsafe home environment or imminent death where family
can no longer cope at home).
• GIHC may be provided in a variety of settings
o Dedicated inpatient hospice facilities, where the patient is cared for by dedicated
hospice staff.
o Contract beds, where the facility (hospital/nursing home) staff provides routine
care, with supplemental services provided by hospice personnel.
4. Continuous Home Care: For hospice patients who qualify for GIHC, but desire to remain in
their own home, continuous care (CC) intends to support the patient and their caregiver through
brief periods of crisis. There is some published data that patients who did not have access to
continuous care were more likely to be transferred from their home prior to death.
• CC provides care for 8-24 hours a day.
• Home health aide and homemaker services or both may be used to cover the care
needs.
• Care must be primarily provided (more than 50%) by an LPN or RN.
Under the MHB patients may be admitted into a hospice program at any level of care as
determined by their individual needs and the patient may transfer between the levels of care as
needed. For patients whose hospice care is covered by a pay source other than Medicare, there
may be limitations or specifications for the different levels of care.
!12
References
1. NHPCO Facts & Figures, 2014. Alexandria, VA: National Hospice and Palliative Care
Organization; 2014. Most current version is available at: http://www.nhpco.org/sites/
default/files/public/Statistics_Research/2014_Facts_Figures.pdf Accessed July 10, 2015.
2. Kinzbrunner BM, et al. 20 Common Problems in End-of-Life Care. New York, NY: Mc-
Graw Hill; 2002.
3. Code of Federal Regulations, Title 42 – Public Health. Chapter IV – Health Care
Financing Administration, Department of Health and Human Services. Subchapter B –
Medicare Program, Part 418 – Hospice Care.
4. Barclay JS, Kuchibhalta M, et al. Association of hospice patients' income and care level
with place of death. JAMA Intern Med. 2013; 173(6):450-456
in August 2005. Version re-copy-edited in April 2009; then again by Sean Marks MD in July 2015
-- reference web-links updated and reference #4 added and incorporated into the text..
!13
!

EMERGENCY DEPARTMENT MANAGEMENT OF HOSPICE PATIENTS
Sangeeta Lamba MD, Tammie E Quest MD, David E Weissman MD
Background Patients enrolled in hospice programs will occasionally be transported to the
Emergency Department (ED). Emergency medicine training focuses on life-prolonging measures
and may fail to address hospice as a system of care. This Fast Fact provides information for
clinicians practicing in EDs on management issues when a hospice patient arrives. Fast Fact
#247 discusses initiating hospice care from the ED and #298 addresses Palliative Care
Consultation in the ED.
Why do Hospice Patients come to the ED? ED providers should never assume that arrival in
the ED equates a desire for aggressive/life-prolonging treatment. Even when a patient/family
requests such services, an assessment is needed to understand the concerns that prompted a
shift in care goals. Frequently such requests arise from fear about the dying process or guilt
about prior medical decisions to limit life-prolonging treatments. Common triggers for an ED visit
include:
• Stress/inability to cope with impending loss of life. This may be expressed as a request to
start a life-prolonging treatment previously used and discontinued (e.g. chemotherapy) or
never begun (e.g. renal dialysis).
• Poor symptom control.
• Malfunction/loss of a support device such as a gastrostomy tube.
• Failure of the hospice program to provide timely patient support and communication.
Management Guidelines
1. Notify hospice staff as soon as possible. Under the Medicare Hospice Benefit, hospice
agencies are legally/financially responsible for the patient’s plan of care and all medical
costs related to the terminal illness. See Fast Facts # 82, 87, 90.
2. Determine the trigger for the ED visit. Pay attention not only to distressing physical signs
and symptoms but also emotional and psycho-social issues. Involve social services,
chaplaincy, and Palliative Care consultative services early if needs are identified.
3. Treat distressing symptoms. See Fast Facts for specific symptom treatment guidelines.
4. If deterioration is imminent and rapid decisions are needed regarding the use of life-
sustaining treatments (e.g. intubation for respiratory failure) a focused discussion around
goals of care must occur in the ED
• Determine the legal decision maker if available and review any completed advance
directives.
• Complete a rapid goals of care discussion (see Fast Facts #223-227).
• Make recommendations. For example, ‘According to what you want for [the patient], I
would/would not recommend….’
5. If the patient is actively dying (see Fast Fact #3) assess for cultural/spiritual needs;
assure privacy and endeavor to identify if there are any preferred locations a patient can be
safely transferred to to die (e.g. back home; to a private hospital room).
6. Laboratory tests/diagnostics should be limited or withheld until discussion with the
patient’s hospice care team. Testing should be based on patient-defined goals of care.
Generally, low burden, non-invasive methods which may reveal reversible pathology or
clarify prognosis should be used first.
7. Therapeutic modalities should be based on patient-defined goals of care rather than
automatic ‘ED indications’ (e.g. antibiotics for pneumonia should only be used if they meet
a patient or surrogate defined goal of care).
8. Disposition should be planned after discussion with hospice staff based on the patient’s
goals. Returning home or a direct admission to an inpatient hospice facility may be the
best disposition rather than hospital admission. At times, hospices can arrange 24h
professional support in the home for patients with difficult to manage symptoms who wish
to remain home (‘continuous care’ – see Fast Fact #87).
!14
9. Notify the inpatient palliative care service if the patient is to be admitted to the hospital.
Hospice agencies may revoke a patient’s enrollment in hospice care if care goals have
changed, or may continue a patient under hospice care during an admission for palliation
(see Fast Fact #87).
Summary Patient-centered care for hospice patients may be enhanced by emergency
clinicians who acquire skills to quickly adapt to a supportive role in the care of a terminally-ill
patient. Recognizing common triggers for the ED visit, using a multi-disciplinary approach with
early involvement of hospice, social services and palliative team consults may assist in providing
optimal care for ED patients under hospice care.
References
1. Chan GK. End-of-life and palliative care in the emergency department: a call for research,
education, policy and improved practice in this frontier area. J Emerg Nurs. 2006. 32(1):
101-3.
2. Smith AK, Fisher J, Schonberg MA, et al. Am I doing the right thing? Provider perspectives
on improving palliative care in the emergency department. Ann Emerg Med. 2009. 54(1):
86-93.
3. Reeves K. Hospice care in the emergency department. J Emerg Nurs. 2008. 34(4):350-1.
4. Lamba S, Quest TE. Hospice care and the Emergency Department: rules, regulations and
referrals. Ann Emerg Med. 2011; 57:282-290.
Author Affiliations: University of Medicine and Dentistry of New Jersey, Newark, New Jersey
(SL); Department of Veterans Affairs, Emory University School of Medicine, Atlanta, GA (TEQ);
Medical College of Wisconsin, Milwaukee, WI (DEW).
Version History: Originally published October 2011; Copy-re-edited August 2015.

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!

INITIATING A HOSPICE REFERRAL FROM THE EMERGENCY DEPARTMENT
Background Patients with an end-stage illness often present to the Emergency Department
(ED) with a crisis event (1). This Fast Fact provides information for ED providers on how to refer
a patient to hospice care directly from the ED (2). Fast Fact #246 suggests strategies for caring
for patients receiving hospice care who present to the ED; Fast Fact #298 covers Palliative Care
consultation in the ED.
1. Assess Medicare Hospice Benefit eligibility (see Fast Fact #82). Fundamentally, this
means the patient has a prognosis that is 6 months or less if his/her disease runs its expected
course, and the patient’s care goals are compatible with hospice (see #3 below). Broad
guidelines for many cancer and non-cancer related conditions exist (3, 4, 5, 6). A useful starting
point is to ask yourself, Would I be surprised if this patient died within the next 6 months? For
disease specific prognostic information, see Fast Facts #13, 99, 124, 125, 141, 143, 150, 189,
191, 213.
2. Discuss hospice as a disposition plan with the patient’s physician. Contact the
patient’s personal physician: discuss the current condition, prognosis, and prior goals of care
conversations. If you are considering hospice care, ask if the physician is willing to be the
following physician for hospice services.
3. Assess whether the patient‘s goals are consistent with hospice care. Generally this
means a patient wants medical treatments and other support aimed at alleviating symptoms and
maintaining quality of life, without life-prolongation. Patients may enroll in hospice care if their
preeminent care goal is symptom relief, even if they are not entirely sure they want to completely
discontinue life-prolonging therapies, as long as the hospice agency indicates they can
accommodate those wishes. These four questions will help you get the discussion started to
elicit if the patient and family are psychologically ready to accept hospice care (see also Fast
Facts #222-227).
• “What have you been told about the status of your illness and what the future holds?”
• “Has anyone talked to you about your prognosis; how much time you likely have?”
• “Are there plans for new treatments designed to help you extend your life?”
• “Has anyone discussed with you hospice services? What do you know about Hospice?”
4. Introduce hospice to the patient and family/surrogates.

• Discuss the core aspects of hospice care and how these features can help the patient
and family (e.g. 24/7 on-call assistance, home visits for symptom management,
coordinated care with the patient’s physician, emotional and chaplaincy support).
• Address concerns and clarify misconceptions.
• Phrase your recommendation for hospice care in positive language, grounded in the
patient’s own care goals. “I think the best way to help you stay at home, avoid the
hospital, and stay as fit as possible for whatever time you have left is to receive hospice
care at your home….”
• Discuss location of hospice care: usually this is the patient’s residence such as a private
home or long-term care facility. Direct admissions to hospice facilities can occur
depending on bed availability and ability of local hospice agencies to arrange an
immediate, direct facility admission. This is not available in all communities and requires
a discussion with the hospice agency.
5. Make a referral and write orders (see Fast Fact #139).

Call a hospice agency; anticipate these questions:
• What is the terminal illness? Who will be the following physician? (Step 2)
!16
• What equipment will be needed immediately (e.g. home oxygen)? Is there a caregiver at
home?
• Code status (patients cannot be denied hospice enrollment if ‘full code’, however the
hospice team will need to know if code status needs to be addressed further.)
Questions you may need to ask the hospice agency:
• How soon can you make an intake visit to the patient’s home? Can you visit the patient
immediately, even in the ED (this is available in some communities)?
• How should I coordinate filling of new prescriptions I want the patient to have?
Example of ED Initiated Hospice Referral Orders:
o Evaluate and Admit/Enroll in hospice care
o Terminal Diagnosis: __________.
o Expected Prognosis: Terminal illness with less than 6 month survival likely if disease runs
its normal expected course [or more specific if indicated].
o Physician who will follow patient: _________.
6. Ensure patient/surrogate understanding and secure the plan. Communicate the plan
following ED discharge; provide the name and contact number for the hospice agency.
7. What if hospice enrollment is appropriate, but cannot be arranged in a timely manner?

If the patient can be cared for at home safely for 1-2 days without extra services, send her or him
home with appropriate prescriptions and care instructions. In most communities, patients can be
enrolled in hospice care within 24-48 hours, even on weekends. If they cannot be cared for
safely at home, observation vs inpatient admission is likely necessary until a safe discharge plan
can be established.
Summary Patient-centered care for hospice-eligible, terminally-ill patients may be enhanced
by emergency clinicians who acquire skills to make early appropriate hospice referrals from the
ED.
References
1. Lamba S, Quest TE. Hospice care and the emergency department: rules, regulations and
2. Education in Palliative and End-of-Life Care-Emergency Medicine Project, Trainers
Guide. Module 5. Emanuel LL, Quest TE, eds. Chicago, IL: Northwestern University;
2008.
3. Stuart B, et al. Medical Guidelines for determining prognosis in selected non-cancer
diseases. 2nd ed. Alexandria, VA: National Hospice Organization; 1996.
4. Centers for Medicare and Medicaid Services, Medicare Coverage Database. LCD (Local
Coverage Determination) for hospice: determining terminal status (L25678). Available at:
http://www.cms.gov/medicare-coverage-database/details/lcd-details.aspx?LCDId=25678
5. Gazelle G. Understanding hospice – an underutilized option for life's final chapter. New
Engl J Med. 2007; 357(4):321-4.
6. Lynn J. Perspectives on care at the close of life. Serving patients who may die soon and
their families: the role of hospice and other services. JAMA. 2001; 285(7):925-32.
Version History: Originally published September 2011; Copy-re-edited August 2015.

!17

MEDICATION DISPOSAL
!18
Susan Nathan MD and Catherine D Deamant MD
Background Patients receiving home hospice or palliative care often have a residual supply
of opioids and other pharmaceuticals at the time of the patient’s death. A number of agencies
have recommendations and resources on safe medication disposal, including the Food and Drug
Administration (FDA), Environmental Protection Agency (EPA), and the Drug Enforcement
Agency (DEA) (1-3). Educating families on proper disposal of medications is an important patient
safety measure.
Medicine Take-Back Events or Programs Ideally, medications should be given to a secure
medication collection site or disposed of through an official take-back program. These programs
dispose of medications in accordance with federal, state and/or local environmental regulations.
Many collected medications are incinerated.
Medication collections sites include police stations, pharmacies, chemical plants; sometimes
programs included locked drop-boxes associated with these facilities. There is no unified
resource that identifies all of these options in every state, but the website http://www.awarerx.org/
get-local provides information on these sites by state. If the patient does not have internet access,
they can call 311 or the FDA: 1-888-INFO-FDA for information about local resources.
Disposal in Household Trash If the patient cannot access a secure collection site, they should
be instructed on safe medication disposal in the household trash. The FDA, EPA and other safety
programs have created consumer education materials and recommend the following (4, 5):
• Remove medications (liquids, tablets, or capsules) from their original container.
• Mix medications (do not crush tablets or capsules) with unpalatable substances (such as
kitty litter or used coffee grounds) and seal in a plastic zip lock bag or empty container
(such as a margarine tub) and place in the trash.
• Remove identifying information about the patient and medication by covering with
permanent marker or scratching off labels.
• Empty pill bottles should be thrown in the trash or recycling (depending upon local
guidelines).
Flushing Medications If a drop-off program is unavailable or impractical, the FDA
recommends flushing down the toilet certain medications that can be harmful to unintentional
users. These medications include all opioids, rectal diazepam, and transdermal methylphenidate
and buprenorphine (1).
In 2013, the FDA issued an update regarding the disposal of fentanyl patches in response to 32
cases of accidental exposure to fentanyl since 1997, most of them involving children younger
than 2 years old (6). The patches should be folded in half, sticky sides together, and flushed down
the toilet. While not explicitly stated, it is reasonable to dispose of transdermal buprenorphine and
methylphenidate similarly.
Environmental Impact of Unused Medications There has been controversy and media
coverage around concerns with flushing medications. The EPA has advised against flushing
medications down the toilet because of environmental concerns (2). However, others have noted
the main way drug residues enter water systems is by passage of drug and drug-metabolites in
urine and feces (7,8). Additionally, there is no clear scientific evidence of actual ecological harm
brought about by pharmaceutical contamination of waste water. Given this, the FDA’s
recommendation to flush certain drugs which are very harmful if unintentionally ingested should
be followed.
Hospice and Medication Disposal There are no consensus guidelines or best practices
specific to the hospice community around disposal of medication after a patient’s death. The
National Hospice and Palliative Care Organization and the Hospice and Palliative Nurses
Association recommend following the FDA and DEA guidelines listed above and stress the
requirement for individual hospice agencies to have organizational policies and procedures on the
disposal of controlled substances in accordance with the Centers for Medicare and Medicaid
Services Hospice Conditions of Participation, Sec. 418.106. (9-11) In a recent study, nearly 1/3
of hospice nurses were not familiar with these rules (12).
!19
Because of prognostic uncertainty in hospice many patients have unused medications at the time
of their death, many of which are opioids or benzodiazepines. There is significant cost associated
with discarded medications (13, 14) and concern by hospice staff about legal and environmental
impact and risk for drug diversion (12). At the time of first ordering controlled medications, the
hospice should provide the patient or patient representative a copy of the hospice written policy
on the management and disposal of controlled drugs. After the patient dies, the medications
remain the property of the family and hospice staff should advise family on safe disposal.
Bottom Line Ideally, medications should be disposed of at take-back programs, or thrown in
the trash. Opioids, including patches, should be flushed down the toilet and not thrown in
the trash. Providers should educate patients and families about safe medication disposal,
particularly with opioids which can be deadly if unintentionally ingested.
References
1. Disposal of Unused Medicines: What You Should Know. US Food and Drug
Administration. Available at: http://www.fda.gov/drugs/resourcesforyou/consumers/
buyingusingmedicinesafely/ensuringsafeuseofmedicine/safedisposalofmedicines/
ucm186187.htm. Accessed Sep 25, 2015.
2. Pharmacetucials and Personal Care Products (PPCPs). US Environmental Protection
Agency. Available at: http://www.epa.gov/ppcp/faq.html. Accessed Sep 25, 20=15.
3. Drug Disposal Information. US Department of Justice. Available at: http://
www.deadiversion.usdoj.gov/drug_disposal/ . Accessed Sep 25, 2015.
4. How to Dispose of Unused Medicines. US Food and Drug Administration. Available at:
http://www.fda.gov/downloads/Drugs/ResourcesForYou/Consumers/
BuyingUsingMedicineSafely/UnderstandingOver-the-CounterMedicines/ucm107163.pdf.
Accessed Sep 25, 2015.
5. How to Dispose of Medicines Properly. US Environmental Protection Agency. Available
at: http://water.epa.gov/scitech/swguidance/ppcp/upload/ppcpflyer.pdf. Accessed Sep 25,
2015.
6. Fentanyl Patch Can Be Deadly to Children. US Food and Drug administration. Available
at: http://www.fda.gov/forconsumers/consumerupdates/ucm300803.htm. Accessed Sep
25, 2015.
7. Daughton C, Ruhoy S. Green pharmacy and pharmEcovigilance: prescribing and the
planet. Expert Rev Clin Pharmacol. 2011; 4(2):211–232.
8. Kolpin D, Furlong E, Meyer M, et al. Pharmaceuticals, hormones, and other organic
wastewater contaminants in U.S. streams, 1999-2000: a national reconnaissance.
Environ Sci Technol. 2002; 36: 1202-1211.
9. COPS—Planning for Success. National Hospice & Palliative Care Organization.
Avabilable at: http://www.nhpco.org/sites/default/files/public/regulatory/Drug_disposal-
COPS_by_topic.pdf. Accessed Sep 25, 2015.
10. Drug Disposal Guidelines. Hospice and Palliative Nurses Association. Available at:https://
www.hpna.org/DisplayPage.aspx?Title=Drug%20Disposal%20Guidelines. Accessed Oct
31, 2014.
11. Conditions of Participation. Centers for Medicare and Medicaid Services. Available at:
http://www.gpo.gov/fdsys/pkg/CFR-2011-title42-vol3/pdf/CFR-2011-title42-vol3-
sec418-106.pdf. Accessed Sep 25, 2015.
12. McCullagh MC, Schim S, Ortner P. Drug disposal among hospice home care nurses: a
pilot study of current practices and attitudes. J Pain Symptom Manage. 2012;
43:287-292.
13. Speer N, Dioso BS, Casner P. Costs and implications of discarded medication in
hospice. J Pall Med. 2013; 16(8):975-78.
14. Hauser JM, Chen L, Paice J. Down the drain: the cost of medications wasted in hospice.
J Pain Symptom Manage. 2006; 31:379-380.
Author Affiliations: Rush University Medical Center, Chicago, IL (SN); Cook County Health and
Hospitals System, Chicago, IL (CD).
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Version History: Originally published January 2015; websites updated and re-copy-edited
September 2015.

BLEEDING MANAGEMENT IN HOSPICE CARE SETTINGS
Pamela Liao, MD, Candice Johnstone, MD, Shayna E. Rich, MD, PhD
Background Bleeding is a distressing, complex, and relatively common symptom in palliative

care (1). It can present at many anatomical sites and vary in acuity and presentation. This Fast
Fact, provides an approach to managing non-catastrophic bleeding in terminally ill patients in
home or hospice settings.
General Considerations Severity is not the only important clinical consideration when
evaluating bleeding in a seriously ill patient. Some imminently dying patients may not benefit from
diagnostic workup or intervention even if the bleeding is profuse, while more stable patients can
benefit from investigations if they would prevent a terminal bleed or symptom burden (2).
Clinicians need to consider goals of care and prognosis in bleeding assessment, as these factors
can dictate the degree of investigation and intervention. Additionally, clinicians should be mindful
of what testing and interventions can be done in the current environment, as many terminal
patients may want to avoid being transferred. A routine CBC or serum INR level, for example,
often can be coordinated at home, whereas an advanced intervention such as a bronchoscopy or
gastroscopy cannot be.
Initial Management Steps Prior to initiating other interventions, clinicians should remember to:
• Apply pressure if anatomically possible with an appropriate gauze or dressing.
• Consult with a pharmacist to identify offending agents (1). For example, medications such as
enoxaparin, oral anticoagulants (see Fast Fact #236 and #278), aspirin, NSAIDs, and
chemotherapeutics all can cause or exacerbate bleeding. Over-the-counter supplements
such as fish oil, omega fatty acids, ginseng, and gingko biloba are known to increase
bleeding risk.
Systemic Treatments:
!21
• Vitamin K: For terminally ill patients on warfarin or with clotting factor deficiencies (e.g. end
stage liver failure), consider an empiric dose of 2.5-3 mg oral or subcutaneous Vitamin K
(3-6) and/or consumption of Vitamin K-rich foods (e.g. green leafy vegetables, broccoli,
prunes, or cabbage).
• Transfusions: Platelet, fresh frozen plasma, and clotting factor concentrate transfusions can
prevent or stop active bleeding in select patients with thrombocytopenia (e.g. platelet count <
50K) or certain coagulopathies (7). Red blood cell transfusions can improve symptoms such
as fatigue, chest pain and shortness of breath, especially when hemoglobin <8. Yet,
transfusions are difficult to coordinate in a home or hospice care setting, as they typically
necessitate transfer to a specialty clinic or hospital for administration. They may even require
revocation of hospice. Therefore, many experts avoid transfusions in imminently dying
patients with comfort goals of care.
Local Site Management Prevention and preparation are crucial aspects of bleeding
management in dying patients at home or a hospice facility. For at-risk patients with
thrombocytopenia, coagulopathy, or specific anatomic concerns, clinicians should ensure that
necessary supplies and therapies are available in the care setting before bleeding occurs.
• Head and Neck: Patients with erosive tumors of the head and neck are at risk for bleeding.
Prophylactic measures such as elevating the head of the bed to 45 degrees, maintaining a
soft diet, and minimizing traumatic brushing/flossing are recommended (8). A suction kit at
bedside can be useful for patients at risk for epistaxis. For active mucosal bleeding, the
effective use of topical agents like silver nitrate, surgicell dressing, or sucralfate gel 1 g in 5
mL water soluble applied to the wound has been described (9). Some experts recommend
trying 5% tranexamic acid (TXA) oral rinse TID either as a 10-mL swish and spit x 10 minutes
or as a soaking gauze (1,9). If pre-fitted dental molds are available, apply them with a topical
agent, in wakeful patients with gingival bleeding (8).
• Respiratory Tract: Elevate the head of the bed and consider prophylactic use of cough
suppressants (see Fast Facts # 199 & 200). For active bleeding from a known location,
position the patient on the side of bleeding to reduce the compressive force on the
contralateral side.
• Urinary Tract: Finasteride may help reduce the recurrence of hematuria in male patients with
benign prostatic hypertrophy (9). For hemorrhagic cystitis, intermittent bladder irrigations with
saline or TXA 5 g in 50 mL water daily or BID may help (10). If bleeding continues, continuous
bladder irrigation with 0.5% or 1% silver nitrate in water solution could be pursued; however,
bladder irrigation can induce bladder spasms, so caution should be heeded.
• Gastrointestinal (GI) Tract: Effective use of TXA given 1-2 g orally 4-6 times per day, or
intravenously at 10 mg/kg 3-4 times per day has been described for active GI bleeding (11).
Intravenous infusion of vasopressin 0.1-0.4 mg/hr can reduce GI bleeding in select patients,
but it requires hospital monitoring (12). Octreotide 50-100 ug SQ BID or as a 48-hour 50 ug/
hr SQ infusion has been described as a home alternative (13). For rectal bleeding, packing
with dressings coated with TXA or sucralafate paste may help (10). For minor, hemorrhoid-
induced bleeding, Sitz baths or over-the-counter hemorrhoid medications may minimize
bleeding by decreasing local inflammation (14).
Advanced Interventions and Treatments When bleeding is brisk, patients and families may
reconsider their choice to stay at home and/or pursue comfort care. Consequently, clinicians may
need to direct these patients to the emergency department for urgent specialist consultation (e.g.,
gastroenterology for possible colonoscopy; urology for possible cystoscopy; interventional
radiology for possible vessel embolization). Short-course radiotherapy is worthy of special
consideration to prevent or treat oozing from a malignant lesion. In some circumstances, it can
be coordinated without revocation of hospice services. Regardless, all interventions must be
considered in the context of the treatment burden and the duration of recovery from treatment,
especially when life-expectancy is limited.
Caring for Caregivers Fast Facts #251 & 297 have more information on the management of
brisk, catastrophic bleeding. When preparing family members for this possibility do so in a
sensitive manner so as not to invoke fear (1). Educate family on how to deliver fast-acting
sedative from an emergency kit if needed, as well on the importance of dark sheets, towels, and
!22
clothing to reduce the visibility of blood (1,9). Social workers and other team members may be
able to coach family members in distraction techniques such as relaxation and mental imagery.
References
1. Pereira J, Phan T. Management of bleeding in patients with advanced cancer. Oncologist.
2004;9(5):561-570. doi: 10.1634/theoncologist.9-5-561.
2. Smith LB, Cooling L, Davenport R. How do I allocate blood products at the end of life? An
ethical analysis with suggested guidelines. Transfusion. 2013;53(4):696-700.
3. Nee R, Doppenschmidt D, Donovan DJ, Andrews TC. Intravenous versus subcutaneous
vitamin K1 in reversing excessive oral anticoagulation. Am J Cardiol. 1999;83(2):286-8.
4. Shields RC, McBane RD, Kuiper JD, Li H, Heit JA. Efficacy and safety of intravenous
phytonadione (vitamin K1) in patients on long-term oral anticoagulant therapy. Mayo Clin
Proc. 2011;76(3):260-6.
5. Patel RJ, Witt DM, Saseen JJ, Tillman DJ, Wilkinson DS. Randomized, placebo-
controlled trial of oral phytonadione for excessive anticoagulation. Pharmacotherapy.
2000;20(10):1159-66.
6. Whitling AM, Bussey HI, Lyons RM. Comparing different routes and doses of
phytonadione for reversing excessive anticoagulation. Arch Intern Med. 1998;158(19):
2136-40.
7. Lassauniere JM, Bertolino M, Hunault M, Zittoun R, Verspieren P, Moh-Klaren J, Jaulmes
D, Colombat P. Platelet transfusions in advanced hematological malignancies: a position
paper. J Palliat Care. 1996;12(1):38-41.
8. Klieb H, Gilbert M. How to manage spontaneous gingival hemorrhage. J Can Dent Assoc.
2014;80:e54.
9. Foley SJ, Solomon LZ, et al. A prospective study of the natural history of hematuria
associated with benign prostatic hyperplasia and the effect of finasteride. The Journal of
urology 2000; 163.2:496-498.
10. NHSScotland. Scottish Palliative Care Guidelines: Bleeding. http://
www.palliativecareguidelines.scot.nhs.uk/guidelines/palliative-emergencies/Bleeding.aspx
Download 6/15/2017.
11. Biggs JC, Hugh TB, Dodds AJ. Tranexamic acid and upper gastrointestinal haemorrhage
—a double-blind trial. Gut. 1976;17(9):729-34.
12. D’Amico G, Pietrosi G, Tarantino I, Pagliaro L. Emergency sclerotherapy versus
vasoactive drugs for variceal bleeding in cirrhosis: a Cochrane meta-analysis.
Gastroenterology. 2003;124(5):1277-91.
13. Lamberts SW, van der Lely AJ, de Herder WW, Hofland LJ. Octreotide. N Engl J Med.
1996;334(4):246-54.
14. Fargo MW, Latimer KM. Evaluation and management of common anorectal conditions.
Am Fam Physician. 2012;85:624-630.
Authors’ Affiliations: University of Toronto, Toronto, ON; Medical College of Wisconsin,
Milwaukee, WI; Haven Hospice, Lake City, FL
Conflicts of Interest: None to disclose.
Version History: Originally edited by Sean Marks MD; first electronically published in September
2017
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!24
!
Non-Pain Symptoms
#1 Diagnosis and Treatment of Terminal Delirium . . . . . . . . . . . . . . . . . . . . .

. . . . . . 3-4
#5 The Causes of Nausea and Vomiting (V.O.M.I.T) . . . . . . . . . . . . . . . . . . . .

. . . . . . 5-6
#15
Constipation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . 7-8
#27 Dyspnea at End-of-

Life . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9-10
#60 Pharmacologic Management of Delirium: Update on Newer Agents . . . . . . .

. 11-13
#81 Management of Hiccups . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . 14-15
#96 Diarrhea in Palliative

Care . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16-17
#109 Death Rattle and Oral
Secretions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .18-19
#114 Myoclonus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . 20-21
#146 Screening for Depression in Palliative

Care . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22-23
#149 Teaching the Family What to Expect When the Patient is

Dying . . . . . . . . . . . 24-25
!1
#182
Xerostomia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . 26-27
#186 Anxiety in Palliative Care – Causes and

Diagnosis . . . . . . . . . . . . . . . . . . . . . . . 28-29
#199 Opioids for Cough . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . 30-31
#200 Non-Opioid Anti-

Tussives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32-34
#218 Managing Wound

Odor . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35-37
#229 Seizure Management in the Dying

Patient . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38-40
#256 Fever Near the End of

Life . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41-43
#309 Pharmacologic Management of Depression in Advanced Illness . . . . . . . . .

. . 44-46
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!

DIAGNOSIS AND TREATMENT OF TERMINAL DELIRIUM
David E Weissman MD and Drew A Rosielle MD
Background Some degree of loss of cognitive function occurs in most patients in the week or
two before death. The typical scenario presented to housestaff is a late-night call from a ward
nurse saying, “Mr. Jones is confused, what should we do?” This Fast Fact reviews assessment
and management issues in terminal delirium. See Fast Fact #60 for a discussion of newer
pharmacological treatments.
Key teaching points:

1. The term “confusion” is not an accurate descriptive term—it can mean anything from delirium,
dementia, psychosis, obtundation, etc. Patients need a focused assessment, including a
brief mini-mental examination. Clinicians should use one of several validated delirium
assessment tools to help quantify and document cognitive function.
2. “Terminal delirium” is not a distinct diagnosis, although it is a commonly used phrase. It
implies delirium in a patient in the final days/weeks of life, where treatment of the underlying
cause is impossible, impractical, or not consistent with the goals of care.
3. Delirium can be either a hyperactive /agitated delirium or a hypoactive delirium. The hallmark
of delirium is an acute change in the level of arousal; supporting features include altered
sleep/wake cycle, mumbling speech, disturbance of memory and attention, and perceptual
disturbances with delusions and hallucinations.
4. The most common identifiable cause of delirium in the hospital setting is drugs: anti-
cholinergics (e.g. anti-secretion drugs, anti-emetics, anti-histamines, tricyclic anti-
depressants, etc.), sedative-hypnotics (e.g. benzodiazepines), and opioids. Other common
causes include metabolic derangements (elevated sodium or calcium, low glucose or
oxygen); infections; CNS pathology; or drug/alcohol withdrawal.
5. The degree of work-up to seek the cause of delirium is determined by understanding the
disease trajectory and overall goals of care (see Fast Fact #65).
6. The drug of choice for most patients is a neuroleptic. There is one controlled clinical trial of
haloperidol versus lorazepam in HIV patients; haloperidol was the superior agent.
!3
Haloperidol is administered in a dose escalation process similar to treating pain. Start
haloperidol 0.5-2 mg PO or IV q1hour PRN. Atypical antipsychotics have also been studied
for delirium are probably as efficacious as haloperidol. There are insufficient data to make a
strong recommendation about the best drug or dosing of antipsychotics for delirium.
7. It is best to think of benzodiazepines as sedatives and anxiolytics but not as therapy for
underlying delirium. On the rare occasion one wants to actually sedate a delirious patient a
benzodiazepine may be indicated. If anxiety is a prominent part of a patient’s delirium, a
benzodiazepine may help. Generally, however, benzodiazepines should be avoided as they
can cause paradoxical worsening of the delirium and agitation.
8. Non-pharmacological treatments should always be used in delirium management: reduce or
increase the sensory stimulation in the environment as needed; ask relatives/friends to stay
by the patient; frequent reminders of time/place.
References
1. Yennaurjalingam S et al. Pain and terminal delirium research in the elderly. Clin Geriatr
Med. 2005;21(1):93-119.
2. Lawlor PG, et al. Occurrence, causes and outcome of delirium in patients with advanced
cancer. Arch Int Med. 2000;160:786-794.
3. Brietbart W, Marotta R, Platt M, et al. A double blind trial of Haloperidol, Chlorpromazine
and Lorazepam in the treatment of delirium. Am J Psych. 1996; 153:231-237.
4. Breitbart W, Alici Y. Agitation and delirium at the end of life. “We couldn’t manage him.”
JAMA. 2008; 300(24):2898-2910.
5. Maneeton B, Maneeton N, Srisurapanont M, Chittawatanarat K. Quetiapine versus
haloperidol in the treatment of delirium: a double-blind, randomized, controlled trial. Drug
Des Devel Ther. 2013; 7:657-67. doi: 10.2147/DDDT.S45575.
published July 2005. Current version re-copy-edited, with additional reference added, March
2009. 3rd Edition edited by Drew A Rosielle MD with additional material added November 2014.
!4
!

THE CAUSES OF NAUSEA AND VOMITING (V.O.M.I.T.)
James Hallenbeck MD
Background By understanding the pathophysiology of nausea and targeting antiemetics to
specific receptors, therapy can be optimized and side effects minimized. An easy way to
remember the causes of vomiting is the VOMIT acronym. In the table below receptors involved in
different types of nausea are highlighted using this acronym. Blockade of these receptors allows
rational, focused therapy.
Cause - Vestibular
• Receptors Involved - Cholinergic, Histaminic
• Drug Class Useful - Anticholinergic, Antihistaminic
• Drug Examples - Scopolamine patch, Promethazine
Cause - Obstruction of Bowel by Constipation (See FF #294 and #295)
• Receptors Involved - Cholinergic, Histaminic, likely 5HT3
• Drug Class Useful - Stimulate myenteric plexus
• Drug Examples - Senna products
Cause - DysMotility of upper gut
• Receptors Involved - Cholinergic, Histaminic, 5HT3, 5HT4
• Drug Class Useful - Prokinetics which stimulate 5HT4 receptors
• Drug Examples - Metoclopramide
Cause - Infection, Inflammation
• Receptors Involved - Cholinergic, Histaminic, 5HT3, Neurokinin 1
• Drug Class Useful - Anticholinergic, Antihistaminic, 5HT3 antagonists, Neurokinin 1
antagonists
• Drug Examples – Promethazine (e.g. for labyrinthitis), Prochlorperazine
Cause - Toxins stimulating the chemoreceptor trigger-zone in the brain such as opioids (see FF
25) or chemotherapy (see FF #285)
• Receptors Involved - Dopamine 2, 5HT3
• Drug Class Useful - Antidopaminergic, 5HT3 Antagonists
• Drug Examples - Prochlorperazine, Haloperidol, Ondansetron
Notes
• 5HT3, 5HT4 refer to the serotonin receptors, subtypes 3 & 4.
• Promethazine and prochlorperazine are very different drugs. Promethazine is most useful
for vertigo and gastroenteritis due to infections and inflammation. Prochlorperazine is
preferred for opioid related nausea.
• There is no evidence supporting the use of lorazepam as a sole agent for nausea.
Sedated patients are more prone to aspiration.
• ‘O’ here relates to ‘obstruction’ of bowels by constipation, not mechanical blockage (see
Fast Facts #45, 119 for management of mechanical obstructions).
• See FF #93 & #279 for information on cannibinoids and cannabis for nausea and
vomiting
References
1. Glare P, et al. Systemic review of the efficacy of antiemetics in the treatment of nausea in
patients with far-advanced cancer. Support Care Cancer. 2004; 12:432-440.
2. Hallenbeck J. Palliative Care Perspectives. New York, NY: Oxford University Press; 2003:
pp75-86.
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!6
!

CONSTIPATION
James Hallenbeck MD
Constipation – it's not fun to have or to treat. As with other symptoms, rational therapy should be
based on a sound understanding of underlying physiology. Our goal in treating constipation is
generally not to "cure" something, but to help the patient return to the best possible balance that
will allow a normal bowel movement to be passed. Four major components affect the production
of a normal BM: solid waste, water, motility and lubrication.
Solid Waste – Too much or too little is a problem. The intestine is most efficient pushing
intermediate volumes. Patients on fiber-poor diets may improve if fiber is added. Note: In patients
on opioids or patients with minimal fluid intake or poor gut motility (e.g. the dying patient)
additional fiber can worsen the situation, causing a 'soft impaction'.
Water Content – Stool water content depends on how much water we drink, our general
hydration status, how much water is absorbed from and secreted into the intestine and how fast
stool moves through the bowel. Any of these variables can be manipulated. It is easiest to limit
absorption (and increase secretion into the gut) by adding osmotically active particles that retain
water (e.g. Magnesium salts, non-absorbable sugars such as sorbitol and lactulose, or
polyethylene glycol [PEG]). Note: Magnesium and phosphorus salts are contraindicated in renal
failure. Hyperosmolar solutions may worsen dehydration by drawing body water into the gut
lumen. Sickly-sweet sorbitol and lactulose may be difficult to for patients to tolerate. PEG is
flavorless and may be better tolerated.
Motility – Patients with low-activity levels (bed-ridden, dying patients and patients with advanced
neurodegenerative disorders) and use of certain drugs (see below) lead to motility problems.
Senna preparations, which stimulate the myenteric plexus are generally favored. Use senna
tablets (or granules, liquid, or tea), starting with 1 tab QHS, may be gradually increased to 4 tabs
BID if needed. Before increasing motility, evacuate existing constipated stool with an enema or
cramping can result.
Lubrication simply eases passage and minimizes pain that can interfere with excretion. Most
commonly used is dioctyl sodium sulfosuccinate (DSS, or docusate), which decreases stool
surface tension much like soap. Usual dosage is 240 mg PO daily or BID. DSS also tastes like
soap, so liquid DSS should never be given PO, but may be given to tube-fed patients. Note: DSS
is commonly used in combination with senna in opioid-induced constipation, but is generally
inadequate as a sole agent. Mineral oil can be used as an enema but should not be given PO, as
pneumonitis can result if aspirated. Glycerin suppositories can provide lubrication and draw-in
water due to osmotically active particles.
Medications that can cause/exacerbate constipation: Opioids, anticholinergics (tricyclic

antidepressants, scopolamine, oxybutinin, promethazine, diphenhydramine), lithium, verapamil,
bismuth, iron, aluminum, aalcium salts. See Fast Facts #294 and #295 for more information on
opioid induced constipation.
References
1. Klaschik E, Nauck F, Ostgathe C. Constipation--modern laxative therapy. Support Care
Cancer. 2003; 11(11):679-685.
2. Mancini I, Bruera E. Constipation in advanced cancer patients. Support Care Cancer.
1998; 6(4):356-364.
Version History: 2nd Edition published August 2005; 3rd Edition May 2015. Current version re-
copy-edited May 2015.
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!

DYSPNEA AT END-OF-LIFE
David E Weissman MD
Introduction Dyspnea is defined as a subjective sensation of difficulty breathing. This Fast

Fact reviews key elements in the assessment and treatment of dyspnea near the end-of-life.
Etiology The causes of dyspnea include a wide spectrum of serious lung or heart conditions,
anemia, anxiety, chest wall pathology, electrolyte disturbances or even urinary retention or
constipation.
Assessment Looking for simple problems is always warranted: is the Oxygen turned on? Is
the tubing kinked? Is there fluid overload from IV fluids or TPN? Is dyspnea part of an acute
anxiety episode, severe pain, constipation or urinary retention? Is there a new pneumothorax or
worsening pleural effusion? Understanding 1) where patients are at in the dying trajectory, and 2)
their identified goals of care, is essential to guide the extent of workup to discover reversible
causes. If the patient is clearly dying (see Fast Fact #3), and the goals of care are comfort, then
pulse oximetry, arterial blood gases, EKG, or imaging are not indicated.
Treatment
• General measures Positioning (sitting up), increasing air movement via a fan or open
window, and use of bedside relaxation techniques are all helpful. In the imminently dying
patient, discontinuing parenteral fluids is appropriate.
• Treatment with opioids Opioids are the drugs of choice for dyspnea at the end-of-life
as well as dyspnea refractory to the treatment of the underlying cause. In the opioid
naïve patient, low doses of oral (5-10 mg) or parenteral morphine (2-4 mg) will provide
relief for most patients; higher doses will be needed for patients on chronic opioids.
When dyspnea is acute and severe, parenteral is the route of choice: 1-3 mg IV every 1-2
hours, or more aggressively if needed, until relief in the opioid naïve patient. In the
inpatient setting, a continuous opioid infusion, with a PCA dose that patients, nurses or
families can administer, will provide the timeliest relief (see Fast Facts #28, 54).
Nebulized morphine has been reported to provide benefit in uncontrolled case reports,
however a controlled trial demonstrated no greater efficacy or lower rate of side effects
compared to subcutaneous morphine.
• Treatment with oxygen Oxygen is often, but not universally, helpful. When in doubt, a
therapeutic trial, based on symptom relief, not pulse oximetry, is indicated in dying
patients. A well-designed randomized, controlled trial of oxygen vs ambient air, delivered
by nasal cannula, in normoxic patients with advanced illness and dyspnea showed no
benefit of oxygen over ambient air delivered by nasal cannula. Patients generally prefer
nasal cannula administration than a mask, especially in setting of imminent death when
agitation from the mask is commonly seen. There is little reason to go beyond 4-6 L/min
of oxygen via nasal cannula in the actively dying patient. Request a face-tent for patients
who are claustrophobic from a mask.
• Treatment with other drugs Anti-tussives can help with cough (see Fast Fact #200),
anit-cholinergics (e.g. scopolamine) will help reduce secretions, anxiolytics (e.g.
lorazepam) can reduce the anxiety component of dyspnea. Other agents that may have
specific disease modifying effects include diuretics, bronchodilators, and corticosteroids.
Family/Team Discussions While there is no evidence that proper symptom management for
terminal dyspnea hastens death, the course and management of terminal dyspnea, especially
when opioids are used, should be fully discussed with family members, nurses and others
!9
participating in care to avoid confusion about symptom relief vs. fears of euthanasia or assisted
suicide (see Fast Fact #8).
References
1. Bruera E, Sweeny C, and Ripamonti C. Dyspnea in patients with advanced cancer. In:
Berger A, Portenoy R and Weissman DE, eds. Principles and Practice of Palliative Care
and Supportive Oncology. 2nd Ed. New York, NY: Lippincott-Raven; 2002.
2. Chan KS et al. Palliative Medicine in malignant respiratory diseases. In: Doyle D, Hanks
G, Cherney N, and Calman N, eds. Oxford Textbook of Palliative Medicine. 3rd Ed. New
York, NY: Oxford University Press; 2005.
3. Viola R et al. The management of dyspnea in cancer patients: a systematic review.
Supp Care Cancer. 2008; 16:329-337.
4. Navigante AH, et al. Midazolam as adjunct therapy to morphine in the alleviation of
severe dyspnea perception in patients with advanced cancer. J Pain Sympt Manage.
2006; 31:38-47.
5. Fohr SA. The double effect of pain medication: separating myth from reality. J Pall Med.
1998; 1:315-328.
6. Bruera E, et al. Nebulized versus subcutaneous morphine for patients with cancer
dyspnea: a preliminary study. J Pain Symptom Manage. 2005 Jun; 29(6):613-8. PMID
15963870
7. Abernethy AP, et al. Effect of palliative oxygen versus room air in relief of
breathlessness in patients with refractory dyspnoea: a double-blind,
randomised controlled trial. Lancet. 2010 Sep 4;376(9743):784-93. http://
www.ncbi.nlm.nih.gov/pubmed/20816546
8. NCCN Clinical Guideline Palliative Care 2015 Pal 11-12.
published July 2005. Re-copy-edited March 2009; new references were added. Revised again
December 2012 and April 2015;
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!

PHARMACOLOGIC MANAGEMENT OF DELIRIUM: UPDATE ON NEWER AGENTS
Earl Quijada MD and J Andrew Billings MD
Background Delirium is common in those with serious medical illness (See Fast Fact #1).
Delirium is an acute change in mental status that fluctuates and has underlying physiologic
causes and can be categorized as hyperactive, hypoactive, or mixed. Common reversible
etiologies include constipation, urinary retention, medications (benzodiazepines, opioids, steroids,
and anticholinergic drugs), electrolyte abnormalities, and sleep deprivation. Initial management
strategies include identifying and treating the underlying cause, as well as non-pharmacological
treatment. However, when these strategies are not effective pharmacological interventions may
be necessary. The below pharmacological interventions are for potentially reversible, hyperactive
delirium.
1st Generation Antipsychotics
Haloperidol Although no medication has been approved by the FDA for the treatment of
delirium, the best studied antipsychotic, and the agent of choice for most patients, is haloperidol
(Haldol), which can be administered safely through oral and parenteral routes. Starting doses are
0.5 – 1 mg PO or IV. Titration can occur by 2 – 5 mg every 1 hour until a total daily requirement is
established, which is then administered in daily or twice daily doses. Recommended maximum
dose is 100 mg/day. Intravenous haloperidol may cause less extrapyramidal symptoms than oral
haloperidol.
Chlorpromazine Chlorpromazine (Thorazine) has more sedative effects than haloperidol for
patients in whom sedation is desired. The starting dose is 25 - 50 mg PO. Titration can occur by
25 - 50 mg every 1 hour until a total daily requirement is established, which is then administered
in daily or twice daily doses. Recommended maximum dose is 2000 mg/day.
2nd Generation Antipsychotics Also known as atypical antipsychotics, no evidence currently
exists for improved efficacy with 2nd generation antipsychotics, so they are not considered to be
first-line treatment. These agents are associated with fewer extrapyramidal side effects than 1st
generation antipsychotics, hence, in Parkinson’s disease and related neuromuscular disorders
and in patients with a history of extrapyramidal reactions from 1st generation antipsychotics this
class of agents may be preferred. For acutely agitated patients requiring onset of action within
minutes, providers should know that these agents do not work as fast as conventional
antipsychotics.
Olanzapine The starting dose for olanazapine (Zyprexa) is 5 mg PO every day; after one week,
the dose can be raised to 10 mg a day; then to 20 mg a day. It is available as an orally
disintegrating tablet.
Quetiapine Quetiapine (Seroquel) is initially given 25 mg PO twice a day which can be raised by
25 – 50 mg per dose every 2 – 3 days up to a target of 300 – 400 mg a day, divided into 2 – 3
doses. Compared to the atypical neuroleptics, it is the most sedating and causes the least
extrapyramidal side effects. It has more orthostasis than olanzapine and risperidone.
Risperidone Resperidone (Resperidal) is given 1 – 2 mg PO at night and is gradually raised 1
mg every 2 – 3 days until an effective dose (usually 4 – 6 mg PO hs) is reached. It has minimal
anticholinergic effects and does not cause orthostasis. It is the least sedating of this class of
antipsychotics
Newer antipsychotics include ziprasidone (Geodon) and aripiprazole (Abilify); their role in the
management of delirium is not firmly established.
Risks The FDA has issued a black-box warning about the increased risk of death when first- or
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second-generation antipsychotics are used to treat dementia-related psychosis in elderly patients.
This warning is based on a number of limited studies which have not been replicated and do not
address the short-term use of antipsychotics to manage delirium. Delirium is a poor prognostic
marker. Goals of care and values must be discussed in the management of delirium.
Benzodiazepines With the exception of treating delirium due to drug withdrawal or

anticholinergic excess, benzodiazepines should be avoided for potentially reversible, hyperactive
delirium unless the agitation is severe and uncontrolled by the neuroleptic. Benzodiazepines can
make delirium worse and precipitate withdrawal syndromes.
Melatonin This hormone is produced naturally in the pineal gland and can help regulate the
sleep-wake rhythm cycle. Randomized placebo-controlled trials have validated the use of both
melatonin and a melatonin analog (ramelteon) in the prevention of delirium in at-risk, hospitalized
patients.
References
1. Breitbart W, Bruera E, Chochinov H, Lynch M. Neuropsychiatric syndromes and
psychological symptoms in patients with advanced cancer. J Pain Symptom Manage.
1995; 10:131-41.
2. Breitbart W, Marotta R, Platt MM, et al. A double-blind trial of haloperidol,
chlorpromazine, and lorazepam in the treatment of delirium in hospitalized AIDS
patients. Am J Psych. 1996; 153:231-7.
3. Jackson KC, Lipman AG. Drug therapy for delirium in terminally ill patients. Cochrane
Database 2004; Syst Rev 2: CD004770.
4. Inouye SK, Bogardus ST Jr, Charpentier PA, et al. A multicomponent intervention to
prevent delirium in hospitalized older patients. N Engl J Med. 1999; 4:340:669-76.
5. Lawlor PG, Gagnon B, Mancini IL, et al. Occurrence, causes, and outcome of delirium
in patients with advanced cancer: a prospective study. Arch Intern Med. 2000;
160:786-94.
6. McIver B, Walsh D, Nelson K. The use of chlorpromazine for symptom control in dying
cancer patients. J Pain Symptom Manage. 1994; 9:341-5.
7. Menza MA, Murray GB, Holmes VF, Rafuls WA. Decreased extrapyramidal symptoms
with intravenous haloperidol. J Clin Psych. 1987; 48:278-280.
8. Sadock B, Sadock V. Kaplan and Sadock’s Pocket Handbook of Psychiatric Drug
Treatment. 3rd Edition. Philadelphia, PA: Lippincott Williams and Williams; 2001.
9. Stahl S. Essential Psychopharmacology: Neuroscientific Basis and Practical
Applications. 2nd Edition. New York, NY: Cambridge University Press; 2000.
10. Schneider LS, Dagerman KS, Insel P. Risk of death with atypical antipsychotic drug
treatment for dementia. Meta-analysis of randomized placebo controlled trials. JAMA
2005; 294:1934-1943.
11. Breitbart W, Alici Y. Evidence-based treatemtn of delirium in patients with cancer.
Journal of Clinical Oncology 2012; 30: 1206-1214.
12. Navari RM, Einhorn LH, et al. A phase II trial for the prevention of chemotherapy
induced nausea and vomiting: a Hoosier Oncology Group Study. Support Care Cancer
2005; 13: 529-34.
13. Hatta K, Kishi Y, et al. Preventive Effects of Ramelteon on DeliriumA Randomized
Placebo-Controlled Trial. JAMA Psychiatry. 2014;71(4):397-403.
14. Al-Aama T, Brymer C, Gutmanis I, Woolmore-Goodwin SM, Esbaugh J, Dasgupta M.
Melatonin decreases delirium in elderly patients: a randomized, placebo-controlled
trial. Int J Geriatr Psychiatry. 2011;26(7):687-694.
15. Irwin SA, Pirrelo RD, et al. Clarifying delirium management: practical, evidence-based
expert recommendations for clinical practice. Journal of Pall Med 2013; 16: 423-435.
published September 2006; 3rd Edition May 2015. Current version re-copy-edited April 2009;
olanzapine orally disintegrating tablet information added. It was re-edited in May 2015.
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!

MANAGEMENT OF HICCUPS
Chad Farmer MD
Background Hiccups (singultus) are distressing to patients and families; when chronic, they
diminish quality of life. A hiccup is an involuntary reflex involving the respiratory muscles of the
chest and diaphragm, mediated by the phrenic and vagus nerves and a central (brainstem) reflex
center. A single episode can last for a few seconds to as long as several days. If they last longer
than 48 hours hiccups are termed persistent; longer than one month, intractable. Etiologies
range from stress/excitement to cancer, myocardial infarction, esophageal or gastric distension,
liver disease, uremia, IV steroids, CNS lesions, chemotherapy, and idiopathic. Irritation of the
vagus nerve or diaphragm is a common pathophysiologic mechanism.
Management Once hiccups have lasted beyond a time-limited annoyance, deciding on
therapeutic intervention should be based on a thorough clinical assessment and, if possible,
treatment directed at the underlying cause. A thorough history, review of medications, focused
review of systems, and physical exam may help guide initial choice of treatment. Many drug and
non-drug treatments have been used, but there is little evidence of any one superior approach to
management; virtually all current data are anecdotal. The patient’s prognosis, current level of
function, and potential adverse effects from any proposed treatment should be considered.
Pharmacologic Therapy
• Anti-Psychotics: Chlorpromazine – the only FDA approved drug for hiccups. Dose: 25-50
mg PO TID or QID. Can also be given by slow IV infusion (25-50 mg in 500-1000 ml of NS
over several hours). Haloperidol – a useful alternative to chlorpromazine; give a 2-5 mg
(SubQ/PO) loading dose followed by 1-4 mg PO TID.
• Anti-Convulsants: Gabapentin – at doses of 300-400 TID has been described as effective
in multiple case reports. Its dual role as an analgesic may make it an especially attractive
therapeutic agent. Phenytoin – reportedly effective in patients with a CNS etiology of their
hiccups. Dose: 200 mg slow IV push followed by 300 mg PO daily. Others: Valproic Acid and
Carbamazepine have been reported to work for selected patients.
• Miscellaneous: Baclofen – the only drug studied in a double blind randomized controlled
study for treatment of hiccups. 5 mg PO q8 hours did not eliminate hiccups but did provide
symptomatic relief in some patients. Metoclopramide – 10 mg PO QID is an option,
especially if stomach distension is the etiology. Nifedipine – 10 mg BID with gradual increase
up to 20 mg TID has been suggested as a relatively safe alternative if other interventions
have failed. Other drugs that have been tried with very limited success include: amitriptyline,
sertraline, inhaled lidocaine, ketamine, edrophonium, methylphenidate, and amantidine.
Non-Pharmacologic Therapy There are many well known, time-honored home remedies:
gargling with water, biting a lemon, swallowing sugar, or producing a fright response. Other
approaches are directed at a) vagal stimulation such as carotid massage or valsalva maneuver;
b) interruption of phrenic nerve transmission via rubbing over the 5th cervical vertebrae; or c)
interrupting the respiratory cycle through sneezing, coughing, breath holding, hyperventilation, or
breathing into a paper bag. Other interventions such as acupuncture, diaphragmatic pacing
electrodes, or surgical ablation of the reflex arc can be considered when other treatments fail.
References
1. Kolodzik PW, Eilers, MA. Hiccups (singultus): review and approach to management.
Ann Emerg Med. 1991; 20:565-573.
2. Lewis J. Hiccups: causes and cures. J Clin Gastro. 1985; 7:539-552.
3. Rousseau, P. Hiccups. Southern Med J. 1995; 2:175-181.
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4. Bondi N, Bettelli, A. Treatment of hiccup by acupuncture in patients under anesthesia
and in conscious patients. Minerva Med. 1981; 72:2231-2234.
5. Ramirez FC, Graham DY. Treatment of intractable hiccup with baclofen: results of a
double-blind, randomized, controlled, cross-over study. A J Gastro. 1992; 87:1789-91.
6. Physicians’ Desk Reference. 61st Edition. Thomson PDR; 2007. Available at http://
pdr.net.
7. Smith HS, Busracamwongs A. Management of hiccups in the palliative care population.
Am J Hosp Pall Care. 2003; 20:149-54.
8. Vaidya V. Sertraline in the treatment of hiccups. Psychosomat. 2000; 41:353-355.
9. Hernandez JL, et al. Gabapentin for intractable hiccup. Am J Med. 2004; 117:279-81.
10. Marinella, Mark A. "Diagnosis and management of hiccups in the patient with advanced
cancer." J support Oncol 7.4 (2009): 122-7.
11. Wilcox SK, Garry A, Johnson MJ. Novel use of amantadine to treat hiccups. Journal of
Pain and Symptom Management 2009; 38: 460-5. Volume 38, Issue 3, September 2009,
Pages 460–465.
edited by Drew A Rosielle and published October 2007; 3rd Edition June 2015. Current version re-
copy-edited April 2009; then again June 2015.
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!
DIARRHEA IN PALLIATIVE CARE
Jeffrey Alderman MD
Diarrhea is a debilitating and embarrassing problem, defined as an abnormal looseness of the
stools (increased liquidity or decreased consistency). Patients with uncontrolled diarrhea are at
increased risk for dehydration, electrolyte imbalance, skin breakdown, and fatigue.
Common Causes Diarrhea can usually be divided into different types and treatment will vary
depending on cause: secretory, osmotic, mechanical, or disordered motility. In palliative care, the
overuse of laxatives, typically seen when the management of constipation is suddenly ‘stepped-
up,’ is a common cause. Other causes include partial intestinal obstruction, pancreatic
insufficiency, Clostridium difficile infection, and radiation enteritis. Chemotherapeutics are another
common cause, especially in advanced cancer where the incidence can be up to 60% (diarrhea
may be even more common with chemotherapy regimens with 5 flourouracil boluses or
combination of irinotecan and fluoropyrimidines). Infectious diarrhea is especially common in HIV
infection (Cryptosporidia, Giardia lambila, E. histolytica, and Cytomegalovirus). Severe
constipation and fecal impaction can also cause diarrhea as backed-up, liquefied stool may be all
that the patient can pass (‘overflow diarrhea’).
Evaluation Review diet, medications, laxatives, procedures, timing of movements in relation to
ingestion of food or liquids, and a description of quantity and quality of stool. When performing a
physical exam, make sure to palpate the abdomen and do a rectal exam. Radiographs are often
not necessary, but may help clarify a partial bowel obstruction or overflow diarrhea. Keep in mind
that patients at the end-of-life are also at risk for developing the same diarrheal illnesses that
occur in the general population (viral/bacterial gastroenteritis, adverse effects of medications).
Treatment
• General Ensure adequate hydration; encourage sips of clear liquids; parenteral hydration
should be considered for severe dehydration. Simple carbohydrates, toast or crackers, will
add back small amounts of electrolytes and glucose; milk and other lactose-containing
products should be avoided.
• Medications include bulk forming agents, antimicrobials, adsorbents, and opioids.
o Kaolin and Pectin (Kaopectate®) is a suspension of adsorbent and bulk-forming agents,
which can provide modest relief from diarrhea. However, kaolin-pectin may take up to 48
hours to produce an effect and can interfere with the absorption of certain medications.
o Antibiotics: infectious diarrhea should be identified and treated with appropriate
antibiotics, particularly C. difficile enteritis.
o Bismuth has an additional antimicrobial effect, and can be added for increased
symptomatic control against organisms such as enterotoxigenic E. Coli.
o Loperamide (Imodium®), an opioid, reduces peristalsis in the gut, increases water
reabsorption, and promotes fecal continence, making it a potent anti-diarrheal agent.
Because it only weakly crosses the blood-brain barrier, loperamide’s side effect profile is
more favorable than other opioids (e.g. codeine or diphenoxylate [Lomotil®]). The initial
dose of loperamide is 4 mg, with titration to 2 mg after each loose stool, with the typical
dose being 4 – 8 mg per day. Although the package insert recommends a maximum of
16 mg in a 24-hour period, up to 54 mg per day of loperamide has been used in palliative
care settings with few adverse effects. Note: loperamide should be used with caution if
an infectious diarrhea is suspected.
o Aspirin and Cholestyramine can reduce the diarrhea in radiation-induced enteritis, as
can addition of a stool bulking agent such as psyllium (Metamucil™).
o Mesalamine and other antiinflammatories are used for inflammatory bowel disease.
o Pancreatic Enzymes such as pancrelipase are used for pancreatic insufficiency.
o Octreotide, although costly, is effective with profuse secretory diarrhea seen in HIV
disease, chemotherapy induced diarrhea, and those with high effluent volume from a
!16
stoma. It may be given via continuous subcutaneous infusion at a rate of 10 – 80 mcg
every hour until symptoms improve.
o Budesonide, probiotics and activated charcoal have been described in the literature
for use in chemotherapy induced diarrhea, but there role in the clinical setting is not yet
established.
References
1. Doyle D, et al, eds. Oxford Textbook of Palliative Medicine. 3rd ed. New York, NY: Oxford
University Press; 2003.
2. Fallon M, O'Neill B. ABC of palliative care. Constipation and diarrhoea. BMJ. 1997;
315:1293-6.
3. Saunders DC. Principles of symptom control in terminal care. Med Clin North Amer. 1982;
6: 1175.
4. Berger A, et al, eds. Principles and Practice of Palliative Care and Supportive Oncology. 3nd
ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2006.
5. McEvoy GK, ed. AHFS Drug Information 2003. Bethesda, MD: American Society of Health-
System Pharmacists; 2003: pp2740-41.
6. Ruppin H. Review: loperamide--a potent antidiarrhoeal drug with actions along the
alimentary tract. Alimentary Pharmacology & Therapeutics. 1987; 1(3):179-90.
7. Stein A, Voigt W, and Jordan K. Chemotherapy-induced diarrhea: pathophysiology,
frequency and guideline-based management. Therapeutic advances in medical oncology
2010; 2: 1 51-63
re-copy-edited April 2009; then again by Sean Marks MD June 2015.

DEATH RATTLE AND ORAL SECRETIONS
Katherine Bickel and Robert Arnold MD
Background As the level of consciousness decreases in the dying process, patients lose their
ability to swallow and clear oral secretions. As air moves over the secretions, which have pooled
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in the oropharynx and bronchi, the resulting turbulence produces noisy ventilation with each
breath, described as ‘gurgling ‘or ‘rattling noises.’ While there is no evidence that patients find
this ‘death rattle’ disturbing, evidence from bereaved surveys suggests the noises can be
disturbing to the patient’s visitors and caregivers who may fear that the patient is choking to
death. However, similar sounds may occur in patients who are not imminently dying, such as in
those with brain injuries or in patients with various disorders leading to increased production or
decreased clearance of secretions. Two sub-types of the death rattle have been proposed,
although the significance regarding treatment has not been established: Type 1 = predominantly
salivary secretions and Type 2 = predominantly bronchial secretions. Death rattle is a good
predictor of near death; one study indicated the median time from onset of death rattle to death
was 16 hours.
Non-Pharmacological Treatments
• Position the patient on their side or in a semi-prone position to facilitate postural drainage
• A minute or two of Trendelenburg positioning can be used to move fluids up into the
oropharynx for easier removal; aspiration risk is increased, however.
• Gentle oropharyngeal suctioning is used although this can be ineffective when fluids are
beyond the reach of the catheter. Frequent suctioning is disturbing to both the patient and
the visitors.
• Reduction of fluid intake.
• Communication with family and caregivers aimed to address associated fears and
interpretations.
Pharmacological Treatments While multiple studies have questioned the utility of

pharmacologic treatments for death rattle, muscarinic receptor blockers (anti-cholinergic drugs)
are the most commonly used class of medication for this symptom. Such agents include
scopolamine, hyoscyamine, glycopyrrolate, and atropine. All of these agents can cause varying
degrees of blurred vision, sedation, confusion, delirium, restlessness, hallucinations, palpitations,
constipation, and urinary retention. The primary difference in these drugs is whether they are
tertiary amines which cross the blood-brain barrier (scopolamine, atropine, hyoscyamine) or
quaternary amines, which do not (glycopyrrolate). Drugs which cross the blood-brain barrier are
apt to cause CNS toxicity (sedation, delirium).
Drug Trade Name Route Starting Dose Onset

scopolamine (hyoscine) Transderm Scop Patch One 1.5 mg ~12 h (24 h to
hydrobromide patch steady state)
hyoscyamine Levsin PO, SL 0.125 mg 30 min
glycopyrrolate Robinul PO 1 mg 30 min

glycopyrrolate Robinul SubQ, IV 0.2 mg 1 min
atropine sulfate Atropine SubQ, IV 0.1 mg 1 min
atropine sulfate multiple Sublingual 1gtt (1% 30 min
ophth. soln)
Pharmacological pearls
• Glycopyrrolate has five times the anti-secretory potency compared to atropine but is
poorly and erratically absorbed orally. The clinical significance of this is unclear.
• The scopolamine patch releases ~1 mg over 72 hours. It takes 24 hours to reach steady
state and for acute symptoms other drugs should be used. The patch should be placed
on hairless skin just behind the ear, is changed every 72 hours, and more than one patch
can be used at a time.
• Hyoscyamine is available in short-acting, sustained-released, orally dispersible tablet,
and oral solution formulations.
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References
1. Back IN, Jenkins K, Blower A, Beckhelling J. A study comparing hyoscine hydrobromide
and glycopyrrolate in the treatment of death rattle. Palliat Med .2001; 15:329-336.
2. Ohio Hospice & Palliative Care Organization. Palliative Care Pocket Consultant. Dubuqe,
IA: Kendall Hunt Publishing; 2001.
3. Twycross R, Wilcock A, eds. Hospice and Palliative Care Formulary USA. Nottingham,
UK: Palliativedrugs.com Ltd; 2006.
4. Wilders H, Menten J. Death rattle: prevalence, prevention and treatment. J Pain
Symptom Manage. 2002; 23:310-317.
5. Wee B, Hillier R. Interventions for noisy breathing in patients near to death. Cochrane
Database of Systematic Reviews 2008, Issue 1. Art. No.: CD005177. DOI:
10.1002/14651858.CD005177.pub2.
6. Shimizu Y, Miyashita M, et al. Care strategy for death rattle in terminally ill cancer patients
and their family members: recommendations from a cross-sectional nationwide survey of
bereaved family members' perceptions. Journal of pain and symptom management 2014;
48: 2-12.
7. Lokker ME, van Zuylen L, et al. Prevalence, impact, and treatment of death rattle: a
systematic review. Journal of pain and symptom management 2014;47: 105-122.
in March 2004. 2nd Edition was edited by Drew A Rosielle and published April 2008; 3rd Edition
June 2015. Re-copy-edited in April 2009; then again June 2015 with references #6 and #7 added
and incorporated into the text.
!
MYOCLONUS
Nicholas DeMonaco and Robert Arnold MD
Background Myoclonus is an abnormal movement described as a sudden, brief, shock-like,

involuntary movement caused by active muscle contraction (positive myoclonus) or inhibition of
ongoing muscle contraction (negative myoclonus). Myoclonus can have a distribution that is
focal, multifocal, or generalized. This Fast Fact discusses its causes, evaluation, and therapy.
!19
Characteristics and Differential Diagnosis Hiccups are an example of normal, physiological
positive myoclonus, while asterixis is an example of negative myoclonus seen with metabolic
encephalopathy. In nocturnal myoclonus or periodic leg movement disorder, there is activity in the
flexor muscles of the legs and feet during light sleep. It can be seen in the setting of chronic
nervous system diseases or in elderly patients with no other abnormalities. The brief, shock-like
movements of myoclonus may be difficult to distinguish from other involuntary movements such
as cramps, spasms, fasciculations, and dystonia. Fasciculations are brief involuntary muscle
twitches that, unlike myoclonus, often do not result in movement across a joint. Dystonia is
characterized as slow, repetitive, patterned, sustained movements (an example is writers cramp).
An acute dystonic reaction is often caused by dopamine blocking medications including certain
antipsychotics (haloperidol), antiemetics (metoclopramide), and calcium-channel blockers.
Causes The etiologies of myoclonus are numerous. Near the end of life, metabolic
abnormalities and medication-induced myoclonus predominate. Metabolic causes include liver
failure, renal failure, hyponatremia, and hypoglycemia. The medications and toxins associated
with myoclonus include opioids, anticonvulsants (gabapentin, phenytoin, valproate, lamotrigine,
and phenobarbitol), tricyclic antidepressants and selective serotonin reuptake inhibitors, contrast
dye, anesthetics, antibiotics (penicillins, cephalosporins, imipenem, and quinolones),
cannabinoids and the chemotherapeutic agent ifosfamide. Opioid-induced myoclonus occurs
commonly and is often misdiagnosed (See Fast Facts #57, 58). When myoclonus occurs due to
toxins or medications, the jerks are usually multifocal or generalized, may be provoked by a
stimulus or voluntary movement, and are often accompanied by encephalopathy. Other causes
of myoclonus include focal CNS damage from tumors, stroke, and encephalitis, generalized CNS
dysfunction such as encephalopathies (viral, metabolic, genetic, or neurodegenerative), seizure
disorders, anoxic injury, and disorders affecting the spinal cord and peripheral nerves.
Treatment Myoclonus can disrupt sleep, make coordinated movements difficult, and be
bothersome to patients or families. Treatment consists of correction of the underlying cause and
symptomatic treatment of the myoclonus. If the offending agent is a non-essential medication, it
should be discontinued. In the case of opioid-induced myoclonus, rotation to a different opioid
may help. Benzodiazepines are the primary symptomatic treatment at end-of-life. While any
benzodiazepine will work, clonazepam and lorazepam are commonly used. A continuous infusion
of midazolam has also been suggested given the drug’s compatibility with morphine and short
half-life, allowing rapid dose titration. Sedation is likely when using benzodiazepines. If sedation
is to be avoided, anticonvulsants such as levetiracetam (1,000-3,000 mg/day) and valproic acid
(1200-2000 mg/day) may be helpful. The muscle relaxant dantrolene in doses of 50-100 mg/day
has been reported as effective.
References
1. Caviness, J. Treatment of myoclonus. Neurotherapeutics. 2014; 11:188-200.
2. Daroff R, Fenichel G., et al. Bradley’s Neurology in Clinical Practice. 6th ed. Philadelpha,
PA: Elsevier Saunders; 2012.
3. Fahn S. Overview, history, and classification of myoclonus. Adv Neurol. 2002; 89:13-17.
4. Gordon MF. Toxin and drug-induced myoclonus. Adv Neurol. 2002; 89:49-76.
5. Jankovic J. Hyperkinetic movement disorders. In: Basow DS. UpToDate. Waltham, MA:
UpToDate; 2003.
6. Mercadante S. Pathophysiology and treatment of opioid-related myoclonus in cancer
patients. Pain. 1998; 74:5-9.
7. Rivest J. Myoclonus (Rev). Can J Neurol Sci. 2003; 30(Suppl 1):S53-58.
in May 2004. Re-copy-edited in April 2009; copy-edited again in June 2015 by Sam Maiser MD in
which references 1 and 2 were added and incorporated into the text.
Sarah Friebert MD.
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!21
!

SCREENING FOR DEPRESSION IN PALLIATIVE CARE
Robert Arnold MD
Background Depression is a significant symptom for approximately 1 in 4 palliative care
patients and is especially common in patients with metastatic cancer (see Fast Fact #21). Up to
80% of the psychological symptoms that occur in cancer patients go unrecognized and untreated.
One reason for this is the difficulty in diagnosing depression in palliative care patients (see Fast
Fact #7). In the primary care literature a number of brief screening instruments such as PRIME-
MD are used to identify depression. However, the symptoms associated with depression in
primary care (weight loss, loss of energy, fatigue, insomnia) also occur in patients without
depression who have a life-threatening disease. Thus, there has been interest in developing a
brief scale that can accurately identify depression in the palliative care population. This Fast Fact
reviews that literature on depression screening tools.
Single question screening: A study of palliative care inpatients found that a single question,
“Are you feeling down, depressed or hopeless most of the time over the last 2 weeks?” correctly
identified patients with 100 percent sensitivity and specificity and a positive predictive value of 1
(Chochinov 1997). Adding a second question about anhedonia (the absence of pleasure from the
performance of acts that would normally be pleasurable), “Have you found that little brings you
pleasure or joy over the last two weeks?”, reduced the specificity and positive predictive value.
Unfortunately, follow-up studies using a single question regarding mood in other palliative care
populations have shown a sensitivity of roughly 55 percent and a specificity of 75 percent.
A four-item algorithm asks questions about energy level, anhedonism, depressed mood, and
psychomotor retardation/agitation. In a study of hospice patients in Australia this tool had a
sensitivity between 62 and 72%, specificity of 75 to 89% and positive predictive value of between
68 and 89% (Robinson 2005).
The four question Brief Case Find for Depression asks questions about sleep, depressed
mood, life satisfaction, and ability to overcome difficulties. In a study of oncology and palliative
care patients this tool had fair agreement with longer depression screening instruments (Jefford
2004).
Other studies have examined 10-20 question depression instruments that have been validated in
other patient populations. The Edinburgh Postnatal Depression Scale (Lloyd-Williams 2000), a
self-assessment scale consisting of ten items each rated on a 4 point scale, had a sensitivity of
70% and specificity of 80% in patients with metastatic cancer receiving palliative care. The
Hospital Anxiety and Depression Scale (Lloyd-Williams 2003) is a 14 item scale with separate
sub-scales for anxiety and depression. In a group of patients with metastatic cancer, summing
the two subscales gave a sensitivity of 77%, specificity was 89% and a positive predicted value of
0.48. Two more recent articles reported lower sensitivity and specificity in patients with advanced
metastatic disease.
Summary and Recommendations

• Clinicians should have a high clinical suspicion for depression—especially in patients
who exhibit feelings of hopelessness, worthlessness, guilt, anhedonia, sustained periods
of feeling sad, and/or those with suicidal ideation and/or suicidal plans.
• The literature does not suggest that any of the above scales are clearly superior for
helping to diagnose depression in a population of palliative care patients.
• Depression screening scales may be helpful in individual cases to provide the clinician
with additional data in formulating a diagnosis; if used, it is suggested that clinicians be
familiar with the sensitivity/specificity data for one scale and consistently use that scale
so as to gain clinical familiarity.
!22
• Psychiatric consultation is indicated in cases of diagnostic uncertainty and/or when
patients present with profound depression and/or are overtly suicidal.
Definitions (Further resources available at: http://www.musc.edu/dc/icrebm/

diagnostictests.html.)
• Sensitivity: The fraction of those with the disease correctly identified as positive by the
test.
• Specificity: The fraction of those without the disease correctly identified as negative by
the test.
• Positive predictive value: The fraction of people with positive tests who actually have
the condition.
References
1. Chochinov HM, Wilson K, Enns G, et al. "Are you depressed?" Screening for depression
in the terminally ill. Am J Psychiatry. 1997; 154(5):674-676.
2. Lloyd-Williams M, Spiller J, Ward J. Which depression screening tools should be used in
palliative care? Pall Med. 2003; 17:40-43.
3. Lloyd-Williams M, Friedman T, Rudd N. Criterion validation of the Edinburgh Postnatal
depression scale as a screening tool for depression in patients with advanced metastatic
cancer. J Pain Symp Man. 2000; 20:259-65.
4. Jefford M, Mileshkin L, Richard K, Thomson J et al. Rapid screening for depression-
validation of the Brief Case-Finding for Depression (BCD) in medical oncology and
palliative care patients. Br J Cancer. 2004; 91:900-6.
5. Robinson JA, Crawford GB. Identifying palliative care patients with symptoms of
depression: an algorithm. Pall Med. 2005; 19:278-87.
in December 2005. Version re-copy-edited in April 2009; revised again July 2015.
!23
!

TEACHING THE FAMILY WHAT TO EXPECT WHEN THE PATIENT IS DYING
Charles F von Gunten MD, PhD
Introduction Family members look to the physician and nurse to help them know what to
expect when a loved one is dying. No matter the underlying causes, there is a common final
pathway that most patients travel. Indicate your desire to be helpful. Say, Many families like to
know what may happen so they will be prepared, is that true for you? If they say yes, describe
the features on this list and answer their questions.
1. Social Withdrawal is normal for the dying patient as the person becomes less concerned
about his or her surroundings. Separation begins first from the world – no more interest in
newspaper or television, then from people – no more neighbors visiting, and finally from the
children, grandchildren and perhaps even those persons most loved. With this withdrawal
comes less of a need to communicate with others, even with close family.
2. Food: The patient will have a decreased need for food and drink as the body is preparing to
die. This is one of the hardest things for some family to accept. There is a gradual decrease
in interest in eating and appetite—even for their favorite foods. Interest may come and go.
The patient is not starving to death—this reflects the underlying disease. Liquids are
preferred to solids—follow the patient’s lead and do not force feed.
3. Sleep: The patient will spend more and more time sleeping; it may be difficult for them to
keep their eyes open. This is a result of a change in the body’s metabolism as a result of the
disease. Tell family to spend more time with the patient during those times when he/she is
most alert; this might be the middle of the night.
4. Disorientation: The patient may become confused about time, place and the identity of
people around him/her. He/she may see people who are not there, such as family members
who have already died. Sometimes patients describe welcoming or beckoning. While the
patient may not be distressed, it is frequently distressing to family or health care
professionals. Gently orient the patient if he or she asks. There is no need to ‘correct’ the
patient if he or she is not distressed.
5. Restlessness: The patient may become restless and pull at the bed linens. These
symptoms are also a change in the body’s metabolism. Talk calmly and assuredly with the
patient so as not to startle or frighten them. If the patient is a danger to himself or others, you
may prescribe sedating neuroleptics (e.g.chlorpromazine), or neuroleptics (e.g. haloperidol)
in combination with benzodiazepines (e.g. lorazepam), to help the patient rest (see Fast Fact
#1).
6. Decreased Senses: Clarity of hearing and vision may decrease. Soft lights in the room may
prevent visual misinterpretations. Never assume that the patient cannot hear you, as hearing
is the last of the five senses to be lost.
7. Incontinence of urine and bowel movements is often not a problem until death is very near.
Invite family to participate in direct care; the nurse can help place absorbent pads under the
patient for more comfort and cleanliness, or a urinary catheter may be used. The amount of
urine will decrease and the urine become darker as death becomes near.
8. Physical Changes as death approaches:
a. The blood pressure decreases; the pulse may increase or decrease.
c. The body temperature can fluctuate; fever is common.
d. There is increased perspiration often with clamminess.
e. The skin color changes: flushed with fever, bluish with cold. A pale yellowish pallor (not
to be confused with jaundice) often accompanies approaching death.
!24
f. Breathing changes also occur. Respirations may increase, decrease or become
irregular; periods of no breathing (apnea) are common.
g. Congestion will present as a rattling sound in the lungs and/or upper throat. This occurs
because the patient is too weak to clear the throat or cough. The congestion can be
affected by positioning, may be very loud, and sometimes just comes and goes.
Anticholinergic medications (like scopolamine or glycopyrrolate) can help (see Fast Fact
#109). Elevating the head of bed and swabbing the mouth with oral swabs give comfort
and give the family something to do.
h. The arms and legs may become cool to the touch. The hands and feet become purplish.
The knees, ankles and elbows are blotchy. These symptoms are a result of decreased
circulation.
i. The patient will enter a coma before death and not respond to verbal or tactile stimuli.
HOW TO KNOW THAT DEATH HAS OCCURRED
• No breathing and heartbeat.
• Loss of control of bowel or bladder.
• No response to verbal commands or gentle shaking.
• Eyelids slightly open; eyes fixed on a certain spot.
• Jaw relaxed and mouth slightly open.
Acknowledgement: This Fact Fact was adapted with permission from a family information
handout (The ‘Blue Sheet’) given to families of San Diego Hospice & Palliative Care Program.
References
1. Twycross R, Lichter I. The terminal phase. In: Doyle D, Hanks GWC, MacDonald N, eds.
Oxford Textbook of Palliative Medicine. 2nd ed. Oxford, England: Oxford University
Press; 1998.
2. Ellershaw J, Ward C. Care of the dying patient: the last hours or days of life. BMJ. 2003;
326(7379):30-4.
3. Ferris FD, von Gunten CF, Emanuel LL. Competency in End of Life Care: the last hours
of living. J Palliat Med. 2003; 6(4):605-613.
in February 2006. Version re-copy-edited in April 2009; revised again July 2015.
!25
XEROSTOMIA
Gary M Reisfield MD, Drew A Rosielle MD, and George R Wilson MD
Background Xerostomia (dry mouth) is a common symptom at the end of life – affecting more
than 75% of hospice patients – and is a cause of significant morbidity and diminished quality of
life. This Fast Fact will review the causes and treatments of xerostomia.
Salivary Functions include hydration, lubrication, and antimicrobial defense of the oral mucosa.
Decreased salivation can lead to oral pain; accelerated dental morbidity; oral infections, fissures,
and ulcerations; halitosis; alteration in taste and enjoyment of food; chewing and swallowing
difficulties; nutritional impairment; trouble producing intelligible speech; and denture-related
problems. Xerostomia is usually—although not always—associated with diminished salivary
secretion (hyposialia).
Etiologies
• Medications with anticholinergic activity are the most common pharmacologic causes of
xerostomia; these include many antiemetics, antihistamines, antipsychotics, antispasmodics,
antidepressants (especially the tricyclics), and bronchodilators. Sympatholytics are also
common culprits, including alpha-blockers (e.g. terazosin), alpha-2 agonists (e.g. clonidine),
and beta-blockers (e.g. metoprolol). Medication-induced xerostomia may also result from
direct interference with or damage to salivary tissue (as with some cancer chemotherapies).
Opioids and benzodiazepines cause dry mouth, although the mechanisms are not known.
• Radiation for head and neck malignancies.
• Medical comorbidities such as HIV/AIDS, diabetes, renal failure, and Sjögren’s syndrome.
• Psychiatric comorbidities such as mood and anxiety disorders.
• Dehydration from any cause including drug-induced.
Treatment
• Address underlying causes. Eliminate unnecessary drugs or substitute less drying ones. If
this is not feasible, titrate to lowest effective dose or modify dosing schedule. Replacing
immediate-release with controlled-release formulations of some drugs may help (e.g. with
oxybutynin and tolterodine for overactive bladder).
• Stimulate residual gland function.
o Sugarless gums and candies can stimulate salivary reflexes. Products sweetened with
xylitol are anticariogenic; those containing vitamin C may reduce salivary viscosity.
o Cholinergic agonists such as pilocarpine and cevimeline. Therapeutic effect is rapid for
drug-related xerostomia; latency is greater (often 8-12 weeks) for xerostomia related to
radiotherapy. Pilocarpine is started at 5 mg po tid and can be titrated to 10 mg po tid.
Cevimeline is dosed at 30 mg po tid. Urinary frequency, dizziness, and sweating are
common side effects and may be attenuated with intake of dairy products. These agents
are contraindicated in asthma, acute iritis, and narrow-angle glaucoma, and should be
used with caution in COPD and cardiac disease.
• Saliva substitutes. Most have limited efficacy; many patients find frequent sips of water
more useful and convenient. Topical products containing olive oil, betaine, and xylitol have
been found effective for medication-induced xerostomia (e.g. Xerostom® products). Newer
products with enzyme systems such as lactoperoxidase, lysozyme, and glucose oxidase (e.g.
Biotène® Oralbalance Dry Mouth Gel)—offer potential antimicrobial and moisturizing benefits.
Due to limited duration of action, they may be particularly useful before eating, speaking, and
sleeping. Recently, custom oral appliances with artificial saliva reservoirs have become
available and may be particularly useful at night.
• Encourage oral hydration. Humidifiers, especially during sleep, may also be helpful.
• Optimize oral hygiene.
o Antimicrobial mouthwashes (alcohol-free). Chlorhexidine gluconate oral rinse, USP
0.12%, twice daily, may be effective in preventing dental caries and oral infections.
o Most toothpaste products contain the surfactant sodium lauryl sulfate (SLS), which
can irritate dry mucosa and inactivate the enzyme systems of the newer artificial
salivas. Biotène® Dry Mouth Toothpaste contains salivary enzymes and is SLS-free.
!26
References
1. Amerongen AVN, Veernan ECI. Current therapies for xerostomia and salivary gland
hypofunction associated with cancer therapies. Support Care Cancer. 2003; 11:226-231.
2. Chambers MS, Rosenthal DI, Weber RS. Radiation-induced xerostomia. Head & Neck.
2007; 29:58-63.
3. Frost PM, Shirlaw PJ, Challacombe SJ, et al. Impact of wearing an intra-oral lubricating
device on oral health in dry mouth patients. Oral Diseases. 2006; 12:57-62.
4. Jensen SB, Pederson AM, Reibel J, Nauntofte B. Xerostomia and hypofunction of the
salivary glands in cancer therapy. Support Care Cancer. 2003; 11:207-225.
5. Miller M, Kearney N. Oral care for patients with cancer: a review of the literature. Cancer
Nurs. 2001; 24:241-254.
6. Scully C. Drug effects on salivary glands: dry mouth. Oral Diseases. 2003; 9:165-176.
7. Shiboski CH, Hodgson TA, Ship JA, Schiodt M. Management of salivary hypofunction
during and after radiotherapy. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2007;
103(suppl 1):S66.e1-S66.e.19.
8. Ship JA, McCutcheon JA, Spivakovsky S, Kerr AR. Safety and effectiveness of topical dry
mouth products containing olive oil, betaine, and xylitol in reducing xerostomia for
polypharmacy-induced dry mouth. J Oral Rehabil. 2007; 34(10):724-734.
Version History: Originally published June 2007. Revised, and 2nd edition published, December
2008. Version re-copy-edited in May 2009; then again July 2015.
!27
!

ANXIETY IN PALLIATIVE CARE – CAUSES AND DIAGNOSIS
Joseph Stoklosa, Kevin Patterson MD, Drew Rosielle MD, and Robert Arnold MD
Background Anxiety is a state of apprehension and fear resulting from the perception of a
current or future threat to oneself. The term is used to describe a symptom and a variety of
psychiatric disorders in which anxiety is a salient symptom. This Fast Fact will discuss the
causes and evaluation of anxiety.
Prevalence Anxiety is commonly reported in those facing life-threatening illnesses. At least
25% and cancer patients and 50% of CHF and COPD patients experience significant anxiety. At
least 3% of patients with advanced cancer and 10% of COPD inpatients meet DSM criteria for
Generalized Anxiety Disorder (see below).
Etiologies
• Anxiety may be present as part of one of several psychiatric disorders (see below).
• Anxiety is often a prominent component of acute or chronic pain, dyspnea, nausea, or cardiac
arrhythmias.
• Adverse drug effects: corticosteroids, psychostimulants, and some antidepressants.
• Drug withdrawal: alcohol, opioids, benzodiazepines, nicotine, clonidine, antidepressants, and
corticosteroids.
• Metabolic causes: hyperthyroidism and syndromes of adrenergic or serotonergic excess.
• Existential and psychosocial concerns about dying, disability, loss, legacy, family, finances,
and religion/spirituality.
Psychiatric Disorders with anxiety as a prominent symptom
• Generalized anxiety disorder is a psychiatric disorder characterized by pervasive and
excessive anxiety and worry about a number of events or activities (such as work or school
performance), occurring more days than not for at least 6 months. The anxiety and worry are
associated with at least 3 of the following 6 symptoms: restlessness, easy fatigue, difficulty
concentrating, irritability, muscle tension, and sleep disturbance.
• Panic disorder is characterized by recurrent panic attacks. See Fast Fact #145 for its
evaluation and management.
• Adjustment disorder occurs within 3 months of a major stressor, and causes marked distress
and functional impairment. Usually it is characterized by a depressed mood but anxiety can
also be its most prominent affective component.
• Acute- or post-traumatic stress disorders occur after an emotionally traumatic life-event
and are characterized by anxiousness and arousal, as well as by numbness, flashbacks,
intrusive thoughts, and avoidance of stimuli which remind the patient of the trauma.
• Phobias are marked, persistent fears brought about by specific situations or objects.
Evaluation
• Complete a thorough history and physical exam, in particular ask about:
o Prior episodes or anxiety, depression, PTSD, alcohol, and drug use.
o Prior and current treatment by a mental health professional.
o Presence of specific trigger situations or thoughts leading to anxiety.
o Presence of apprehension, dread, insomnia, and hypervigilance; as well as physical
symptoms such as diaphoresis, dyspnea, muscle tension, and tremulousness.
• Seek help from a professional familiar with the psychiatric disorders when anxiety is a
prominent and functionally impairing part of a patient’s symptoms.
• Symptoms that can be confused with anxiety are agitated delirium (see Fast Facts #1,60) and
akathisia, an unpleasant sense of motor restlessness from dopamine-blocking medications
such as antipsychotics and some antiemetics.
• Formal screening tools exist, but there is no consensus on the benefit of their routine use.
Commonly used tools which evaluate for anxiety as a symptom include the Edmonton
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Symptom Assessment Scale, the Memorial Symptom Assessment Scale, and the Hospital
Anxiety and Depression Scale.
References
1. Block SD. Psychological issues in end-of-life care. J Palliat Med. 2006; 9:751-772.
2. Mikkelsen RL, et al. Anxiety and depression in patients with chronic obstructive
pulmonary disease (COPD). A review. Nordic J Psychiatry. 2004; 58:65-70.
3. Friedmann E, et al. Relationship of depression, anxiety, and social isolation to chronic
heart failure outpatient mortality. Am Heart J. 2006; 11:152.
4. Tremblay A and Breitbart W. Psychiatric dimensions of palliative care. Neurol Clin. 2001;
19(4):949-67.
5. Bjelland I, et al. The validity of the Hospital Anxiety and Depression Scale. An updated
literature review. J Psychosom Res. 2002; 52(2):69-77.
6. Bruera E, Kuehn N, Miller MJ, Selmser P, Macmillan K. The Edmonton Symptom
Assessment System (ESAS): a simple method of the assessment of palliative care
patients. J Palliat Care. 1991; 7:6-9.
7. Portenoy RK, Thaler HT, Kornblith AB, et al. The Memorial Symptom Assessment Scale:
an instrument for the evaluation of symptom prevalence, characteristics and distress. Eur
J Cancer. 1994; 30A(9):1326-36.
Version History: Originally published August 2007. Version copy-edited in May 2009; then
again July 2015.
!29
!

OPIOIDS FOR COUGH
Sean Marks MD and Drew A Rosielle MD
Background Cough is a common, and at times distressing, symptom. Up to 40% of advanced
cancer patients report cough, and while a smaller percentage find their cough distressing, severe
cough can lead to dyspnea, nausea/vomiting, sleep impairment, chest and throat pain, and
impaired communication. This Fast Fact will focus on the use of opioids for the symptomatic
treatment of cough. Fast Fact #200 will address other agents for cough.
Etiologies & Evaluation Common etiologies of cough include infections of the upper and lower
airway, asthma and COPD, lung cancer or lung metastases, interstitial pulmonary processes
(such as lymphangitic tumor spread or pulmonary edema), gastroesophageal reflux, aspiration,
and drugs. Common drug causes include ACE inhibitors, NSAIDs, and inhalant medications.
Evaluating for reversible causes is appropriate if consistent with the goals of care and prognosis.
If feasible, treatment should be directed at the underlying cause. Many patients however will
benefit from symptomatic therapy for a distressing cough while waiting for acute therapy to work
or have a chronic cough not amenable to treatment (e.g. cough due to advanced lung cancer).
Opioids are the only clearly effective centrally-acting anti-tussive drugs and are thought to work
by suppressing the brainstem cough center through mu and kappa opioid receptor agonism.
They are the first-line symptomatic treatment for severe, distressing cough. All opioids used to
treat cough have typical opioid side effects such as sedation, constipation, and nausea.
• Codeine: Duration of action is 4 hours; usual adult dose is 10-20 mg every 4-6 hours. It has
shown to be effective for acute and chronic cough in several placebo-controlled trials. It is
available alone or as an elixir with guaifenesin.
• Dextromethorphan: Duration of action 3-6 hours; usual adult dose is 10-20 mg every 4-6
hours. It is the most commonly used anti-tussive. Confirmed to be as effective as codeine
for cough in multiple studies. It is available alone or as an elixir with guaifenesin. Note:
dextromethorphan inhibits the cytochrome P450 system and thereby affects the metabolism
of many drugs. Dextromethorphan can also cause a serotonin syndrome if used with
serotonergic drugs such as antidepressants.
• Hydrocodone: Duration of action 4-6 hours; usual dose 5-10 mg every 4 hours. Hydrocodone
is only available as a combination product in the US: as a short-acting elixir with the
anticholinergic drug homatropine or as an extended release elixir with the antihistamine
chlorpheniramine (dosed at 10 mg every 12 hours). These other agents magnify
hydrocodone’s sedative effects, and limit the maximum dose a patient can take.
Hydrocodone has been shown to be as effective as codeine in head to head studies but with
fewer gastrointestinal side-effects. For this reason it is considered by many experts as the
anti-tussive of choice (Homsi 2001).
• All opioid analgesics have anti-tussive activity and their use has been mostly based on
convention; there is no strong evidence that any one opioid has superior efficacy for cough.
For patients already taking opioids for pain, it is unclear whether adding a second opioid such
as codeine for cough is effective. One uncontrolled, open-label study showed hydrocodone
to be helpful in this setting; it has not been repeated (Homsi 2001).
Fast Fact #200 will discuss non-opioid agents for cough, as well as address some general
treatment strategies.
References
!30
1. Homsi J, Walsh D, Nelson KA. Important drugs for cough in advanced cancer. Support
Care Cancer. 2001; 9:565-74.
2. Estfan B, LeGrand S. Management of cough in advanced cancer. J Support Oncol.
2004; 2:523-7.
3. Von Gunten CF. Interventions to manage symptoms at the end of life. J of Pall Med.
2005; 8(1): 88-94.
4. Adam J. Pan-Glasgow palliative care algorithm 2005 – Palliation of cough. Palliative
Care Formulary 2nd Edition. Radcliffe Medical Press Ltd. 2002.
5. Davis CL. ABC of palliative care: breathlessness, cough and other respiratory problems.
BMJ. 1997; 315: 931-4.
6. Homsi J, Walsh D, Nelson KA, Sarhill N, Rybicki L, LeGrand SB, Davis M. A phase II
study of hydrocodone for cough in advanced cancer. Am J Hospice Palliat Care. 2002;
19:49-56.
7. Turturro MA, Paris PM, Yealy DM, Menegazzi JJ. Hydrocodone versus codeine in acute
musculoskeletal pain. Ann Emerg Med. 1991; 20:1100-03.
8. Irwin RS. Complications of cough. Chest. 2006; 129:54S-58S.
9. Homsi J, et al. Symptom evaluation in palliative medicine: patient report vs systematic
assessment. Support Care Cancer. 2006; 14:444-453.
10. Chung KF. Currently available cough suppressants for chronic cough. Lung 2008 [E-pub
ahead of print, available Oct 2, 2007]. DOI: 10.1007/s00408-007-9030-1.
Conflict of Interest Statement: the authors have disclosed no relevant conflicts of interest.
Authors’ Affiliations: Medical College of Wisconsin, Milwaukee, WI (SM); University of
Minnesota Medical School and Fairview Health Services, Minneapolis, MN (DAR).
Version History: Originally published March 2008. Copy-edited in June 2009. 2nd edition
published in July 2013; minimally revised to reflect that gabapentin is a newly appreciated
centrally acting anti-tussive; copy edited again July 2015.
!31
!

NON-OPIOID ANTI-TUSSIVES
Background Cough is a common and at times distressing symptom. Fast Fact #199 discussed
opioids for the symptomatic treatment of cough. This Fast Fact will address non-opioid anti-
tussives.
Controversies Commonly used prescription and over-the-counter anti-tussive formulations

which contain some combination of antihistamines (e.g. diphenhydramine), a mucolytic (e.g.
guaifenesin), and/or dextromethorphan are often used for acute cough due to upper respiratory
infections and acute bronchitis. Evidence for these agents in the acute setting is poor (either no
better than placebo or sweet syrup) and cannot be recommended. Due to concerns about
inadvertent overdose and lack of efficacy, these products are now being actively discouraged for
use in the pediatric setting.
Centrally-acting non-opioid anti-tussives

• Gabapentin: the pathophysiology of refractory chronic cough is thought to resemble central
sensitization as seen in neuropathic pain. A randomized, double-blind placebo controlled trial
demonstrated that gabapentin can meaningfully improve cough-specific quality of life and
reduce cough frequency and severity compared with placebo. Doses up to 1800 mg a day
were studied.
• Other neuromodulating agents: paroxetine, amitriptyline, and benzodiazepines have been
anecdotally reported to have efficacy in chronic, refractory cough but lack published
controlled evidence.
Peripherally-acting anti-tussives
• Sweet syrups are commonly used as cough suppressants, whether as bases for prescription
elixirs (such as codeine with guaifenesin) or home remedies (honey, simple syrup). The
mechanism of action is unknown; some authors hypothesize it acts as a protective barrier to
sensory receptors in the throat that heighten the cough reflex. A few controlled trials have
shown sweet syrups reduce coughing in upper respiratory infections.
• Benzonatate inhibits cough by anesthetizing stretch receptors in the respiratory tract. Its
duration of action is 3-8 hours; dosed at 100-200 mg three times a day. No published
controlled studies confirm its effectiveness but multiple uncontrolled studies support its use.
Side effects are uncommon but include sedation, headache, bronchospasm, and nausea.
Empirically many experts recommend adding it to an opioid.
• Antihistamines and anticholinergics are often part of combination anti-tussive elixirs with or
without an opioid. Anticholinergics such as hyoscyamine and scopolamine are most helpful
in the setting of copious upper respiratory secretions leading to cough. See Fast Fact #109
for dosing information.
• Expectorants thin bronchial secretions and ease expectoration. Examples include
guaifenesin (200-400 mg every 4 hours) and nebulized acetylcysteine or hypertonic saline.
Empirically they have been recommended for severe, chronic, wet coughs. Because they
may increase fluid in the respiratory tract, they are not recommended if the cough reflex is
diminished.
• Nebulized local anesthetics are thought to work by anesthetizing afferent receptors in the
respiratory tract. There have been no trials evaluating their effectiveness; anecdotally they
have been reported to be effective for refractory cough. Published regimens include lidocaine
2% solution, 5 mL nebulized every 6 hours; and bupivacaine 0.25%, 5 mL nebulized every 8
hours. Bronchospasm is a potential side effect.
• Other agents such as bronchodilators and corticosteroids have not been shown to be
effective apart from specific indications (e.g. for COPD or asthma exacerbations).
!32
Recommendations Treatment for cough should be directed at the underlying cause if feasible
and consistent with a patient’s prognosis and goals of care. When symptomatic treatment for a
distressing cough is necessary, it is reasonable to start with an opioid product, adding
benzonatate if needed. A trial of anticholinergics and expectorants for the indications described
above is reasonable, but they should be stopped after a couple days if they have no effect.
Sweet syrups appear to be helpful in upper respiratory infections; their role otherwise is uncertain.
If these strategies fail to control distressing symptoms, gabapentin should be tried for chronic
cough.
References
Care Cancer. 2001; 9:565-74.
2004; 2:523-7.
2005; 8(1):88-94.
BMJ. 1997; 315:931-4.
16. Sutton PP, Gemmell HG, Innes N, Davison J, Smith FW, Legge JS, Friend JA. Use of
nebulised saline and nebulised terbutaline as an adjunct to chest physiotherapy. Thorax.
1988; 43(1):57-60.
19. Lingerfelt BM, et al. Nebulized lidocaine for intractable cough near the end of life. J
Support Oncol. 2007; 7:301-2.
20. Chung KF. Currently available cough suppressants for chronic cough. Lung. 2008 [E-
pub ahead of print, available Oct 2, 2007]. DOI: 10.1007/s00408-007-9030-1.
21. Paul IM, Beiler J, McMonagle A, Shaffer ML, Duda L, Berlin CM. Effect of honey,
dextromethorphan, and no treatment on nocturnal cough and sleep quality for coughing
children and their parents. Arch Pediatr Adolesc Med. 2007; 161:1140-1146.
22. Schroeder K, Fahey T. Systematic review of randomized controlled trials of over the
counter cough medicines for acute cough in adults. BMJ. 2002; 324:1-6.
23. Fuller RW, Jackson DM. Physiology and treatment of cough. Thorax. 1990; 45:425-30.
24. Smith SM, SchroederK, Fahey T. Over-the-countermedications for acute cough in
children and adults in ambulatory settings. Cochrane Database of Systematic Reviews
2008, Issue 1. Art. No.: CD001831. DOI: 10.1002/14651858.CD001831.pub3.
25. Ryan NM, Birring SS, Gibson PG. Gabapentin for refractory cough: a randomized,
double-blind, placebo-controlled trial. Lancet 2012; 380(9853):1583-89. PMID: 22951084
Version History: Originally published March 2008. Copy-edited in June 2009. Revised and 2nd
Edition published July 2013; mostly to reflect new evidence about gabapentin. Copy-edited again
July 2015.
!33
!34
!

MANAGING WOUND ODOR
Bansari Patel APN and Deon Cox-Hayley DO
Background Foul-smelling non-healing wounds are common in patients nearing the end-of-
life, whether from pressure ulcers, vascular disease, or tumors. Strong wound odors can lead to
social and physical isolation, altered patient body image and self-worth, and can challenge
caregivers. This Fast Fact will discuss a practical approach to ameliorating wound odors. See
also Fast Facts #40 and #41 (pressure ulcers), #46 (malignant wounds), and #185 (topical
opioids).
Pathophysiology Foul odors from wounds result from the metabolic by-products of anaerobic
and certain gram negative organisms. Deeper infection (e.g. cellulitis, necrotizing infections) are
not necessary for significant odor generation.
Management While it should be addressed, treatment of the underlying cause of the wound is
often limited in patients with advanced illnesses. In all circumstances, attempts at ameliorating
wound odor are important – whether by treating the cause of the odor or hiding the odor.
• Addressing the cause of the odor:
o Remove the wound bed contaminants (e.g. debride the wound of necrotic tissue).
o Control infection. There are several approaches, all aimed at controlling anaerobic growth.
• Topical Metronidazole is available as a commercially produced gel. Metronidazole
functions as an anti-inflammatory as well as anti-infective agent against anaerobes
which reduces odors. Metronidazole gel is applied directly to the wound once or twice
daily. Studies have shown decreases in wound odor in 2-3 days, and application is
usually continued for up to 2 weeks. Courses can be repeated if needed. In one study,
63% of patients had complete eradication of odor after a course of metronidazole gel,
with the remainder reporting improvements. Costs can range from a few dollars for
compounded gels to ~$90-150 for 45 gm of commercial gel. Metronidazole tablets can
also be broken and the powder contents sprinkled into the wound. Applying dressings
soaked in a mixture of normal saline and intravenous metronidazole solution has also
been reported as helpful for controlling odor.
• Systemic Metronidazole can be used if there is evidence of deep tissue infection
causing foul odor. 500 mg 3 or 4 times daily IV or orally is used, instead of or in addition
to topical metronidazole. Systemic side effects such as nausea and diarrhea can
occur.
• Topical Silver Sulfadiazine ($4-$20) has been shown to be helpful in controlling odors
of superficial wounds. In several studies, silver containing dressings were more
effective than nonsilver dressings in reducing odors.
• Cadexomer Iodine is an antimicrobial agent containing slow release iodine and has
been shown to decrease bacterial counts and odor from venous ulcers. Ointment,
powder and impregnated bandage forms are available. Cadexomer iodine has the
added benefit of absorbing exudate and can be particularly helpful when exudate
absorption and odor control are both needed. It can cause a burning sensation upon
application.
• Yogurt or buttermilk, applied for 15 minutes after a wound is cleaned, have been
reported to control malignant wound odor, though studies are limited. They are thought
to control bacterial proliferation by lowering a wound’s pH.
• Honey can be bacteriocidal, and has been increasingly studied for wound healing.
There is some evidence that it may be effective in managing odor as well as wound
pain.
• Hiding the odor:
o Aromatics: Scented candles, air freshener sprays, peppermint and other essential oils,
coffee beans or grounds, and cider vinegar in a pan are all used to hide odors.
!35
o Adsorbents: Charcoal adsorbs aromatic molecules. A basket of charcoal (briquettes) can be
placed discreetly in a patient’s room. Various commercially available charcoal dressings are
also available, although expensive. These dressings are applied over the primary dressing
and may be re-used as long as they remain dry. Baking soda can be applied between
dressing layers to help absorb odor. Cat litter can also be used similarly to charcoal
briquettes.
Support and Education There can be great psychosocial distress associated with malodorous
wounds: embarrassment, shame, and isolation. In addition to wound care specialists,
psychological and spiritual support services can be important in helping patients and families
cope with a chronic wound. Educate the patient and caregivers about the management of chronic
wounds, and commit to controlling odor as much as possible. Health care providers should be
trained to avoid demonstrating distress at odors in front of or in hearing distance of patients or
families.
References
1) Alvarez O, Meehan M, Ennis W, et al. Chronic Wounds: Palliative Management for the Frail
Population Part III. Wounds. 2002; 14(8S):13-18.
2) Bates-Jensen B, Seaman S, Early L. Skin Disorders: Tumor Necrosis, Fistulas, and
Stomas. In: Ferrel B, Coyle N,
eds. Textbook of Palliative Nursing. New York, NY: Oxford University Press; 2006:
pp330-333.
3) Cooper RA, Jenkins L. A comparison between medical grade honey and table honeys in
relation to antimicrobial efficacy. Wounds. 2009; 29(2):29-36.
4) Fonder M, Lazurus G, Cowan D, et al. Treating the chronic wound: A practical approach to
the care of nonhealing wounds and wound care dressings. J Am Acad Dermatol. 2008;
58:185-206.
5) Kalinski C, Schneph M, Laboy D, et al. Effectiveness of a Topical Formulation Containing
Metronidazole for Wound Odor and Exudate Control. Wounds. 2005; 17(4):84-90.
6) McDonald A, Lesage P. Palliative Management of Pressure Ulcers and Malignant Wounds
in Patients with Advanced Illness. J Palliat Med. 2006; 9(2):285-295.
7) Sussman C, Jensen-Bates B. Wound Care: A Collaborative Practice Manuel. Philadelphia,
PA: Lippincott Williams & Wilkins; 2006.
8) Woo K, Krasner D, Kennedy, B, et al. Palliative Wound Care Management Strategies for
Palliative Patients and Their Circles of Care. Advances in Skin &Wound Care. 2015; 28(3):
130-140.
Author Affiliations: University of Chicago, Chicago, Illinois.
Version History: Originally published August 2009; copy-edited August 2015 by Krista Wiger
MD: reference #8 added and incorporated into the text.
!36
!37
!

SEIZURE MANAGEMENT IN THE DYING PATIENT
Jennifer Connelly MD and David E Weissman MD
Background Seizure management in the dying patient without intravenous (IV) access, such
as is in the home environment, is challenging. In this population they can be due to primary or
metastatic brain cancers, strokes, toxic/metabolic causes like hypoglycemia, or pre-existing
epilepsy. The incidence of seizures in dying patients is unknown, and while likely uncommon,
they can cause tremendous distress to patients and families. This Fast Fact reviews
management strategies for seizures near the end of life.
Seizure Prophylaxis Up to 40% of patients with brain tumors have a seizure at the time of
diagnosis and another 20% eventually develop seizures. Although antiepileptic drugs (AEDs) are
commonly started as prophylaxis at the time of brain tumor diagnosis, they have not been found
to prevent seizures and the American Academy of Neurology Clinical Practice Guidelines do not
support this practice (1). Thus, prophylactic AEDs can be safely discontinued in patients with
brain tumors who have never had a seizure. For brain tumor patients with a seizure history
(especially those with a history of status epilepticus), AEDs should be continued when possible.
In one study, tapering AEDs in the last week of life was associated with seizures in 35% of
patients with high-grade gliomas. For patients who lose an enteric route and have no intravenous
access, rectal administration of prophylactic AEDs is possible. Clinical judgment should be used
as to whether to continue AEDs in this setting as it can be appropriate to simply stop them,
particularly if the patient’s prognosis is very short. Phenobarbital, pentobarbital, carbamazepine,
valproic acid, and lamotrigine can all be given rectally. Rectal absorption of other prophylactic
AEDs is undefined and they should not be administered. No AEDs need dose adjustments for
rectal administration. Carbamazepine should be divided into small doses administered 6-8 times
a day. Lamotrigone is administered rectally by crushing and suspending the chewable tablets in
10 mL of water. When clinically indicated, drug levels of lamotrigine should be monitored as
rectal absorption is erratic. There is no data for the use of rectal levetiracetam in humans.
Seizure Management
• Single self-limited seizure: Check for treatable causes such as hypoglycemia. If no reversible
cause is identified, initiation of maintenance AED therapy should be considered, particularly if
the patient is expected to survive more than a few weeks.
• Acute seizure or status epilepticus:
o Non-IV routes: Studies, mainly in the pediatric population, have shown intranasal (IN)
midazolam at a dose of 0.2 mg/kg to be an effective and convenient agent to abort an
acute seizure. It has a quick onset of action of only 4-8 minutes and a time to maximal
concentration of 15-30 minutes. Rectal diazepam (0.3 mg/kg) used to be the drug of
choice for this indication and can be considered, but it has a longer onset of action, is more
expensive, and appears to be less preferred by patients compared with IN midazolam.
Once the initial seizure is controlled, diazepam 20 mg PR nightly should be considered to
reduce the occurrence of further seizure events. Other rectal benzodiazepines are
available (clonazepam, lorazepam, and midazolam), but take longer to reach peak serum
levels. Sublingual lorazepam is also available, but is not well-studied.
o IV routes: When available, IV or subcutaneous (SC) benzodiazepines should be used to
stop a seizure in progress; IV lorazepam is preferred due to its onset of action and half-life.
SC dosing is equivalent to IV for lorazepam, midazolam, and clonazepam. If seizure
activity persists, additional anti-epileptic medication should be provided using a loading and
then maintenance dose. Patients with refractory seizures who have short prognoses and
comfort-oriented goals of care should be considered for an anti-epileptic sedative such as a
continuous midazolam or barbiturate infusion with the goal of deep sedation (see Fast
Facts #106,107).
Parenteral AED Dosing and Routes.
!38
Drug Status loading dose Maintenance dose
Diazepam 0.2 mg/kg or 10-20 mg PR 20 mg PR nightly
Lorazepam 0.1 mg/kg IV, IM, or SC
Midazolam 0.1-0.3 mg/kg IV or SC Titrate to control refractory seizures if needed
Clonazepam 1 mg IV or SC
Phenytoin 20 mg/kg IV 4-5 mg/kg/day IV divided TID
Fosphenytoin 20 mg/kg IV or IM 4-5 mg/kg/day IV or IM divided TID
Phenobarbital 10-15 mg/kg 1-3 mg/kg/day IV or IM

1200 mg/day SC (2)
* Levetiracetam: Doses up to 2,500 mg IV have been used successfully and safely when added to
standard status epilepticus regimens. A typical maintenance dose is 500-1500 mg PO or IV BID.
Family Education Family members should be counseled that all medications used to manage
seizures can cause sedation and cardiopulmonary depression. Family members who have
witnessed prior seizures often have great fear about seizure recurrence. Many hospice agencies
have established seizure protocols and medication kits which can be stored at home, and will
collaborate with physicians and families on establishing a ‘seizure plan’ for acute seizures.
Review seizure safety with families, including not putting anything in the patient’s mouth and
making sure the patient is in a safe environment.
References
1. Glantz MJ, Cole BF, Forsyth PA, et al. Practice parameter: anticonvulsant prophylaxis in
patients with newly diagnosed brain tumors: report of the Quality Standards
Subcommittee of the American Academy of Neurology. Neurol. 2000; 54:1886-1893.
2. Krouwer H, Pallagi J, Graves N. Management of seizures in brain tumor patients at the
end of life. J Palliat Med. 2000;3:465-475.
3. Davis M, Walsh D, LeGrand S, et al. Symptom control in cancer patients: the clinical
pharmacolog and therapeutic role of suppositories and rectal suspensions. Support Care
Cancer. 2002; 10:117-138.
4. Brown L, Bergen DC, Kotagal P, et al. Safety of Diastat when given at larger-than-
recommended doses for acute repetitive seizures. Neurol. 2001; 56:1112.
5. Voltz R, Borasio GD. Palliative therapy in the terminal stage of neurological disease. J
Neurol. 1997; 244[Suppl 4]:S2-S10.
6. Droney J, Hall E. Status epilepticus in a hospice inpatient setting. J Pain Symptom
Manage. 2008; 36:97-105.
7. Sizoo E, Koekkoek J, Postma T, et al. Seizures in patients with high-grade glioma: a
serious challenge in the end-of-life phase. BMJ Support and Palliat Care. 2014; 4:77-80.
8. Uges J, van Huizen M, Engelsman J, et al. Safety and pharmacokinetics of intravenous
levetiracetam infusion as add-on in status epilepticus. Epilepsia. 2009; 50(3):415-421.
9. Holsti M, Dudley N, Schunk J, et al. Intranasal midazolam vs rectal diazepam for
the home treatment of acute seizures in pediatric patients with epilepsy. Arch
Pediatr Adolesc Med. 2010;164(8):747-753.
10. Ivaturi VD, Riss JR, Kriel RL, Cloyd JC. Pharmacokinetics and tolerability of
intranasal diazepam and midazolam in healthy adult volunteers. Acta Neurol
Scand. 2009;120(5):353-357.
11. Wusthoff CJ, Shellhaas RA, Licht DJ. Management of common neurologic
symptoms in pediatric palliative care: seizures, agitation and spasticity. Pediatr
Clin North Am. 2007;54:709-733.
Author Affiliations: Medical College of Wisconsin, Milwaukee, WI.
!39
Version History: Originally published April 2010; copy-edited August 2015 by Sam Maiser MD –
references #7 and #8 added and incorporated into the text; updated again in June 2018 with
references #9-11 added and incorporated into the text.
Care Network of Wisconsin (PCNOW) and the Center to Advance Palliative Care (www.capc.org).
Fast Facts and Concepts are editorially independent of PCNOW and the Center to Advance
Palliative Care, and the authors of each individual Fast Fact are solely responsible for that Fast
Fact’s content. The full set of Fast Facts are available at http://www.mypcnow.org/#!fast-facts/
cb1h or http://www.capc.org/fast-facts/ along with contact information, and how to reference Fast
Facts.
!40
FEVER NEAR THE END OF LIFE
Mallory Strickland BS and Erica Stovsky MD
Introduction Clinically significant fever is defined as an increase in body temperature
(generally > 38.5°C) in conjunction with an elevation of the hypothalamic set point. Hyperthermia
is an uncontrolled elevation in body temperature without a change in the thermoregulatory center.
This Fast Fact reviews the key elements in assessment and treatment of fever in patients near
the end-of-life.
Pathophysiology Fever is mediated by exogenous pyrogens (microbes or their products) and
pyrogenic cytokines (i.e. IL-1,IL-6, IFN a, TNF) which induce the synthesis of prostaglandin E2
(PGE2). Centrally, PGE2 increases production of cAMP, which raises the hypothalamic set point
to febrile levels. Peripherally, this induces myalgias and arthralgias. Pyrogens/pyrogenic
cytokines are produced by infection, inflammation, trauma/tissue necrosis, and tumors. Drugs can
induce fever through various metabolic and immune responses as well as by mimicking
endogenous pyrogens, inflicting direct tissue damage and interfering with heat loss. Common
drugs in palliative care settings which cause fever include antibiotics, anti-psychotics (neuroleptic
malignant syndrome) and opioid withdrawal. Fever associated with brain injuries is common,
perhaps due to direct hypothalamic injury.
Assessment The extent of evaluation will depend on the patient’s condition and overall goals
of care. When indicated, a thorough history and physical exam is needed, looking for a) signs of
infection, b) in cancer patients, evidence of disease progression, and c) a medication review. A
typical infection laboratory and radiographic workup can be pursued if it will affect management.
Common etiologies and clinical findings are reviewed below.
• Infection: look for a history of exposure (e.g. influenza), normal barrier violation (e.g.
aspiration, skin ulcer), and neutropenia (for instance, if receiving chemotherapy). Associated
signs/symptoms include elevated WBC, chills, spiking temperatures, and if severe,
hypotension, tachycardia, mental status changes and neutropenia. Note: Newborns, the
elderly, patients with chronic hepatic or renal failure, the immunocompromised, and those
taking glucocorticoids can have serious infections without a fever.
• Neoplastic Fever: a diagnosis of exclusion. It is uncommon in solid tumors, more common in
lymphomas. It is less likely to manifest as chills, hypotension, tachycardia, and mental status
changes; however elevated ESR and CRP are common. It tends to be responsive to NSAIDs.
• Medication-Induced: there is no predictable time of onset from medication initiation to fever
presentation. It resolves when suspected drug is stopped.
• DVT/PE: thought to cause fever through inflammation. Fever is inconsistently associated with
DVT/PE in the literature, however these are common events in the end-of-life population.
Treatment Benefits and burdens of all therapeutic options should be weighed in the context of
the patient’s overall clinical picture, including whether a fever is actually distressing to a dying
patient. When deciding if to treat the fever, ask patients who can communicate if the fever is
uncomfortable, and whether or not breaking the fever is more uncomfortable than the fever itself.
Although empiric, there is no compelling reason to think that treatment of fever actually reduces
suffering for dying, unresponsive patients. Education and reassurance for family and other
caregivers is most important in those situations.
• Non-pharmacological Interventions
o Cooling blankets, ice packs, sponging, and fans. While these can bring down body
temperature, they are noisy, labor-intensive, and distract family and other caregivers
from more meaningful interactions at the death-bed.
• Pharmacologic Interventions
o Discontinue any non-essential drugs if drug-induced fever is suspected.
o Antipyretics work by inhibiting production of PGE2. Acetaminophen 650-1000mg* PO/
PR/IV q4-6 hours PRN (maximum dose 4 g/day*) is considered first line given its low
side effect profile. NSAIDs (oral, IV, rectal, subcutaneous) are also effective. Naproxen
250mg* q12hrs is particularly effective in neoplastic fever, and possibly diagnostic when
!41
infection is ruled out. The order can state “PRN for symptomatic fever” to discourage
focus on the temperature measurement alone.
o Antibiotic therapy has been shown to be inconsistently useful in alleviating fever
symptoms in terminally ill patients. While evidence is unclear as to the utility of providing
antibiotic therapy, discussions should address their use as a potential treatment that may
or may not improve symptoms and prolong life/delay death; time-limited trials can be
appropriate.
o Glucocorticoids (oral, IM, IV) are also purported to be effective, however most of the
data supporting their use exist in the neurological and head injury literature.
*Discussed doses are for adults.
References:
1. Dinarello CA, Porat R. Chapter 16. Fever and Hyperthermia. In: Longo DL, Fauci AS,
Kasper DL, Hauser SL, Jameson JL, Loscalzo J, eds. Harrison's Principles of Internal
Medicine. 18th ed. New York: McGraw-Hill; 2012. Available at: http://
www.accessmedicine.com/content.aspx?aID=9095580. Accessed March 22, 2012.
2. Zhukovsky DS. Fever and sweats in patient with advanced cancer. Hematol Oncol Clin
North Am. 2002;16(3):579-88, viii. PMID: 12170569.
3. Zell JA, Chang JC. Neoplastic fever: a neglected paraneoplastic syndrome. Support Care
Cancer. 2005;13(11):870-7. PMID: 15864658.
4. Oh DY, Kim JH, et al. Antibiotic use during the last days of life in cancer patients. Eur J
Cancer Care. 2006; 15:74-79.
5. Vitetta L, Kenner D, Sali A. Bacterial infections in terminally ill hospice patients. J Pain
Symptom Manage. 2000; 20:326-334.
6. Nakagawa S, Yoshie T, et al. Can anti-infective drugs improve the infection-related
symptoms of patients with cancer during the terminal stages of their lives? J Palliat Med.
2010; 13:535-540.
7. Chen LK, Yu-Ching C, et al. Antibiotic prescription for fever episodes in hospice patients.
Supp Care Cancer. 2002; 10: 538-541.
8. Acetaminophen (systemic). In: USP DI® Volume I: Drug Information for the Health Care
Professional [Internet database]. Greenwood Village, Colo: Thomson Micromedex.
Updated periodically.
9. Tabor PA. Drug-induced fever. Drug Intell Clini Pharm. 1986; 20:413-20.
Authors’ Affiliation Drexel University College of Medicine, Philadelphia, PA (SM); University of

Pittsburgh Medical Center, Pittsburgh, PA (ES).
Version History First electronically published in May 2012; re-copy-edited in November 2015 by
Sean Marks MD
!42
!43
!

PHARMACOLOGIC MANAGEMENT OF DEPRESSION IN ADVANCED ILLNESS
Leah Rosenberg, MD; Jane deLima Thomas, MD
Adults with serious illness have a higher incidence of major depressive disorders than healthy
adults, with an estimated incidence of 15% (1). In this Fast Fact, we will provide a clinical
framework for selecting pharmacologic agents for seriously ill patients with depression. See Fast
Facts # 7, 43 and 146 for assistance in diagnosing and screening for depression in palliative care
patients.
Determine the patient’s prognosis Because most traditional antidepressants take more than
4 weeks to become effective, they should only be considered in patients expected to live at least
that long (2). Use is also limited to patients who are able to swallow oral medications or place
them in a feeding tube. For patients with a prognosis < 4 weeks, a psychostimulant such as
methylphenidate or dextroamphetamine may act within 1-2 days and be safe in patients without
significant cardiovascular disease or delirium. Although the data on psychostimulants are
somewhat mixed, controlled trials have shown benefit as both a monotherapy or to augment the
effects of another anti-depressant (3-5). See Fast Fact #61.
Consider co-morbid symptoms When choosing an antidepressant, consider the patient’s

other co-morbid symptoms such as insomnia, neuropathic pain, or poor appetite (6). Other
considerations include the patient’s past responses to specific agents and possible drug
interactions. Common classes of antidepressants include serotonin-selective reuptake inhibitors
(SSRIs), serotonin-selective norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants
(TCAs), and others.
SSRIs Also called “second generation antidepressants”, these are the most commonly
prescribed antidepressants. SSRIs should be started at a low dose and then titrated to the
minimum effective dose to minimize adverse effects such as QTc prolongation, sexual
dysfunction, headaches, nausea and diarrhea. Fluoxetine is associated with emotional activation
and may worsen anxiety. Paroxetine can be sedating and lead to withdrawal phenomena with
missed doses. Because sertraline, citalopram, and escitalopram have lower side effect profiles
and are neither activating nor sedating, they may be better choices for palliative care patients (7).
The starting dose of sertraline is 25-50 mg/day with a usual effective dose of 50-200 mg/day; it is
available in a concentrated liquid formulation for patients with dysphagia related issues. Both
citalopram and escitalopram have been shown to have few drug interactions. The starting dose of
citalopram is 20 mg/day with a maximum daily dose of 40 mg. The starting dose of escitalopram
is 10 mg/day with a usual effective dose of 10-20 mg/day (8-10).
SNRIs inhibit serotonin and norepinephrine reuptake, two neurotransmitters important in

endogenous pain pathways (11). This class may be helpful for neuropathic pain, vasomotor
instability, and anxiety-predominant depression. In particular, venlafaxine has shown
effectiveness for the amelioration of hot flushes and the prevention of chemotherapy-induced
polyneuropathy (CIPN); duloxetine has shown efficacy for the treatment of CIPN (12). SNRIs may
prolong bleeding times and therefore may not be safe in patients with active bleeding or
intracranial metastases. The starting dose for venlafaxine is 37.5 mg with a usual effective dose
of 75-225 mg/day. It requires close monitoring for missed-dose withdrawal and hypertension. The
starting dose for duloxetine is 30 mg with a usual effective dose of 60-120 mg/day. It has been
associated with hepatic insufficiency and a worsening of acute-angle glaucoma.
!44
TCAs are an older class of anti-depressants that can be cost-effective when used at lower doses.
They also are proven adjuvant analgesics for neuropathic and chronic low back pain.
Unfortunately, their anticholinergic properties can induce delirium, prolong the QTc interval, and
be dangerous in overdose. Therefore, their use is limited to heart-healthy patients under the age
of 65 with comorbid neuropathic pain and insomnia. Although the preponderance of supporting
data for the analgesic effects is for amitriptyline (usual starting dose 10-25 mg/day; usual effective
dose is 150 mg/day), nortriptyline is felt to be less sedating (usual starting dose 25 mg/day; usual
effective dose is 50-100 mg/day).
Other Medications Mirtazapine has histaminergic side effects that can be helpful especially for
cancer patients who often experience insomnia, poor appetite, and nausea (13). It has few drug
interactions but can be associated with orthostatic hypotension. Its usual starting dose is 7.5-15
mg/nightly; usual effective doses are 15-30 mg/day. Buproprion is thought to be less sedating
and have a lower incidence of sexual side effects, but it may lower the seizure threshold. The
usual starting dose for buproprion is 150 mg/day; the usual effective dose is 150-300 mg/day
(14). Single-dose treatment with NMDA antagonist ketamine has shown promise in early
investigational studies (15). Aripiprazole may augment the antidepressant effects of SSRIs and
SNRIs as early as a week after initiation (16).
Summary Recommendations:
• For patients with prognoses of weeks, consider the use of a psychostimulant like
methylphenidate.
• Consider duloxetine or venlafaxine when neuropathic pain is present.
• When polypharmacy is present, consider citalopram, escitalopram or mirtazapine.
• If the patient has insomnia, nausea, or anorexia, consider the use of mirtazapine.
• Closely monitor patients initiated on an antidepressant for adverse effects and dose titration.
• Refer to a mental health clinician for pre-existing major depression, the presence of comorbid
psychiatric illness, suicidal ideation, refractory symptoms, or psychiatric polypharmacy.
• Refer to social work and/or spiritual support services if the depression appears to be
escalating in relation to social or spiritual factors.
References:
1. Hotopf M, Chidgey J, Addington-Hall J, Ly KL. Depression in advanced disease: a

systematic review Part 1. Prevalence and case finding. Palliat Med. 2002 Mar;16(2):
81-97.
2. Block SD. Assessing and managing depression in the terminally ill patient. Ann Intern
Med. 2000;132(3):209-218.
3. Woods SW, Tesar GE, Murray GB, Cassem NH. Psychostimulant treatment of depressive
disorders secondary to medical illness. J Clin Psychiatry. 1986 Jan;47(1):12-5.
4. Olin J, Masand P. Psychostimulants for depression in hospitalized cancer patients.
Psychosomatics. 1996 Jan-Feb;37(1):57-62.
5. Lavretsky H, Reinlieb M, et al. Citalopram, methylphenidate, or their combination in
geriatric depression: a randomized, double-blind, placebo-controlled trial. Am J
Psychiatry 2015; 172:561-69.
6. Janberidze E, Hjermstad MJ, Brunelli C, Loge JH, Lie HC, Kaasa S, Knudsen AK; EURO
IMPACT. The use of antidepressants in patients with advanced cancer--results from an
international multicentre study. Psychooncology. 2014 Oct;23(10):1096-102.
7. Lloyd Williams M, Friedman T, Rudd N. A survey of antidepressant prescribing in the
terminally ill. Palliat Med 1999;13:243–8.
8. Rayner L, Price A, Hotopf M, Higginson IJ. Expert opinion on detecting and treating
depression in palliative care: A Delphi study. BMC Palliative Care. 2011;10:10.
9. Sanchez C, Reines EH, Montgomery SA. A comparative review of escitalopram,
paroxetine, and sertraline: are they all alike? International Clinical Psychopharmacology.
2014;29(4):185-196.
10. Preskorn SH. Recent pharmacologic advances in antidepressant therapy for the elderly.
Am J Med 1993;94:2S–12S.
!45
11. Marks DM, Shah MJ, Patkar AA, Masand PS, Park G-Y, Pae C-U. Serotonin-
Norepinephrine Reuptake Inhibitors for Pain Control: Premise and Promise.Current
Neuropharmacology. 2009;7(4):331-336.
12. Piccolo J, Kolesar JM. Prevention and treatment of chemotherapy-induced peripheral
neuropathy. Am J Health Syst Pharm. 2014 Jan 1;71(1):19-25.
13. Theobald DE, Kirsh KL, Holtsclaw E, et al. An open-label, crossover trial of mirtazapine
(15 and 30 mg) in cancer patients with pain and other distressing symptoms. J Pain
Symptom Manage 2002;23:442–7.
14. Shopsin B. Bupropion: a new clinical profile in the psychobiology of depression. J Clin
Psychiatry 1983;44:140–2.
15. Mathew SJ, Shah A, Lapidus K, et al. Ketamine for Treatment-Resistant Unipolar
Depression: Current Evidence. CNS drugs. 2012;26(3):189-204.
16. Thase ME, Trivedi MH, et al. Examining the efficacy of adjunctive aripiprazole in major
depressive disorder: A pooled analysis of 2 studies. Prim Care Companion J Clin
Psychiatry 2008;10:440–447.
Author Affiliations: Massachusetts General Hospital and Dana-Farber Cancer Institute, Boston,
MA.
Version History: First electronically published in January 2015
Conflicts of Interests: none reported
!46
!
Nutrition Hydration
#10 Tube Feed or Not Tube

Feed? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-3
#84 Swallow Studies, Tube Feeding, and the Death Spiral. . . . . . . . . . . . . . . .

. . . . . 4-5
#128 The Speech Pathologist and Swallowing Studies. . . . . . . . . . . . . . . . . . .

. . . . . . 6-7
#133 Non-Oral Hydration in Palliative Care . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . 8-9
#134 Non-Oral Hydration Techniques in Palliative Care. . . . . . . . . . . . . . . . . .

. . . . . 10-11
#190 Parenteral Nutrition in Advanced Cancer Patients . . . . . . . . . . . . . . . . .

. . . . . .12-13
#220 Hypodermoclysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . 14-16
#318 Prophylactic Feeding Tubes in Head and Neck Cancers . . . . . . . . . . . . . .

. . . . . 17-19
!1
\

TUBE FEED OR NOT TUBE FEED?
James Hallenbeck MD
Background Tube feeding is frequently used in chronically ill and dying patients. The evidence
for much of this use is weak at best. The Fast Fact reviews data on the use of tube feeding in
advanced illness.
For prevention of aspiration pneumonia
• Numerous observational studies have demonstrated a high incidence of aspiration
pneumonia in those who have been tube fed. Reduction in the chance of pneumonia has
been suggested for non-bed-ridden post-stroke patients in one prospective, non-randomized
study. For bedridden post-stroke patients, no reduction was observed.
• Three retrospective cohort studies comparing patients with and without tube feeding
demonstrated no advantage to tube feeding for this purpose.
• Swallowing studies, such as videofluoroscopy, lack both sensitivity and specificity in
predicting who will develop aspiration pneumonia. Croghan’s (1994) study of 22 patients
undergoing videofluoroscopy demonstrated a sensitivity of 65% and specificity of 67% in
predicting who would develop aspiration pneumonia within one year. In this study no
reduction in the incidence of pneumonia was demonstrated in those tube fed.
• Swallowing studies may be helpful in providing guidance regarding swallowing techniques
and optimal food consistencies for populations amenable to instruction. See Fast Fact #128
for discussion of the role of swallowing studies.
For life prolongation via caloric support
• Data is strongest for patients with reversible illness in a catabolic state (such as acute
sepsis).
• Data is weakest in advanced cancer. No improvement in survival has been found (see
exceptions noted below).
• Individual patients may have weight stabilization or gain with tube feeding. However, when
cohorts of patients have been studied in non-randomized retrospective or prospective
studies, no survival advantage between tube fed and hand fed cohorts has been
demonstrated.
• Tube feeding may be life-prolonging in select circumstances:
→ Patients with good functional status and proximal GI obstruction due to cancer
→ Patients receiving chemotherapy/XRT involving the proximal GI tract.
→ Selected HIV patients
→ Patients with Amyotrophic Lateral Sclerosis
For enhancing quality of life
• Where true hunger and thirst exist, quality of life may be enhanced (such as in very proximal
GI obstruction).
• Most actively dying patients (see Fast Fact #3) do not experience hunger or thirst. Although
dry mouth is a common problem, there is no relation to hydration status and the symptom of
dry mouth – see Fast Fact #133.
• A recent literature review using palliative care and enteral nutrition as search terms found no
studies demonstrating improved quality of life through tube feeding (results were limited to a
few observational studies).
• Tube feeding may adversely affect quality of life if patients are denied the pleasure of eating.
!2
Summary
Although commonly used, current data does not provide much support for the use of artificial
enteral nutrition in advanced dementia, or in patients on a dying trajectory from a chronic illness.
A recommendation to use, or not use, tube feeding should be made only after first establishing
the overall Goals of Care (see Fast Fact #16). Recommendations for how to discuss the issue
tube feeding with patients/families can be found in Fast Fact #84.
References
1. Loeb MB, Becker M, Eady A, Walker-Dilks C. Interventions to prevent aspiration
pneumonia in older adults: a systematic review. J Am Geriatr Soc. 2003;51(7):1018-1022.
2. Meier DE, Ahronheim JC, Morris J, Baskin-Lyons S, Morrison RS. High Short-term
Mortality in Hospitalized Patients With Advanced Dementia: Lack of Benefit of Tube
Feeding. Arch Intern Med. 2001; 161(4):594-599.
3. Nakajoh, K., T. Nakagawa, et al. Relation between incidence of pneumonia and
protective reflexes in post- stroke patients with oral or tube feeding. J Intern Med . 2000;
247: 39-42.
4. Finucane T, Christmas C, Travis K. Tube feeding in patients with advanced dementia.
JAMA. 1999; 282:1365-1369.
5. Finucane T, Bynum J. Use of tube feeding to prevent aspiration pneumonia. Lancet.
1996; 348:1421-1424.
6. Croghan J, Burke E, Caplan S, Denman S. Pilot study of 12-month outcomes of nursing
home patients with aspiration on videofluroscopy. Dysphagia. 1994; 9:141-146.
!3
!

SWALLOW STUDIES, TUBE FEEDING, AND THE DEATH SPIRAL
David E Weissman MD
Introduction The reflex by families and doctors to provide nutrition for the patient who cannot
swallow is overwhelming. It is now common practice for such patients to undergo a swallowing
evaluation and if there is significant impairment to move forward with feeding tube placement
(either nasogastric or gastrostomy) – see Fast Fact #128. Data suggest that in-hospital mortality
for hospitalizations in which a feeding tube is places is 15-25%, and one year mortality after
feeding tube placement is 60%. Predictors of early mortality include: advanced age, CNS
pathology (stroke, dementia), cancer (except early stage head/neck cancer), disorientation, and
low serum albumin.
The Tube Feeding Death Spiral The clinical scenario, the tube feeding death spiral, typically
goes like this:
1. Hospital admission for complication of “brain failure” or other predictable end organ
failure due to primary illnesses (e.g. urosepsis in setting of advanced dementia).
2. Inability to swallow and/or direct evidence of aspiration and/or weight loss with little oral
intake.
3. Swallowing evaluation followed by a recommendation for non-oral feeding either due to
aspiration or inadequate intake.
4. Feeding tube placed leading to increasing “agitation” leading to patient-removal or
dislodgement of feeding tube.
5. Re-insertion of feeding tube; hand and/or chest restraints placed.
6. Aspiration pneumonia.
7. Intravenous antibiotics and pulse oximetry.
8. Repeat 4 – 6 one or more times.
9. Family conference.
10. Death.
Note: at my institution, the finding of a dying patient with a feeding tube, restraints, and pulse
oximetry is known as Weissman’s triad.
Suggestions
• Recognize that the inability to maintain nutrition through the oral route, in the setting of a
chronic life-limiting illness and declining function, is usually a marker of the dying
process. Discuss this with families as a means to a larger discussion of overall end of life
goals.
• Ensure that your colleagues are aware of the key data and recommendations on tube
feedings (see Fast Fact #10).
• Ensure there is true informed consent prior to feeding tube insertion—families must be
given alternatives (e.g. hand feeding, comfort measures) along with discussion of goals
and prognosis.
• Assist families by providing information and a clear recommendation for or against the
use of a feeding tube. Families who decide against feeding tube placement can be
expected to second guess their decision and will need continued team support.
• If a feeding tube is placed establish clear goals (e.g. improved function) and establish a
timeline for re-evaluation to determine if goals are being met (typically 2-4 weeks).
References
1. Finucane TE, et al. Tube feeding in patients with advanced dementia. JAMA. 1999;
282:1365-1369.
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2. Finucane TE, Bynum JP. Use of tube feeding to prevent aspiration pneumonia. Lancet.
1996; 348:1421-24.
3. Cowen ME et al. Survival estimates for patients with abnormal swallowing studies. JGIM.
1997; 12:88-94.
4. Rabeneck L, et al. Long term outcomes of patients receiving percutaneous endoscopic
gastrostomy tubes. JGIM. 1996; 11:287-293.
5. Grant MD, et al. Gastrostomy placement and mortality among hospitalized Medicare
beneficiaries. JAMA. 1998; 279:1973-1976.
6. Mitchell SL. Clinical Crossroads: a 93-year-old man with advanced dementia and eating
problems. JAMA. 2007; 298:2527-2536.
7. Cervo FA, Bryan L, Farber S. To PEG or not to PEG. A review of evidence for placing
feeding tubes in advanced dementia and the decision-making process. Geriatrics. 2006;
61:30-35.
edited by Drew A Rosielle MD and published October 2007; 3rd Edition June 2015.
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!

THE SPEECH PATHOLOGIST AND SWALLOWING STUDIES
Carol Monteleoni MS, CCC-SLP
Background Speech pathologists can facilitate communication among members of the

medical team, and between the team and the patient/family, to make treatment decisions that
honor patient wishes. Speech pathology services for symptom control to enable the individual to
maintain activities of daily living and basic functional skills are reimbursable under the Medicare
Hospice Benefit (see Fast Facts #82, 87, 90). Swallowing studies are used to evaluate a patient’s
ability to safely ingest oral food and oral secretions, yet the role of swallowing studies to facilitate
optimal care near the end of life is not clear. This Fast Fact will review the indications and
contraindications for a swallowing study and the role of the speech pathologist.
Potential Indications for a swallowing evaluation (Bedside or Instrumental)
• Acute stroke or other neurological condition affecting oral motor function (see Fast Facts
#201, 300).
• Tracheostomy or recent endotracheal extubation.
• Changes to oropharyngeal anatomy secondary to tumor, surgery, trauma, etc.
• Observed difficulty swallowing food or liquid.
• Recurrent upper respiratory infections or pneumonias.
• Reduced oral food intake; unexplained weight loss or fever.
Contra-indications for swallowing evaluation (Instrumental only)
• Imminent death—death expected within 2 weeks (See Fast Fact #3).
• Death expected within weeks from any progressive terminal illness.
• Reduced level of arousal (e.g. coma/obtundation).
Types of swallowing studies
• Bedside dysphagia evaluation involves an in-depth feeding/swallowing history, oral
peripheral examination, and trial swallows of various food consistencies. Bedside
evaluation cannot rule out silent aspiration.
• Instrumental swallowing evaluation is performed via modified barium swallow
(videofluoroscopy), fiber-endoscopic evaluation of swallowing (FEES), or fiber-
endoscopic evaluation of swallowing with sensory testing (FEEST). All of these
instrumental assessments require the patient to be alert, cooperative, and able to follow
simple commands.
Speech Pathologist Role The decision to perform a swallowing evaluation should be made
based on the overall goals of care and expected prognosis. Consultation with your
speech pathologist prior to ordering an evaluation can help clarify how you will use any
new information to improve patient comfort and satisfaction. If performed, the speech
pathologist will evaluate the patient’s swallowing and recommend feeding strategies
which may include:
• Appropriate food consistencies.
• Positioning of the head and neck.
• Timing of meals
• Promoting family involvement.
Using the Speech Pathologist’s Assessment Decisions regarding feeding management

should not be made based solely upon the speech pathologist’s assessment of swallowing
dysfunction, which may be a sign of the final stage of life in many terminal conditions. In addition,
feeding tube placement decisions in this population should not be based on the likelihood of
aspiration. In patients with advanced dementia and other terminal conditions, feeding tubes have
not been found to reduce the incidence of aspiration and can significantly impair the dying
patient’s quality of life (see Fast Facts #10, 84).
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References:
1. Finucane TE, Christmas C, Travis K. Tube feeding in patients with advanced dementia.
JAMA. 1999; 282:1365-1369.
2. Levy A, Dominguez-Gasson L, Brown E, Frederick C. Technology at End of Life
Questioned. The ASHA Leader. 2004; July 20: pages 1, 14.
3. Ahronheim JC. Nutrition and hydration in the terminal patient. Clinics in Geriatrics. 1996:
12(2):379-391.
4. Monteleoni C, Clark E. Using rapid-cycle quality improvement methodology to reduce
feeding tubes in patients with advanced dementia: before and after study. BMJ. 2004;
329:491-494.
5. Pollens R. Role of the speech-language pathologist in palliative hospice care. J Palliat
Med. 2004; 7(5):694-702.
in December 2004. Version re-copy-edited in April 2009; revised again July 2015 by Mary Rhodes
MD.
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!

NON-ORAL HYDRATION IN PALLIATIVE CARE
Robin Fainsinger MD
Background At the center of the debate with regard to hydration in terminally ill patients is the
desire to maintain comfort and avoid unnecessary/distressing procedures. There is no
controversy that terminally ill patients should be encouraged to maintain adequate oral hydration
for as long as possible. However there is debate and controversy around the use of parenteral
hydration. This Fast Fact discusses medical decision-making about non-oral hydration in
palliative care settings; Fast Fact #134 discusses techniques of hydration.
Arguments Against Hydration

• Comatose patients do not experience symptom distress.
• Parenteral fluids may prolong dying.
• With less urine there is less need to void and use catheters.
• With less gastrointestinal fluid there can be less nausea and vomiting.
• With less respiratory tract secretions there can be less cough and pulmonary edema.
• Dehydration can help reduce distressing edema or ascites.
• Dehydration may be a “natural” anesthetic to ease the dying process.
• Parenteral hydration can be uncomfortable (e.g. needles/catheters) and limit patient
mobility.
Arguments For Hydration

• Dehydration can lead to pre-renal azotemia, which in turn can lead to accumulation of
drug metabolites (notably opioids), leading to delirium, myoclonus and seizures.
Hydration can reverse these symptoms in some patients leading to improved comfort.
• There is no evidence that fluids prolong the dying process.
• Providing hydration can maintain the appearance of “doing something,” even though
there may be no medical value, and thus ease family anxiety around the time of death.
Ethical/Legal Issues In the United States, the following ethical/legal standards exist:
• Competent patients or their surrogates can accept or refuse hydration based on relevant
information.
• Non-oral hydration is considered a medical intervention, not ordinary care. As such,
there is no legal or ethical imperative to provide it unless the benefits outweigh the
burdens.
Recommendation There is published medical literature to support both the use of, and the
withholding of, non-oral hydration in patients near death; thus, there is no consensus on the
single best approach to care. A Cochrane review of 6 relevant studies showed that sedation
and myoclonus were improved with hydration in adult palliative care patients; however,
discomfort from fluid retention was significantly higher in the hydration group and survival
seemed to be the same between the groups. Key issues to be considered when determining
the role of non-oral hydration include the following:
• Expressed wishes of the patient or surrogate decision-maker regarding use of hydration.
• Patient-defined goals; the presence of a specific goal may direct the clinician to use
hydration as a means to improve delirium and potentially delay death.
• Symptom burden: symptoms related to total body water excess may improve by
withholding hydration, while delirium may lessen with hydration.
• Burden to the patient and caregivers of maintaining the non-oral route of hydration.
• Family distress concerning withholding hydration/nutrition.
• When in doubt, a time limited hydration trial is an appropriate recommendation.
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Clinician Self-Reflection Finally, it is important to recognize that health care providers often
have biases for or against non-oral hydration near the end-of- life. Self-reflection upon these
biases is crucial to help patients and families make decisions that are based on the best interests
and goals of the patient/family unit.
References
1. Fainsinger RL. Hydration. In: Ripamonti C, Bruera E, eds. Gastrointestinal Symptoms in
Advanced Cancer Patients. New York, NY: Oxford University Press; 2002.
2. MacDonald N. Ethical considerations in feeding or hydrating advanced cancer patients.
In: Ripamonti C, Bruera E, eds. Gastrointestinal Symptoms in Advanced Cancer
Patients. New York, NY: Oxford University Press; 2002.
3. Lawlor PG. Delirium and dehydration: Some fluid for thought? Supp Care Cancer.
2002; 10:445-454.
4. Sarhill N, Walsh D, Nelson K, Davies M. Evaluation and treatment of cancer related fluid
deficits: volume depletion and dehydration. Supp Care Cancer. 2001; 9:408-419.
5. Bruera E, Sala R, Rico M, et al. Effects of parenteral hydration in terminally ill cancer
patients: a preliminary study. J Clin Oncol. 2005; 23:2366-2371.
6. Good P, Richard R, et al. Medically assisted hydration for adult palliative care patients.
Cochrane Database Syst Rev 2014; 4: 1-25.
in April 2005. Version re-copy-edited in April 2009; copy-edited again July 2015 in which
reference #6 was added and incorporated into the text.
!9
!

NON-ORAL HYDRATION TECHNIQUES IN PALLIATIVE CARE
Robin Fainsinger MD
Background The decision to use or withhold non-oral hydration near the end-of-life is complex
(see Fast Fact #133). This Fast Fact reviews the technical aspects of providing non-oral
hydration. Fast Fact #190 discusses the related issue of parenteral nutrition in advanced cancer
patients. 
 
Nasogastric and Gastrostomy Tubes The use of enteral feeding tubes to provide nutrition is
beyond the scope of this Fast Fact (see Fast Facts #10, 84). If already in place, enteral feeding
tubes provide easy access for supplemental hydration. Placement of enteral tubes solely for
hydration management in the last few weeks of life is generally not indicated, as other less
burdensome methods of hydration can be provided (see below).
Intravenous Hydration This method includes hydration via peripheral or central catheters. For
short-term use, especially as a time-limited trial, intravenous hydration is a reasonable step.
However, both peripheral and central catheters are plagued with problems of site selection,
placement, and maintenance; clot formation; local skin irritation; and local or systemic bacterial
infections.
Hypodermoclysis (subcutaneous infusions) Hypodermoclysis offers a number of

advantages compared to the intravenous route due to greater ease of site access, the possibility
of temporary disconnection to facilitate patient mobility, and ease and suitability for home
administration. Thrombocytopenia may be a relative contraindication. Solutions with electrolytes
should be used (e.g. 0.9% sodium chloride), as non-electrolyte solutions (e.g. 5% dextrose) can
draw fluid into the interstitial space. Continuous infusion rates up to 120 ml/hr have been
reported; patients can tolerate boluses of up to 500 ml/hr two to three times per day. Traditionally
the use of hyaluronidase to promote absorption was recommended. More recent experience has
demonstrated that most patients will achieve good absorption of subcutaneous fluids without
hyaluronidase. Winged infusion sets with 25 – 27 gauge needles are recommended.
The upper chest is the commonly used site for hypodermoclysis. Utilization of the lower
abdomen and upper thigh as sites for hypodermoclysis can be associated with scrotal edema in
males. Most experts recommend avoiding the upper arm as a site for hypodermoclysis.Check
the site frequently for redness, irritation, excessive edema, or a dislodged needle. If there is a
problem with absorption it recommended to a) slow the infusion rate and consider using an
infusion pump, or b) consider dividing the total volume into two separate subcutaneous sites.
Rectal Hydration (proctoclysis) Rectal hydration is an alternative only when other resources
are not available. A 22 French nasogastric catheter can be inserted approximately 40 cm into the
rectum. The patient can be positioned as for any rectal procedure. Tap water can be used, and
the rectal infusion increased from 100 ml to a maximum of 400 ml per hour, unless fluid leakage
occurs before the maximum volume is achieved. The majority of patients can successfully
tolerate this approach at a volume of 100 to 200 ml per hour.
Fluid Volumes For all routes, a reasonable goal is 1-1.5 L/day in fluid volume.
References
2. Steiner N, Bruera E. Methods of hydration in palliative care patients. J Palliat Care. 1998;
14(2):6-13.
3. Centeno C, Bruera E. Subcutaneous hydration with no hyaluronidase in patients with
advanced cancer. J Pain Symptom Manage. 1999; 17(5):305-306.
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4. Bruera E, Pruvost M, Schoeller T. Proctoclysis for hydration of terminally ill cancer patients.
5. Lanuke K, Fainsinger RL, de Moissac D. Hydration management at the end-of- life. J Palliat
Med. 2004; 7(2):257-263.
6. Edmonton Regional Palliative Care Program. Hypodermoclysis (HDC) Administration
Protocol for Palliative Care Patients. Edmonton, Alberta: 2003. Available at: http://
www.palliative.org/newpc/_pdfs/management/
3A7%20Hypodermoclysis%20Admin%20Protocol%20for%20PC%20Patients.pdf .
Accessed July 2015.
7. Dalal S, Bruera E. Dehydration in cancer patients: to treat or not to treat. J Support Oncol.
2004; 2:467-487.
April 2005. Re-copy-edited in April 2009; then again in July 2015 -- web-links updated.
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!

PARENTERAL NUTRITION IN ADVANCED CANCER PATIENTS
Mehrnoush Mirhosseini MD and Robin Fainsinger MD
Background Concerns about anorexia and weight loss are commonly expressed by advanced
cancer patients and their families. Parenteral nutrition is a controversial and expensive treatment
that is sometimes considered to assist with nutrition in advanced cancer patients. PN involves
the intravenous delivery of a mixture of lipids, carbohydrates, amino acids, vitamins, and
minerals. This Fast Fact reviews the role of PN in advanced cancer patients.
The Problem Weight loss in advanced cancer is frequently due to insufficient caloric intake as
well as cancer-mediated hypermetabolism and hypercatabolism. These latter problems are
caused by catabolic proinflammatory cytokines and eicosanoids and are responsible for much of
the accelerated muscle wasting (cachexia) seen in advanced cancer. Patients and families
frequently worry about malnutrition and starvation and request help from physicians to ameliorate
these.
The Role of PN PN is usually considered outside the standard of care for most patients with
advanced cancer. This is based on clinical research findings and other observations:
1. With a few specific exceptions (such as head and neck cancer patients undergoing
radiation therapy), caloric supplementation of any kind has not been shown to benefit
advanced cancer patients, and – if indicated – can almost always be achieved enterally.
2. There is no physiologic basis to assume that PN would affect the inflammatory and
catabolic aspects of cachexia.
3. PN brings potential risks and burdens: laboratory testing, indwelling intravenous lines,
infections, metabolic derangements, liver and pancreatic dysfunction.
Patients with progressive weight loss should have careful clinical assessments for potentially
reversible causes (such as inadequate caloric intake or depression). Education and emotional
and family support are the cornerstones of treatment otherwise. Drug interventions are an active
focus of research although their efficacy remains controversial (see Fast Facts #93, 100).
PN guidelines There does remain however a small subset of advanced cancer patients for
whom PN may be an appropriate therapy to improve quality and/or length of life. The following
guidelines have been suggested to identify patients appropriate for PN:
• Enteral nutrition (including tube feeding) is not an option or there is a specific benefit
expected from parenteral nutrition (e.g. inoperable malignant bowel obstruction, short
bowel syndrome, and malabsorption). These are patients for whom a non-functional GI
tract, and not cachexia itself, is the major problem.
• Death is probable from starvation or malnutrition earlier than anticipated from disease
progression alone.
• The patient has a life expectancy of at least several months to allow a proper trial of PN
(Karnofsky Performance Scale Score >50 or ECOG performance status ≤2).
• The patient has a good self-assessed quality of life; life-prolongation is consistent with their
goals of care and the potential risks of PN are acceptable to the patient.
• The patient or caregiver can safely accommodate PN if at home: the home environment is
safe and clean; someone is able to set-up and administer the PN; and the patient can be
clinically monitored, including laboratory investigation.
• Typically close monitoring of electrolytes, liver and renal function, and triglycerides is
required. In addition, careful assessments of the patient’s response to treatment and global
clinical course are needed to ensure PN remains an appropriate intervention.
Summary
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PN can be an important palliative treatment, but for only a small group of cancer patients. Careful
patient selection and monitoring is important to ensure that PN is meeting patient-defined goals of
care.
References
1. Moynihan T, Kelly DG, Fisch MJ. To feed or not to feed: Is that the right question? J Clinical
Oncol. 2005; 23(25):6526-6529.
2. Bondly C, Jotoi A. Overview of the management of the anorexia/weight loss syndrome. In:
Bruera E, Higginson I, Ripamonti C, Von Gunten CF, eds. Textbook of Palliative Medicine.
New York, NY: Oxford University Press; 2006:538-545.
3. Strasser F, Bruera E. Update on anorexia and cachexia. Hematol Oncol Clin North Am.
2002; 16:589-617.
4. Nitenberg G, Raynard B. Nutritional support of the cancer patient: Issues and dilemmas. Crit
Rev Oncol Hematol. 2000; 34:137-168.
5. MacDonald N, Easson AM, Mazurak VC, Dunn GP, Baracos VE. Understanding and
managing cancer cachexia. J Am Coll Surg. 2003; 197:143-161.
6. Mirhosseni N, Fainsinger RL, Baracos V. Parenteral nutrition in advanced cancer:
Indications in clinical practice guidelines. J Palliat Med. 2005; 8(5):914-918.
7. Turelli GF, Campos AC, Meguid MM. Use of TPN in terminally ill cancer patients. Nutrition.
1999; 15(9):665-667.
8. Dy SM. Enteral and parenteral nutrition in terminally ill cancer patients: A review of the
literature. Am J Hosp Palliat Care. 2006; 23(5):369-377.
9. CH Regional Palliative Care Program. Clinical Practice Guidelines: Home parenteral nutrition
and cancer selection criteria for patients with advanced cancer. Available at: http://
palliative.org/NewPC/_pdfs/management/
3A10%20Home%20Parenteral%20Nutrition%20and%20Cancer%20Selection%20Criteria%2
0Guideline.pdf. Accessed July 28, 2015.
Version History: Originally published October 2007. Version re-copy-edited in May 2009; then
again July 2015 – reference #9 updated.
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!

HYPODERMOCLYSIS
Arif H Kamal MD and Eduardo Bruera MD
Background This Fast Fact discusses subcutaneous fluid infusions, also known as
hypodermoclysis (HDC). The use of parenteral hydration in dying patients is controversial and is
discussed in Fast Fact #133. While this Fast Fact discusses subcutaneous fluid infusions for
purposes of hydration, similar techniques can also be used to deliver medications (see Fast Fact
#28).
Historical and Current Practice Hypodermoclysis was a widely accepted route for parenteral
hydration in the 1940s and 1950s before falling out of favor after several reports of adverse
reactions, likely related to the use of hypertonic and electrolyte-free solutions. Due to its ease of
use, and subsequent research demonstrating its safety and efficacy, HDC has become more
widely used. In the US, HDC is mostly used in geriatric and palliative care settings, although it is
used more widely elsewhere in the world.
HDC vs. Intravenous Hydration Decisions for parenteral hydration in dying patients are
complex and individual decision making is paramount. When parenteral hydration is indicated,
clinicians are generally faced with a decision to use HDC or intravenous (IV) hydration (see Fast
Fact #134).
• Advantages of HDC over IV: Starting and maintaining a subcutaneous infusion catheter
is relatively pain-free. It can be done by trained patients or family caregivers, preventing
the need for frequent skilled nursing visits or trips to medical centers to maintain a
working IV. HDC provides greater potential sites for needle placement (arm, back,
abdomen, thighs), and equipment costs are generally lower than with IVs. Subcutaneous
catheters can be easily disconnected from IV tubing and re-used later, allowing a patient
to receive intermittent fluid treatments. Portable infusion devices are not needed with
HDC. HDC infusions may also cause less agitation in patients with dementia versus IV
(1).
• Disadvantages: HDC is limited by a continuous infusion rate of 1-2 ml/min or 1.5-3 L/day
(2). This is adequate for most clinical situations, and additional catheters can be added if
needed. Bolus infusions (up to 500 ml/hour) are possible with HDC, but often require
hyaluronidase (see below). Both HDC and IV infusions have similar rates of local
adverse events (e.g. erythema, cellulitis) and lifespan of infusion site (3). HDC can be
technically difficult in patients with substantial peripheral edema, as well as in cachectic
patients with little subcutaneous tissue. Patients and families may have pre-conceived
attitudes about greater benefits with IV routes even while acknowledging increased
burden (4).
Technique
• Equipment needed: Small butterfly needle (usually 22 gauge) or angiocatheter, skin
preparation (alcohol or iodine), sterile occlusive dressing, solution bag (saline or saline-
dextrose combination), tubing with drip chamber. The use of an electrolyte free solution
like 5% dextrose is discouraged due to third-spacing risks which can cause tissue
sloughing or rarely circulatory collapse.
• Procedure: After cleaning the local site, insert the needle bevel up into the subcutaneous
tissue. Attach to fluid and tubing and cover with occlusive dressing. Select an infusion
fluid and set drip rate or fluid bolus. Normal saline (NS) is typically used although half-
normal saline or 2/3 D5W in 1/3 NS have been used in clinical practice. Drip rates can be
set to 20-125 ml/hour with gravity (no pump required) or 1-2 ml/minute. Some patients
may prefer drips set to gravity 24 hours per day at a low rate (e.g. 50 ml/hour), overnight
hydration (e.g. 100 ml/hour), or intermittent fluid boluses (e.g. 500 ml). The volume of
infusion needed to keep acceptable levels of hydration in many palliative care patients is
lower than healthy patients and postulated to be ~1 L/day (5). No evidence exists for the
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frequency of site change. Some change only when there are symptoms or needle
displacement while others choose a fixed time (e.g. every 3 or 7 days) or fluid volume
(e.g. every 1.5 L) Teflon cannulas, although expensive, can be used for a week and are
helpful for patients who have trouble maintaining a catheter site (6). Local anesthetic
creams may be helpful during catheter placement to reduce discomfort, especially in
children.
• Recombinant human hyaluronidase: RHH is an enzyme that temporarily lyses the
subcutaneous interstitial space to promote diffusion of fluid. It can be used for site
discomfort or if a faster rate of absorption is desired. Previous preparations were of
bovine origin and were associated with local allergic reactions, anaphylaxis, and pain,
making its role controversial. RHH has shown no human allergenicity (7). Recent studies
have investigated RHH versus placebo in a randomized trial with gravity-driven infusion.
The RHH group showed higher obtainable fluid rates, decreased discomfort, and similar
local reactions. Doses of 150 U to 750 U given as steady push prior to the infusion can
yield fluid rates of 380 to 520 ml/hour (8).
Cautions Uncommon local reactions include edema, local pain, or erythema. Interventions
include slowing the rate, changing the site, or using RHH. Rare complications include cellulitis
and vascular puncture. Systemic complications such as pulmonary edema can occur with all
types of artificial hydration.
References
1. O'Keeffe ST, Lavan JN. Subcutaneous fluids in elderly hospital patients with cognitive
impairment. Gerontology. 1996; 42(1):36-39.
2. Berger EY. Nutrition by hypodermoclysis. J Am Geriatr Soc. 1984; 32(3):199-203.
3. Slesak G, Schnurle JW, Kinzel E, Jakob J, Dietz PK. Comparison of subcutaneous and
intravenous rehydration in geriatric patients: a randomized trial. J Am Geriatr Soc. 2003;
51(2):155-160.
4. Mercadante S, Ferrera P, Girelli D, Casuccio A. Patients' and relatives' perceptions about
intravenous and subcutaneous hydration. J Pain Symptom Manage. 2005; 30(4):
354-358.
5. Dalal S, Bruera E. Dehydration in cancer patients: to treat or not to treat. J Support
Oncol. 2004; 2(6):467-479, 483.
6. Macmillan K, Bruera E, Kuehn N, Selmser P, Macmillan A. A prospective comparison
study between a butterfly needle and a Teflon cannula for subcutaneous narcotic
administration. J Pain Symptom Manage. 1994; 9(2):82-84.
7. Yocum RC, Kennard D, Heiner LS. Assessment and implication of the allergic sensitivity
to a single dose of recombinant human hyaluronidase injection: a double-blind, placebo-
controlled clinical trial. J Infus Nurs. 2007; 30(5):293-299.
8. Thomas JR, Yocum RC, Haller MF, von Gunten CF. Assessing the role of human
recombinant hyaluronidase in gravity-driven subcutaneous hydration: the INFUSE-LR
study. J Palliat Med. 2007; 10(6):1312-1320.
Author Affiliations: Mayo Clinic, Rochester, MN (AK) and University of Texas M.D. Anderson
Cancer Center, Houston, TX (EB).
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!16
!

PROPHYLACTIC FEEDING TUBES IN HEAD AND NECK CANCERS
Samuel Hardy MD, Krista Haas APN, Vincent J. Vanston MD, Mark Angelo MD
Clinical Background Patients with head and neck cancer are at risk for reduced oral intake
resulting from swallowing difficulties caused by their cancer treatment or obstructive tumors (1,2).
International guidelines recommend feeding tube placement for these patients when such
swallowing difficulties lead to malnutrition or hunger (3). This indication for feeding tube
placement is distinct from feeding tube placement for anorexia and cachexia from progressive
cancer, which has been generally discouraged by most experts and clinical guidelines (4) -- see
Fast Fact #10. Many clinicians now recommend prophylactic feeding tube placement, or feeding
tube placement prior to the onset of cancer treatment or the onset of swallowing difficulties, in the
hopes of preventing malnutrition especially among head and neck cancer patients with curative
goals of care (5).
Unfortunately, there is a paucity of robust clinical trials comparing the use of prophylactic feeding
tube placement in head and neck cancer versus a “watch and wait” approach in which feeding
tube placement is considered only when swallowing difficulties and/or malnutrition arise.
Therefore, patient values and clinician preference may end up being stronger factors in clinical
decision-making than the current body of medical evidence. As such, palliative care clinicians
may get involved in this clinical-decision making process to foster optimal patient centered care.
This Fast Fact will review some of the benefits and burdens of prophylactic feeding tube
placement in head and neck cancer patients.
Head and Neck Cancer Patients Who May Need Feeding Tubes A single-institution
retrospective review suggested that the following factors may be independently associated with
the eventual need for feeding tube placement in head and neck cancer patients (6):
• Body mass index < 25 (at baseline)
• A tumor T classification (which relates to the original size and/or location of the primary
tumor) ≥ 3
• A cumulative cisplatin dose of 200 mg/m2
Potential Risks of Feeding Tube Placement in Head and Neck Cancer

• Procedure-related morbidity: A retrospective review of percutaneous endoscopy gastrostomy
(PEG) tube placement in head and neck cancer (included both prophylactic feeding tube
placement and other) showed a procedure-related morbidity rate of 7.4% (7). Post-procedure
complications include tube dislodgement and cellulitis.
• Hospitalizations: The hospitalization rate for PEG-related complications in that review was
7.8% (7).
• Dysphagia leading to gastrostomy tube dependence: PEG feeding is associated with
paryngo-esophageal and upper esophageal stricture attributable to muscle disuse and
atrophy from reduced swallowing. While, there is a clinical concern prophylactic PEG
feedings can increase the risk for long term dysphagia, a prospective study of head and neck
cancer patients receiving prophylactic PEG tubes showed that 86% were able to have the
PEG tubes removed within 1 year (8).
• Metastasis: Although rare, metastasis of primary tumor to the gastrostomy site has been
reported (9).
Comparative Evidence Although the comparative evidence is not robust, retrospective and
prospective studies have compared prophylactic versus as needed feeding tube placement in
head and neck cancer patients receiving chemoradiotherapy.
• Nutritional outcomes: One clinical trial showed modest improvement in malnutrition in the
prophylactic group (10). Among other lower quality studies, no consistent difference in BMI at
!17
6 months post-treatment or amount of weight loss during and at the end of treatment have
been identified (11-17).
• Unplanned interruptions of chemoradiotherapy: Only one of five studies found that
prophylactic feeding tube placement prevented unplanned interruptions of chemotherapy or
radiotherapy (11-15).
• Disease-free survival: appears to be similar in both approaches (10, 13-17).
• Quality of life: Feeding tubes can be associated with psychological suffering from interference
with family life, intimate relationships, and social activities (18). However, two non-blinded,
prospective, randomized trials suggested that, following an initial decline, prophylactic
gastrostomy placement may improve quality of life at 6 months for patients with unresectable
squamous cell cancers treated with radiation and chemotherapy (10,14).
Recommendations To best assist head and neck cancer patients with this challenging clinical
dilemma, clinicians should first identify the intent of therapy and prognosis. In cases in which it is
clear that the patient is experiencing refractory cachexia from an untreatable terminal cancer,
feeding tube placement should be avoided. In other cases, clinicians may wish to frame the issue
around trade-offs – “What are the trade-offs you are and are not willing to make at this point in
your medical care?” For patients who prioritize the pleasure from oral feeding or would find the
potential interruptions to their family or social life from tube feeding placement (e.g. PEG-related
hospitalizations) particularly objectionable, a “watch and wait” approach should be supported by
treating clinicians. In other patients who prioritize maximizing nutritional status as they undergo
an often grueling cancer treatment, prophylactic feeding tube placement may be prudent,
especially if know risk factors are present.
References
1. Wiggenraad RGJ, Flierman L, Goossens A, et al. Prophylactic gastrostomy placement
and early feeding tube may limit loss of weight during chemoradiotherapy for advanced
head and neck cancer, a preliminary study. Clin. Otolaryngol. 2007;32: 384–390.
2. Atasoy BM, Yonal O, Demirel B, Dane F, Yilmaz Y, et al. The impact of early
percutaneous endoscopic gastrostomy placement on treatment completeness and
nutritional status in locally advanced head and neck cancer patients receiving
chemoradiotherapy. Eur Arch Otorhinolaryngol. 2012;269:275-282.
3. Arends J, Bodoky G, Bozzetti F, Fearon K, et al. ESPEN guidelines on enteral nutrition,
non-surgical oncology. Clin. Nutr. 2006;25:245-259.
4. Dy SM. Enteral and parenteral nutrition in terminally ill cancer patients: a review of the
literature. American Journal of Hospice and Palliative Medicine. 2006 Oct 1;23(5):369-7
5. Bossola M. Nutritional interventions in head and neck cancer patients undergoing
chemoradiotherapy: A narrative review. Nutrients 2015;7(1):265-276.
6. Wiggenraad RGJ, Flierman L, Goossens A, et al. Prophylactic gastrostomy placement
and early feeding tube may limit loss of weight during chemoradiotherapy for advanced
head and neck cancer, a preliminary study. Clin. Otolaryngol. 2007;32: 384–390.
7. Atasoy BM, Yonal O, Demirel B, Dane F, Yilmaz Y, et al. The impact of early
percutaneous endoscopic gastrostomy placement on treatment completeness and
nutritional status in locally advanced head and neck cancer patients receiving
chemoradiotherapy. Eur Arch Otorhinolaryngol. 2012;269:275-282.
8. Strom T, Trotti AM, Kish J, Rao NG, et al. Risk factors for percutaneous endoscopic
gastrostomy tube placement during chemoradiotherapy for oropharyngeal cancer. JAMA
Otolaryngol. Head Neck Surg. 2013;139:1242-1246.
9. Rutter CE, Yovino S, et al. Impact of early percutaneous endoscopic gastrostomy tube
placement on nutritional status and hospitalization in patients with head and neck cancer
receiving definitive chemoradiation therapy. Head Neck. 2011;33:1441-1447.
10. Crombie JM, Ng S, et al. Swallowing outcomes and PEG dependence in head and neck
cancer patients receiving definitive or adjuvant radiotherapy +/- chemotherapy with a
proactive PEG: A prospective study with long term follow up. Oral Oncol. 2015 Jun;51(6):
622-628.
11. Paccagnella A, Morello M, et al. Early nutritional intervention improves treatment
tolerance and outcomes in head and neck cancer patients undergoing concurrent
chemoradiotherapy. Support Care Cancer. 2010;18:837-845.
!18
12. Salas S, Baumstarck-Barrau K, et al. Impact of the prophylactic gastrostomy for
unresectable squamous cell head and neck carcinomas treated with radio-chemotherapy
on quality of life: Prospective randomized trial. Radiother Oncol. 2009;93(3):503-509.
13. Nugent B, Parker MJ, McIntyre IA. Nasogastric tube feeding and percutaneous
endoscopic gastrostomy tube feeding in patients with head and neck cancer. J. Hum.
Nutr. Diet. 2010;23:277-284.
14. Lewis SL, Brody R, et al. Feeding tube use in head and neck cancer patients. Head
Neck. 2013;36(12):1789-1795.
15. Chen AM, Li BQ, et al. Evaluating the role of prophylactic gastrostomy tube placement
prior to definitive chemoradiotherapy for head and neck cancer. Int. J. Radiat. Oncol. Biol.
Phys. 2010;78:1026-1032.
16. Silander E, Nyman J, et al. Impact of prophylactic percutaneous endoscopic gastrostomy
on malnutrition and quality of life in patients with head and neck cancer: A randomized
study. Head Neck. 2012;34:1-9.
17. Williams GF, Teo MT, et al. Enteral feeding outcomes after chemoradiotherapy for
oropharynx cancer: A role for prophylactic gastrostomy? Oral Oncol. 2012;48:434-440.
18. Olson R, Karam I, et al. Population-based comparison of two feeding tube approaches for
head and neck cancer patients receiving concurrent systemic-radiation therapy: Is a
prophylactic feeding tube approach harmful or helpful? Support. Care Cancer.
2013;21:3433-3439.
19. Kramer S, Newcomb M, Hessler J, Siddiqui F. Prophylactic vs reactive PEG tube
placement in head and neck cancer. Otolaryngol. Head Neck Surg. 2014(3);150:407-412.
20. Rogers S, Thomson R, O’Toole , & Lowe, D. (n.d.). Patients experience with long-term
percutaneous endoscopic gastrostomy feeding following primary surgery for oral and
oropharyngeal cancer. Oral Oncol. 2007;43(5):499-507.
Conflicts of Interest: None

Authors’ Affiliations: MD Anderson Cancer Center at Cooper. Camden, NJ.
Version History: Originally edited by Sean Marks MD; first electronically published August 2016.
!19
!
Opioid Products
#2 Converting to Transdermal
Fentanyl . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-3
#50 Choosing an Opioid Combination

Product . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .4-5
#53 Sublingual
Morphine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . 6-7
#75 Methadone for the Treatment of Pain . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . 8-10
#80 Controlled Release of

Oxycodone . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11-12
#103 Oral Transmucosal Fentanyl

Citrate . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13-14
#185 Topical Opioids for

Pain . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15-17
#268 Low-Dose
Buprenorphine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. .18-20
#290 Tramadol in Palliative Care . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . . .21-23
#307 Opioid
Pharmacokinetics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . 24-27
!1
!

CONVERTING TO TRANSDERMAL FENTANYL
Quick—what dose of the transdermal fentanyl patch (Duragesic®) is equianalgesic to a 3 mg/hr

morphine continuous infusion? Conversions to and from fentanyl transdermal are notoriously
tricky, requiring knowledge of the published conversion data, general opioid pharmacology, and a
generous dose of common sense. See also Fast Fact #36 on opioid dose conversions.
Step 1:. Calculate the 24 hr morphine dose: 3 mg/hr x 24 hrs = 72 mg IV morphine/24 hrs.
Step 2: Convert the IV dose to the equianalgesic oral morphine dose using a ratio of:
1 mg IV = 3 mg oral. Thus, 72 mg IV = 216 mg po/24 hours.
Step 3: Convert the oral morphine dose to transdermal fentanyl. There are two methods:
Method 1 – Standard Table. Look up the FDA prescribing information for transdermal fentanyl
(Reference 1, pp 29-30). It says that 135-224 mg of morphine per 24 hours = 50 mcg/hr patch.
Note: this range of morphine is very broad which may result in significant under-dosing.
Method 2 - Alternate Formula. In 2000, Brietbart, et al published an alternative method, based

on the results of a multi-center trial by Donner, et al, that relied on a fixed dose conversion ratio to
calculate the fentanyl transdermal dose. Brietbart recommended the ratio of:
2 mg oral morphine/24 hr = 1 mcg/hr of transdermal fentanyl—rounded to the nearest patch size.
In the case example above, 216 mg of oral morphine per day is approximately equianalgesic to
the 100 mcg/hr fentanyl patch.
Note: using this formula, 25 mcg/hr of transdermal fentanyl is roughly equivalent to 50 mg oral
morphine/24 hours. This dose may be excessive when used in the opioid naïve or the elderly.
Key Considerations
• All equianalgesic ratios/formulas are approximations; clinical judgment is needed when
making dose or drug conversions.
• The FDA Prescribing Information indicates that their table should only be used when
converting from another opioid to transdermal fentanyl.
• The risk of sedation/respiratory depression with transdermal fentanyl is probably

increased in the elderly or patients with liver and renal impairment due to its long half-life,
thus, choose the lower end of the dosing spectrum.
• When in doubt, go low and slow, using prn breakthrough doses generously while finding
the optimal dosage of a long-acting drug.
!2
• The ‘Alternate Formula’ by Brietbart, et al is best used by experienced practitioners as it
tends to give higher fentanyl patch doses than the FDA PI.
Other teaching points about Duragesic:

• Start at the lowest dose, 12 mcg/hr, in an opioid naïve patient; there is no maximum
dose.
• Therapeutic blood levels are not reached for 13-24 hours after patch application and drug
will be continue to be released into the blood for at least 24 hours after patch removal.
• Opioid withdrawal symptoms can occur during dose conversions—care must be taken to
avoid this by use of breakthrough opioids.
• Some patients will need to have their patches changed every 48 hours.
• The recommended upward dose titration interval is no more frequently than every 72
hours.
• Place patches on non-irradiated, hairless skin.
• Direct heat applied over the patch can increase drug absorption with increased toxic
effects.
• There are no data that cachectic patients have reduced efficacy due to loss of
subcutaneous fat; albeit cachectic patients may require higher dosing (6).
References:
1. Duragesic Prescribing Information. US Food & Drug Administration. http://
www.accessdata.fda.gov/drugsatfda_docs/label/2005/19813s039lbl.pdf. Accessed Nov
4, 2014.
2. Donner B, et al. Direct conversion from oral morphine to transdermal fentanyl. Pain.
1996; 64:527-534.
3. Payne R, et al. QOL and cancer pain: satisfaction and side effects with Transdermal
fentanyl versus oral morphine. J Clinical Oncology. 1998:16:1588-1593.
4. Breitbart W. An alternative algorithm for dosing transdermal fentanyl for cancer-related

pain. Oncology. 2000; 14:695-702.
5. Gourlay GK. Treatment of cancer pain with transdermal fentanyl. The Lancet Oncology.
2001; 2:165-172.
6. Heiskanen T, Matzke S, Haakana S et al. Transdermal fentanyl in cachectic cancer

patients. Pain. 2009; 144:218-22. doi: 10.1016/j.pain.2009.04.012
published July 2005; 3rd Edition May 2015. Current version re-copy-edited March 2009;
information about the lowest patch dose added. Revised November 2014 by Drew A Rosielle MD;
FDA reference updated; Reference 6 added; additional cautionary language added.
!3

CHOOSING AN OPIOID COMBINATION PRODUCT
David E Weissman MD
Introduction
There are over 50 different opioid combination products, available in a range of tablet strengths
and liquids. Opioid combination products are typically used for moderate pain that is episodic
(e.g. breakthrough pain) on a PRN basis. These products contain either acetaminophen, aspirin
or ibuprofen, with an opioid: codeine (e.g. Tylenol #2-4), hydrocodone (e.g. Lorcet, Lortab,
Vicodin, Vicoprofen), oxycodone (e.g. Percocet, Percodan, Tylox, Roxicet) or propoxyphene (e.g.
Darvocet, Wygesic). Other formulations also may contain caffeine and/or a barbiturate. This
Fast Fact will review information for rationally choosing among the various products.
Intrinsic Analgesic Potency

Milligram for milligram, oxycodone and hydrocodone are the most potent opioids in this group;
they are roughly equianalgesic to each other. Codeine is less potent and propoxyphene the least
potent of the group; propoxyphene products are probably no more potent than aspirin or
acetaminophen alone.
Toxicity
The dose limiting property of all the combination products is the aspirin, acetaminophen or
ibuprofen, not the opioid (see below). Patients receiving any of the four opioids may experience
classic opioid side effects: nausea, constipation, pruritus or sedation, along with the potential for
tolerance and physical dependence with chronic use. Differences in side effect severity among
the different opioids is largely idiosyncratic. There is anecdotal experience that codeine is the
most, and hydrocodone the least, emetogenic among the four opioids. Propoxyphene’s major
metabolite is a CNS stimulant, increasing the likelihood of seizures in an overdose situation. It is
also cardiotoxic, with lidocaine-like effects. Because of limited efficacy and increased toxicity,
propoxyphene is not recommend, especially in the elderly (1). Multiple countries have banned
propoxyphene; as of 2009 this is under consideration in the US.
Cost
Generic products are readily available and typically less expensive.
Range of available doses

Codeine products: 15-60 mg codeine/tablet
Oxycodone or hydrocodone: 2.5–10 mg opioid/tablet
Propoxyphene: 50-100 mg propoxyphene/tablet
!4
Acetaminophen doses range from 325–750 mg/tablet
Recommendations for use

• Propoxyphene should rarely, if ever, be prescribed; it should not be used in the elderly.
• Prescribe generic products whenever possible.
• Prescribe only one combination product at any given time. Avoid writing orders that
include multiple products (e.g. “X” for mild pain, “Y” for moderate pain, etc). Rather,
prescribe only one product, assess efficacy and toxicity, and modify accordingly.
• Prescribe codeine, oxycodone and hydrocodone products at a q4h interval; not q 4-6 or
q6h (see Fast Fact #18) (2).
• Pay very close attention to the total daily dose of acetaminophen/aspirin/ibuprofen. Note:
the dose of acetaminophen per tablet can range from 325-750 mg. Thus, with a
recommended limit of < 4 grams per day, this equals 12 tablets @ 325 mg or 5 tablets @
750 mg tablet. Patients with renal or liver dysfunction are at higher risk for adverse
effects from the non-opioid (3).
References
1. AGS Panel on Chronic Pain in Older Persons. The Management of chronic pain in older
persons. J Am Geriatric Soc. 1998; 46:635-651.
2. Jacox A, Carr DB, Payne R, et al. Management of Cancer Pain. Clinical Practice
Guideline No. 9. AHCPR Publication No. 94-0592. Agency for Health Care Policy and
Research, U.S. Department of Health and Human Services, Public Health Service, 1994.
Available at: http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=hstat6.chapter.18803.
3. MB Max, R Payne, WT Edwards, et al. Principles of analgesic use in the treatment of

acute pain and cancer pain. 4th Edition. Glenview, IL: American Pain Society; 1999.
4. Zwillich T. FDA Panel Urges Ban of Pain Drug [news story]. WebMD. Jan 30 2009.
Available at: http://www.webmd.com/pain-management/news/20090130/fda-panel-urges-
ban-of-a-pain-drug.
!5

SUBLINGUAL MORPHINE
Debra Gordon RN, MS, FAAN, Sean Marks MD, Bridget Protus PharmD
Background The preferred route of administration of analgesics for most patients

in pain is oral (PO) considering the longer duration of action and convenience of use
in non-hospital settings compared with subcutaneous and intravenous formulations.
Soluble tablets of morphine were once commonly used for off-label sublingual (SL)
administration in patients who were unable to swallow pills or large quantities of
solutions. Although some hospice pharmacies still may be able to compound
soluble morphine for sublingual use, the manufacture of soluble tablets of morphine
has not been available in the United States since 2007. Instead, most pharmacist
experts recommend the use of concentrated oral solution (20 mg/mL) of morphine or
oxycodone for this clinical application.
Pharmacology of SL Morphine SL administration of morphine via soluble tablets

was used to treat breakthrough pain to hasten analgesic onset and peak; however,
available data do not support more rapid absorption of soluble morphine tablets
when compared with more traditional oral formulations of morphine (1-3). Indeed,
several clinical studies found no substantial advantage to the use of soluble
morphine tablets over oral morphine (4-6).
• Mean time to maximum concentration has been shown to be shorter for PO
morphine (0.8 + 0.35hr) compared with soluble morphine tablets (1.75 + 1.30
hr), indicating that soluble morphine tablets are likely swallowed and absorbed
gastrointestinally rather than through the oral mucosa (3).
• The bioavailability (amount of drug eventually made available to the systemic
circulation) of soluble morphine tablets are relatively low: only 9%
• Agents are most readily absorbed through the oral mucosa when they are
potent, non-ionized at physiological pH, and lipid soluble (see Fast Fact #103).
Morphine has a relatively low potency for an opioid, is 90% ionized at the pH of
the mouth, and is one of the least lipid soluble opioids. These factors likely
explain its poor performance as a SL or buccal medication.
Pharmacology of Concentrated Oral Solutions of Morphine and Oxycodone In

lieu of the poor evidence supporting the efficacy of soluble morphine tablets, they
are not manufactured in the United States anymore. Instead, the use of
!6
concentrated (20 mg/mL) of oral morphine solution has been more commonly
utilized for imminently dying patients who are unable to tolerate pills or significant
volumes of an opioid solution.
• The bioavailability of the oral solution is 23.8%.
• Concentrated oral morphine solution is considered to be equianalgesic with
soluble morphine tablets.
• The amount of SL absorption of the 20 mg/mL concentrated oral morphine
solution is estimated to be only 18-20%. Its clinical effect is more likely due to
the dose being swallowed with saliva and absorbed gastrointestinally.
• Oxycodone also comes available as a 20 mg/mL solution. The most
concentrated oral solution available for methadone is a 10 mg/mL solution.
Hydromorphone is not available in a concentrated oral solution.
Formulation and Dosing

• There are several forms of short acting PO morphine available, however, only
the soluble tablets or the concentrated oral solution are suitable for SL use.
Nonsoluble morphine sulfate immediate release (MSIR) tablets will not be
absorbed sublingually, even when crushed, because they will not liquefy under
the tongue.
• A usual starting dose for an opioid naïve patient is 5-15 mg PO or every 3
hours. The equianalgesic ratio of IV to PO morphine is 1:3 (10mg of IV
morphine is approximately equianalgesic to 30 mg PO/SL morphine).
This Fast Fact was adapted with permission from the University of Wisconsin
Hospital & Clinics, Madison, WI Pain Patient Care Team ‘Pain Management
Fast Facts – 5 Minute Inservice’ series.
References:
1. Osborne R, Joel S, Trew D, Slevin M. Morphine and metabolite behavior
after different routes of morphine administration: demonstration of the
importance of the active metabolite morphine-6-glucourinide. Clinical
Pharmacology Therapy. 1990; 47:12-19.
2. David T, Miser AW, Loprinzi CL, Kaur JS, Burnham NL, Dose AM, Ames
MM. Comparative morphine pharmacokinetics following sublingual,
intramuscular, and oral administration in patients with cancer. The Hospice
Journal. 1993; 9(1):85-90.
3. Colluzzi PH. Sublingual morphine: efficacy reviewed. J Pain Sympt Manage.
1998; 16(3):184-192.
4. Pannuti F, Rossi AP, Lafelice G, et al. Control of chronic pain in very
advanced cancer patients with morphine hydrochloride administered by oral,
rectal, and sublingual routes: clinical report and preliminary results on
morphine pharmacokinetics. Pharmacological Research Communications.
1982; 14(4):369-380.
5. McQuay HJ, Moore RA, Bullingham RE. Sublinqual morphine, heroin,
methadone, and buprenorphine: kinetics and effects. In: Foley KM & Inturrisi
CE, eds. Advances in Pain Research and Therapy, Vol 8. New York, NY:
Raven; 1986: pp 407-412.
6. Robinson JM, Wilkie DJ, et al. Sublingual and oral morphine administration.
Review and new findings. Nursing Clin N America. 1995; 30(4):725-743.
published July 2006; 3rd Edition May 2015. Further copy-editing changes occurred March 2017.
!7
Facts.

METHADONE FOR THE TREATMENT OF PAIN
Gail Gazelle MD and Perry G Fine MD
Introduction Methadone, a potent opioid agonist, has many characteristics that make it useful
for the treatment of pain when continuous opioid analgesia is indicated. Although available for
decades, its use has gained renewed interest due to its low cost, inactive metabolites, and many
routes of administration. This Fast Fact will introduce methadone’s pharmacology and clinical
use as an analgesic.
Pharmacology Unlike morphine, methadone is a racemic mix; one stereoisomer acts as a

NMDA receptor antagonist, the other is a mu-opioid receptor agonist. The NMDA mechanism
plays an important role in the prevention of opioid tolerance, potentiation of opioid effects. and is
the theoretical basis for its use in neuropathic pain syndromes, although this latter impression is
largely anecdotal.
Methadone is highly lipophilic with rapid GI absorption and onset of action. It has a large initial
volume of distribution with slow tissue release. Oral bioavailability is high, ~ 80%. Unlike
morphine there are no active metabolites and biotransformation to an active drug is not required.
The major route of metabolism is hepatic with significant fecal excretion; renal excretion can be
enhanced by urine acidification (pH <6.0). Unlike morphine, no dose adjustment is needed in
patients with renal failure since there are no active metabolites.
Prescribing Methadone is available in tablet, liquid and injectable forms; oral preparations can
be used rectally. Parenteral routes include IV bolus dosing or continuous infusion. Any clinician
with a Schedule II DEA license can prescribe methadone for pain; a special license is only
required to prescribe methadone for the treatment of addiction. In some jurisdictions, it is
necessary to apply the words “for pain” on the prescription.
Cautions Unlike morphine, hydromorphone, or oxycodone, methadone has an extended

terminal half-life of up to 190 hours. This half-life does not match the observed duration of
analgesia (6-12 hours) after steady state is reached. This long half-life can lead to increased risk
for sedation and respiratory depression, especially in the elderly or with rapid dose adjustments.
Rapid titration guidelines for other opioids do not apply to methadone. Given recent reports that
high-dose methadone may be associated with development of QT interval prolongation and
Torsades de Pointes, EKG monitoring may be appropriate when changes in dosage are made
(depending upon life expectancy and goals of care).
Pediatrics With close monitoring by an experienced prescriber, methadone has been used
safely in children, although the safety, effectiveness, and the pharmacokinetics of methadone in
!8
patients below the age of 18 years have not been established by the Food and Drug
Administration.
Potency An important property of methadone is that its apparent potency, compared to other
opioids, varies with the patient’s current exposure to other opioids. See below for a suggested
dosing guide for opioid tolerant patients (Reference 1).
Daily oral morphine dose equivalents Conversion ratio of oral morphine to oral
methadone
<100 mg 3:1 (i.e. 3 mg morphine = 1 mg methadone)
101-300 mg 5:1
301-600 mg 10:1
601-800 mg 12:1
801-1000 mg 15:1
>1001 mg 20:1
Due to incomplete cross-tolerance, it is recommended that the initial dose is 50-75% of the
equianalgesic dose.
Key Points
• Compared to morphine, methadone is inexpensive, safe in renal failure, will provide a
longer duration of action, and has a theoretic advantage in neuropathic pain, although the
latter point has not been reliably demonstrated.
• Because of its long and variable elimination half-life methadone is not an ideal opioid
when rapid dose adjustments are needed; do not increase oral methadone more
frequently than every 4 days.
• Dose conversion to:from other opioids and methadone is complex and particularly more
dangerous than other opioids; consultation with pain or palliative specialists familiar with
methadone use is recommended.
• Patient and family education is essential as they may misinterpret prescription of

methadone to mean that their physician believes that they are an addict.
References
• Ayonrinde OT, Bridge DT. The rediscovery of methadone for cancer pain management.
Med J Austral. 2000; 173:536-40.
• Bruera E, Sweeney C. Methadone use in cancer patients with pain: a review. J Pall Med.
2002; 5(1):127-38.
• Bruera E, Palmer J, Bosnjak S, et al. Methadone versus Morphine as a first-line strong

opioid for cancer pain: A randomized double-blind study. J Clin Oncol. 2004;
22:185-192.
• Davies D, DeVlaming D, Haines C. Methadone Analgesia for Children with Advanced

Cancer. Pediatr Blood Cancer 2008; 51:393-397.
• Iribarne C, Dreano Y, Bardou LG, et al. Interaction of methadone with substrates of

human hepatic cytochrome P450 3A4. Toxicology. 1997; 117:13-23.
• Krantz MJ, Lewkowiez L, Hays H, et al. Torsade de Pointes associated with very-high-
dose methadone. Ann Intern Med. 2002; 137:501-4.
!9
• McLean S, Twomey F. Methods of rotation from another strong opioid to methadone for
the management of cancer pain: A systematic review of the available evidence. Journal
of pain and symptom management. 2015; doi:10.1016/j.jpainsymman.2015.02.029.
• Morley JS, Makin MK. The use of methadone in cancer pain poorly responsive to other
opioids. Pain Rev. 1998; 5:51-8.
• Rowbotham MC. The debate over opioids and neuropathic pain. In: Kalso E, McQuay HJ,
Wiesenfeld-Hallin Z, eds. Opioid Sensitivity of Chronic Noncancer Pain. (Progress in Pain
Research and Management, Vol 14). Seattle, WA: IASP Press; 1999: pp 307-317.
• Roxane Laboraties. (2015). Dolophine (methadone hydrochloride): Highlights of

prescribing information. Retrieved from http://www.accessdata.fda.gov/drugsatfda_docs/
label/2015/006134s038lbl.pdf.
• Webster LR, Fine PG. Review and critique of opioid rotation practices and associated
risks of toxicity. Pain Medicine. 2012; 13: 562-570.
published July 2006; 3rd Edition June 2015. Current version re-copy-edited April 2009; then re-
copy-edited again by Sam Maiser MD on June 2015 -- additional references were included, the
pediatric section was added, and clarification about the role of methadone in neuropathic pain
was included.
!10
!

CONTROLLED RELEASE OXYCODONE
David E Weissman MD
Background Controlled release oxycodone (CRO) has received considerable attention in the
lay press over the past several years. Much of the coverage has been negative, related to the
illicit use of CRO due to diversion outside of legitimate medical practice. Within legitimate
medical practice, CRO is an effective long-acting oral opioid product, very similar to controlled
release morphine. This Fast Fact reviews CRO usage in palliative care.
Indication CRO is indicated for moderate to severe pain requiring continuous, around-the-clock
analgesia for an extended period of time in patients ≥ 18 years of age. The Food and Drug
Administration have not established the safety and effectiveness in pediatric patients, although it
has been used successfully in select pediatric populations.
Pharmacology Oxycodone is a semi-synthetic opioid that interacts with both mu- and kappa-
opioid receptors, but behaves in most respects identically to morphine. CRO has greater oral
bioavailability than morphine, and a bi-phasic absorption pattern, with peaks at 37 minutes and
6.2 hours. Peak pain relief occurs in one hour. Unlike morphine, oxycodone has minimally active
metabolites, demonstrating little to no analgesic or anti-analgesic properties. Oxycodone should
be used with caution in patients with renal and liver impairment and avoided in hemodialysis
patients. CRO can lead to all the traditional opioid side effects. Anecdotal reports suggest less
nausea, hallucinosis, and nausea compared to morphine, although these observations have not
been substantiated in controlled trials.
Equianalgesic Information Studies comparing round the clock immediate-release oxycodone

to controlled-release oxycodone products demonstrate equivalent results. The conversion factor
between morphine and oxycodone has been controversial, but the most commonly accepted data
suggests that 30 mg of morphine is equivalent to 20 mg of oxycodone. Since all equianalgesic
values are rough guidelines, prescribers need to use their clinical judgment in determining the
most appropriate starting dose (see Fast Fact #36).
Dosage The starting dose of CRO in an opioid naïve patient is 10 mg q12 hours; it can be dose
escalated every 24-48 hours (see Fast Fact #20). CRO must be taken intact; pills cannot be cut
or crushed without risk of rapid absorption and subsequent overdose. CRO is not approved for
rectal administration.
Cost CRO is more expensive than generic long-acting morphine; there is currently no generic
CRO product on the market.
Diversion CRO has been associated with greater diversion to the illicit drug market than
morphine. Illicit users will commonly crush the tablet and then chew, snort, or dissolve the
product in water for intravenous injection. CRO can bring $1-per-milligram or more on the illicit
market.
Summary CRO oxycodone is an effective long-acting oral opioid. Due to cost and concerns
about diversion, controlled release morphine is the drug of first choice for a long-acting oral opioid
product. There are no data that CRO offers any analgesic benefit compared to morphine. Data
for the use of CRO in the pediatric palliative population is lacking.
References
!11
Czarnecki M, Jandrisevits M, Theiler S, et al. Controlled-Release oxycodone for the
management of pediatric postoperative pain. J Pain Symptom Manage 2004; 27:379-386.
Hain R, Miser A, Devins, et al. Strong opioids in pediatric palliative medicine. Pediatr Drugs.
2005; 7:1-9.
Kral LA. Commonsense oxycodone prescribing and safety. Pain Treatment Topics. June 2007.
Available at: http://www.pain-topics.org/opioid_rx/oxycodone.php#OxyRx. Accessed August 27,
2007.
Mucci-LoRusso P, Berman BS, Silberstein PT, et al. Controlled-release oxycodone compared with
controlled-release morphine in the treatment of cancer pain: a randomized, double-blind, parallel-
group study. Eur J Pain. 1998; 2:239-249.
Principles of analgesic use in the treatment of acute pain and cancer pain. Glenview, IL: American
Pain Society 5th Ed; 2003.
Foral PA, Ineck JR, Nystrom KK. Oxycodone accumulation in a hemodialysis patient. South Med
J. 2007; 100:212-214.
Rischitelli DG, Karbowicz SH. Safety and efficacy of controlled-release oxycodone: a systemic
literature review. Pharmacotherapy. 2002; 22:898-904
SAMHSA (Substance Abuse and Mental Health Services Administration). Results from the 2005
National Survey on Drug Use and Health: National Findings. Available at: http://
www.oas.samhsa.gov/nsduh/2k5nsduh/2k5Results.pdf. Accessed August 27, 2007.
Criteria for Use of Controlled-release Oxycodone: Treatment Algorithm. Veteran Affairs Pharmacy
Benefits Management. August 2003. Available at: http://www.pbm.va.gov/Clinical%20Guidance/
Criteria%20For%20Use/Oxycodone%20CR,
%20Criteria%20for%20Use%20and%20Treatment%20Algorithm.pdf.
was edited by Drew A Rosielle and published October 2007; 3rd Edition was edited by Sam
Maiser MD in June 2015. Current version re-copy-edited June 2015; pediatric information added.
!12
!

ORAL TRANSMUCOSAL FENTANYL CITRATE
Debra Gordon RN, MS, FAAN and Mark Schroeder MD
Introduction Oral transmucosal fentanyl citrate (OTFC, ActiqÔ) is a solid formulation of

fentanyl that resembles a lozenge on a handle. It is intended for oral transmucosal
administration. Fentanyl is also available as an oravescent buccal tablet (FentoraÔ), a
sublingual tablet (AbstralTM), a buccal film (OnsolisTM), a nasal spray (LazandaTM), and a
sublingual spray (SubsysTM), – these products are all dosed differently. Do not interchange
these products on a mcg-per-mcg basis – these products are all dosed differently. Do not
interchange these products on a mcg-per-mcg basis. This Fast Fact only discusses OTFC
(ActiqÔ).
Indications OTFC is indicated for breakthrough cancer pain in patients 16 years or older
already receiving and who are tolerant (receiving at least equivalent of 60 mg oral morphine per
24 hours) to opioid therapy for underlying persistent cancer pain. Off-label pediatric use has been
described in the literature especially among cancer patients who are opioid tolerant.
Pharmacology Compared to morphine and hydromorphone fentanyl is a lipid-soluble opioid

and, when placed in saliva under normal conditions of the mouth, is 80% non-ionized making it
the only opioid suitable for transmucosal absorption. Fentanyl is ~ 100 times more potent than
morphine. However, bioavailability of OTFC depends on the fraction of the dose that is absorbed
through the oral mucosa (~25%) and the fraction that is swallowed (~75%; but swallowed dose is
only partially bioavailable). OTFC can produce a rapid onset of analgesia, even during unit
consumption (fentanyl begins to cross the blood-brain barrier in as little as 3-5 minutes), with
peak effect at 20-40 minutes after the start of administration. Total duration of activity is 2 to 3
hours. The amount of fentanyl absorbed from each single dose remains stable over multiple
administrations. This fact, combined with fentanyl's short half-life, reduces the risk of a
cumulative increase in serum level with repetitive doses.
Prescribing Information
OTFC is available in 200, 400, 600, 800, 1200, & 1600 mcg dosage strengths.
Do not substitute ACTIQ™ on a mcg per mcg basis for other oral fentanyl products including the
oravescent buccal tablet (Fentora™).
OTFC should always be started at 200 mcg dose and then individually titrated based on patient
response; there is no conversion factor for OTFC and the patient’s existing opioid requirement.
If the first 200 mcg dose is inadequate, the patient should wait for 15 minutes (30 minutes after
start of first unit) and take a second unit. If pain is relieved after the second dose of 200 mcg, the
dose to use for the next episode of breakthrough pain would be 400 mcg. The patient should be
instructed not to take more than two units per pain episode during the initial titration period.
OTFC has typical opioid dose-related side effects: somnolence, nausea, and dizziness.
OTFC (along with all other transmucosal immediate-release fentanyl products) are available in
the outpatient setting only through a Risk Evaluation and Mitigation Strategy (REMS) program.
Enrollment in the program is mandatory for outpatients, prescribers, pharmacies, and distributors.
Patient Information Consumption Technique and Storage Place unit next to buccal
mucosa, between cheek and gum, moving the unit gently side to side. 15 minutes is the ideal
amount of time to consume a unit to achieve the desired onset and peak effect. OTFC units are
designed for one time administration. Patients should be instructed to remove the unit from their
mouth if excessive opioid-related side effects develop. The following factors will decrease
transmucosal absorption:
• Reduced saliva.
!13
• Use of liquids that reduce oral pH prior to OTFC administration (coffee, cola, fruit juices).
• Placement of OTFC on tongue or gums (lowered absorption at these sites).
• Chewing OTFC.
Instruct patients to utilize the manufacturer’s safety containers to store the dosage units, and
discard any unused portion of the OTFC by dissolving it under hot tap water. Partially used units
should not be stored and re-used. The drug should be stored at room temperature, and not be
frozen. The Average Wholesale Price is $564 for thirty 200 mcg lozenges.
This Fast Fact was adapted with permission from the University of Wisconsin Hospital & Clinics,
Madison, WI Pain Patient Care Team ‘Pain Management Fast Facts – 5 Minute Inservice’ series.
References
Fine PG, Streisand JB. A review of oral transmucosal fentanyl citrate: potent, rapid and
noninvasive opioid analgesia. J Palliat Med. 1998; 1:55-63.
Portenoy RK, Payne R, Coluzzi P, et al. Oral transmucosal fentanyl citrate (OTFC) for the
treatment of breakthrough pain in cancer patients: a controlled dose titration study. Pain. 1999;
79: 303-312.
Physicians Desk Reference 2003. Montvale, NJ: Thomson Healthcare; 2003.
Lam JKW, Xu Y, et al. Oral transmucosal drug delivery for pediatric use. Advanced drug delivery
reviews 2014;73: 50-62.
in December 2003. 2nd Edition was edited by Drew A Rosielle in April 2009; 3rd Edition by Sean
Marks in June 2015.
!14
!

TOPICAL OPIOIDS FOR PAIN
Juliet Jacobsen MD, DPH
Background Clinical experience and preliminary research have suggested that topical opioids
can be effective local analgesics. This Fast Fact reviews the mechanism of action, research data,
and dosing information on topically applied opioids.
Mechanism of action The insight that opioids exert a local analgesic effect is based on
several observations: 1) opioid receptors have been found on peripheral nerves and inflamed
tissue, 2) morphine and its metabolites are largely undetectable systemically when applied
topically to skin ulcers (suggesting the analgesic effect is local), and 3) peripheral opioid
injections for local analgesia, such as intra-articular morphine after knee surgery, have been
found to be effective in several trials. Of note, animal studies suggest that opioids can accelerate
wound healing by up-regulating nitric-oxide synthase. The relevance of this for humans is
unknown and there is no consensus regarding whether or not topical opioids benefit or impede
wound healing in humans.
Research data Several small case series have shown rapid relief using topical opioids in
patients with pain due to skin infiltration of tumor, skin ulcers of malignant and non-malignant
origin, severe oral mucositis, knee arthritis, and tenesmoid pain. Most studies have evaluated
morphine, although diamorphine and methadone have also shown efficacy.
Skin ulcers: Three randomized, double-blinded, placebo-controlled studies totaling 34 patients
assessed the efficacy of topical opioids for treating painful ulcers (mostly sacral pressure ulcers).
These studies found significantly lower pain scores in patients treated with topical opioids
compared with placebo. In general, pain decreased 2-3 points on a 0-10 pain scale. Another
blinded, controlled trial of 18 patients showed topical morphine to be no more effective than
placebo. This study’s outcome however was complete pain relief, not just significant analgesic
response as in the other studies. Itching and burning are common side effects reported by both
patients receiving morphine and placebo vehicle-gel. No systemic side effects were reported.
Mucositis: A dose-response relationship has been reported for patients with painful oral
mucositis; rinses with 0.2% morphine solution showed better pain relief than those with 0.1%.
One non-blinded, randomized study of 26 patients that compared morphine mouthwash (an oral
rinse of 0.2% morphine solution) with “magic” mouthwash (a mixture of equal parts lidocaine,
diphenhydramine, and magnesium aluminum hydroxide) found significantly decreased duration
and intensity of pain in the morphine mouthwash group.
Administration Topical opioid gels and mouthwashes are not available commercially and need
to be prepared by a compounding pharmacist.
Gel: Most studies used a mixture of 10 mg of morphine sulfate injection (10 mg/ml) in 8 gm of
Intrasite gel. Patients are instructed to cover their wound with the gel (usually using 5-10 ml) and
then loosely dress it with gauze. Duration of analgesia varies widely; preparations usually need
to be applied one to three times per day. Both morphine sulfate and diamorphine hydrochloride
mixed with Intrasite gel have been found to be stable irrespective of temperature and light
exposure for up to 28 days.
Mouthwash: The morphine mouthwash which has been studied is an oral rinse of 15 ml of 0.2%
morphine solution (2000 mg morphine clorhydrate diluted in 1000 ml of water). It can be taken
every 3 hours as needed. Patients should be instructed to hold the mouthwash in their mouth for
2 minutes then spit out. They should be counseled carefully to not swallow the mouthwash to
avoid systemic effects from the morphine. Because of this it is most useful for patients with
predominantly oral (not esophageal) pain.
!15
Conclusion There are limited trial data to support the use of topical morphine gel and
mouthwash for painful cutaneous ulcers and oral mucositis. In patients taking systemic opioids
the added benefit of topical ones (e.g. limited systemic side effects) is diminished.
References
Carnel SB, Blakesless DB, Oswald SG, Barnes M. Treatment of radiation and chemotherapy-
induced stomatitis. Otolaryngol Head Neck Surg. 1990; 102:326-30.
Cerchietti LC, Navigante AH, Bonomi MR et al. Effect of topical morphine for mucositis-
associated pain following concomitant chemoradiotherapy for head and neck carcinoma. Cancer.
2002; 95:2230-2236. Note: Erratum published in Cancer 2003; 97(4):1137. DOI: 10.1002/cncr.
11257.
Flock P. Pilot study to determine the effectiveness of diamorphine gel to control pressure ulcer
pain. J Pain Symptom Manage. 2003; 25:547-554.
Gallagher RE, Arndt DR, Hunt K. Analgesic effects of topical methadone; a report of four cases.
Clin J Pain. 2005;21:190-192.
Kalso E, Tramer MR, Carroll D et al. Pain relief from intra-articular morphine after knee surgery: a
qualitative systematic review. Pain. 1997; 71:127-34.
Krajnik M, Zylicz Z, Finlay I et al. Potential uses of topical opioids in palliative care – report of 6
cases. Pain. 1999; 80:121-125.
Picard PR, Tramer MR, McQuay HJ et al. Analgesic efficacy of peripheral opioids (all except intra-
articular): a qualitative systematic review of randomized controlled trials. Pain. 1997; 72:309-318.
Poonawala T, Levay-young BK, Hebbel RP, Gupta K. Opioids heal ischemic wounds in the rat.
Wound Repair Regen. 2005; 13:165-74.
Porzio G, Marchetti P. Topical morphine in the treatment of painful ulcers. J Pain Symptom
Manage. 2005; 30:304-305.
Twillman RK, Long TD, Cathers TA. Treatment of painful skin ulcers with topical opioids. J Pain
Symptom Manage. 1999; 17:288-292.
Vernassiere C, Cornet C, Trechot P et al. Study to determine the efficacy of topical morphine on
painful chronic skin ulcers. J Wound Care. 2005; 14:289-93.
Zeppetella G, Paul J, Ribeiro MDC. Analgesic efficacy of morphine applied topically to painful
ulcers. J Pain Symptom Manage. 2003; 25:555-558.
Zeppetella G, Joel SP, Ribeiro MD. Stability of morphine sulphate and diamorphine hydrochloride
in intrasite gel. Palliat Med. 2005; 19:131-6.
Zeppetella G, Ribeiro MDC. Morphine in Intrasite gel applied topically to painful ulcers. J Pain
Symptom Manage. 2005; 29:118-119.
Version History: Originally published August 2007. Version re-copy-edited in May 2009.
Correction of morphine mouthwash solution strength in May 2010, per Reference 2 Erratum;
version copy-edited again July 2015.
!16
independent clinical judgment and consult other relevant and up-to-date experts and resources.
Some Fast Facts cite the use of a product in a dosage, for an indication, or in a manner other
than that recommended in the product labeling. Accordingly, the official prescribing information
should be consulted before any such product is used.
!17
!

LOW-DOSE BUPRENORPHINE PATCH FOR PAIN
Julie W Childers MD and Robert Arnold MD
Background Buprenorphine is an opioid agonist/antagonist that is used sublingually for opioid

addiction treatment (see Fast Fact #221). In 2010, the Food and Drug Administration approved a
buprenorphine transdermal system (the ‘Butrans®’ patch) for use in the United States. This Fast
Fact reviews the use of buprenorphine for pain, with an emphasis on the new low-dose
transdermal patch.
Pharmacology Buprenorphine is a partial agonist at the mu-opioid receptor and an antagonist

at the kappa- and delta-opioid receptors. It provides analgesia with decreased incidence of
sedation, euphoria and respiratory depression compared to other opioids (1). A ceiling effect for
pain relief, previously identified in animals and humans, has not been found at the lower doses
used for analgesia. In doses available transdermally (up to 70 mcg/hour), buprenorphine does
not antagonize the effect of other opioids used for breakthrough pain (2).
Equianalgesic Ratios Buprenorphine is effective parenterally for post-operative pain; 0.3 mg

is equianalgesic to 10 mg IV morphine. A trial of sublingual buprenorphine for pain (an off-label
use in the U.S.) found that 0.4 mg is as effective for acute pain as 5 mg IV morphine (3). The
transdermal buprenorphine to oral morphine equianalgesic ratio has been reported to be between
1:70 to 1:115 (e.g., 100 mg of oral morphine/24 hours ≈ 0.87-1.42 mg transdermal buprenorphine/
24hr ≈ 36-59 mcg/hr transdermal buprenorphine). The transdermal buprenorphine:fentanyl ratio
is reported to be 0.8 mcg buprenorphine to 0.6 mcg fentanyl (4) (e.g., 20 mcg/hour of transdermal
buprenorphine is approximately equivalent to 15 mcg/hour of transdermal fentanyl).
Using the Low-Dose Buprenorphine Patch The U.S. formulation of the buprenorphine
transdermal system is recommended for opioid tolerant patients requiring up to 80 mg/day of oral
morphine equivalents. The patch is available in strengths of 5, 10, and 20 mcg/hour, and is worn
for seven days at a time. The 20 mcg/hour patch is not intended for initial use, but patients
accustomed to the patch may be titrated to this dose. The safety and efficacy of transdermal
buprenorphine has not been fully established in children. In children >13 years of age, the dosing
is felt to be equivalent to adults. Buprenorphine reaches a steady state level 48 hours after
application of the first patch, and, with a terminal half-life of 26 hours, levels decline slowly after
patch removal. Withdrawal symptoms tend to be milder than with other long-acting opioids (5).
Use of more than one patch at a time is not recommended due to risk of QT prolongation, with a
mean QTc prolongation of 9.2 ms at a dose of 40 mcg/hour (6). Note: in Europe doses between
70-210 mcg/hour have been used for cancer pain with a different patch system (7).
Initiating the Low-Dose Buprenorphine Patch (Manufacturer’s Recommendations) (6)

Baseline Daily Oral Morphine Equivalent Starting Patch Dose
<30 mg 5 mcg/hour
30-80 mg 10 mcg/hour
>80 mg/day Usage not recommended
Clinical Applications The buprenorphine patch has shown to be non-inferior to other opioids in
studies of chronic lower back pain, osteoarthritis, and cancer pain (8). Because of its kappa
antagonism, it has theoretical advantages in the treatment of neuropathic pain, though evidence
for this is limited to case reports (9, 10). It has also been shown experimentally to have
antihyperalgesic effects (11). Other advantages of buprenorphine include a decreased risk of
respiratory depression and a lack of accumulation in renal failure, including in hemodialysis
patients (12). Some studies have reported less constipation, nausea, and sedation with
!18
buprenorphine (13,14). In a trial comparing transdermal buprenorphine in patients over 65 with
younger patients, older patients had equivalent analgesia without any differences in accumulation
of buprenorphine or its metabolites (15).
Cost The average wholesale price (in 2015) for a month’s supply of four 10 mcg patches is
$336.
Summary The low-dose transdermal buprenorphine patch is effective for mild to moderate
chronic pain, both malignant and nonmalignant. However, given the dose limitations of the
buprenorphine patch as marketed in the U.S., as well as the cost, the usefulness of this
medication for most patients and clinicians is very limited. The low-dose buprenorphine patch
may be a reasonable second- or third-line option in patients with low opioid requirements who
experience intolerable side effects with other opioids.
References
1. Johnson RE, Fudula PJ, Payne R. Buprenorphine: considerations for pain management.
2. Mercadante S, Villari P, Ferrera P, et al. Safety and effectiveness of intravenous morphine

for episodic breakthrough pain in patients receiving transdermal buprenorphine. J Pain
Symptom Manage. 2006;32:175-9.
3. Jalili M, Fathi M, Moradi-Lakeh M, Zehtabchi S. Sublingual Buprenorphine in Acute Pain

Management: A Double-Blind Randomized Clinical Trial. Ann Emerg Med. 2012;
59:276-80. PMID 22115823.
4. Mercadante S, Casuccio A, Tirelli W, Giarratano A. Equipotent doses to switch from high

doses of opioids to transdermal buprenorphine. Support Care Cancer. 2009; 17: 715-8.
5. Jasinski DR, Pevnick JS, Griffith JD. Human pharmacology and abuse potential of the
analgesic buprenorphine: a potential agent for treating narcotic addiction. Arch Gen
Psychiatry. 1978;35: 501-16.
6. Purdue Pharma. Available at: http://www.purduepharma.com/pi/prescription/

ButransPI.pdf. Accessed February 23, 2012.
7. Mercadante S, Ferrera P, Villari P. Is there a ceiling effect of transdermal buprenorphine?

Preliminary data in cancer patients. Support Care Cancer. 2007;15: 441-4.
8. Pergolizzi JV Jr, Mercadante S, Echaburu AV, et al. The role of transdermal

buprenorphine in the treatment of cancer pain: an expert panel consensus. Curr Med
Res Opin. 2009; 25:1517-28.
9. Rodriguez-Lopez M. Transdermal buprenorphine in the management of neuropathic pain.

Rev Soc Esp Dolor. 2004;11(Suppl V):11-21.
10. Penza P, Campanella A, Martini A, et al. Short- and intermediate-term efficacy of

buprenorphine TDS in chronic painful neuropathies. J Peripher Nerv Syst. 2008;13:
283-288.
11. Koppert W, Ihmsen H, Körber N, et al. Different profiles of buprenorphine-induced

hyperalgesia and antihyperalgesia in a human pain model. Pain. 2005;118: 15-22.
12. Pergolizzi J, Aloisi AM, Dahan A, et al. Current knowledge of buprenorphine and its
unique pharmacological profile. Pain Pract. 2010;10: 428-50.
!19
13. Likar R, Vadlau EM, Breschan C, Kager I, Korak-Leiter M, Ziervogel G. Comparable
analgesic efficacy of transdermal buprenorphine in patients over and under 65 years of
age. Clin J Pain. 2008;24:536-43.
14. Bach V, Kamp-Jensen M, Jensen NH, et al. Buprenorphine and sustained release
morphine – effect and side-effects in chronic use. The Pain Clinic. 1991;4:87–93.
15. R. Likar, H. Kayser and R. Sittl. Long-term management of chronic pain with transdermal
buprenorphine: a multicenter, open-label, follow-up study in patients from three short-
term clinical trials. Clin Ther. 2006; 28: 943–52.
Conflicts of Interest Statement: The authors have no relevant conflicts of interest to disclose.
Authors’ Affiliation: University of Pittsburgh Medical Center, Pittsburgh, PA.
Version History: First published July 2013. Re-copy-edited in September 2015 with pricing
information updated and pediatric information added.
!20
!

TRAMADOL IN PALLIATIVE CARE
Jennifer Pruskowski PharmD and Robert M Arnold MD
Background Tramadol is an important medication in palliative care. It is a Step II agent on the

World Health Organization’s (WHO) pain ladder (1) and has FDA approval for the treatment of
moderate to severe pain in adults. This Fast Fact will review tramadol’s pharmacology, its
benefits, and limitations. Note that tramadol has similarities with tapentadol which is discussed in
Fast Fact #228.
 
Pharmacology The analgesic effects of tramadol are likely due to mu-opioid agonist activity,
and weak monoamine reuptake inhibition (specifically blocking norepinephrine and serotonin) in
the CNS. Tramadol is a prodrug and must be metabolized via CYP2D6 to its pharmacologically
active metabolite (O-desmethyl tramadol) (2). It is excreted 90% in the urine; therefore specific
dosing adjustments are necessary in renal impairment (CrCl <30 mL/min). There are also dosing
adjustments in the elderly and end-stage liver failure. Clinicians should be aware of tramadol’s
significant drug interactions with other CYP2D6 inhibitors (fluoxetine, paroxetine and amitriptyline)
and CYP3A4 inhibitors (ketoconazole and erythromycin), which increase the risk of seizures and
serotonin syndrome.  
 
Dosing Tramadol is available as both generic and proprietary formulations: a 50 mg immediate-
release (IR) tablet and 100 mg, 200 mg, and 300 mg extended-release (ER) tablet (Ultram ER®).
Immediate-release tramadol also comes formulated with acetaminophen. Tramadol should be
started at 25 mg/day in the morning and increased by 25-50 mg every 3 days. The maximum
daily dose of tramadol is 400 mg/day (50-100mg every 4-6 hours). In patients with renal
impairment (CrCl <30 mL/min), the dosing interval is 12 hours with a maximum daily dose of 200
mg/day. The maximal recommended dose for adult patients with cirrhosis is 50 mg every 12
hours. For elderly patients over 75 years old, the total daily should not exceed 300 mg/day.
Approximately 120 mg of oral tramadol is equivalent to 30 mg of oral morphine (3). Oral
morphine tablets are roughly half the cost of tramadol IR tablets, and one-sixth the price of
tramadol ER tablets.  
 
Adverse Drug Reactions Tramadol’s adverse drug reaction profile is similar to other opioids,
although it has a lower incidence of respiratory depression (4) and likely has a lower abuse
potential. An early comparative study suggested that tramadol has less abuse potential than
morphine (5) and more recent preclinical studies suggest that abuse-related behavioral effects of
tramadol may be of lesser magnitude than other mu-opioid receptor agonists (6). However, there
have been several reports of its abuse and misuse (7). Hence, in August of 2014 tramadol was
made a Schedule IV controlled medication.
Cautions Tramadol carries four specific cautions:

Seizures have been reported with higher than recommended dosage and with concomitant use of
SSRI/SNRIs, MAOIs, triptans, and other drugs that reduce the seizure threshold (8).
Serotonin-syndrome may occur only with the concomitant use of other serotonergic drugs and is
characterized as a triad of clinical changes: cognitive (mental-status chances, agitation and
hallucinations), neuromuscular (hyperreflexia, incoordination) and autonomic (tachycardia, labile
blood pressure). Although the prevalence of serotonin-syndrome is unknown, the majority of
cases present within 24 hours (and most within 6 hours), of a change in dose or initiation of a
serotonergic medication (9).
A large population cohort study from the UK comparing tramadol with codeine found a
significantly increased risk of hospitalization from hypoglycemia, especially in the first 30 days of
initiation and non-diabetic patients (10).
Lastly in May of 2010, the FDA strengthened the warning for suicide risk for patients at high risk
(defined as those who are addiction-prone, taking tranquilizers, or antidepressant drugs)(11).
!21
Research Data Most of the literature examining tramadol’s role in palliative care involves the
management of cancer pain (12). In comparison studies, tramadol was favored over sublingual
buprenorphine due to the lower prevalence of adverse drug reactions, but morphine was
preferred in patients with more severe pain (13). It has been shown to be safe and effective
following surgical procedures, for neuropathic pain (14), as well as a variety of other pain
conditions.  
 
Summary Tramadol has an important position as a Step II agent on the WHO pain ladder,
where it is effective for a variety of syndromes in patients with mild to moderate pain intensity. Its
recommended dosing adjustments, potential ceiling effect, cost, pertinent drug-interactions, and
risk for significant adverse drug reactions may limit its chronic use in patients with significant pain.
References
1. World Health Organization (WHO). Cancer pain relief with a guide to opioid availability,
2nd ed. Geneva, Switzerland: WHO, 1996.
2. Gonçalves JA, Silva P, Araújo P. Does tramadol have a role in pain control in palliative
care? Am J Hosp Palliat Care. 2014 Jun 16. pii: 1049909114539036. [Epub ahead of
print]
3. McPherson M, and American Society of Health-System Pharmacists. (2010).

Demystifying opioid conversion calculations: A guide for effective dosing. Bethesda, MD:
American Society of Health-System Pharmacists.
4. Scott LJ, Perry CM. Tramadol: a review of its use in perioperative pain. Drugs. 2000 Jul;
60(1):139-76.
5. Preston KL, Jasinski DR, Testa M. Abuse potential and pharmacologic comparison of
tramadol and morphine. Drug Alcohol Depend 1991. 27:7-17
6. O’Connor EC, Mead AN. Tramadol acts as a weak reinforce in the rat self-administration
model, consistent with its low abuse liability in humans. Pharmacol Biochem Behav
2010; 96: 279-86.
7. Cicero TJ, et al. Rates of abuse of tramadol remain unchanged with the introduction of
new branded and generic products: results of an abuse monitoring system, 1994-2004;
Pharmacoepidemiol Drug Saf 2005; 14:851-859.
8. Tramadol [package insert]. Raritan, NJ: Ortho-McNeil Pharmaceutical, Inc; 2008.
9. Mason PJ, Morris VA, Balcezak TJ. Serotonin syndrome. Presentation of 2 cases and
review of the literature. Medicine (Baltimore). 2000 Jul;79(4):201-9.
10. Fournier J, Azoulay L, Yin H, Montastruc J, Suissa S. Tramadol Use and the Risk of
Hospitalization for Hypoglycemia in Patients With Noncancer Pain. JAMA Intern Med.
Published online December 08, 2014. doi:10.1001/jamainternmed.2014.6512.
11. US Food and Drug Administration (FDA) Safety Alerts for Human Medical Products.
Ultram (tramadol hydrochloride), Ultracet (tramadol hydrochloride/acetaminophen): Label
Change. Accessed 16 September 2014. Available at: http://www.fda.gov/Safety/
MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm213264.htm
12. Leppert W, Łuczak J. The role of tramadol in cancer pain treatment--a review. Support
Care Cancer. 2005 Jan;13(1):5-17.
!22
13. Leppert W. Tramadol as an analgesic for mild to moderate cancer pain. Pharmacol Rep.
2009 Nov-Dec;61(6):978-92.
14. Hollingshead J, Dühmke RM, Cornblath DR.Tramadol for neuropathic pain. Cochrane
Database Syst Rev. 2006 Jul 19;(3):CD003726.
Authors’ Affiliations: University of Pittsburgh Medical Center, Pittsburgh, PA.

Version History: First published May 2015.
!23
!

OPIOID PHARMACOKINETICS
Jennifer Pruskowski, PharmD, and Robert M Arnold, MD
Background Pharmacokinetics is the science of what the body does to a drug after
administration, in contrast to pharmacodynamics -- the effect of a drug on the body. Knowledge
of opioid pharmacokinetics parameters is critical for the safe and effective administration.
Absorption The proportion of active drug (whether given intravenously or absorbed from the
gastrointestinal, respiratory, or cutaneous system) that enters the systemic circulation is defined
as bioavailability. The wide bioavailability range amongst different opioids is partially attributable
to differences in first pass metabolism, when the drug is metabolized directly by the liver from the
gastrointestinal tract before it reaches the systemic circulation. Clinicians should be aware of the
bioavailability for the opioid being prescribed because it indirectly affects PO: IV conversion
ratios.
Distribution refers to the movement of drug between the blood and various tissues in the body.
The parameter used to describe this movement is the volume of distribution (Vd). The targeted
tissue for opioids is the central nervous system (CNS). To activate the targeted receptors, opioids
must cross the blood-brain-barrier (1). Those opioids with a higher Vd are usually more lipophilic,
and more likely to distribute faster and more strongly both into and out of the blood-brain-barrier.
In clinical practice these opioids also tend to have a quicker onset, and shorter duration of
analgesic action.
Metabolism The most important area of opioid pharmacokinetics is metabolism. The

metabolism process may involve the Cytochrome (CYP) P-450 enzymes, particularly CYP 2D6
and 3A4, or other enzymes such as UDP-glucuronyltransferase (2). The spectrum of interpatient
analgesic variability and clinically significant drug interactions of opioids are mostly due to the
CYP enzymes.
Interpatient Variability CYP 2D6 influences the metabolism of codeine, hydrocodone,

oxycodone, and tramadol, and has been found to have many genetic polymorphisms. Based on
phenotypic profiles, patients can be poor, intermediate, or extensive metabolizers (3). This can
potentially lead to inadequate analgesia or over-sedation. Fentanyl and methadone are primary
metabolized by CYP 3A4. Although CYP 3A4 also has many genetic polymorphisms, none have
be shown to be of major clinical relevance (4). UDP-glucuronyltransferase, the primary enzyme
responsible for the metabolism of morphine, hydromorphone, oxymorphone, and tapentadol,
does not possess significant interpatient variability.
Clinically Significant Drug Interactions There are three types of CYP P-450 enzyme
subcategories: substrates, inhibitors, and inducers. Substrates require P-450 enzymes for
metabolism. When enzyme inhibitors or inducers are concomitantly administered with substrates,
the serum levels of these substrates are altered. Enzyme inhibitors may increase opioid serum
levels leading to over-sedation; enzyme inducers may decrease opioid serum levels leading to
inadequate analgesia. Table 1 summarizes drug interactions between opioids and commonly
prescribed medications (5).
Enzym Substrates Inhibitors Inducers

e
!24
Carbamazepine,
Amiodarone, ciprofloxacin, clarithromycin,
Codeine, dexamethasone,
diltiazem, erythromycin, fluconazole,
fentanyl, efavirenz, modafinil,
CYP fluoxetine, fluvoxamine, itraconazole,
methadone, oxcarbazepine,
3A4 ketoconazole, nefazodone, ritonavir,
oxycodone, phenobarbital,
verapamil, voriconazole
tramadol phenytoin, rifampin, St.
John’s wort, troglitazone
Codeine, Amiodarone, bupropion, celecoxib,
hydrocodon chlorpromazine, citalopram,
e, diphenhydramine, doxepin, duloxetine,
CYP methadone, escitalopram, fluoxetine, haloperidol, None reported
2D6 morphine, hydroxyzine, metoclopramide, paroxetine,
oxycodone, quinidine, ritonavir, sertraline, terbinafine,
tramadol thioridazine
Excretion The vast majority of opioids are excreted as metabolites through the kidneys, with
the exception of methadone which is primarily excreted via bile. Patients with renal and/or liver
dysfunction may have altered drug clearance (see Fast Facts #161 and #260). Clinicians should
be aware of opioid-individual terminal elimination half-lives (T ½), as these dictate the speed of
opioid titrations. When given consistently, opioids reach steady state after four T½. Opioid
titrations should be avoided until the opioid regimen has reach steady state.
Summary Table 2 summarizes the pharmacokinetic parameters of commonly used oral opioids.
These parameters are critical for the safe and effective use of these medications, as they
commonly translate into individual pharmacodynamics properties (6-17).
Opioid
Absorption Distribution Metabolism Excretion
(Route)
Major
Vd (L/kg Metaboli
Bioavailibility Active Urine T½
unless sm
(%) Enzyme( Metabolite (%) (Hours)
noted)
s)
Codeine CYP3A4
53 3-6 Morphine 90 3
(PO) and 2D6
Fentanyl
N/A 4-6 CYP3A4 None 75 20-27
(TDS)
Hydrocodone CYP2D6
NR NR Hydromorphone 26 3.3-4.4
IR (PO) δ and 3A4
Hydro-
morphone IR 24 4 UGT Unknown 75 2-3
(PO)
CYP3A4
Methadone , 2D6,
36-100 1-8 None <10 7-59
(PO) 2B6,
2C19
Morphine IR
<40 4 UGT M6G 90 2-4
(PO)
!25
Oxycodone
CYP3A4
IR 60-87 2.6 Oxymorphone 19-64 2-4
and 2D6
(PO)
Oxymor-
phone IR 10 1.94-4.22 L UGT 6-OH 33-38 7-9
(PO)
Tramadol IR CYP3A4
75 2.6 M1 90 6.3
(PO) and 2D6
Tapentadol
540 +/- 98
IR 32 UGT None 99 4-5
L
(PO)
Key: PO: oral; TDS: transdermal system; IR: immediate-release; δ: hydrocodone IR is available
only in combination with acetaminophen; Vd: Volume of distribution; L: liters; N/A: non-applicable;
CYP: Cytochrome enzyme; UGT: UDP-glucuronosyltransferase; M6G: Morphine-6-glucuronide;
6-OH: 6-OH-Oxymorphone; M1: O-desmethyltramadol; NR: not reported
References
1. Trescot AM, Datta S, Lee M, Hansen H. Opioid pharmacology. Pain Physician. 2008 Mar;
11(2 Suppl):S133-53.
2. Smith HS. Opioid metabolism. Mayo Clin Proc. 2009 Jul;84(7):613-24.
3. Hajj A, Khabbaz L, Laplanche JL, Peoc'h K. Pharmacogenetics of opiates in clinical

practice: the visible tip of the iceberg. Pharmacogenomics. 2013 Apr;14(5):575-85.
4. Daly AK. Significance of the minor cytochrome P450 3A isoforms. Clin Pharmacokinet.
2006;45(1):13-31.
5. Overholser BR, Foster DR. Opioid pharmacokinetic drug-drug interactions. See comment
in PubMed Commons belowAm J Manag Care. 2011 Sep;17 Suppl 11:S276-87.
6. Lugo RA, Satterfield KL, Kern SE. Pharmacokinetics of methadone. J Pain Palliat Care
Pharmacother. 2005;19(4):13-24.
7. Lötsch J. Opioid metabolites. J Pain Symptom Manage. 2005 May;29(5 Suppl):S10-24.
8. Product Information: Codeine sulfate oral tablets, Codeine sulfate oral tablets. Roxane
Laboratories, Columbus, OH, 2009.
9. Grond S, Radbruch L, Lehmann KA. Clinical pharmacokinetics of transdermal opioids:

focus on transdermal fentanyl. Clin Pharmacokinet. 2000 Jan;38(1):59-89.
10. Product Information: LORTAB(R) 5/325 oral tablets, hydrocodone bitartrate

acetaminophen oral tablets. UCB, Inc. (per DailyMed), Smyrna, GA, 2013.
11. Product Information: DILAUDID(R) oral liquid, tablets, hydromorphone hydrochloride oral
liquid, tablets. Purdue Pharma L.P, Stamford, CT, 2009.
12. Smith MT. Neuroexcitatory effects of morphine and hydromorphone: evidence implicating
the 3-glucuronide metabolites. Clin Exp Pharmacol Physiol. 2000 Jul;27(7):524-8.
13. Lugo RA, Kern SE. Clinical pharmacokinetics of morphine. J Pain Palliat Care
Pharmacother. 2002;16(4):5-18.
!26
14. Lugo RA, Kern SE. Clinical pharmacokinetics of oxycodone. J Pain Palliat Care
Pharmacother. 2004;18(4):17-30.
15. Product Information: OPANA(R) oral tablets, oxymorphone hcl oral tablets. Endo
Pharmaceuticals Inc, Chadds Ford, PA, 2006.
16. Product Information: ULTRAM(R) oral tablets, tramadol hydrochloride oral tablets. Ortho-
McNeil Pharmaceutical Inc, Raritan, NJ, 2007.
17. Product Information: NUCYNTA(R) oral immediate-release tablets, tapentadol oral

immediate-release tablets. Janssen Pharmaceuticals, Inc. (per DailyMed), Titusville, NJ,
2011.
Authors Affiliations: University of Pittsburgh Medical Center, Pittsburgh, PA.

Version History: First electronically published November 2015.
!27
!
Opioid Toxicity
#25 Opioids and
Nausea . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . 2-3
#39 Using
Naloxne . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . 4-5
#57 Neuroexcitatory Effects of Opioids: Patient Assesment. . . . . . . . . . . . . . . . . . . .

. . . . . . . .6-7
#58 Neuroexcitatory Effects of Opioids:

Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .8-9
#142 Opioid-Induced
Hyperalgesia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
10-11
#161 Opioid Use in Renal Failure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . 12-13
#175 Opioid Allergic

Reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
14-15
#248 Counseling Patients on Side Effects and Driving when Starting Opioids. . . . . . . . .
. . . . 16-18
#260 Opioid Use in Liver Failure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . .19-21
#294 Opioid Induced Constipation Part I: Established Management

Strategies . . . . . . . . . . . 22-24
#295 Opioid Induced Constipation Part II: Newer Therapies . . . . . . . . . . . . . . . . . . .

. . . . . . . 25-27
!1
!

OPIOIDS AND NAUSEA
David E Weissman MD
Background Why do patients get nauseated and vomit after receiving an opioid? Commonly
described as an “allergy”, opioid-induced nausea/vomiting is not an allergic reaction. In fact,
rather than indicating a pathologic reaction, nausea indicates normal functioning of the brain.
Opioid-induced nausea occurs through the following mechanisms:
• At the base of the 4th ventricle lies the chemoreceptor trigger zone (CTZ), a “sampling
port”, to detect substances that do not belong in the blood. Adjacent to the CTZ lies the
medullary vomiting center which controls the complex muscular sequence of vomiting.
When the CTZ detects a noxious chemical in the blood, a signal is sent to the VC and the
vomiting reflex is initiated. Of note, this is the same mechanism when patients vomit after
receiving chemotherapy.
• Opioids can directly stimulate the vestibular apparatus—patients note a spinning
sensation with their nausea.
• Opioids cause constipation which can lead to nausea via stimulation of afferent
cholinergic pathways.
Do all opioids produce the same degree of nausea? There is little research data on this topic.
In clinical practice, morphine and codeine are often mentioned as the worst offenders. Some
clinical studies along with preclinical data in rats suggest that the transdermal fentanyl patch may
have less nausea and constipation than morphine.
Why are some patients more sensitive to the emetic effects of opioids than others?
Unknown
What is the natural history of opioid-induced nausea? Most patients develop tolerance to the
emetic effects, so that within 3-7 days, at a constant opioid dose, the emetic effect will abate.
What are management approaches?
!2
• Dose adjustment—if good pain relief is achieved but associated with nausea, it may be
possible to lower the opioid dose, still retain good analgesia, but eliminate the nausea.
• Switching opioids—there is variability in emetic reaction to different opioids. Note: since
tolerance to nausea develops, one never knows if a reduction in nausea is from the
change of drug or tolerance.
• Anti-emetics— Whenever possible, choose a drug directed at the most likely cause of
nausea (see Fast Fact # 5). There are little published data to guide physicians in specific
choice of anti-emetic for opioid-induced nausea.
• Start with low-cost dopamine antagonists (e.g. prochlorperazine, haloperidol, or
metoclopromide) or anti-cholinergics (e.g. scopolamine);
• Anti-histamines may be helpful for patients who note a spinning sensation.
• 5HT3 antagonists (e.g. ondansetron) can be used for more refractory cases. Two
multi-center randomized trials have examined control of emesis associated with
opioids not used for anesthesia. In one, 16 mg of ondansetron was more effective
than 8 mg or placebo. In the other trial, stopped early due to lack of patient accrual,
24 mg ondansetron was no better than placebo or metoclopramide.
• Non-pharmacological approaches: there is little evidence to support non-pharmacological
treatments for nausea outside of chemotherapy associated nausea; suggested
approaches include acupressure and behavioral treatments.
References
1. Hardman JG, Limbird LE, et al, eds. Goodman and Gillman’s The Pharmacological Basis
of Therapeutics. 9th Ed. New York, NY: McGraw-Hill; 1996.
2. Herndon CM, et al. Management of opioid-induced gastrointestinal effects in patients
receiving palliative care. Pharmacotherapy. 2002; 22:240-250.
4. Hardy J, et al. A double-blind, randomised, parallel group, multinational, multicentre study
comparing a single dose of ondansetron 24 mg p.o. with placebo and metoclopramide 10
mg t.d.s. p.o. in the treatment of opioid-induced nausea and emesis in cancer patients.
Support Care Cancer. 2002; 10:231-236.
5. Pan CX, et al. Complementary and aternative medicine in the management of pain,
dyspnea nd nausea and vomiting near the end-of-life: a systematic review. J Pain Sym
Manage. 2000; 20:374-387.
6. Megens AHP, Artois K, et al. Comparison of the analgesic and intestinal effects of
fentanyl and morphine in rats. Journal of Pain and Symptom Management 1998; 15:
253-7.
7. Ahmedzai S, Allan E, et al. The TTS-fentanyl multicenter study group: transdermal
fentanyl in cancer pain J Drug Dev 1994;6: 93-7.
!3
!4
!

USING NALOXNE
Colleen J Dunwoody MS, RN and Robert Arnold MD
Background Naloxone (Narcan®), a semisynthetic opioid antagonist, is indicated for the
complete or partial reversal of life-threatening CNS/respiratory depression induced by opioids.
Naloxone is often inappropriately used in the hospital setting, administered as a full ampule (0.4
mg) in response to physiologically normal opioid-induced decrease in respiratory rate or mild
sedation. This probably comes from application of principles of use in the Emergency Department
to other settings. Of note, it is normal to have a lower respiratory rate during sleep, especially on
opioids. Mild bradypnea, which is not associated with physiologic consequences like hypoxemia,
should be closely monitored.
Depending on the dose administered, naloxone administration to a patient physically dependent
on opioids will cause the abrupt return of pain and can precipitate an abstinence (withdrawal)
syndrome, with symptoms ranging from mild anxiety, irritability and muscle aches to life-
threatening tachycardia and hypertension. Once thought to be devoid of side effects, naloxone
can cause cardiovascular collapse and pulmonary edema, probably through abrupt increase in
sympathetic nervous system activity associated with opioid reversal.
Key Teaching Points
1. Review treatment goals; naloxone administration is not indicated for patients on opioids
who are dying (see Fast Fact #3), as all dying patients will at some point have an altered
mentation and respiratory changes. It may be necessary to write specific orders not to
administer naloxone.
2. Patients should meet all of the following criteria before naloxone is administered:
a) Depressed mental status: difficult to arouse or unarousable (if the patient wakes
to voice or light shake, the diagnosis is sleeping, not opioid overdose).
b) Shallow respirations or rate less than 8/minute, associated with evidence of
inadequate ventilation (e.g. low oxygen saturation, hypotension). Note:
some people breathe at 6-8 per minute when they sleep yet are well
ventilated.
3. Stop opioid administration.
4. Dilute 0.4 mg naloxone (one ampule) with normal saline to a total volume of 10 ml (1 ml =
0.04 mg naloxone).
5. Remind the patient to breathe; though narcotized, patients report hearing concerned staff
and being unable to open their eyes or respond. Reminders to “take a deep breath” are
often followed.
6. Administer 1 ml IV (0.04 mg) q1min until the patient is responsive. A typical response is
noted after 2-4 ml with deeper breathing and greater level of arousal. Gradual naloxone
administration should prevent acute opioid withdrawal.
7. If the patient does not respond to a total of 0.8 mg naloxone (2 amps), consider other
causes of sedation and respiratory depression (e.g. benzodiazepines, stroke).
8. The duration of action of naloxone is considerably shorter than the duration of action of
most short-acting opioids. A repeat dose of naloxone, or even a continuous naloxone
infusion, may be needed.
9. Wait until there is sustained improvement in consciousness before restarting opioids at a
lower dose.
!5
Final notes: After the patient is stable, review events leading up to the patient requiring
naloxone and address oversights and errors which lead to this complication of opioid therapy.
Review your institution’s policy on naloxone administration. Is it appropriate? If not, write one;
see (2) for a recommended nursing protocol.
References
1. Burke DF, Dunwoody CJ. Naloxone: A Word of Caution. Orthopaedic Nursing. 1990;
9:44-46.
2. McCaffery M, Pasero C, eds. Pain: Clinical Manual. 2nd edition. St. Louis MO: Mosby,
1999: p270.
3. O’Malley-Dafner L, Davies P. Naloxone-Induced Pulmonary Edema. AJN. 2000; 100(11):
24AA-JJ.
published August 2005; 3rd Edition May 2015. Current version re-copy-edited March 2009; then
again May 2015.
!6
!

NEUROEXCITATORY EFFECTS OF OPIOIDS: PATIENT ASSESSMENT
Robin K Wilson PhD and David E Weissman MD
Background Everyone recognizes the common opioid side effects: constipation, nausea,
pruritis, and urinary retention. Less well appreciated are the neuroexcitatory effects, commonly
seen among patients on chronic opioids. Among these, myoclonus is typically the herald
symptom. This Fast Fact will discuss risk factors and patient assessment of the neuroexcitatory
opioid side effects, particularly myoclonus; Fast Fact #58 will discuss treatment options.
Physiology and Risk Factors Myoclonus can occur in patients on chronic therapy with most
opioids including morphine, hydromorphone, fentanyl, meperidine, and sufentanil. Higher doses
more frequently result in myoclonus, but the dose relationship is variable. Myoclonus can occur
with all routes of administration. Current research implicates the 3-glucuronide opioid metabolites
as one likely cause of neuroexcitatory side effects with some suggestion that symptoms may not
develop until a neurotoxic threshold is surpassed, although current understanding is limited. Co-
morbid factors including renal failure, electrolyte disturbances, and dehydration can also
contribute to myoclonus development.
Clinical Scenarios Myoclonus – the uncontrollable twitching and jerking of muscles or muscle
groups – usually occurs in the extremities, starting with only an occasional random jerking
movement. A patient's spouse may be the first to recognize this symptom. With continued
administration, the jerking may increase in frequency; at the extreme, there is constant jerking of
random muscle groups in all extremities. As myoclonus worsens, patients may develop other
neuroexcitatory signs: hyperalgesia (increased sensitivity to noxious stimuli), delirium with
hallucinations, and eventually grand mal seizures. Well meaning clinicians may misinterpret the
hyperalgesia as increasing pain, leading to a vicious cycle of increasing dose, increasing
hyperalgesia, increasing dose, worsening delirium, and finally seizures. After identifying a patient
with possible opioid toxicity, the clinician should complete a physical examination and chart
review.
Physical Examination
• Assess frequency of myoclonic jerks. Stand at the bedside and observe a patient for
30-60 seconds. Watch for and count the number of uncontrolled jerking movements.
• Determine if there is evidence of a new or worsening delirium. Complete a bedside mini-
mental assessment.
• Assess hydration status.
• Estimate prognosis: hours, days, weeks, months or years? A longer prognosis demands
a more definitive change in treatment.
Chart review
• Review the recent opioid analgesic history. What is the current drug and dose? How has
the dose changed over the past few days and weeks?
• Review the medication list for potentially exacerbating drugs. (e.g. haloperidol,
phenothiazines)
• Review recent laboratory studies if available. Check renal and liver function, and for low
magnesium, glucose or sodium.
References:
!7
1. Cherny N, Ripamonti C, Pereira J, et al. Strategies to manage the adverse effects of
oral morphine: an evidence based report. J Clin Oncol. 2001; 19:2542-2554.
3. Smith M. Neuroexcitatory effects of morphine and hydromorphone: evidence implicating
the 3-glucuronide metabolites. Clinical and Experimental Pharmacology and Physiology.
2000; 27:524-528.
4. Paramanandam G, Prommer E, Schwenke DC. Adverse Effects in Hospice Patients with
Chronic Kidney Disease Receiving Hydromorphone Journal of Palliative Medicine.
September 2011, 14(9): 1029-1033.
5. Wright A, Mather L, Smith M. Hydromorphone-3-glucuronide, a more potent neuro-
excitant than its structural analogue morphine-3-glucuronide. Life Sciences. 2001;
69:409-420.
May 2015.
!8
!

NEUROEXCITATORY EFFECTS OF OPIOIDS: TREATMENT
Robin K Wilson PhD and David E Weissman MD
Background Fast Fact #57 reviewed the pharmacology and patient assessment aspects of
opioid induced neurotoxicity, notably myoclonus. This Fast Fact discusses treatment.
General Approach Decisions about the most appropriate treatment approach need to take into
account features of the physical examination (the frequency and intensity of symptoms, hydration
status, and estimated prognosis) and information from the medical record (temporal pattern of
opioid use and dose escalation, other medications, the presence of electrolyte abnormalities and
major organ dysfunction). Whenever medically appropriate, easily treatable causes or
exacerbating factors should be corrected (e.g. correct hypomagnesemia).
Treatment Strategies The range of options for management of pain and direct opioid
neurotoxic effects divides into strategies to treat the myoclonus and strategies to reduce the
offending opioid.
1. Observation. Mild myoclonus may trouble family members more than the patient. If the
patient is satisfied with current therapy, explaining the cause/progression of symptoms
may be all that is necessary.
2. Opioid dose reduction. Seeing that some observational studies suggest that
neuroexcitatory symptoms from opioid may not develop until a certain neuroexcitatory
threshold of 3-glucoronide metabolites is surpassed, myoclonus may resolve over a few
days with a decrease in opioid dose. However, make sure you are not reducing the
opioid dose solely to control myoclonus at the expense of good pain control.
3. Rotate to a dissimilar opioid. Rotating to a lower dosage of a structurally dissimilar
opioid will often reduce myoclonus and other neuroexcitatory effects within 24 hours,
while achieving comparable pain control (Fast Fact #175 discusses opioid structural
classes.) Rotation is especially important in patients with opioid-induced hyperalgesia.
As a general rule, decrease the morphine equianalgesic dose by at least 50% when
switching to a new medication (see Fast Fact # 36). For patients on very high doses,
rotate to a new opioid at 20-25% of the morphine equianalgesic dose. Historically,
methadone and fentanyl have been considered to be better opioids to rotate to as they
have no active metabolites (which are implicated in the neuroexcitatory effects of other
opioids). This observation is empiric, and has not been evaluated in clinical trials;
clinicians should be cautious of using methadone without familiarity with its pharmacology
(see Fast Facts #75, 86).
4. Adjuvant and other analgesic therapy. Adjuvant analgesics (e.g. anticonvulsants,
antidepressants, corticosteroids) or non-drug therapies (e.g. acupuncture, TENS, heat,
cold) may allow for opioid reduction, with preservation of analgesia.
5. Benzodiazepines and other drugs to reduce myoclonus. The addition of a
benzodiazepine can reduce myoclonus without alteration of the opioid dose, although
increasing sedation may be an unwanted side effect. Start with clonazepam 0.5-1 mg at
night or 0.5 mg 2-3 times a day. Alternative agents include lorazepam orally or
sublingually, starting at 1-2 mg q8 hours. A continuous infusion of midazolam is an
expensive but effective option. Alternatives to benzodiazepines include baclofen,
gabapentin, and nifedipine. Start baclofen at 5 mg 3 times a day and increase as
needed/tolerated to 20 mg 3 times a day. Start gabapentin at 100 mg 3 times a day and
increase as needed to 900-3600 mg total a day. Nifedipine (10 mg 3 times a day) can
also be used.
References
!9
1. Abrahm J. Advances in pain management for older adult patients. Clinics in Geriatric
Medicine. 2000; 16:269-311.
2. Cherny N, Ripamonti C, Pereira J, et al. Strategies to manage the adverse effects of
oral morphine: an evidence based report. J Clin Oncol. 2001; 19:2542-2554.
3. Ferris D. Controlling myoclonus after high-dosage morphine infusions. American Journal
of Health-System Pharmacy. 1999; 56:1009-1010.
4. Hagen N, Swanson R. Strychinine-like multifocal myoclonus and seizures in extremely
high-dose opioid administration: treatment strategies. J Pain Symptom Manage. 1997;
14:51-57.
6. Paramanandam G, Prommer E, Schwenke DC. Adverse Effects in Hospice Patients with
Chronic Kidney Disease Receiving Hydromorphone Journal of Palliative Medicine.
September 2011, 14(9): 1029-1033.
7. Mercadante S. Gabapentin for opioid-related myoclonus in cancer patients. Support
Care Cancer. 2001; 9:205-206.
8. Watanabe S. Methadone: the renaissance. J Pall Care. 2001; 17:117-120.
published July 2006; 3rd Edition May 2015. Current version re-copy-edited April 2009; discussion
of fentanyl and methadone added; edited again May 2015.
!10
!

OPIOID-INDUCED HYPERALGESIA
Winifred G Teuteberg MD
Background Opioid-induced hyperalgesia is a clinical phenomenon, characterized by

increasing in pain in patients who are receiving increasing doses of opioids. This Fast Fact
reviews the clinical findings and treatment options. See also Fast Fact #215 on opioid poorly-
responsive pain.
Clinical features of opioid hyperalgesia:

• History
o Increasing sensitivity to pain stimuli (hyperalgesia).
o Worsening pain despite increasing doses of opioids.
o Pain that becomes more diffuse, extending beyond the distribution of pre-existing
pain.
o Can occur at any dose of opioid, but more commonly with high parenteral doses
of morphine or hydromorphone and/or in the setting of renal failure.
• Physical Examination
o Pain elicited from ordinarily non-painful stimuli, such as stroking skin with cotton
(allodynia)
o Presence of other opioid hyperexcitability effects: myoclonus, delirium or seizures
(see Fast Facts #57,58).
Proposed mechanisms:
• Toxic effect of opioid metabolites (e.g. morphine-3-glucuronide or hydromorphone-3-
glucronide).
• Central sensitization as a result of opioid-related activation of N-methyl-D-asparate
(NMDA) receptors in the central nervous system.
• Increase in spinal dynorphin activity.
• Enhanced descending facilitation from the rostral ventromedial medulla.
• Activation of intracellular protein kinase C.
Therapies:
• Reduce or discontinue the current opioid.
• Change opioid to one with less risk of neurotoxic effects: fentanyl or methadone (see
Fast Fact #75).
• Add an infusion of a non-opioid NMDA receptor antagonist such as ketamine (see Fast
Fact #132).
• Add a non-opioid adjuvant such as gabapentin, baclofen, acetaminophen or an NSAID.
• Initiate epidural, intrathecal, regional or local anesthesia and taper/discontinue systemic
opioids.
• Increase hydration if clinically appropriate.
Conclusion Opioids can lead to a paradoxical increase in pain. Opioid-induced hyperalgesia

should be considered in any patient with increasing pain that is not responding to increasing
opioids. Referral to pain/palliative care professionals is appropriate to help develop a
management strategy.
References
1. Mao J. Opioid-induced abnormal pain sensitivity: implications in clinical opioid therapy.
Pain. 2000; 100:213-217.
2. Portenoy RK, Forbes K, Lussier D, Hanks G. Difficult pain problems: an integrated
approach. In: Doyle D, Hanks G, Cherny N, Calman K, eds. Oxford Textbook of
Palliative Medicine. 3rd ed. New York, NY: Oxford University Press; 2004: p439.
3. Laird D, Lovel T. Paradoxical pain (letter). Lancet. 1993; 341:241.
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4. Walker SM, Cousins MJ. Reduction in hyperalgesia and intrathecal morphine
requirements by low-dose ketamine infusion (letter). J Pain Symptom Manage. 1997;
14:129-133.
5. Carroll IR, et al. Management of perioperative pain in patients chronically consuming
opioids. Reg Anesth Pain Med. 2004; 29:576-591.
in September 2005. Version re-copy-edited in April 2009; then again in July 2015.
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!

OPIOID USE IN RENAL FAILURE
Robert Arnold MD, Peg Verrico RPh, Sara N Davison MD
Background Chronic pain is common in chronic kidney disease impacting 50% of
hemodialysis patients, 82% of whom experience moderate to severe pain. The absorption,
metabolism, and renal clearance of opioids are complex in renal failure. However, with the
appropriate selection and titration of opioids, patients with renal failure can achieve analgesia with
minimal risk of adverse effects. This Fast Fact reviews recommendations for opioid use in the
setting of renal failure and in patients receiving chronic dialysis.
Not Recommended for Use:
• Meperidine is not recommended in renal failure due to accumulation of
normeperidine, which may cause seizures.
• Codeine has been reported to cause profound toxicity which can be delayed
and may occur after trivial doses. We recommend that codeine be avoided in
patients with a Glomerular Filtration Rate (GFR) <30 mL/min.
• Dextropropoxyphene is associated with central nervous system (CNS) and cardiac
toxicity and is not recommended for use in patients with renal failure.
• Morphine is not recommended for chronic use in renal insufficiency (GFR <30 mL/min)
due to the rapid accumulation of active, nondialyzable metabolites that are neurotoxic. If
morphine must be used, avoid long-acting preparations and monitor closely for toxicity
Use with Caution:
• Oxycodone is metabolized in the liver with 19% excreted unchanged in the urine. There
are reports of accumulation of both the parent compound and metabolites in renal failure
resulting in CNS toxicity and sedation.
• Hydromorphone, as the parent drug, does not substantially accumulate in hemodialysis
patients. Conversely, an active metabolite, hydromorphone-3-glucuronide, quickly
accumulates between dialysis treatments but appears to be effectively removed during
hemodialysis. With careful monitoring, hydromorphone may be used safely in dialysis
patients. However, it should be used with caution in patients with a GFR < 30mL/min who
have yet to start dialysis or who have withdrawn from dialysis.
Safest in Renal Insufficiency:
• Fentanyl is considered relatively safe in renal failure as it has no active metabolites.
However, very little pharmacokinetic data exist regarding fentanyl in end stage renal
disease. While some studies have shown decreased clearance in renal failure, most
studies do not show drug accumulation. Fentanyl is not dialyzable due to high protein
binding and a high volume of distribution.
• Methadone is considered relatively safe in renal failure. It has no active metabolites and
limited plasma accumulation in renal failure due to enhanced elimination in the feces.
However, precautions regarding the use of methadone exist (See Fast Facts # 75, 86). It
does not appear to be removed by dialysis.
Opioid Dosing Given the lack of pharmacokinetic and pharmacodynamic data of
opioids in renal failure, it is difficult to advocate for specific analgesic treatment
algorithms. However, the following guide has been proposed (Broadbent 2003) for the
initial dosing of the safer opioids in renal impairment and renal failure.
• Creatinine Clearance > 50 mL/min: normal dosing.
• Creatinine Clearance of 10-50 mL/min: 75% of normal.
• Creatining Clearance < 10 mL/min: 50% of normal.
The “normal opioid dose” for any given patient is the dose that adequately relieves pain without
unacceptable adverse effects (see Fast Fact #20). Rarely, do opioids need to be adjusted when
GFR is > 50 mL/min. While opioids can be used when GFR is <50, they require closer monitoring
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and constant reassessment to ensure that accumulation of active metabolites does not result in
toxicity. This should not preclude the effective use of opioids in these patients.
References:
1. Chambers EJ, Germain M, Brown E, eds. Supportive Care for the Renal
Patient. New York, NY: Oxford University Press; 2004.
2. Davison SN. Pain in hemodialysis patients: prevalence, cause, severity, and
management. Am J Kidney Diseases. 2003; 42(6):1239-1247.
3. Murphy EJ. Acute pain management pharmacology for the patient with
concurrent renal or hepatic disease. Anaes Intensive Care. 2005; 33(3):311-22.
4. Dean M. Opioids in renal failure and dialysis patients. J Pain Symptom Manage.
2004; 28(5):497-504.
5. Broadbent A, Khor K, Heaney A. Palliation and chronic renal failure: opioid and
other palliative medications – dosage guidelines. Progress in Palliative Care.
2003; 11(4):183-90.
in August 2006. Version re-copy-edited in April 2009; then again July 2015.
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!

OPIOID ALLERGIC REACTIONS
Hunter E Woodall MD, Asriani Chiu MD, and David E Weissman MD
Background Patient reports of opioid “allergies” are common, most often due to symptoms of
nausea, vomiting, itching, hypotension, or constipation. This Fast Fact will review signs,
symptoms, and management options of opioid allergies and pseudo-allergies.
Pathophysiology Allergies can be defined as an exaggerated immune reaction to an antigen.
There are different types of allergic, or hypersensitivity, reactions (immediate, cytotoxic, immune
complex, or delayed), but the common feature is that all such reactions are mediated by the
immune system. In contrast, the vast majority of opioid side effects are not immune related.
Opioid side effects can be divided into three categories: those that have no element of an
immune reaction, those that mimic an immune reaction, and those that are immune mediated.
Side effects with no immune mechanism: these include nausea/vomiting, constipation
sedation, delirium, respiratory depression, and urinary retention.
Side effects that mimic immune reactions: common signs/symptoms include mild itching,
uticaria, brochospasm, or hypotension. Note: if all these occur soon after an opioid dose, and the
patient appears acutely ill, this may represent an anaphylactoid reaction (see below). For most
patients, these symptoms are mild and self-limited. The etiology most commonly involves direct
mast cell degranulation with histamine release, unrelated to a true immune-mediated reaction.
Such reactions to opioids are usually idiosyncratic and may or may not recur with re-challenge of
the same opioid; they are not a contraindication to continued opioid use, since an alternative
opioid may be well tolerated. Hypotension can also occur due to arterial and venous vasodilation,
thus, hypotension is more common in a volume depleted patient. Opioids can also have negative
inotropic effects and induce a vagally-mediated bradycardia leading to hypotension – again, not a
true allergic reaction.
Immune mediated reactions:
• Allergic dermatitis in response to opioids has been described. It is characterized as
erythroderma, scarlatina, eczema, or exudative vesicular eruptions; these may represent
a Type IV (delayed) hypersensitivity reaction. Patients can undergo diagnostic patch
testing for confirmation.
• Anaphylaxis/Anaphylactoid Reactions. Anaphylaxis is a systemic IgE mediated
reaction resulting in the immediate release of potent mediators; anaphylactoid reactions
are clinically the same, but not IgE mediated. Early symptoms include nasal congestion,
flushing, pruritus, angioedema; if the process worsens, patients can develop nausea,
diarrhea, urinary urgency, brochospasm, hypotension, and death. Opioids can lead to an
anaphylactoid reaction, but such events are very rare.
Management True allergic reactions appear to be rare. If you suspect an immune-mediated

skin rash you should consult a dermatologist or allergist to establish a definitive diagnosis and
determine the need for desensitization or appropriate alternatives. Anaphylactoid reactions
require emergent management with epinephrine and histamine blockers. For milder histamine-
related symptoms, common practice is to rotate to an opioid in a different pharmacologic class
(see below) along with use of anti-histamines or steroids. Anecdotal reports suggest that
methadone and fentanyl cause fewer instances of itching.
Opioid Class Drugs
Phenanthrenes morphine; codeine; hydrocodone; oxycodone; oxymorphone;

hydromorphone; levorphanol.
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Phenylpiperadines fentanyl; meperidine; sufentanil; remifentanyl
Diphenylheptanes methadone; propoxyphene
References
1. Gilbar PJ, Ridge AM. Inappropriate labeling of patients as opioid allergic. J Oncol
Pharmacy Practice. 2004; 10:177-182.
2. VanArsdel PP, Jr. Pseudoallergic drug reactions. Introduction and general review.
Immunol Allergy Clin NA. 1991; 11:635-44.
3. Erush SC. Narcotic allergy. P&T. 1996; 21:250-2, 292.
4. Fisher MM, Harle DG, Baldo BA. Anaphylactoid reactions to narcotic analgesics. Clin Rev
Allergy. 1991; 9:309-18.
5. Hermens JM. Comparison of histamine release in human skin mast cells induced by
morphine, fentanyl, and oxymorphone. Anesthesiology. 1985; 62(2):124-9.
6. Kroigaard M, Garvey LH, Menne T, Husum B. Allergic reactions in anaesthesia: are
suspected causes confirmed on subsequent testing? Br J Anesth. 2005; 95(4):468-71.
7. Tcheurekdjian H, Gundling K Continuous hydromrphone infusion for opioid intolerance. J
Allergy Clin Immunol. 2006; 118:282-4
8. Joint Council of Allergy Asthma and Immunology. Practice parameters for drug
hypersensitivity. Ann All Asthma Immunol. 1999; 83:S665-700.
in February 2007. Version copy-edited in April 2009; then again in July 2015.
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!

COUNSELING PATIENTS ON SIDE EFFECTS AND DRIVING WHEN STARTING OPIOIDS
Randall E Schisler MD, Hunter Groninger MD, and Drew A Rosielle MD
Background Opioids have side effects which can limit their acceptability to patients. This Fast
Fact gives expert opinion recommendations about patient counseling when initiating opioid
therapy. See Fast Fact #83 for a discussion of patient fear of opioids, including addiction and
tolerance.
Key Symptoms Patients should be reassured that most opioid side effects are short-lived or
otherwise manageable, and they should seek help immediately for intolerable side effects.
• Constipation
o Background for clinicians: Very common, reported by 23-84% of patients in various
studies. It does not diminish over time, even on a steady dose. Opioids delay gastric
emptying, decrease peristalsis, decrease secretions, and slow small bowel transit time.
o Key counseling points:
▪ Most patients need an ongoing bowel regimen involving stimulant laxatives (stool
softeners such as docusate or bulking agents like fiber are ineffective), which should be
used as maintenance therapy to prevent constipation, not just rescue therapy to treat it
after it has developed (1). See Fast Facts #294 and #295 for more information.
▪ Patients should aim for an unstrained bowel movement at least every other day. “If you
have not had a bowel movement in 4 days, call me for advice.”
• Nausea
o Background for clinicians: Nausea occurs in ~25% of patients given opioids (2). There
are many effective strategies to prevent and ameliorate opioid-induced nausea – see
Fast Fact #25 for more details. Make sure patients have access to your anti-emetic of
choice. There is no consensus as to whether anti-emetics should be given
prophylactically when initiating or increasing opioids.
▪ Nausea is usually transient and resolves in several days on a stable dose (3).
▪ Patients should use their prescribed anti-emetic if nausea develops, but should contact
you immediately if ineffective and/or vomiting occurs so you can prescribe alternative
agents.
• Sedation (See also the section on driving below.)
o Background for clinicians: Sedation occurs in 20-60% of patients (2), usually during
opioid initiation or around the time of dose increases. Mild-to-moderate sedation usually
resolves in a few days; if persistent, it may improve with drug therapy (4). Moderate-to-
severe sedation responds to dose reduction, but may also necessitate opioid rotation.
▪ Reassure patients that mild-to-moderate sedation usually resolves in a few days.
▪ Encourage patients to accept mild sedation (e.g. noticeable drowsiness, falling asleep
unintentionally during relaxing activities such as watching TV or reading) for a few days
as long as they are in a safe environment. Moderate (falling asleep during stimulating
activities such as eating or having a conversation) or severe sedation should prompt a
call to you immediately to discuss next steps.
Less Common Symptoms

o Pruritus is rare and does not require extensive pre-emptive counseling. “If you feel itchy
it might go away after a few days. If it’s really bothering you or not going away, call me
and we can make some changes.” See Fast Fact #37.
o Urinary retention is rare but potentially an emergency. Counsel patients to seek
medical care immediately if they lose the ability to urinate. See Fast Fact #287 for further
information.
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Driving Safety There are no large, randomized studies directly examining the risk of driving
while on opioids (6). Opioids can slow reaction time, cause drowsiness, or cloud judgment when
they are first started or increased (7). Most experts agree that driving or operating heavy
machinery is unsafe and should be avoided until a stable dose has been reached (8). Multiple
smaller studies suggest that many patients on chronic opioids (defined as no dose change within
the last week) have no increased risk of motor vehicle collisions compared to the general
population and no reduction in concentration or perception compared to controls(9). According to
one study, which videotaped patients while actually driving, those on chronic opioid therapy
versus healthy controls displayed neither a difference in driving errors in community or obstacle
course driving nor in tests of attention (10). Counseling bottom line: patients who have been
on a stable dose for a week, who feel no cognitive changes (drowsiness, ‘fuzziness,’ difficulties in
concentrating) can drive.
For commercial driving, the Federal Motor Carriers Safety Administration generally prohibits
opioid use, but with the caveat that these rules “do not apply to the possession or use of a
substance administered to a driver by or under the instructions of a licensed medical
practitioner…who has advised the driver that the substance will not affect the driver's ability to
safely operate a motor vehicle” (11). Individual states, employers, and insurance agencies may
have further restrictions, and patients should be advised to investigate these prior to driving
commercially.
References
1) McMillan SC. Assessing and managing opiate-induced constipation in adults with cancer.
Cancer Control. 2004; 11(3):3-9.
2) Meuser T, Pietruck C, Radbruch L, Stute P, Lehmann KA, Grond S. Symptoms during
cancer pain treatment following WHO-guidelines: a longitudinal follow-up study of
symptom prevalence, severity and etiology. Pain. 2001; 93:247–57.
3) Cherny N, Ripamonti C, Pereira J, et al. Strategies to manage the adverse effects of oral
morphine: an evidence-based report. J Clin Oncology. 2001; 19:2542–54.
4) Bruera E, Miller MJ, Macmillian K, Kuehn N. Neuropsychological effects of
methylphenidate in patients receiving a continuous infusion of narcotics for cancer pain.
Pain. 1992; 48(2):163-166.
5) Kjellberg F, Tramer MR. Pharmacological control of opioid-induced pruritus: a quantitative
systematic review of randomized trials. Eur J Anesth. 2001; 18(6):346-357.
6) Chapman S. The effects of opioids on driving ability in patients with chronic pain. Bull
Am Pain Soc. 2001; 11:1.
7) Galski T, Williams JB, Ehle HT. Effects of opioids on driving ability. J Pain Symptom
Manage. 2000; 19(3):200-8.
8) Canadian Guideline for Safe and Effective Use of Opioids for Chronic Non-Cancer Pain.
National Opioid Use Guideline Group. April 30, 2010. Available at: http://
nationalpaincentre.mcmaster.ca/opioid/documents.html. Accessed June 30, 2011.
9) Fishbain DA, Cutler RB, Rosomoff HL, Rosomoff RS. Are opioid-dependent/tolerant
patients impaired in driving-related skills? A structured evidence-based review. J Pain
Symptom Manage 2003; 25(6):559-577.
10) Byas-Smith MG, Chapman SL, Reed B, Cotsonis G. The effect of opioids on driving and
psycho-motor performance in patients with chronic pain. Clin J Pain. 2005;.21(4):345-52.
11) Drugs and Other Substances. US Department of Transportation Federal Motor Carrier
Safety Administration Rules & Regulations. Available at: http://www.fmcsa.dot.gov/
rulesregulations/administration/fmcsr/fmcsrruletext.aspx?reg=392.4. Accessed May 11,
2011.
12) Swegle JM, Logemann C. Management of common opiate induced adverse effects. Am
Fam Physician. 2006; 74(8):1347-1354.
Authors’ Affiliations: Carolinas Medical Center/Northeast, Concord, NC (RES); National

Institutes of Health, Bethesda, MD (HEG); University of Minnesota Medical School and Fairview
Health Services, Minneapolis, MN (DAR).
Version History: Originally published December 2011; Copy-re-edited August 2015.
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!

OPIOID USE IN LIVER FAILURE
Carlene Oliverio PharmD, BCPS, Natalie Malone PharmD, Drew A Rosielle MD
Background Most opioids are at least partially metabolized by the liver, complicating their use
in liver failure. This Fast Fact discusses the use of opioids in patients with liver failure (see also
Fast Facts #161 about opioid use in renal failure, #176 and #177 about managing ascites and
#189 about prognostication in end-stage liver disease). Note: while there are plenty of
pharmacokinetic data about opioids & liver failure, all the clinical recommendations below are
empiric and not based on clinical outcomes research.
Hepatic Opioid Metabolism There are two different types of chemical reactions involved in
hepatic drug metabolism. The first, oxidation/reduction reactions, occurs through the cytochrome
(CYP) P450 enzyme system. The CYP450 enzymes most relevant in palliative medicine include
CYP1A2, 2D6, 2C9, 2C19, 3A3 and 3A4; most opioids are metabolized by these enzymes. In
hepatic failure, opioid clearance is reduced and drug bioavailability is increased. These changes
can be secondary to reduced hepatic blood flow (limiting first-pass metabolism) or decreased
CYP450 enzyme levels in these patients. Conjugation and glucuronidation comprise the second
group of chemical reactions in the liver. These reactions are less affected in hepatic disease due
to glucuronidation enzyme preservation and also because of extrahepatic glucuronidation
processes. Glucuronidated opioid metabolites are generally renally excreted. Changes such as
decreased serum albumin and ascites can also alter opioid volume of distribution which can lead
to either increased or decreased drug concentrations, although there is no practical way to ‘test’
for or predict this apart from close clinical observation.
Morphine Morphine is metabolized by glucuronidation to two major metabolites, morphine-3-

glucuronide (M3G) and morphine-6-glucuronide (M6G). M6G is an active analgesic that is more
potent than morphine, while M3G has no analgesic effect but contributes to neurotoxic side
effects such as confusion. Morphine accumulation has been reported in liver disease which can
result from decreased plasma clearance and/or increased elimination half-life of the parent drug.
In patients with early liver disease, initial lower doses should be used, but at normal dosing
intervals. However, as the disease progresses to advanced hepatic failure, longer dosing intervals
may be necessary.
Oxycodone Oxycodone is metabolized to two different metabolites by CYP2D6 and 3A4.

However, neither metabolite contributes significantly to analgesia. In advanced liver failure,
oxycodone’s maximum concentration increases 40%, and immediate-release oxycodone’s half-
life increases to 4.6-24.4 hours (average 14 hours; its usual half-life is ~3.5 hours). Initial
oxycodone dosing in patients with severe hepatic failure should be reduced to 30%-50% of the
recommended starting dose.
Codeine & Meperidine Both these drugs should be avoided entirely in patients with liver failure.
Codeine is a prodrug that is hepatically converted to morphine by CYP2D6. In patients with liver
dysfunction, pain control can be compromised if codeine is not metabolized. Meperidine is
metabolized by CYP3A4 to normeperidine and also by hydrolysis. In hepatic disease, meperidine
clearance is reduced and its half-life is prolonged. Seizures, a major side effect of meperidine and
normeperidine, can occur at reduced doses in patients with hepatic failure (see Fast Fact #71).
Hydromorphone & Hydrocodone Hydromorphone is glucuronidated to metabolites which

have no analgesic properties but can be neurotoxic (see Fast Facts #57, 58, 142).
Hydrocodone is a prodrug metabolized by CYP2D6 to hydromorphone and other metabolites,
and is only available in combination with non-opioids such as acetaminophen. Hydrocodone
dose titrations are limited by the non-opioid component, and overconsumption of acetaminophen-
containing products is hepatotoxic. In patients with severe liver disease, initial starting doses of
!20
each drug should be reduced to 50% of normal and as the disease progresses, prolonged dosing
intervals may also be necessary.
Fentanyl Fentanyl is primarily metabolized by CYP3A4 and quickly redistributes to muscle

and fat upon administration. In single-bolus studies, intravenous fentanyl’s pharmacokinetics
were unchanged by liver failure, however its half-life is prolonged in liver failure with repeated
dosing or high dose therapy. Transdermal fentanyl has not been adequately studied in liver
failure. Hepatic failure can alter skin permeability and drug absorption; the clinical relevance of
this, if any, has not been determined. Some experts suggest fentanyl is a preferred opioid in liver
failure (1, 4), although this judgment appears to be entirely empiric.
Methadone Methadone is metabolized by CYP3A4, 2D6 and 1A2. Methadone’s clearance is

reduced in severe liver disease. Notably, however, hepatitis C infection stimulates CYP3A4
activity and may actually increase methadone clearance, particularly early on (before overt liver
failure occurs).
Clinical Management Pearls As in any clinical setting, the ‘right dose’ of an opioid analgesic
medication is that which provides adequate pain relief in conjunction with an acceptable side
effect profile. This statement is especially true in end stage liver disease (ESLD). Opioid doses
should not be decreased solely out of concern for hepatic disease (e.g., if a patient with ESLD
appears to tolerate and require q3 hour dosing of oxycodone, that dosage should continue). In
general, lower doses of most opioids should be initiated in patients with ESLD, and clinicians
should be cautious prescribing opioids at ‘regular’ dosing intervals until patients have
demonstrated an ability to tolerate them. Patients with deteriorating liver function should be
closely monitored for signs of drug accumulation and need for dose reductions, assuming the
level of analgesia remains acceptable. Finally, potential drug interactions involving the CYP450
enzyme system must always be considered as there is potential for non-opioid medications to
either induce or inhibit the metabolism of any opioid that is a CYP450 enzyme substrate.
References
1. Rhee C, Broadbent AM. Palliation and liver failure: palliative medications dosing
guidelines. J Pall Med. 2007; 10:677-685.
2. Zichterman A. Opioid pharmacology and considerations in pain management. May 2007.
US Pharmacist (Web). Available at: http://www.uspharmacist.com/continuing_education/
ceviewtest/lessonid/105473/. Accessed July 19, 2012.
3. Davis M. Cholestasis and endogenous opioids: liver disease and exogenous opioid
pharmacokinetics. Clin Pharmacokinet 2007; 46:825-850.
4. Johnson SJ. Opioid safety in patients with renal or hepatic dysfunction. June 2007. Pain
Treatment Topics (Web). Available at: http://pain-topics.org/pdf/Opioids-Renal-Hepatic-
Dysfunction.pdf#search="opioids and liver failure". Accessed July 3, 2012.
5. Tegeder I, Lotsch J, Geisslinger G. Pharmacokinetics of opioids in liver disease. Clin
Pharmacokinet. 1999; 37:17-40.
Authors’ Affiliations: Lake Health System & Ohio Northern University, Concord, OH (CO);
Mount Carmel St. Ann’s Hospital, Westerville, OH (NM); University of Minnesota Medical School
& Fairview Health Services, Minneapolis, MN (DAR).
Version History: First published August 2012. Copy-edited by Sean Marks in September 2015.
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!

OPIOID INDUCED CONSTIPATION PART 1: ESTABLISHED MANAGEMENT STRATEGIES
Andrew Badke MD and Drew A Rosielle MD
Background Opioid induced constipation (OIC) affects 45-90% of patients (1, 2) and can cause
significant morbidity. It is the most common reason patients avoid and/or discontinue opioids (3,
4) and can often result in an increase in hospital length of stay (5) and overall healthcare costs
(6). This Fast Fact will describe the physiology of OIC and describe established treatment
strategies. Fast Fact # 295 will discuss newer management strategies.
Physiology OIC is mediated through several different mechanisms including ineffective GI

motility, inhibition of mucosal transport of electrolytes and fluids, and interference with the
defecation reflex (7). The greatest risk factor for developing OIC is duration of opioid therapy.
Route of delivery or increased opioid dosing does not appear to affect the risk of developing OIC
(2). While patients usually develop tolerance to most other side effects from opioids, they do not
develop tolerance to OIC (1).
Non-pharmacologic Therapies Physical activity, scheduled toileting, fiber, and adequate fluid
intake have been traditional non-pharmacologic mainstays for preserving GI regularity in
constipation (8). However, there is no specific evidence in favor for any of these interventions to
treat OIC and adherence may be challenging for chronically ill patients.
Pharmacologic Therapies In general, patients with regular opioid exposure will require
pharmacologic therapy to appropriately manage OIC. Both stimulant and osmotic laxatives have
shown to be effective in treating OIC and are considered the cornerstone of treatment. Failure of
oral pharmacologic therapy usually requires more invasive rectal based interventions or one of
the newer treatment modalities (see Fast Fact #295).
• Stimulant Laxatives: Senna and bisacodyl are the main stimulant laxatives available in the
US and work by increasing enteric muscle contraction and GI motility. The onset of action for
oral senna and bisacodyl is around 6-12 hours. Starting dose for senna is two 8.6 mg tabs;
bisacodyl is one 10mg tab. However, higher doses are usually needed for OIC. Senna can be
safely dosed up to 12 tabs daily and bisacodyl up to 30 mg (9). Both medications are
relatively inexpensive. Because stimulant laxatives cause intestinal contractions their use can
be limited by abdominal cramps and pain. This can sometimes be avoided by dividing the
total dose into smaller more frequent doses (9).
• Osmotic Laxatives: These include non-absorbable sugar molecules such as polyethelyne
glycol (PEG), lactulose, and sorbitol, as well as poorly absorbed salt-based molecules like
milk of magnesia and magnesium citrate. Osmotic laxatives have limited intestinal absorption
leading to an increase in colonic intraluminal water through oncotic pressure. With increased
intraluminal volume and distension, reflex peristalsis subsequently occurs. Additionally, the
increase in intraluminal water also leads to softer stool and allows for easier intestinal transit.
The starting daily dose for PEG is 17 g, for lactulose is 15 ml, and 30 ml for 70% sorbitol
solution. Osmotic laxatives will have a linear effect on bowel function with dose increases; the
maximum effective daily dose of PEG is 68 g (10), lactulose is 60 ml, and for sorbitol is 150
ml. The onset of action for osmotic laxatives tends to be variable ranging from 12 to 48 hours,
but when used regularly patients will have a more consistent effect. Osmotic laxatives
generally do not lead to a loss of fluids or electrolytes as they only bind to orally taken fluid.
With this, PEG requires 125 ml of fluid per 17 g dose (11) and similarly ~200 ml is
recommended with every 30 ml of lactulose (12). Major side effects from osmotic laxatives
include abdominal cramping, pain, and flatulence. Lactulose and sorbitol tend to have more
of these side effects than PEG (11). While sorbitol and lactulose have shown similar efficacy,
sorbitol tends to be more cost effective (13). Magnesium based compounds (milk of
magnesia and magnesium citrate) are also effective, but the magnesium load can be
dangerous for patients with renal insufficiency.
!23
• Rectal Based Laxatives: Unfortunately, there is a lack of clinical research to support rectal
based laxatives, but anecdotally they are often used for refractory constipation. Stimulant
suppositories such as bisacodyl and rectal vault lubricants such as glycerin are inexpensive.
Their onset is usually within 10-15 minutes and can be dosed daily (9). Warm tap water and
milk of molasses enemas (12) can be dosed more frequently (up to every two hours). They
work by causing rectal distension and reflex defecation. Other enema formulations, such as
phosphate or saline enemas, should be used with caution in renal insufficiency due to
concern for electrolyte shifts.
• Manual Evacuation: Digital stimulation and manual disimpaction may be necessary if fecal
impaction is suspected. Due to the discomfort associated with manual evacuations, these are
often interventions of last resort and may require pre-medication with pain medications and/or
anxiolytics.
• Ineffective Therapies: Docusate sodium not demonstrated efficacy in randomized controlled
studies for OIC compared with placebo (14). Bulk forming laxatives (psyllium or fiber) require
at least 1.5 L of water to be effective and can actually lead to worsened constipation with
inadequate fluid intake. Consequently, most guidelines do not routinely recommend their use
(11,15,16).
Practical Advice A consistent bowel regimen is essential in preventing constipation in patients

on chronic opioid therapy. Providers should educate their patients about the signs and symptoms
of OIC and seek appropriate consultation in a timely manner. A scheduled stimulant laxative
regimen such as Senna 2 tabs twice daily should be prescribed at the onset of regular opioid use
regardless of opioid dosing. The goal for the bowel regimen should be an unforced bowel
movement at least every other day. If a patient has not had a bowel movement in 48 hours,
increasing stimulant laxative dose and/or adding an osmotic laxative is appropriate. Failure of oral
laxative therapy usually requires rectal based interventions and/or one of the newer treatment
modalities (see Fast Fact #295).
References
1. Bell TJ, Panchal SJ, Miaskowski C, Bolge SC, Milanova T, Williamson R. The Prevalence,
Severity, and Impact of Opioid-Induced Bowel Dysfunction: Results of a US and European
Patient Survey (PROBE 1). Pain Medicine. 2009; 10(1):35–42.
2. Tuteja AK, Biskupiak J, Stoddard GJ, Lipman AG. Opioid-Induced Bowel Disorders and
Narcotic Bowel Syndrome in Patients with Chronic Non-Cancer Pain. Neurogastroenterology
and Motility: The Official Journal of the European Gastrointestinal Motility Society. 2010;
22(4): 424–30, e96.
3. Poulsen J, Lykke CB, Olesen AE, Nilsson M, Drewes AM. Clinical Potential of Naloxegol in
the Management of Opioid-Induced Bowel Dysfunction. Clinical and Experimental
Gastroenterology. 2014; 7:345–58.
4. Tamayo AC, Diaz-Zuluaga PA. Management of Opioid-Induced Bowel Dysfunction in Cancer
Patients. Supportive Care in Cancer: Official Journal of the Multinational Association of
Supportive Care in Cancer 2004; 12(9):613–18.
5. Pappagallo, M. Incidence, Prevalence, and Management of Opioid Bowel Dysfunction.
American Journal of Surgery. 2001; 182 (5A Suppl): 11S – 18S.
6. Hjalte F, Berggren AC, Bergendahl H, Hjortsberg C. The Direct and Indirect Costs of Opioid-
Induced Constipation. Journal of Pain and Symptom Management. 2010; 40(5): 696–703.
7. Kumar L, Barker C, Emmanuel A. Opioid-Induced Constipation: Pathophysiology, Clinical
Consequences, and Management. Gastroenterology Research and Practice. 2014: 141737.
8. Librach S, Bouvette LM, De Angelis C, Farley J, Oneschuk D, Pereira JP, Syme A.
Consensus Recommendations for the Management of Constipation in Patients with
Advanced, Progressive Illness. Journal of Pain and Symptom Management 2010; 40(5): 761–
73.
9. Twycross R, Sykes N, Mihalyo M, Wilcock, A. Stimulant Laxatives and Opioid-Induced
Constipation. Journal of Pain and Symptom Management 2012; 43(2): 306-13.
10. Di Palma, Jack A., Julie R. Smith, and Mark vb Cleveland. Overnight Efficacy of Polyethylene
Glycol Laxative. The American Journal of Gastroenterology 97, no. 7 (July 2002): 1776–79.
!24
11. Klaschik, E., F. Nauck, and C. Ostgathe. Constipation--Modern Laxative Therapy. Supportive
Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
11, no. 11 (November 2003): 679–85.
12. Bisanz, Annette. Self-Help for Severe Constipation. MD Anderson Cancer Center: Patient
Education 2007: 1-4, retrieved from http://www.fredonc.com/pdfs/constipation.pdf. 4/15/2015.
13. Volicer L, Lane P, Panke J, Lyman P. Management of Constipation in Residents with
Dementia: Sorbitol Effectiveness and Cost. Journal of the American Medical Directors
Association 2005; 6(3): S32–34.
14. Tarumi Y, Wilson MP, Szafran O, and Spooner GR. Randomized, Double-Blind, Placebo-
Controlled Trial of Oral Docusate in the Management of Constipation in Hospice Patients.
Journal of Pain and Symptom Management 2013; 45(1): 2–13.
15. Kyle, G. Constipation and Palliative Care - Where Are We Now? International Journal of
Palliative Nursing 2007; 13(1): 6–16.
16. Larkin PJ, Sykes NP, Centeno C, Ellershaw JE, Elsner F, Eugene B, Gootjes JRG, et al. The
Management of Constipation in Palliative Care: Clinical Practice Recommendations.
Palliative Medicine. 2008; 22(7): 796–807.
Authors’ Affiliations: University of Utah, Salt Lake City, UT (AB); University of Minnesota Health,
Minneapolis, MN (DAR).
Version History: First electronically published April 2015
!25
!

OPIOID INDUCED CONSTIPATION PART II: NEWER THERAPIES
Background Fast Fact #294 introduces OIC and discusses well-established treatments. This
Fast Fact discusses emerging management approaches. In general, these agents are used for
refractory OIC, which implies persistent and distressing symptoms despite exposure to typically
effective doses of stimulant and osmotic laxatives. When exactly to use these emerging
therapies remains largely empiric.
Opioid Antagonists Since the majority of symptoms associated with OIC are secondary to
stimulation of µ-opioid receptors in the gut, opioid antagonists offer an attractive pharmacologic
rationale for OIC (1).
Naloxone: Until recently, naloxone was the only available opioid antagonist for OIC treatment.
Typically, patients orally ingest the contents of IV ampules. Naloxone has a high first pass
metabolism, so it is possible for patients who take it orally to have peripheral µ-opioid receptor
antagonism without significant impact on central receptors which could lead to opioid withdrawal
and loss of analgesia (2). In a small, non-controlled study, 80% of chronic opioid users had bowel
evacuation in 1-4 hours after naloxone administration. Unfortunately, over two-thirds reported a
10-15% loss of analgesia and nearly one-third had withdrawal symptoms (3). Therefore, if used, it
is recommended to start at a low dose of 0.8 mg twice daily. Effective doses typically need to be
at least 10% of equivalent daily morphine dose, so naloxone usually requires slow up-titration
with max dosing of 12 mg daily (2).
Methylnaltrexone bromide: Methylnaltrexone is a peripherally-acting µ-opioid receptor antagonist.

It is a methylated form of naltrexone and formulated as a subcutaneous injection. It is less able to
cross the blood brain barrier, reducing the risk of altering analgesia or inducing central opioid
withdrawal. An industry-funded randomized controlled trial of chronic opioid users showed that
weight based methylnatrexone dosing led to laxation in nearly half of subjects within 4 hours as
opposed to 15% of placebo (4). A subsequent meta-analysis of 6 separate trials with
methylnaltrexone demonstrated the number needed to treat (NNT) is 3 for OIC patients that have
failed to respond to standard laxative therapy (5). Its use is limited by cost which averages $55
per dose, and it is also contraindicated when bowel obstruction is suspected or for patients with
compromised bowel integrity. The most common side effects are nausea, diarrhea, and cramping
– which can be severely painful.
Naloxegol: Two oral peripheral acting µ-opioid receptor antagonists are available in the US:
alvimopam, which is only approved for post-operative ileus, and naloxegol (pegylated naloxone),
which has recently been approved for OIC in non-cancer patients. Two separate phase-three
clinical trials showed an increase from 1 to >3 bowel movements per week in non-cancer patients
on chronic opioids with daily dosed naloxegol compared to placebo. There was also a significant
improvement in a subset of patients who had failed traditional laxative therapy as well (7). Both
12.5 mg and 25 mg have been studied; the 25 mg dose has a higher success rate but is
associated with more abdominal pain, nausea, vomiting and diarrhea (7). Its current price is
approximately $300 for 30 pills.
Other Agents
Lubiprostone: Lubiprostone is a selective chloride channel-2 activator that acts locally on the
small intestine to increase fluid secretion and GI motility. It is FDA approved for OIC. Two
randomized controlled trials in non-cancer chronic opioid users demonstrated an increase in
frequency of spontaneous bowel movements by week 8. Moreover, approximately 40% of
subjects had a bowel movement at 24 hours, 60% within 48 hours, and 27% of subjects had > 3
bowel movements per week (8,9). The most studied dose is 24 mcg orally twice per day.
!26
Common side effects included nausea, diarrhea and abdominal distension. Curiously,
lubiprostone does not appear to be effective for methadone induced constipation (10).
Linactolide has a different mechanism than lubiprostone, but is also a small intestinal
secretogogue. It currently is approved for irritable bowel syndrome. Though there is interest in its
efficacy in OIC, it has yet to be specifically studied in this population.
Prucalopride is a serotonin receptor type-4 agonist which is available in Canada and parts of
Europe and Asia to treat chronic constipation. It is a prokinetic agent which has shown promise
for treating OIC in a phase 2 study (5). It is unclear if or when it will be released in the US.
Practical Advice Traditional oral and rectal laxatives have been the mainstay of treatment in
OIC for many years. However, recent development of novel approaches to treat OIC show
promise for the future. Of the pharmacologic interventions described above, methylnatrexone has
been the best studied and shown to be the most efficacious. It is reasonable to give
methylnaltrexone after failure of oral laxatives (see Fast Facts #294) in OIC, and potentially can
be used prior to using more invasive rectal based interventions. With time and more clinical trials,
other oral formulations targeting OIC may become more standard of care. Patient and caregiver
education about the importance of adherence to recommended therapy and guidance about signs
and symptoms of OIC is essential to ensure effective treatment.
References
17. Holzer, Peter. Opioids and Opioid Receptors in the Enteric Nervous System: From a
Problem in Opioid Analgesia to a Possible New Prokinetic Therapy in Humans.
Neuroscience Letters. 2004; 361(1–3): 192–95.
18. Choi YS, Billings JA. Opioid Antagonists: A Review of Their Role in Palliative Care, Focusing
on Use in Opioid-Related Constipation. Journal of Pain and Symptom Management. 2002;
24(1): 71–90.
19. Latasch L, Zimmermann M, Eberhardt B, Jurna I. Treament of morphine-induced
constipation with oral naloxone. Der Anaesthesist. 1997; 46 (3): 191–94.
20. Thomas J, Karver S, Cooney GA, Chamberlain BH, Watt CK, Slatkin NE, Stambler N,
Kremer AB, Israel RJ. Methylnaltrexone for Opioid-Induced Constipation in Advanced
Illness. The New England Journal of Medicine. 2008; 358 (22): 2332–43.
21. Ford AC, Brenner DM, Schoenfeld PS. Efficacy of Pharmacological Therapies for the
Treatment of Opioid-Induced Constipation: Systematic Review and Meta-Analysis. The
American Journal of Gastroenterology. 2013; 108(10): 1566–74.
22. Twycross R, Sykes N, Mihalyo M, Wilcock A. Stimulant Laxatives and Opioid-Induced

Constipation. Journal of Pain and Symptom Management. 2012; 43(2): 306–13. doi:
10.1016/j.jpainsymman.2011.12.002.
23. Chey WD, Webster L, Sostek M, Lappalainen J, Barker PN, Tack J. Naloxegol for Opioid-
Induced Constipation in Patients with Noncancer Pain. The New England Journal of
Medicine. 2014; 370(25): 2387–96.
24. Cryer B, Katz S, Vallejo R, Popescu A, Ueno R. A Randomized Study of Lubiprostone for
Opioid-Induced Constipation in Patients with Chronic Noncancer Pain. Pain Medicine. 2014;
15(11): 1825–34.
25. Jamal M, Mazen, Mareya SM, Woldegeorgis F, Joswick TR, Ueno R. 848a Lubiprostone
Significantly Improves Treatment Response in Non-Methadone Opioid-Induced Bowel
Dysfunction Patients with Chronic, Non-Cancer Pain: Results from a Phase 3, Randomized,
Double-Blind, Placebo-Controlled Clinical Trial. Gastroenterology 2012; 142(5):144 –145S.
26. Brenner DM, Chey DM. An Evidence-Based Review of Novel and Emerging Therapies for
Constipation in Patients Taking Opioid Analgesics. The American Journal of
Gastroenterology Supplements 2014; 2(1): 38–46.
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!28
!
Opioids Writing Orders

#18 Short Acting Oral Opioid Dosing
Intervals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-3
#20 Opioid Dose Escalation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . 4-5
#28 Subcutaneous Opioid

Infusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6-7
#36 Calculating Opioid Dose

Conversions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .8-9
#51 Choosing an Opioid Combination

Product . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10-11
#72 Opioid Infusion Titration

Orders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12-13
#74 Oral Opioid Orders: Good and Bad

Examples . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .14-15
#92 Patient Controlled Analgesia in Palliative Care . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . .16-17
#94 Writing Discharge and Outpatient Opioid

Prescriptions . . . . . . . . . . . . . . . . . . . . . . . . . . 18-19
#215 Opioid Poorly-Responsive Cancer Pain . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . 20-21
!1
!

SHORT-ACTING ORAL OPIOID DOSING INTERVALS
David E Weissman MD
Background Oral opioids are among the most commonly prescribed drugs in palliative care.
Despite national analgesic guidelines, the use of excessive intervals for short-acting oral opioids
continues to pose a significant barrier to good analgesic care. Understanding the pharmacological
rational for dosing intervals is key to proper prescribing and patient counseling.
Short-Acting Oral Opioids Short-acting products are administered as either single agents
(oral morphine, hydromorphone, oxycodone and codeine) or as combination products containing
acetaminophen, aspirin or ibuprofen. For all these products, the peak analgesic effect occurs in
60-90 minutes with an expected total duration of analgesia of 2-4 hours. Standard reference
sources generally cite a 4 hour dosing interval for the single-agent opioids, but 4-6 or 6 hour
intervals for combination products (PDR, Micromedex). However, the Agency for Health Care
Policy and Research (AHCPR) Clinical Practice Guideline (1994) recommends dosing intervals
for all short-acting opioids at an interval or every 3-4 hours, an interval more consistent with
patient reports of pain relief and the half-life of oral opioids.
Is there a danger to more frequent drug administration? There is no danger of dosing

intervals as often as every 2 hours for single agent products (e.g. morphine), in patients with
normal renal function and who are currently tolerating the opioid without sedation, as the peak
effect will be reached in 60-90 minutes and there is rapid renal excretion. For combination
products, the concern is excessive acetaminophen. Thus, if patients need opioids on an every
four hour basis, it is appropriate to change to single agents without acetaminophen and/or add a
long-acting opioid product so as to keep the total daily acetaminophen dose at less than 4 grams.
Note: Transmucosal fentanyl citrate and oral oxymorphone have different pharmacokinetics than
the agents mentioned above and are dosed differently – see Fast Facts #103 and #181.
Summary
• Prescribe the products listed above at intervals no greater than every 4 hours.
• Closely monitor daily acetaminophen intake when combination products are used.
• Provide explicit patient/family counseling regarding safe and allowable dosing intervals.
• Review your institutional opioid policies – ask if there is a hospital policy or guidelines for
oral opioid doing intervals; if not, such guidelines should be developed to help guide
practice.
See related analgesic Fast Facts:

# 20 Opioid dose escalation
# 51 Opioid combination products
# 70 PRN range orders
# 74 Good and bad analgesic orders
# 82 Why patients do not take their opioids
# 94 Writing discharge/outpatient opioid prescriptions
#161 Opioid use in renal failure
#198 Regulatory issues for prescribing Scheduled II opioids at the end of life
#248 Counseling patients on side effects and driving when starting opioids
!2
References:
1. Acute Pain Management Guideline Panel. Acute pain management: Operative or
Medical Procedures and Trauma Clinical Practice Guideline. AHCPR Publication No.
92-0032. Available at: http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=hstat6.chapter.
32241.
2. Cleary JF. Pharmacologic management of cancer pain. J Palliat Med. 2007;
10:1369-1394.
3. Physicians Desk Reference. Available at: http://pdr.net.
4. Micromedex. Available at: http://www.micromedex.com.
!3
!

OPIOID DOSE ESCALATION
David E Weissman MD
Background A common question from trainees is how fast, and by how much, can opioids be
safely dose escalated? I like to use the analogy of furosemide (Lasix) when discussing this topic.
I have never seen a resident order an increase in Lasix from 10 mg to 11 mg, yet that is precisely
what often happens with opioids, especially parenteral infusions. Like furosemide, dose
escalation of opioids should be done on the basis of a percentage increase. In fact, this is
reflexively done when opioid-non-opioid fixed combination products are prescribed; going from
one to two tablets of codeine/acetaminophen represents a 100% dose increase. The problem
arises when oral single agents (e.g. oral morphine) or parenteral infusions are prescribed.
Increasing a morphine infusion from 1 to 2 mg/hr is a 100% does increase; while going from 5 to
6 mg/hr is only a 20% increase, and yet many orders are written, “increase drip by 1 mg/hr, titrate
to comfort.” Some hospitals and nursing units even have this as a standing pre-printed order or
nursing policy.
Key Points: In general, patients do not notice a change in analgesia when dose increases are
less than 25% above baseline. There is a paucity of clinical trial data on this subject. A common
formula used by many practitioners is:
• For ongoing moderate to severe pain increase opioids doses by 50-100%, irrespective of
starting dose.
• For ongoing mild to moderate pain increase by 25-50%, irrespective of starting dose.
• These guidelines assume the patient is tolerating the opioid well (with no or minimal
sedation); clinicians will need to be more cautious and should consider expert help for
patients with ongoing uncontrolled pain despite sedation from opioids or another cause.
When dose escalating long-acting opioids or opioid infusions, do not increase the long-acting
drug or infusion basal rate more than 100% at any one time, irrespective of how many bolus/
breakthrough doses have been used. These guidelines apply to patients with normal renal and
hepatic function. For elderly patients, or those with renal/liver disease, dose escalation
percentages should be reduced (see Fast Facts # 161 for Opioid use in renal failure and # 260 for
Opioid use in liver failure).
The recommended frequency of dose escalation depends on the half-life of the drug.
• Short-acting oral single-agent opioids (e.g. morphine, oxycodone, hydromorphone), can
be safely dose escalated every 2 hours.
• Sustained release oral opioids can be escalated every 24 hours.
• For methadone, levorphanol, or transdermal fentanyl no more frequently than every 72
hours is recommended.
• Note: transbuccal fentanyl products have specific guidelines for dose escalation. See the
manufacturers’ prescribing information and Fast Fact #103
See related analgesic Fast Facts:

#18 Oral opioid dosing intervals
# 51 Opioid combination products
# 70 PRN range orders
# 74 Good and Bad analgesic orders
# 215 Opioid poorly-responsive cancer pain
References:
!4
1. Hanks G, Cherny NI, Fallon M. Opioid analgesic therapy. In: Oxford textbook of Palliative
Medicine. 3rd Ed. Doyle D, Hanks G, Cherny N, Claman K, eds. New York, NY: Oxford
2. Weissman DE, Ambuel B, Hallenbeck J. Improving End-of-Life Care: A resource guide for
physician education. 3rd Edition. Milwaukee, WI: Medical College of Wisconsin; 2001.
3. Handbook of Cancer Pain Management. 5th Edition. Wisconsin Cancer Pain Initiative;
1996.
published July 2005; 3rd Edition May 2015. Current version re-copy-edited May 2015 after a
revision in December 2012 to add clarifying language about opioid escalation in sedated patients;
transbuccal fentanyl language added.
!5
!

SUBCUTANEOUS OPIOID INFUSIONS
David E Weissman MD
Background
A parenteral opioid infusion is the standard of care for managing moderate-severe pain or
dyspnea when the oral/rectal route is unavailable and/or frequent dose adjustments are needed.
As death nears, the burden of maintaining intravenous (IV) access, especially in the home
setting, can be enormous. An alternative delivery route supported by major pain societies such
as European Association of Palliative Care is the subcutaneous (SQ) route for continuous
infusions, Patient Controlled Analgesia (PCA), or intermittent bolus opioid injections.
Drugs
Morphine, hydromorphone (Dilaudid), fentanyl, and sufentanil can all be safely administered as
SQ bolus doses or continuous SQ infusion. Methadone infusions cause frequent skin irritation;
one case series reported successful use of methadone with concurrent dexamethasone infusion
and frequent site rotation.
Dosing equivalents
Dose conversion ratios between the IV and SQ route for all the above listed opioids are not well
established. For morphine, the ratio appears to be close to 1 mg IV = 1mg SQ.
Pharmacokinetics
SQ infusions can produce the same blood levels as chronic IV infusions. There is no data to
suggest that cachectic, febrile or hypotensive patients have problems with drug absorption.
Volume and Drug Choice

The limiting feature of a SQ infusion is the infusion rate; in general, SQ tissue can absorb up to 3
ml/hr. At low opioid requirements morphine is generally the drug of choice based on availability
and cost; a switch to hydromorphone is indicated for a high opioid requirement due its higher
intrinsic potency (approximately 4-6 times as potent as morphine), thus the need for a smaller
infusion volume.
Administration
Use a 25 or 27 gauge butterfly needle—place on the upper arm, shoulder, abdomen or thigh.
Avoid the chest wall to prevent iatrogenic pneumothorax during needle insertion. The needle can
be left indefinitely without site change unless a local reaction develops—typically, patients can
keep the same needle in place for up to one week at a time.
Toxicity
Local skin irritation, itching, site bleeding or infection can occur. Of these, skin irritation is the
most common, managed by a needle site change.
Patient acceptance
Patients readily appreciate the ease of SQ administration as an alternative to IV access.
References
!6
1. Caraceni A, Hanks G, et al. Use of opioid analgesics in the treatment of cancer pain:
evidence-based recommendations from the EAPC. The Lancet Oncology 2012; 13: e58-
e68.
2. Bruera E, Brenneis C, Michaud M, et al. Use of the subcutaneous route for the
administration of narcotics in patients with cancer pain. Cancer. 1988; 62:407-411.
3. Storey P. Subcutaneous infusion for control of cancer symptoms. J Pain Symptom
Manage. 1990; 5:33-41.
4. Waldman CS, Eason JR, Rambohul E, et al. Serum morphine levels—a comparison
between continuous SQ and IV infusion in post-operative analgesia. Anaesthesia. 1984;
39:768-771.
5. Mathew P, Storey P. Subcutaneous methadone in terminally ill patients: manageable local
toxicity. J Pain Symptom Manage. 1999; 18:49-52.
published July 2005; 3rd Edition May 2015. Current version re-copy-edited March 2009; then
again May 2015.
!7
!

CALCULATING OPIOID DOSE CONVERSIONS
ROBERT ARNOLD MD AND DAVID E WEISSMAN MD
Introduction A variety of published conversion tables exist to provide clinicians a rough guide
for making calculations when switching between different opioid routes or preparations. Listed
below are methods for common conversions using standard published conversion ratios. The
examples assume a change in drug or route at a time of stable pain control using equianalgesic
doses. See Fast Fact #2 about conversions involving transdermal fentanyl; #75 and #86 about
methadone; and #181 about oxymorphone.
Caution: Published values in equianalgesic tables should be considered a rough clinical guide
when making dose conversions; substantial inter-individual variation exists. The final prescribed
dose needs to take into account a patients’ age, renal, pulmonary and hepatic function; their
current pain level and opioid side effects such as sedation; as well as prior and current opioid
use.
Opioid Equianalgesic Conversion Ratios for use with the following examples:
Morphine 10 mg parenteral = Morphine 30 mg oral = Hydromorphone 1.5 mg parenteral =
Hydromorphone 7.5 mg oral = Hydrocodone 30 mg oral = Oxycodone 20-30 mg oral (see
Reference 1).
A. Change route, keeping drug the same (e.g. oral to IV morphine)
Example: Change 90 mg q12 Extended Release Morphine to Morphine by IV continuous
infusion
1. Calculate the 24 hour current dose: 90mg q 12 = 180 mg Morphine/24 hours

2. Use the oral to parenteral equianalgesic ratio: 30 mg PO Morphine = 10 mg IV Morphine
3. Calculate new dose using ratios: 180/30 x 10 = 60 mg IV Morphine/24 hours or 2.5 mg/
hour infusion
4. Some experts recommend starting the new opioid at 75% of the calculated dose to
account for inter-individual variation in first pass clearance.
B. Change drug, keep the same route (e.g. po morphine to po hydromorphone)

There is incomplete cross-tolerance between different opioids, but the exact amount will differ.
Thus, equianalgesic tables are only approximations. Depending on age and prior side effects,
most experts recommend starting a new opioid at 50% of the calculated equianalgesic dose, in
the setting of well-controlled pain.
Example: Change 90 mg q 12 Extended Release Morphine to oral Hydromorphone.
1. Calculate the 24 hour current dose: 90 Q12 x 2 = 180 mg PO Morphine/24 hrs

2. Use the equianalgesic ratio: 30 mg PO Morphine = 7.5 mg PO Hydromorphone
3. Calculate new dose using ratios: 180/30 X 7.5 = 45 mg oral Hydromorphone/24 hours.
4. Reduce dose 50% for cross-tolerance: 45 x 0.5 = 22 mg/24 hours = 4 mg q4h
C. CHANGING DRUG AND ROUTE (E.G. ORAL MORPHINE TO IV HYDROMORPHONE)

Example: Change from 90 mg q12 Extended Release Morphine to IV Hydromorphone as a
continuous infusion.
1. Calculate the 24 hour current dose: 90 Q12 x 2 = 180 mg PO Morphine/24 hrs

2. Use the equianalgesic ratio of PO to IV morphine: 30 mg po Morphine = 10 mg IV
Morphine
3. Calculate new dose using ratios: 180/30 x 10 = 60 mg IV Morphine/24 hours
4. Use the equianalgesic ratio of IV Morphine to IV Hydromorphone: 10 mg Morphine = 1.5
mg Hydromorphone
!8
5. Calculate new dose using ratios: 60/10 x 1.5 = 9 mg IV Hydromorphone/24 hours
6. Reduce dose 50% for cross-tolerance: 9 x 0.5 = 4.5 mg/24 hours = 0.2 mg IV continuous
infusion
7. Note: one would also get the same amount of hydromorphone if you directly converted
from oral morphine to IV hydromorphone using the 30 mg :1.5 mg ratio
References:
1. Gammaitoni AR, Fine P, Alvarez N, McPherson ML. Clinical application of opioid
equianalgesic data. Clin J Pain. 2003; 19:286-297.
2. Pereira J et al. Equianalgesic dose rations for opioids: a critical review and proposals for
long-term dosing. J Pain Sym Manage. 2001; 22:672-687.
3. Anderson R et al. Accuracy in equianalgesic dosing: conversion dilemmas. J Pain Sym
Manage. 2001; 21:397-406.
published July 2005; 3rd Edition May 2015. Re-copy-edited March 2009; references updated.
Revised December 2012; hydrocodone and oxycodone added to the equianalgesic table using
standard values; copy-edited again May 2015.
!9
!

CHOOSING AN OPIOID COMBINATION PRODUCT
DAVID E WEISSMAN MD
Introduction
There are over 50 different opioid combination products, available in a range of tablet strengths
and liquids. Opioid combination products are typically used for moderate pain that is episodic
(e.g. breakthrough pain) on a PRN basis. These products contain either acetaminophen, aspirin
or ibuprofen, with an opioid: codeine (e.g. Tylenol #2-4), hydrocodone (e.g. Lorcet, Lortab,
Vicodin, Vicoprofen), oxycodone (e.g. Percocet, Percodan, Tylox, Roxicet) or propoxyphene (e.g.
Darvocet, Wygesic). Other formulations also may contain caffeine and/or a barbiturate. This
Fast Fact will review information for rationally choosing among the various products.
• Intrinsic Analgesic Potency
Milligram for milligram, oxycodone and hydrocodone are the most potent opioids in this group;
they are roughly equianalgesic to each other. Codeine is less potent and propoxyphene the least
potent of the group; propoxyphene products are probably no more potent than aspirin or
acetaminophen alone.
• Toxicity
The dose limiting property of all the combination products is the aspirin, acetaminophen or
ibuprofen, not the opioid (see below). Patients receiving any of the four opioids may experience
classic opioid side effects: nausea, constipation, pruritus or sedation, along with the potential for
tolerance and physical dependence with chronic use. Differences in side effect severity among
the different opioids is largely idiosyncratic. There is anecdotal experience that codeine is the
most, and hydrocodone the least, emetogenic among the four opioids. Propoxyphene’s major
metabolite is a CNS stimulant, increasing the likelihood of seizures in an overdose situation. It is
also cardiotoxic, with lidocaine-like effects. Because of limited efficacy and increased toxicity,
propoxyphene is not recommend, especially in the elderly (1). Multiple countries have banned
propoxyphene; as of 2009 this is under consideration in the US.
• Cost
Generic products are readily available and typically less expensive.
Range of available doses
• Codeine products: 15-60 mg codeine/tablet
• Oxycodone or hydrocodone: 2.5–10 mg opioid/tablet
• Propoxyphene: 50-100 mg propoxyphene/tablet
• Acetaminophen doses range from 325–750 mg/tablet
Recommendations for use
1. Propoxyphene should rarely, if ever, be prescribed; it should not be used in the elderly.
2. Prescribe generic products whenever possible.
3. Prescribe only one combination product at any given time. Avoid writing orders that
include multiple products (e.g. “X” for mild pain, “Y” for moderate pain, etc). Rather,
prescribe only one product, assess efficacy and toxicity, and modify accordingly.
4. Prescribe codeine, oxycodone and hydrocodone products at a q4h interval; not q 4-6 or
q6h (see Fast Fact #18) (2).
5. Pay very close attention to the total daily dose of acetaminophen/aspirin/ibuprofen. Note:
the dose of acetaminophen per tablet can range from 325-750 mg. Thus, with a
recommended limit of < 4 grams per day, this equals 12 tablets @ 325 mg or 5 tablets @
750 mg tablet. Patients with renal or liver dysfunction are at higher risk for adverse
effects from the non-opioid (3).
References
1. AGS Panel on Chronic Pain in Older Persons. The Management of chronic pain in older
persons. J Am Geriatric Soc. 1998; 46:635-651.
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2. Jacox A, Carr DB, Payne R, et al. Management of Cancer Pain. Clinical Practice
Guideline No. 9. AHCPR Publication No. 94-0592. Agency for Health Care Policy and
Research, U.S. Department of Health and Human Services, Public Health Service, 1994.
Available at: http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=hstat6.chapter.18803.
3. MB Max, R Payne, WT Edwards, et al. Principles of analgesic use in the treatment of
acute pain and cancer pain. 4th Edition. Glenview, IL: American Pain Society; 1999.
4. Zwillich T. FDA Panel Urges Ban of Pain Drug [news story]. WebMD. Jan 30 2009.
Available at: http://www.webmd.com/pain-management/news/20090130/fda-panel-urges-
ban-of-a-pain-drug.
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!

OPIOID INFUSION TITRATION ORDERS
David E Weissman MD
Introduction This Fast Fact will discuss appropriate ways to write opioid infusion titration
orders. See Fast Fact # 34 for further information on the appropriate symptom management
during a ventilator withdrawal.
A bad example: ‘Morphine 2-10mg/hour, titrate to pain relief.’ This order is commonly written for
terminally ill patients and in the context of terminal ventilator withdrawals.
What is wrong with this order?
1. It places full responsibility for dose titration upon the nurse.
2. It provides no guidance regarding how fast to titrate (e.g. every hour, every shift?) or dose
titration intervals (e.g. for poorly treated pain, should the dose be raised from 2 to 3 mg, 2
to 10 mg, other?).
3. It poses the potential for overdosage by too zealous dose escalation and provides only
one option for poorly controlled pain – increasing the continuous infusion rate.
4. Given that it takes at least 8 hours to achieve steady-state blood levels after a basal dose
change, it makes no pharmacological sense to dose escalate the basal dose more
frequently than q 8 hours.
A better way to write this order: ‘Morphine 2 mg/hour and morphine 2 mg q 15 minutes for
breakthrough pain (or 2 mg via PCA dose). RN may dose escalate the PRN dose to a maximum
of 4 mg within 30 minutes for poorly controlled pain.’
Why is this better?
1. This order is preferred as it provides a basal rate and a breakthrough dose. The
breakthrough dose has a peak effect within 5-10 minutes. Thus, if the breakthrough dose
is inadequate it can be safely increased, as often as every 15-30 minutes, to achieve
analgesia – without a need for rapid upward titration of the basal rate.
2. Reassess the need for a change in the basal rate no more frequently than every 8 hours;
use the number of administered bolus doses as a rough guide when calculating a new
basal rate. However, never increase the basal rate by more than 100% at any one time.
When increasing the basal rate, always administer a loading dose so as to more rapidly
achieve steady-state blood levels.
REFERENCES
1. Principles of Analgesic Use in the Treatment of Acute and Cancer Pain. 5th Ed. Glenview,
IL: American Pain Society; 2003. Available at: http://www.ampainsoc.org/pub/
principles.htm.
2. Acute Pain Management Guideline Panel. Acute pain management: Operative or
32241.
3. Management of Cancer Pain. Clinical Practice Guideline No. 9; AHCPR Publication No.
94-0592.Rockville, MD. Agency for Health Care Policy and Research, US Department of
Health and Human Services, Public Health Service; 1992, 1994. Available at: http://
www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=hstat6.chapter.18803.
May 2015.
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!13
!
FASTS FACTS AND CONCEPTS #74

ORAL OPIOID ORDERS: GOOD AND BAD EXAMPLES
David E Weissman MD
Introduction This Fast Fact will illustrate poorly written opioid orders and provide preferred
alternatives.
Scenario 1: Episodic (non-continuous) moderate-to-severe pain
Bad Example: ‘Oxycodone w/ acetaminophen (Percocet), 1-2 PO q 4-6hour PRN severe pain,
and acetaminophen w/codeine (Tylenol #3) 1-2 PO q4-6 PRN moderate pain.’
Discussion: This order has several problems.
1) The duration of short-acting opioids is typically 3-4 hours - rarely 6 hours. Studies
document that when given a range, nurses and doctors are most likely to give the
lowest dose at the longest interval, leading to inadequate analgesia.
2) Only one opioids/non-opioid combination should be prescribed at a time: assess for
response and change to different product if the first agent does not produce the
desired effect.
3) The use of descriptors (‘mild,’ ‘moderate,’ ‘severe’) allows for subjective interpretation
of pain severity by the nurse, rather than judging pain severity directly based on
patient report. There is a very poor correlation of pain ratings between patients and
clinicians.
4) Should both drugs be used, there is risk of exceeding 4 grams/day of
acetaminophen.
Preferred order: ‘Oxycodone w/ acetaminophen, 1-2 tabs PO q 4 hours PRN pain.’
Scenario 2: Order for an oral long-acting opioid

Bad Example: ‘Morphine extended-release 60 mg q 6 hours and transdermal fentanyl patch 25
mcg/hour, changed q 72 hours.’
Discussion: This order has two problems. First, none of the oral long-acting products (e.g. MS
Contin, OxyContin, Kadian) should be prescribed less than Q8h; Q12 is the preferred dosing
interval. Second, there is no rationale for using two different long-acting products at the same
time. Prescribe only one drug, then dose escalate to desired effect or unacceptable toxicity.
Remember to always prescribe a PRN product for breakthrough pain. While the oral long-acting
products can be dose escalated every 24 hours, the transdermal fentanyl patch can only be
safely dose escalated every 2-3 days. Thus, it is a poor choice for poorly controlled pain
Preferred order: ‘Morphine extended-release 150 mg q 12 hours.’ (The dose of 150 mg
q12 hours is derived from the following equianalgesic relationships: morphine 60 mg q6 hours
is 240 mg/day; transdermal fentanyl 25mcg/hr = approximately 60 mg/day of oral morphine.
240 + 60 = 300 mg or 150 mg q12 hours. See Fast Fact #2.)
References
1) Acute Pain Management Guideline Panel. Acute pain management: Operative or
32241.
2) Management of Cancer Pain. Clinical Practice Guideline No. 9; AHCPR Publication No.
94-0592.Rockville, MD. Agency for Health Care Policy and Research, US Department of
Health and Human Services, Public Health Service; 1992, 1994. Available at: http://
www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=hstat6.chapter.18803.
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3) Drayer RA, et al. Barriers to better pain control in hospitalized patients. J Pain Sym
Manage. 1999; 17:434-440.
4) Friedman FB. PRN analgesics: controlling the pain or controlling the patient? RN. 1983;
43:67-78.
5) Principles of Analgesic Use in the Treatment of Acute and Cancer Pain. 5th Ed. Glenview,
IL: American Pain Society; 2003. Available at: http://www.ampainsoc.org/pub/
principles.htm.
published July 2006; 3rd Edition June 2015. Current version re-copy-edited April 2009; then again
June 2015.
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!

PATIENT CONTROLLED ANALGESIA IN PALLIATIVE CARE
ERIC PROMMER MD
Introduction Patient Controlled Analgesia (PCA) is a technique allowing patients to self-

administer parenteral analgesics. The primary advantage of PCA is to shorten the interval from
the time of patient-defined need to the time of actual analgesic administration. PCA is an
effective, safe, and well-accepted treatment for post-operative pain, sickle cell crisis pain (as
young as age 4), and cancer pain. In general, PCA will provide the same degree of analgesia
compared to other delivery systems with the same or less total amount of medication. PCA
allows for more immediate relief of incident (breakthrough) pain and can provide patients with a
greater sense of personal control over their pain.
Indications The primary indication for PCA is the patient who requires parenteral analgesia
(e.g. severe pain and/or oral/transdermal/rectal route not useable) and has incident pain or other
pain patterns that are not predictable. PCA is also indicated for use as a method of rapid dose
titration and dose finding in acute, severe pain. Relative contraindications include patients who a)
do not have the cognitive ability to understand how to use a PCA device, or b) have an
anticipated need for parenteral opioids less than 24 hours.
PCA devices Most devices have a drug reservoir and infusion system whereby PCA
administration can occur with or without a background continuous infusion. Thus, PCA devices
need the following orders: 1) PCA dose in mg or mcg (‘patient initiated dose,’ ‘patient demand
dose,’ or ‘bolus dose’), 2) Delay Interval (’lockout’) – in minutes (period during which the patient
cannot obtain additional demand medication), 3) Continuous infusion (CI) Rate in mg/hr or
mcg/hr (if CI is used), and 4) Hour Limit – maximum amount of drug to be dispensed in a defined
period of time. Often the one hour limit is set to deliver 3-5 times the estimated required hourly
dose. (Note: due to the need for frequent dose adjustments, the Hour Limit is often omitted in
palliative care.) Most palliative care patients will need both PCA demand and CI dosing. Opioids
used in PCA devices include morphine, hydromorphone, fentanyl, and methadone. IV or SQ are
the most common routes of administration; PCA can also be used with epidural, intrathecal, or
intraventricular opioid administration (see Fast Facts #28, 85, and 98).
Dosing in opioid-naïve patients The following information is for morphine, the first-line drug of
choice for most patients. Note: dosing and delay interval information will differ with other
opioids. Start dosing: PCA demand dose = 1-3 mg morphine; Delay Interval = 8-10 min. Initial
CI (if any) is dependent on the clinical situation. For instance, 1 mg/hour of IV morphine is
approximately equivalent to 35 mg bid of oral morphine ER. This may be excessive for opioid-
naïve patients; conversely many opioid-naïve patients with severe pain will easily tolerate this, so
the decision to immediately start a CI depends on clinician judgment. If not started immediately,
one can initiate a CI after four hours by summing the total demand dose given over 4 hours and
converting that into an hourly rate (e.g. if 16 mg is given over four hours, CI would be 4 mg/hour).
A new PCA demand dose can then be calculated at 50% of the hourly CI rate (4 mg/hr ÷ 2 = 2 mg
PCA demand dose, Delay Interval 8-10 min).
Dosing in non-naïve patients Convert their current total oral/transdermal dose to a total 24
hour IV dose; divide by 24 to give the hourly CI rate in mg/hour (see Fast Fact #36 on dose
conversions). The PCA demand dose is initially calculated at 50% of the hourly rate.
Risk of Overdose The patient who is pushing his or her own PCA button will fall asleep before
serious signs of overdose occur as long as only the patient pushes the button. Note: special care
is needed for patients with sleep apnea as they will be more sensitive to opioids.
Dose titration and Loading Doses See Fast Facts #20 Opioid Dose Escalation, #54 Opioid
Infusions in the Imminently Dying Patient, and #72 Opioid Infusion Titration Orders.
Common Sense Cautions These dosing recommendations are rough guidelines—clinicians
need to take into account pain severity, patient age, renal and pulmonary function, co-morbid
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illness, and other psychoactive medications. When in doubt, it is advised to use a lower CI rate
(with upward dose adjustments of the CI rate no more frequently than every 8 hours), while
adjusting the PCA dose at frequent intervals (q30-60 minutes) to effectively control pain.
References:
1. Bruera E, Ripamonti C. Current status of patient-controlled analgesia in cancer patients.
Oncology (Williston Park). 1997; 11:373-384.
2. Citron ML. Ripamonti-Bruera article reviewed. Oncology (Williston Park).1997;
11:384-386.
3. McCaffery M, Pasero C, eds. Pain: Clinical Manual. 2nd Ed. St Louis, MO: Mosby; 1999.
4. Caraceni, Augusto, et al. Use of opioid analgesics in the treatment of cancer pain:
evidence-based recommendations from the EAPC. The Lancet Oncology 2012; 13.2:
e58-e68.
re-copy-edited April 2009; web sites updated; then again June 2015.
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!

WRITING DISCHARGE AND OUTPATIENT OPIOID PRESCRIPTIONS
Colleen Dunwoody MS, RN and Robert Arnold MD
Background Assuring continuity in pain relief in the outpatient setting or following hospital
discharge is an important aspect of patient care. Poorly written prescriptions or orders can be
inconvenient for the patient as well as the clinician, but can also lead to prescriptions not being
filled, inadequate pain control, and patient suffering. This Fast Fact will touch on some practical
considerations in writing opioid prescriptions. See also Fast Fact #89 for writing orders for
patients in long term care facilities, #74 for a general discussion of proper opioid order writing,
and #198 for further discussion of regulatory issues.
Regulations Different states have different rules concerning controlled substances: amount of
drug that may be dispensed, number of refills, faxing of orders and telephone prescriptions, and
requirements for special prescription forms or blanks. Review your state regulations. See the
website below for state-by-state listings.
Legibility The DEA and NPI numbers and your name must be legible. Print your name after
your signature or otherwise indicate the spelling of your name on a personalized prescription.
Frequency Consider if the frequency you are prescribing is the recommended frequency.
Third party payers may not pay for medications prescribed to be taken more frequently than
recommended in the literature. For example, transdermal fentanyl patches changed q48 hours
and oxycodone ER q8 hours may not be paid by insurers without a specific reason. Oxycodone
ER and morphine ER may not, and should not, be dispensed when the frequency is PRN or less
than 8 hours.
Strength There are more than two dozen combination opioids available; it is good practice to
always write the correct strength for combination opioids (e.g. oxycodone/acetaminophen 5 mg/
325 mg). Be sure to check the available pill/tablet doses when prescribing long acting opioids.
When writing prescriptions for different strengths, it is helpful for both the patient and pharmacist
to specify that on the prescriptions. For instance, if someone is taking morphine ER 75 mg q12
hours they would require prescriptions for both morphine ER 60mg tabs and 15mg tabs, one
should write: “Morphine ER 15 mg tabs. Take one tab PO q12 hours. Take along with your 60 mg
tabs to make a total of 75 mg every 12 hours.”
Acetaminophen Identify whether the 3000-4000 mg/day maximum will be exceeded when
writing the frequency. Pay extra attention to combination products via which the patient may be
receiving extra acetaminophen. Most pharmacists will not dispense doses likely to exceed this
recommended maximum daily dose. If there is any doubt one should write “…not to exceed X
pills in 24 hours.”
Tampering Write the number after the numeric ‘10’ (ten) to prevent someone altering the
prescription (e.g. changing 10 to 40 by changing a 1 to a 4).
Substitutions and Corrections Pharmacists will not correct an improperly written prescription,
and some may not accept prescriptions that have obvious corrections (e.g. items crossed out)
because there is no way of knowing who did the correction. Nor will a prescription for an opioid
be filled when written on a prescription printed with "not for controlled substances". Pharmacists
also will not make substitutions; if you write for ‘morphine ER 80 mg,’ the pharmacist will not fill it
since the medicine is not available as an 80 mg tablet.
Communication When prescribing opioids that are infrequently used or in high doses,
communicate with the pharmacist before the patient is discharged or leaves your office to assure
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availability. Pharmacists prefer communication from physicians and nurses in advance so
medications can be stocked.
** In 2011, the FDA and acetaminophen manufacturers announced plans to lower the
recommended maximum daily dose from 4000 mg to 3000 mg/day due to rare instances of
hepatotoxicity for patients receiving 4000 mg daily. As of June 2015 the official prescribing
information has not been updated to reflect those announced changes. However, in 2014, the
FDA urged all acetaminophen drug manufacturers to halt production of combination products with
more than 325 mg of acetaminophen per dosage in order to help curb acetaminophen toxicity.
References
• Pain & Policy Studies Group. Madison, WI. Available at: http://www.painpolicy.wisc.edu/.
State profiles available at: http://www.painpolicy.wisc.edu/domestic/state_profiles/
index.html.
• New Initiative to Help Encourage Appropriate Use of Acetaminophen. McNeil Consumer
Healthcare. Available at: http://www.tylenol.com/page2.jhtml?id=tylenol/news/newdosing.inc.
Accessed August 2, 2012.
• FDA Drug Safety Communication: Prescription Acetaminophen Products to be Limited to
325 mg Per Dosage Unit; Boxed Warning Will Highlight Potential for Severe Liver Failure.
http://www.fda.gov/Drugs/DrugSafety/ucm239821.htm. Accessed June 2015.
edited by Drew A Rosielle and published October 2007; 3rd Edition June 2015. Re-copy-edited
April 2009. Updated in June 2015 by Sean Marks MD with acetaminophen dose changes.
!19
!

OPIOID POORLY-RESPONSIVE CANCER PAIN
Tamara Sacks MD, David E Weissman MD, and Robert Arnold MD
Background Relief of cancer pain from opioids is rarely all or nothing; most patients
experience some degree of analgesia alongside opioid toxicities. When the balance of analgesia
versus toxicity tips away from analgesia, the term ‘opioid poorly-responsive pain’ is invoked.
While opioid poorly-responsive pain is not a discreet syndrome, it is a commonly encountered
clinical scenario. This Fast Fact reviews key points in its assessment and management.
Differential Diagnosis of Opioid Poorly-Responsive Pain

1. Cancer-related pain
a. Cancer progression (new fracture at site of known bone metastases).
b. Causes of pain (eg. neuropathic pain, skin ulceration, rectal tenesmus, muscle pain)
that are known to be less responsive to systemic opioids or opioid monotherapy.
c. Psychological/spiritual pain related to the cancer experience (existential pain of
impending death).
2. Opioid pharmacology/technical problems
a. Opioid tolerance (rapid dose escalation with no analgesic effect).
b. Dose-limiting opioid toxicity (sedation, delirium, hyperalgesia, nausea – see Fast Facts
#25, 142).
c. Poor oral absorption (for PO meds) or skin absorption (e.g. transdermal patch adhesive
failure).
d. Pump, needle, or catheter problems (IV, subcutaneous, or spinal opioids).
3. Non-cancer pain
a. Worsening of a known non-cancer pain syndrome (diabetic neuropathy).
b. New non-cancer pain syndrome (dental abscess).
4. Other psychological problems
a. Depression, anxiety, somatization, hypochondria, factitious disorders.
b. Dementia and delirium both can effect a patient’s report of and experience of pain.
c. Opioid substance use disorders or opioid diversion.
Management Strategy
1. Initial Steps
a. Complete a thorough pain assessment including questions exploring psychological and
spiritual concerns. If substance abuse or diversion is suspected, complete a substance
abuse history (see Fast Facts #68, 69).
b. Complete a physical examination and order diagnostic studies as indicated.
c. Escalate a single opioid until acceptable analgesia or unacceptable toxicity develop, or
it is clear that additional analgesic benefit is not being derived from dose escalation. If
this fails, consider:
i. Rotating to a different opioid (e.g. morphine to methadone).
ii. Changing the route of administration (e.g. oral to subcutaneous).
d. Treat opioid toxicities aggressively.
e. Use (start or up-titrate) adjuvant analgesics, especially for neuropathic pain syndromes.
f. Integrate non-pharmacological treatments such as behavioral therapies, physical
modalities like heat and cold, and music and other relaxation-based therapies – see
Fast Fact #211.
2. Additional steps – Pain refractory to the initial steps requires multi-disciplinary input and care
coordination.
a. Hospice/Palliative Medicine consultation to optimize pain assessment, drug
management, and assessment of overall care goals.
b. Mental health consultation for help in diagnosis and management of suspected
psychological factors contributing to pain.
!20
c. Chaplain/Clergy assistance for suspected spiritual factors contributing to pain.
d. Interventional Pain and/or Radiation Oncology consultation.
e. Rehabilitation consultations (Physiatry, Physical and Occupational Therapy) to
maximize physical analgesic modalities.
f. Pharmacist assistance with drug/route information.
References
1. Mercadante F, Portenoy RK. Opiate Poorly Responsive Cancer Pain Parts 1-3. J Pain
Symptom Management. 2001; 21(2):144-150, 21(3):255-264, 24(4):338-354.
2. Smith TJ, Staats PS, Deer T, et al. Randomized clinical trial of an implantable drug delivery
system compared with comprehensive medical management for refractory cancer pain:
impact on pain, drug-related toxicity, and survival. J Clin Oncol. 2002; 20(19):4040-9.
3. Fallon M. When morphine does not work. Support Care Cancer. 2008; 16(7):771-5.
4. Quigley C. Opioid switching to improve pain relief and drug tolerability. Cochrane Database
of Systematic Reviews. 2004, Issue 3. Art. No.: CD004847. DOI:
10.1002/14651858.CD004847.
5. Hanks GW. Opioid-responsive and opioid-non-responsive pain in cancer. Br Med Bull.
1991; 47(3):718-31.
6. Hanks G, Forbes K. Opioid responsiveness. Acta Anaesthesiologica Scand.
1997; 41:154-158.
Author Affiliations: University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania (TS, RA),
and Medical College of Wisconsin, Milwaukee, Wisconsin (DEW).
Version History: Originally published May 2009; copy-edited August 2015.
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!
Pain Miscellaneous Topics

#49 Gapapentin for Neuropathic
Pain . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-3
#85 Epidural
Analgesia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . 4-5
#117 Pediatric Pain Assessment Scales . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . .6-7
#148 The Lidocane Patch . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . 8-9
#187 Non-Tricyclic Antidepressants for Neuropathic Pain . . . . . . . . . . . . . . . . . . . . .

. . . . . . . 10-12
#271 Anti-Epileptic Drugs for Pain . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . . .13-15
#272 Postherpetic
Neuralgia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
16-18
#288 Pregabalin in Palliative Care . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . 19-22
#363 Opioids for Neuropathic Pain . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . .23-25
1
!

GAPAPENTIN FOR NEUROPATHIC PAIN
Anita Kishore, Linda King MD, and David E Weissman MD
Introduction Gabapentin (Neurontin) has FDA indication to treat postherpetic neuralgia and
partial onset seizures. Controlled clinical trials in diabetic neuropathy and postherpetic neuralgia
show that gabapentin at 2400-3600 mg/day has a similar efficacy to tricyclic antidepressants and
carbamazepine. Consistent, though less compelling clinical evidence supports its use for
neuropathic cancer pain, pain associated with HIV infection, chronic back pain and others
(readers wanting more in depth research findings are urged to consult Reference 1). Due to this
emerging evidence, it is widely used for the treatment of neuropathic pain. The exact mechanism
and site of action of gabapentin is unknown. Gabapentin is generally well-tolerated, easily
titrated, has few drug interactions, and does not require laboratory monitoring. However, cost
may be a limiting factor for some patients. Patients suitable for gabapentin should have a clear
neuropathic pain syndrome, characterized by sharp, shooting, lancinating and/or burning pain, in
a nerve root (radicular) or stocking/glove distribution. See Fast Fact #289 for a comparison of
gabapentin with pregabalin a similar neuropathic analgesic.
Adult Dosing Gabapentin is started at low doses (100 mg to 300 mg total daily) and increased
by 100 – 300 mg every 1-3 days to effect. A typical schedule might be: day 1-2: 300 mg nightly;
day 3-4: 300 mg twice daily; day 5-7: 600 mg twice daily; day 8 onwards: 600 mg three times a
day. The usual effective total daily dose is 900-3600 mg, administered in three divided doses per
day. Titration should proceed more slowly in elderly patients. If gabapentin is discontinued, it
should be done over a minimum of a week to prevent withdrawal seizures.
Pediatric Use There is limited data available assessing its effectiveness in neuropathic pain in
children. The American Pain Society recommends that gabapentin be considered for pediatric
neuropathic pain especially when concurrent analgesics are found to be too sedating. Their
recommended initial dose is 2 mg/kg/day with a usual dosage range of 8 to 35 mg/kg/day divided
into 3 daily doses.
Dosing in Renal Failure Gabapentin doses must be reduced for patients with renal
insufficiency.
• Creatinine Clearance (CrCl) 30-60 ml/min: maximum daily dose is 1400 mg, divided.
• CrCl 16-30 ml/min: maximum daily dose is 700 mg, given once daily.
• CrCl 15ml/min: maximum daily dose is 300 mg, once daily. Doses should decrease
proportionally for CrCl less than 15 ml/min (e.g. 300 mg every other day for a CrCl of ~7.5 ml/
min).
• For patients on hemodialysis a supplemental dose is usually given after dialysis (usually
100-300 mg).
Adverse Reactions Sedation, confusion, dizziness, and ataxia are the most common side
effects, especially with rapid dose titration. Tolerance to these effects appears to develop within a
few days if the dose is held at the highest tolerated dose until symptoms improve or stabilize.
2
Dosage Formulations Gabapentin is available in 100 mg, 300 mg, and 400 mg capsules, 600
mg and 800 mg tablets, and as a liquid (250mg/5mL).
Cost Gabapentin is more expensive than older agents used for neuropathic pain (tricyclic
antidepressants and older anti-epileptic drugs such as carbamazepine). Generic gabapentin is
available, although can cost ~$100 for 90 600 mg tablets.
Other Palliative Care Uses of Gabapentin Small scale published trials have shown efficacy in
the treatment of severe chronic hiccups, pruritus, postoperative pain, restless leg syndrome and
hot flashes. Perhaps more compelling is its potential efficacy for chronic cough for which a
randomized double-blind placebo controlled trial demonstrated significant improvement in cough-
specific quality of life, cough frequency, and cough severity.
Summary Gabapentin is a safe and effective adjuvant analgesic for neuropathic pain.
Physicians should become comfortable using and titrating gabapentin in patients with neuropathic
pain syndromes.
References
1. Moore R, Wiffen PJ, Derry S, Toelle T, Rice AS C. Gabapentin for chronic neuropathic
pain and fibromyalgia in adults. Cochrane Database of Systematic Reviews 2014, Issue
4. Art. No.: CD007938. DOI: 10.1002/14651858.CD007938.pub3
2. Mishra S, Bhatnagar S, et al. A comparative efficacy of amitriptyline, gabapentin, and
pregabalin in neuropathic cancer pain: a prospective randomized double-blind placebo-
controlled study. American Journal of Hospice and Palliative Medicine 2012;29:177-182.
3. Caraceni A, et al. Gabapentin for neuropathic cancer pain: a randomized controlled trial
from the gabapentin cancer pain study group. J Clin Onc. 2004; 22:2909-2917.
4. American Pain Society. Principles of Analgesic Use in the Treatment of Acute Pain and
Cancer Pain. 6th ed, Glenview, IL: American Pain Society, 2008.
5. Micromedex Drug Database. Thompson Reuters. http://www.micromedex.com.
6. Giampiero P, Aielli F, et al. Gabapentin in the treatment of hiccups in patients with
advanced cancer: a 5-year experience. Clin Neuropharm 2010; 33:179-180.
7. Anand S, Gabapentin for pruritus in palliative care. Am J of Hospice and Pall Med 2012;
30:192-196.
8. Dauri M, Faria S, Gatti A, et al. Gabapentin and Pregabalin for the Acute Post-operative
Pain Management. A Systematic-Narrative Review of the Recent Clinical Evidences. Curr
Drug Targets 2009, 10(8):716-33.
9. Saletu M, Anderer P, Saletu-Zyhlarz GM, et al. Comparative Placebo-Controlled
Polysomnographic and Psychometric Studies on the Acute Effects of Gabapentin Versus
Ropinirole in Restless Legs Syndrome. J Neural Transm 2010, 117(4):463-73.
10. Butt DA, Lock M, Lewis JE, et al. Gabapentin for the Treatment of Menopausal Hot
Flashes: A Randomized Controlled Trial. Menopause 2008; 15(2):310-8.
published August 2005; 3rd Edition May 2015. Version re-copy-edited April 2009; then again May
2015; renal dosing information adjusted to reflect current recommendations, and updated cost
information added.
3

EPIDURAL ANALGESIA
Debra Gordon RN and Mark Schroeder MD
Background Epidural analgesia with local anesthetics, opioids, and/or alpha-agonists can
provide superior regional analgesia over conventional systemic routes (IV or PO). In contrast to
drugs administered systemically, drugs administered in the epidural space are extremely potent
since the drug is delivered close to the site of action (opioid and alpha receptors in the spinal
dorsal horn or local anesthetic blockade of nerve roots). Because of this, systemic side effects
such as nausea, sedation, and constipation, are minimized. In palliative care, epidural analgesia
may be appropriate for patients with regional pain (e.g. pelvic pain from cervical cancer) and/or
patients who do not tolerate or obtain relief from oral/parenteral drugs and non-drug therapies.
Indwelling Epidural Catheters In patients with refractory cancer pain, anesthesiologists

typically place a more durable and longer lasting epidural catheter than the epidural catheters
used for childbirth. These indwelling epidural catheters, are tunneled under the skin, directed
away from the spine, and covered it with clear adhesive dressing to reduce infection. Indwelling
epidural catheters can remain in place for weeks to months and can be utilized in the home
setting; however, longer catheter durations are associated with higher risks of serious adverse
effects such as a deep epidural infection. The best estimate is that one in 35 patients with an
epidural catheter in place for 74 days for cancer pain can be expected to get a deep epidural
infection and 1 in 500 may die of such complications. .
Medications The epidural solution typically contains a local anesthetic such as bupivacaine
along with an opioids such as fentanyl and morphine. Clonidine is sometimes utilized when
neuropathic pain is present. If the patient is getting a low dose of the anesthetic, lower leg
movement and function is often preserved; at higher doses, however, patients may lose
ambulation. Drugs administered epidurally are distributed by three main pathways:
• Diffusion through the dura into the CSF, then to the spinal cord or nerve roots.
• Vascular uptake by the vessels in the epidural space into systemic circulation.
• Uptake by the fat in the epidural space; creating a drug depot from which the drug can
eventually enter the CSF or the systemic circulation.
Patient Controlled Epidural Analgesia (PCEA) Epidural analgesia can be administered by

intermittent boluses (by a clinician or by patient controlled epidural analgesia using an appropriate
pump); continuous infusion; or a combination of both. PCEA is used to supplement a basal rate,
to allow a patient to manage breakthrough pain in order to meet their individual analgesic
requirements. Like IV PCA, PCEA can provide more timely pain relief, more control for the
patient, and convenience for both the patient and nurse to reduce the time required to obtain and
administer required supplemental boluses. Unlike IV PCA, the lockout interval of PCEA varies
widely based on the lipid solubility of the opioid administered, from 10 minutes with fentanyl to
60-90 minutes when morphine is used. If local anesthetic is used, the lockout interval should be
at least 15 minutes to allow for peak effect of the supplemental local anesthetic dose.
Management Due to the proximity of drug delivery to its site of action, frequent assessment of
pain relief, side effects, and signs or symptoms of technical complications (catheter dislodgement,
epidural hematoma or abscess, pump malfunction, etc.) are necessary. This should be done
every hour for the first 24 hours, then every 4 hours. Assess and document on the pain
management flowsheet:
4
• Patient’s pain rating using patient-specific pain scale (e.g. 0-10), both at rest and with
activity.
• Level of sedation & respiratory rate, preferably by the same nurse during each shift.
• Side effects: pruritis, nausea, urinary retention, orthostatic hypotension, motor block.
• Sign of catheter insertion site infection or epidural abscess such as back pain,
tenderness, erythema, swelling, drainage, fever, malaise, neck stiffness, progressive
numbness, or motor block.
• Changes in sensory/motor function that may indicate an epidural hematoma including
unexplained back pain, leg pain, bowel or bladder dysfunction, motor block.
This Fast Fact was adapted with permission from the University of Wisconsin Hospital &
Clinics, Madison, WI Pain Patient Care Team ‘Pain Management Fast Facts – 5 Minute
Inservice’ series.
References
1. Pasero C, Portenoy RK, McCaffery M. Opioid Analgesics. In: McCaffery M, Pasero C,
eds. Pain: Clinical Manual. 2nd Ed. St Louis, MO: Mosby: 1999: pp161-299.
2. Mann C, et al. Postoperative patient-controlled analgesia in the elderly: risks and benefits
of epidural versus intravenous administration. Drugs & Aging. 2003; 20(5):337-45.
3. Antok E, et al. Patient-controlled epidural analgesia versus continuous epidural infusion
with ropivacaine for postoperative analgesia in children. Anesthesia & Analgesia. 2003;
97(6):1608-11.
4. Ruppen W, Derry S, et al. Infection rates associated with epidural indwelling catheters
for seven days or longer: systemic review and meta-analysis. BMC Pall Care 2007; 6:1-8.
5. D’arcy Y. Using tunneled epidural catheters to treat cancer pain. Nursing 2003; 33(9):17.
edited by Drew A Rosielle MD and published October 2007; 3rd Edition June 2015 by Sean Marks
– references # 4 and #5 added and incorporated into the text.
5
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PEDIATRIC PAIN ASSESSMENT SCALES
Gena Walker and Robert Arnold MD
Background Neonates and infants do experience pain. In fact, research has shown that
neonates may experience as much pain as older children and long-term consequences from
exposure to repeated painful stimuli. Untreated pain leads to increased sensitivity to subsequent
stimuli. Assessing pain in neonates and young children requires use of age appropriate scales.
There is no empirical evidence demonstrating the superiority of one assessment tool, but
research suggests that the same scale(s) should be used within an institution.
Behavioral Observational Scales: The primary method of pain assessment for infants, children
less than 3 yrs old, and developmentally disabled patients. Validated tools include:
• CRIES: Assesses Crying, Oxygen requirement, Increased vital signs, facial Expression,
Sleep. An observer provides a score of 0-2 for each parameter based on changes from
baseline. For example, a grimace, the facial expression most often associated with pain,
gains a score of 1 but if associated with a grunt will be scored a 2. The scale is useful for
neonatal postoperative pain.
• NIPS: Neonatal/Infants Pain Scale has been used mostly in infants less than 1 yr of age.
Facial expression, cry, breathing pattern, arms, legs, and state of arousal are observed
for 1 minute intervals before, during, and after a procedure and a numeric score is
assigned to each. A score >3 indicates pain. An example is available at: http://
www.anes.ucla.edu/pain/assessment_tool-nips.htm.
• FLACC: Face, Legs, Activity, Crying, Consolability scale has been validated from 2 mo to
7 years. FLACC uses 0-10 scoring. An example is available at: http://
www.anes.ucla.edu/pain/assessment_tool-flacc.htm.
• CHEOPS: Children’s Hospital of Eastern Ontario Scale. Intended for children 1-7 yrs old.
Assesses cry, facial expression, verbalization, torso movement, if child touches affected
site, and position of legs. A score >/= 4 signifies pain. An example is available at: http://
www.anes.ucla.edu/pain/assessment_tool-cheops.htm.
Self report: Children 3 years of age and older can rank their pain using one of several validated
scales including:
• Wong-Baker Faces scale: 6 cartoon faces showing increasing degrees of distress. Face
0 signifies “no hurt” and face 5 the “worst hurt you can imagine.” The child chooses the
face that best describes pain at the time of assessment. An example is available at: http://
www1.us.elsevierhealth.com/FACES/.
• Bieri-Modified: 6 cartoon faces starting from a neutral state and progressing to tears/
crying. Scored 0-10 by the child. Used for children >3 years.
• Visual analogue scale: Uses a 10 cm line with one end marked as no pain and the
opposite end marked as the worst pain. The child is asked to make a mark on that line
that is then measured in cm from the no pain end.
Parent or Caregiver Report:
• INRS: Individualized Numeric Rating Scale. This is a validated pain assessment tool for
nonverbal children with intellectual disability. Essentially, it is an adaptation of the numeric
rating scale that incorporates the parents’ and/or caregiver’s descriptions of the child’s
past and current responses to pain. Once described, the responses are then stratified on
a scale from 0 to 10.
6
References
1. Hockenberry M, Wilson D, et al. Wong’s Nursing Care of Infants and Children. 7th
Edition. St Louis, MO: Mosby; 2003: pp1052-1053.
2. Berde CB, Sethna NF. Analgesics for the treatment of pain in children. N Engl J Med.
2002; 347:1094-1101.
3. Zempsky WT, Schechter, NL. What’s new in the management of pain in children.
Pediatrics in Review. 2003; 24:337-347.
4. Merkel SI, Voepel-Lewis T, Shayevitz JR, Malviya S. The FLACC: a behavioral scale for
scoring postoperative pain in young children. Pediatr Nurs. 1997; 3(3):293-7.
5. Hicks CL, von Baeyer CL, Spafford PA, et al. The Faces Pain Scale-Revised: toward a
common metric in pediatric pain measurement. Pain. 2001; 93(2):173-83.
6. Cancer Pain Management in Children (web-site). Texas Cancer Council. Available at:
http://www.childcancerpain.org.
7. Solodiuk J, Curley MA. Pain assessment in nonverbal children with severe cognitive
impairments: the Individualized Numeric Rating Scale (INRS). J Pediatr Nurs 2003;
18:295-299.
8. Solodiuk JC, Scott-Sutherland J, et al. Validation of the Individualized Numeric Rating
Scale (INRS): a pain assessment tool for nonverbal children with intellectual disability.
Pain 2010; 150:231-236.
Sarah Friebert MD.
7
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THE LIDOCAINE PATCH
Drew A Rosielle MD
Background The Lidocaine Patch 5% is a topical analgesic developed to treat peripherally

generated neuropathic pain. It is approved in the US for treating post-herpetic neuralgia (PHN).
This Fast Fact reviews its mechanism of action, research data, and dosage information.
Mechanism of Action The lidocaine patch is believed to provide analgesia by reducing

aberrant firing of sodium channels on damaged pain fibers directly under the patch. Less than
5% of the lidocaine is absorbed, an insufficient dose to cause systemic effects or local anesthesia
(patients do not feel numb under the patch) (1,2). It was initially expected that only superficial
pain qualities would be affected by the patch; however there is evidence that non-superficial
qualities of pain (e.g. “dull” or “deep” pain) are also diminished by the patch (3,4). Nociceptive
pain generation (such as sensitivity to pinprick, or hot or cold painful stimuli) is not affected.
Tachyphylaxis has not been formally investigated; case reports have indicated some individuals
have used the patch successfully for over a decade.
Research Data Most of the research using the lidocaine patch, and all of the randomized,
placebo-controlled trials, have been in neuropathic pain syndromes. It has shown modest
(10-20 mm decrease in pain on the 100 mm visual analog scale) but significant efficacy in PHN in
randomized, placebo-controlled trials (1). Several controlled, blinded studies evaluating the
efficacy of the patch for acute pain syndromes (surgical/incisional pain, acute rib fractures) have
not shown the patch to be superior to placebo for these syndromes (5,6,7). Due to its ease of use
and lack of toxicity or drug interactions, it is being used much more widely than PHN. Multiple
case-reports, open-label studies, and unpublished anecdotal reports have found the patch
efficacious for a range of neuropathic conditions (e.g. diabetic neuropathy, post-surgical
neuralgia), chronic low back pain, osteoarthritis, bony metastases, vertebral compression
fractures, and on open decubitus ulcer beds (8,9). Note: this latter practice is directly warned
against by the manufacturer and there are no published data as to the patch’s safety when used
on open wounds. Great caution is necessary in interpreting results of non-blinded, non-controlled
clinical reports due to the high likelihood of a placebo effect (10).
Administration/Toxicity The lidocaine patch comes as a 10x14 cm adhesive patch containing

700 mg of lidocaine. A box of 30 patches costs approximately $300 USD (priced August 2015 at
www.drugs.com). One to three patches, or only a portion of a patch, can be placed directly over
painful areas. Due to concerns about systemic lidocaine toxicity, up to a maximum of 3 patches
applied simultaneously for 12 hours a day has been approved. Onset of analgesia is within a few
hours and patients should be able to determine whether the patch is helpful within a week. Some
patients find that pain worsens when the patch is off for 12 hours or if it is left on for more than 18
hours, therefore extended dosing has been investigated. Several pharmacokinetic studies have
shown that systemic lidocaine levels remain well within the safe range with doses of up to 4
patches on for 24 hours (11). Adverse reactions are rare, mild, and mostly topical (rash). The
patch is contraindicated in advanced liver failure due to decreased clearance of lidocaine.
Summary The lidocaine patch 5% is an expensive, safe, and modestly effective topical
analgesic for post-herpetic neuralgia. It has not been proven to be effective for other pain
syndromes, and clinicians should strongly consider reports of its efficacy to be related to placebo
mechanisms.
References
1. Davies PS, Galer BS. Review of lidocaine patch 5% studies in the treatment of postherpetic
neuralgia. Drugs. 2004; 64:937-947.
2. Gammaitoni AR, Alvarez NA, Galer BS. Safety and tolerability of the lidocaine patch 5%, a
8
targeted peripheral analgesic: a review of the literature. J Clin Pharmacol. 2003; 43:111-117.
3. Devers A, Galer BS. Topical lidocaine patch relieves a variety of neuropathic pain conditions:
an open-label study. Clin J Pain. 2000; 16:205-208.
4. Galer BS, et al. The lidocaine patch 5% effectively treats all neuropathic pain qualities:
results of a randomized, double-blind, vehicle-controlled, 3-week efficacy study with use of
the neuropathic pain scale. Clin J Pain. 2002; 18:297-301.
5. Bischoff JM, Petersen M, et al. Lidocaine patch (5%) in treatment of persistent inguinal
postherniorrhaphy pain: a randomized, double-blind, placebo-controlled, crossover trial.
Anesth. 2013; 119:1444-52.
6. Ingalls NK, Horton ZA, et al. Randomized, double-blind, placebo-controlled trial using
lidocaine patch 5% in traumatic rib fractures. J Am Coll Surg. 2010;210:205-9.
7. Chevilla AL, Sloan JA, et al. Use of a lidocaine patch in the management of postsurgical
neuropathic pain in patients with cancer: a phase III double-blind crossover study (N01CB).
Support Care Ca. 2009; 17:451-60.
8. Gimbel J, et al. Lidocaine patch treatment in patients with low back pain: results of an open-
label, nonrandomized pilot study. Am J Therap. 2005; 12:311-319.
9. Garzón-Rodríguez C, Casals Merchan M, et al. Lidocaine 5 % patches as an effective short-
term co-analgesic in cancer pain. Preliminary results. Support Care Ca. 2013; 21:3153-8.
10. Hashmi JA, Baliki MN, Huang L, et al. Lidocaine patch (5%) is no more potent than placebo
in treating chronic back pain when tested in a randomised double blind placebo controlled
brain imaging study. Mol Pain. 2012; 8:29.
11. Gammaitoni AR, Davis MW. Pharmacokinetics and tolerability of lidocaine patch 5% with
extended dosing. Ann Pharm. 2002; 36:236-240.
in January 2006. Re-copy-edited in April 2009. Updated with newer research findings in August
2015.
9
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NON-TRICYCLIC ANTIDEPRESSANTS FOR NEUROPATHIC PAIN
Pippa Hawley B.Med, FRCPC
Background Tricyclic antidepressants (TCAs) have long been recognized as effective agents
for neuropathic pain. Due to their sedating and anticholinergic side effects there has been much
interest in newer antidepressant agents with different side effect profiles. This Fast Fact reviews
the use of non-tricyclic antidepressants for neuropathic pain.
Pharmacology Serotonin (5HT) and norepinephrine (NE) mediate descending inhibition of

ascending pain pathways in the brain and spinal cord. Experience has suggested that newer
antidepressants which enhance NE action are more effective analgesics than many older
antidepressants which predominantly enhance 5HT action. TCAs are thought to cause analgesia
by NE and 5HT reuptake inhibition; they also have other pharmacologic properties that may
contribute to analgesia such as reducing sympathetic activity, NMDA-receptor antagonism,
anticholinergic activity, and sodium-channel blockade. Non-tricyclic antidepressants seem to be
less efficacious for neuropathic pain (see below): this may in part be because of their ‘cleaner’
pharmacodynamic profiles.
Clinical Evidence Most randomized controlled trials of non-tricyclic antidepressants for pain
have been for diabetic peripheral neuropathy or post-herpetic neuralgia. There have been a few
well controlled studies in the treatment and prevention of chemotherapy induced peripheral
neuropathy (CIPN) but limited good data in other neuropathic conditions.
• Selective Serotonin Reuptake Inhibitors (SSRIs): Fluoxetine is not effective for
neuropathic pain. Paroxetine and citalopram have shown only mild benefit for HIV-related
and diabetic neuropathy in small studies. Other SSRIs have not been evaluated.
• Serotonin Norepinephrine Reuptake Inhibitors (SNRIs):
o Venlafaxine: Low doses of are predominantly serotonergic, but higher doses add
substantial noradrenergic effects. Doses of 150-225 mg/day appear to have mild to
moderate analgesic effect (30-50% reduction in pain) with a number needed-to-treat
(NNT) of 4.6 in painful diabetic neuropathy (only one out of every 4-5 patients treated will
benefit). In contrast, TCAs have shown a NNT of 2-3. Pilot data, in additional to one
randomized controlled trial, support the use of extended release venlafaxine in preventing
the onset of CIPN if given at doses of 25 mg to 75 mg a day one hour prior to
chemotherapy infusion as well as 11 days after. One head-to-head trial showed
venlafaxine 225 mg/day had the same tolerability as 150 mg/day of imipramine (a TCA),
but venlafaxine was less effective for pain. Side-effects of venlafaxine include nausea,
sedation, headache and dizziness. The usual starting dose is 37.5 mg daily, increasing
weekly in 37.5 mg increments. Use of venlafaxine for analgesia is not FDA approved; a
75 mg tab costs approximately $3.70 (average US wholesale price).
o Duloxetine: has been shown to have a mild to moderate analgesic effect in industry-
sponsored trials in diabetic peripheral neuropathy (NNT 5.2). In addition, a randomized
controlled trial showed relatively small but significant neuropathic pain relief compared
with placebo. Onset of analgesia is at about 1 week, with maximum effect at about 4
weeks. A dose of 60 mg a day has been best studied for both diabetic peripheral
neuropathy and CIPN; 60 mg BID may lead to increased analgesia but at the expense of
an increased risk of nausea, sedation, constipation, sweating, and insomnia. Duloxetine
has an FDA indication for use in diabetic peripheral neuropathic pain in the USA. A 60
mg tab costs approximately $3.50.
• Other Antidepressants Buproprion is a dopamine and norepinephrine reuptake inhibitor
with mild analgesic effect according to one study involving 41 patients with a mix of
neuropathic pain syndromes. Mirtazapine has a complicated pharmacology with unknown
analgesic effects.
10
Summary There are relatively well defined and preferred therapies for neuropathic pain
including newer generation anticonvulsants (such as gabapentin), TCAs, and opioids in select
patients. In patients with ongoing pain despite treatment with these agents, or who are intolerant
to them, venlafaxine or duloxetine may be helpful. There are no comparative studies between
non-tricyclics for neuropathic pain, thus an agent should be selected based on its side-effect
profile, cost, and familiarity with use.
References
1. Attal N, et al. EFNS guidelines on pharmacological treatment of neuropathic pain. Eur J
Neurology. 2006; 13:1153-1169.
2. Saarto T, Wiffen PJ. Antidepressants for neuropathic pain. Cochrane Database of
10.1002/14651858.CD005454.pub2.
3. Moulin DE, et al. Pharmacological management of chronic neuropathic pain. Consensus
statement and guidelines from the Canadian Pain Society. Pain Res Manage. 2007;
12(1):13-21.
4. Rowbotham MC, et al. Venlafaxine extended release in the treatment of painful diabetic
neuropathy: A double-blind, placebo-controlled study. Pain. 2004; 110:697-706. (Erratum
in 2005; 113:248).
5. Durand JP, Alexandre J, et al. Clinical activity of venlafaxine and topiramate against
oxaliplatin-induced disabling permanent neuropathy. Anticancer Drugs 2005; 16:587-591.
6. Durand JP, Deplanque G. Efficacy of venlafaxine for the prevention and relief of
oxaliplatin-induced acute neurotoxicity: results of EFFOX, a randomized, double-blind,
placebo-controlled phase III trial. Ann Oncol 2012 23 (1):200-205.
7. Sindrup SH, et al. Venlafaxine vs imipramine in painful polyneuropathy. A randomized,
controlled trial. Neurology. 2003; 60:1284-1289.
8. Goldstein DJ, et al. Duloxetine vs placebo in patients with painful diabetic neuropathy.
Pain. 2005; 116:109-18.
9. Lavoie Smith EM, Pang H, et al. Effect of duloxetine on pain, function, and quality of life
among patients with chemotherapy-induced painful peripheral neuropathy: a randomized
clinical trial. JAMA 2013; 309:1359-1367.
10. Bomholt SF, Mikkelse JD, Blackburn-Munro G. Antinociceptive effects of the
antidepressants amitriptyline, duloxetine, mirtazapine and citalopram in animal models of
acute, persistent and neuropathic pain., Neuropharmacology. 2005; 48(2):252-263.
11. Semenchuk MR, Sherman S, Davis B. A double blind randomized controlled trial of
buproprion SR for the treatment of neuropathic pain. Neurology. 2001; 57(9):1583-8.
Version History: Originally published September 2007. Version re-copy-edited in May 2009;
revised again July 2015 by Sean Marks MD – references #5, #6, and #9 added and incorporated
into the text.
11
12
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ANTI-EPILEPTIC DRUGS FOR PAIN
Seth Hepner and René Claxton MD
Introduction Tri-cyclic antidepressants (TCAs), serotonin-norepinephrine reuptake inhibitors
(SNRIs) and anti-epileptic drugs (AEDs) are the mainstays of adjuvant therapy for neuropathic
pain. This Fast Fact reviews the evidence for the use of AEDs in the treatment of neuropathic
pain. For a more in-depth look at gabapentin, pregabalin, and antidepressants for neuropathic
pain see Fast Facts #49, 187, 288, and 299. Due to lack of head-to-head data, evidence is
presented as numbers needed to treat (NNT) and numbers needed to harm (NNH). For instance,
an NNT of 5 for 50% pain reduction means for every 5 patients treated with a drug, only 1 of them
would achieve a 50% reduction in pain. All data presented and doses mentioned are for adults
and based on investigations of patients with chronic pain. Given the paucity of research about the
use of adjuvants for pain management in patients with life-limiting illnesses, many clinicians
empirically extrapolate available data to palliative care patients.
Gabapentin is effective in treating central and peripheral neuropathic pain. According to a 2011
Cochrane review of the effect of gabapentin on chronic neuropathic conditions (including post-
herpetic neuralgia, painful diabetic neuropathy, mixed neuropathic pain), the NNT is 5.8 (4.8-7.2)
to achieve at least moderate benefit. Adverse effects are frequent, usually tolerable and include
drowsiness, dizziness and edema (1). Gabapentin should be dose adjusted for renal dysfunction.
It should be withdrawn gradually to avoid precipitating seizures. Maximum dose is 3,600 mg/day
(2).
Pregabalin is effective in treating peripheral and central neuropathic pain. Its effectiveness
increases as the dose approaches 600 mg/day. At a dose of 600 mg/day, the NNT to decrease
pain by 50% for the following conditions is: 3.9 (range 3.1-5.1) for post-herpetic neuralgia; 5.0
(range 4.0-6.6) for diabetic neuropathy; and 5.6 (range 3.5-14) for central neuropathic pain. There
was no difference in incidence of side effects among participants taking pregabalin vs placebo
and no indication of a dose response to side-effects (3). Dosing starts at 150 mg/day in divided
doses either twice or three times daily (2).
Carbamazepine is effective for neuropathic pain, specifically trigeminal neuralgia, but is not
considered first-line therapy due to its adverse effects. A meta-analysis reported that
carbamazepine reduced chronic neuropathic pain compared to placebo with NNT of 1.7.
However, adverse events occur frequently: NNH = 2.6 (4). Common side effects include
leukocytosis, thrombocytopenia, dizziness, drowsiness, ataxia, nausea/vomiting and blurred
vision. Additionally, there is a risk of agranulocytosis, aplastic anemia, and Stevens Johnson
syndrome. Laboratory tests (BUN, complete blood count, sodium, liver function tests, urinalysis)
and serum drug levels should be checked at baseline and during treatment. Dosing starts at
100-200 mg twice a day and is titrated by 200 mg/day every 3 – 5 days until pain relief is
achieved. Maximum dose is 1,200 mg/day (2).
Oxcarbazepine is an analogue of carbemazepine which is equally effective at treating trigeminal
neuralgia (5) but with fewer side effects (6). Oxcarbazepine can be started at 300 mg twice a day
and titrated up by 300 mg/day every 3 days to therapeutic effect. Maximum dose is 2,400 mg/day
(2).
Valproic acid was evaluated in a 2011 meta-analysis for the treatment of neuropathic pain. There
were insufficient data for reliable pooled analysis, and the authors recommend against its use as
first line therapy (7). Several small studies (n<60) showed benefit (maximum of 1200 mg/day in
divided doses) over placebo in the treatment of diabetic neuropathy (8). However, studies of
valproic acid have failed to find an effect (9). Adverse effects include liver function test
abnormalities, dizziness, drowsiness and nausea. Maximum dose is 60 mg/kg/day (2).
Topiramate has not demonstrated convincing efficacy for painful diabetic neuropathy. In three
studies totaling more than 1200 participants, topiramate did not show a statistically significant
effect (9). A subsequent randomized controlled trial of 317 patients with diabetic neuropathy
showed a benefit over placebo with a NNT of 6.9. Serious adverse events include convulsion,
13
bradycardia, and syncope (10). Additional adverse effects include sedation, nausea, diarrhea and
metabolic acidosis (2). Dosing starts at 50 mg/day and can be titrated up to 400 mg/day (10).
Lacosamide has weak evidence supporting its use. In a randomized, placebo controlled study,
patients treated with lacosamide (100-400 mg/day) for diabetic neuropathy showed a decrease in
baseline pain by 2 or more points on an 11-point scale compared to controls, NNT 10.9. Side
effects were similar (12). Subsequent trials have failed to show similar effects except for a
subgroup analysis of 400 mg/day (9). Dosing starts at 50 mg twice daily. Abrupt discontinuation
can precipitate seizures (2).
Using other AEDs including phenytoin and levetiracetam is not supported by clinical research.
Although, a single small study (n=92) demonstrated benefit for lamotrigine in treating painful HIV-
related neuropathy at doses of 200-400 mg daily (12, 9, 13).
Summary TCAs, SNRIs, and the AEDs gabapentin and pregabalin are the best adjuvant
analgesics for neuropathic pain. For patients who are intolerant to or who have pain refractory to
the above medications, one can consider therapy with carbamazepine, oxcarbazepine, valproic
acid, topiramate or lacosamide, keeping in mind they are associated with more side effects and
lower rates of efficacy.
References
1. Moore RA, Wiffen PJ, Derry S, McQuay HJ. Gabapentin for chronic neuropathic pain and
fibromyalgia in adults. Cochrane Database of Systematic Reviews. 2011, Issue3, Art No.:
CD007938. DOI: 10.1002/14651858.CD007938.pub2
2. Micromedex® Healthcare Series [Internet database]. Greenwood Village, Colo: Thomson
Reuters (Healthcare) Inc. Updated periodically.
3. Moore RA, Straube S, Wiffen PJ, Derry S, McQuay HJ. Pregabalin for acute and chronic
pain in adults. Cochrane Database of Systematic Reviews. 2009, Issue 3. Art. No.:
CD007076. DOI: 10.1002/14651858.CD007076.pub2.
4. Wiffen PJ, Derry S, Moore RA, McQuay HJ. Carbamazepine for acute and chronic pain in
adults. Cochrane Database of Systematic Reviews. 2011, Issue 1. Art. No.: CD005451.
DOI: 10.1002/14651858.CD005451.pub2.
5. Zakrzewska J, Linskey M. Trigeminal Neuralgia. Clinical Evidence. 2009; 3(1207).

Retrieved Nov 15, 2011 from http://clinicalevidence.bmj.com/ceweb/conditions/nud/
1207/1207.jsp
6. Finnerup NB, et al. Algorithm for neuropathic pain treatment: An evidence based
proposal. Pain. 2005; 18:289-305.
7. Gill D, Derry S, Wiffen PJ, Moore RA. Valproic acid and sodium valproate for neuropathic
pain and fibromyalgia in adults.Cochrane Database of Systematic Reviews. 2011, Issue
10. Art. No.: CD009183. DOI: 10.1002/14651858.CD009183.pub2.
8. Kochar DK, et al. Sodium valproate for painful diabetic neuropathy: A randomized
double-blind placebo-controlled study. Quarterly J Med. 2004; 97:33-8.
9. Finnerup NB, et al. The evidence for pharmacological treatment of neuropathic pain.
Pain. 2010; 150: 573-581.
10. Raskin P, et al. Topiramate vs placebo in painful diabetic neuropathy: analgesic and
metabolic effects. Neurology. 2004; 63(5):865-73.
11. Rauck RL, et al. Lacosamide in painful diabetic peripheral neuropathy: A phase 2 double
blind placebo-controlled study. Clin J Pain. 2007; 23:150-8.
12. Goodyear-Smith F, Halliwell J. Anticonvulsants for neuropathic Pain: gaps in the

evidence. Clin J Pain. 2009; 25: 528-536.
14
13. Wiffen PJ, Derry S, Moore RA. Lamotrigine for acute and chronic pain. Cochrane
Database of Systematic Reviews. 2011, Issue 2. Art. No.: CD006044. DOI:
10.1002/14651858.CD006044.pub3.

Conflict of Interest Disclosure: the authors have disclosed no relevant conflicts of interest.
Version History: First published September 2013. Re-copy-edited by Sean Marks in September
2015.
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!

POSTHERPETIC NEURALGIA
Shannon Ryan-Cebula MD and Hunter Groninger MD
Background Postherpetic neuralgia (PHN) is a syndrome of zoster-associated pain persisting
more than 3 months after resolution of an initial herpes zoster (HZ) rash (‘shingles’).
Epidemiology Inconsistencies in diagnosis and data collection make the incidence of HZ and
PHN difficult to estimate (1,2). PHN develops rarely in those under 50 years. However, it occurs
in 20% of persons 60 to 65 with HZ and its incidence rises to 30% in persons over 80 years old
(1,2). Risk factors for PHN include severe acute shingles-related pain, rash severity (i.e., more
than 50 lesions), increasing age, and immunocompromised status (3,4).
Pathophysiology In acute HZ, reactivation of the virus from the dorsal root ganglia of spinal or
cranial nerves causes inflammation and damage to the affected nerve tissue, resulting in acute
pain. Subsequently, primary afferent neurons responding to the acute neuronal damage of zoster
reactivation can cause sensitization of the nociceptive dorsal horn neurons, resulting in a
prolonged exaggerated response to non-noxious stimuli (1). This central sensitization is thought
to be a key mechanism in the development and maintenance of the pain of PHN.
Natural History Most HZ patients experience resolution of the rash and acute HZ pain within
two months (1). For those who develop PHN, prolonged severe disabling symptoms rarely remain
beyond 6 months (5). A small subset may experience irreversible damage to skin and sensory
abnormalities that can result in ongoing pain for years (2). For all patients with acute HZ and/or
PHN, physical and emotional quality-of-life can be affected (6-8).
Prevention In adults over 60 years old, live vaccination against the zoster virus reduces
overall incidence of HZ by 50% and PHN by two-thirds. It is contraindicated in patients with
immune deficiencies (primary or acquired such as patients with leukemia), including patients
taking immunosuppressants or high dose corticosteroids (9). Initiating antiviral drugs within 72
hours of rash onset reduces acute and chronic pain associated with HZ. There is no clear benefit
to initiation after this window (10-12). Best available evidence does not support the routine use of
glucocorticoids in preventing PHN (10).
Pain management strategies PHN is a quintessential neuropathic pain syndrome and the
approach to treatment is similar to other neuropathic syndromes. Recent guidelines cite strong
evidence for using tricyclic antidepressants (TCAs), gabapentinoids (gabapentin, pregabalin),
opioids, lidocaine 5% patch, and capsaicin 8% patch to manage PHN (13,14). (See Fast Facts
#49, 148, 255, and 271.) Strong evidence also supports combined therapy of gabapentin plus
opioids or TCAs (14). Second-line therapies include topical salicylate and topical capsaicin
0.075% cream. Epidural steroid injections and acupuncture are likely no better than placebo (14).
While serotonin norepinephrine reuptake inhibitors such as duloxetine are commonly used for
neuropathic syndromes (see Fast Fact #187), there are currently no published trials regarding
their use for PHN.
Cost There is limited literature regarding cost effectiveness among commonly used agents. The
following table provides current information regarding starting dose, effective dose, and cost (15).
Drug Starting dose (cost in USD/ Typical effective dose

month) (cost/month)
Gabapentin 300 mg capsule 900 mg/day ($19) 1800 mg/day ($99)

Pregabalin 50 mg capsule 150 mg/day ($180) 450 mg/day ($180)
16
Desipramine 25 mg tablet 25 mg/day ($38) 100 mg/day ($99)
Nortriptyline 50 mg capsule 50 mg/day ($20) 75 mg/day ($20)
Lidocaine 5% patch 1 patch per 12 hours ($217) 1 patch/12 hours ($217)
Capsaicin 8% patch 1 patch per 90 days ($265) 1 patch/ 90 days ($265)
References
1. Delaney A, Colvin LA, Fallon MT, et al. Postherpetic neuralgia: from preclinical models to
the clinic. Neurotherapeutics. 2009; 6:630–637.
2. Watson P. Postherpetic neuralgia. Clin Evid Handbook. June 2011;301-303.
3. Nagasako EM, Johnson RW, Griffin DR, Dworkin RH. Rash severity in herpes zoster:
correlates and relationship to postherpetic neuralgia. J Am Acad Dermatol. 2002; 46(6):
834.
4. Jung BF, Johnson RW, Griffin DR, Dworkin RH. Risk factors for postherpetic neuralgia in
patients with herpes zoster. Neurol. 2004; 62(9):1545-51.
5. Thyregod HG, et al. Natural history of pain following herpes zoster. Pain. 2007;
128:148-156.
6. Johnson RW, Bouhassira D, et al. The impact of herpes zoster and post-herpetic
neuralgia on quality of life. BMC Med. 2010; 8:37.
7. Weinke T, Edte A, et al. Impact of herpes zoster and post-herpetic neuralgia on patients’
quality of life: a patient-reported outcomes survey. Z Gesundh Wiss. 2010; 18(4):
367-374.
8. Drolet M, Brisson M, Schmader KE, et al. The impact of herpes zoster and postherpetic
neuralgia on health related quality of life: a prospective study. CMAJ. 2010; 182(16):
1731-6.
9. Center for Disease Control and Prevention (2013). Herpes Zoster Vaccination for Health
Care Professionals. Retrieved from http://www.cdc.gov/vaccines/vpd-vac/shingles/hcp-
vaccination.htm. Accessed March 6, 2013.
10. Thakur R, Philip AG. Treating herpes zoster and post herpetic neuralgia: an evidence
based approach. J Fam Pract. 2012; 61(9 Suppl):S9-15.
11. Dworkin RH, Schmader KE. Epidemiology and natural history of herpes zoster and
postherpetic neuralgia. In Watson CPN, Gershon AA, eds. Herpes Zoster and
Postherpetic Neuralgia. 2nd ed. New York, NY: Elsevier Press; 2001:39-64.
12. Tyring S, Barbarash RA, Nahlik JE, et al. Famciclovir for the treatment of acute herpes
zoster: effects on acute disease and postherpetic neuralgia. A randomized, double-blind,
placebo-controlled trial. Ann Intern Med. 1995; 123:89-96.
13. Attal N, Cruccu G, et al. EFNS guidelines on the pharmacological treatment of
neuropathic pain: 2010 revision. Eur J Neurol. 2010; 17:1113-1123.
14. Dubinsky RM, Kabbani H, El-Chami Z, Boutwell C, Ali H. An evidence based report of
the quality standards subcommitee of the American Academy of Neurology. Neurol.
2004; 63:959-965.
15. Drugstore.com Online Pharmacy. Available at http://www.drugstore.com. Accessed
February 22, 2013.
Authors’ Affiliations: National Institutes of Health Clinical Center, Bethesda, MD.

Conflicts of Interest Disclosure: The authors have not disclosed any relevant conflicts of
interest.
Version History: First published September 2013. Re-copy-edited by Sean Marks in September
2015.
17
18
!

PREGABALIN IN PALLIATIVE CARE
Background Pregabalin (Lyrica®) is a second generation antiepileptic drug that was
developed after gabapentin (See Fast Fact #049). This Fast Fact will review pregabalin and its
role in palliative care. A comparison between pregabalin and gabapentin is also available (See
Fast Fact #289).  
 
Pharmacology Pregabalin binds to the alpha-2 (α-2δ) subunit of voltage-gated calcium
channels in the CNS, subsequently inhibiting the release of excitatory neurotransmitters. Its oral
bioavailability is ≥90% and can be taken with or without food. Peak plasma concentrations occur
within 1.5 hours. Pregabalin does not bind to plasma proteins, undergoes negligible metabolism,
and does not affect the major CYP450 enzymes in humans. It is unlikely to have significant drug
interactions (1,2).  
 
Dosing Starting dose for pregabalin is 150 mg/day in two to three divided doses, and may be
increased to 300 mg/day within 1 week. Maximum daily dose is 450 mg/day and 600 mg/day (in
divided doses) for fibromyalgia and other neuropathic pain disorders, respectively.  
Dosing in Renal Impairment and Failure Pregabalin must be adjusted for patients with a
CrCl <60 mL/min, as it is approximately 90% renally eliminated (2).
Total Daily Dose of Pregabalin (mg/day).

CrCl (mL/min) Columns represent typical ‘step-up’ Dose Regimen
doses
≥ 60 150 300 450 600 BID or TID

30-60 75 150 225 300 BID or TID
15-30 25-50 75 100-150 150 Once daily or
BID
< 15 25 25-50 50-75 75 Once daily
Supplementary Dosage Following Hemodialysis:*
Patients on the 25 mg once daily regimen: 25 or 50 mg
Patients on the 25–50 mg once daily regimen: 50 or 75 mg
Patients on the 50–75 mg once daily regimen: 75 or 100 mg
Patients on the 75 mg once daily regimen: 100 or 150 mg
Adverse Drug Reactions and Cautions Dizziness is the most commonly reported side effect,
followed by somnolence which is the most frequent reason for discontinuation. Other side effects
are dose-dependent and reversible -- dry mouth, angioedema, peripheral edema, blurred vision,
weight gain, and difficulty with concentration/attention (3).  
 
Research Data Pregabalin is FDA indicated for several non-cancer pain syndromes including:
diabetic peripheral neuropathy, post-herpetic neuralgia, fibromyalgia, and neuropathic pain
associated with spinal cord injury, as well as an adjunctive therapy for adult patients with partial
onset seizures. The number needed to treat for a 50% reduction in diabetic neuropathic pain is 4
when pregabalin is dosed at 600 mg/day (4). There is limited information for its use in cancer-
related neuropathic pain (5). In a double-blind, placebo-controlled, randomized trial in patients
with neuropathic cancer pain, pregabalin was compared to gabapentin, amitriptyline and placebo;
VAS scores were significantly lower in the pregabalin group, and there were clinically significant
19
morphine sparing effects of pregabalin (6). One randomized, controlled trial suggests low-dose
pregabalin (25-50 mg/day) as an effective adjuvant for cancer related bone pain (7).  
 
Cost Pregabalin comes in a 25 mg, 50 mg, 75 mg, 100 mg, 150 mg, 200 mg, 225 mg, and 300
mg oral capsules, and 20 mg/mL oral solution. It is not available as a generic formulation.
Pregabalin is approximately eight to ten times more costly than amitriptyline, and three times
more costly than venlafaxine ER and gabapentin.  
 
Summary Pregabalin is a relatively expensive medication that may have a role in management
of neuropathic pain associated with in cancer, several non-cancer syndromes, and as an adjuvant
to opioids for painful bone metastases.
References:
1. Bockbrader HN, Wesche D, Miller R, Chapel S, Janiczek N, Burger P. A comparison of
the pharmacokinetics and pharmacodynamics of pregabalin and gabapentin. Clin
Pharmacokinet. 2010 Oct;49(10):661-9.
2. Pregabalin (Lyrica®) [package insert]. New York, NY: Pfizer Parke-Davis; 2004.
3. Eisenberg E, River Y, Shifrin A, et al. Antiepileptic drugs in the treatment of neuropathic
pain. Drugs 2007; 67 (9): 1265-89.
4. Bril V, England J, Franklin GM, Backonja M, Cohen J, Del Toro D, Feldman E, Iverson
DJ, Perkins B, Russell JW, Zochodne D; American Academy of Neurology; American
Association of Neuromuscular and Electrodiagnostic Medicine; American Academy of
Physical Medicine and Rehabilitation. Evidence-based guideline: Treatment of painful
diabetic neuropathy: report of the American Academy of Neurology, the American
Association of Neuromuscular and Electrodiagnostic Medicine, and the American
Academy of Physical Medicine and Rehabilitation. Neurology. 2011 May 17;76(20):
1758-65
5. Bennett MI, Laird B, van Litsenburg C, Nimour M. Pregabalin for the management of
neuropathic pain in adults with cancer: a systematic review of the literature. Pain Med.
2013 Nov;14(11):1681-8.
6. Mishra S, Bhatnagar S, Goyal GN, Rana SP, Upadhya SP. A comparative efficacy of
amitriptyline, gabapentin, and pregabalin in neuropathic cancer pain: a prospective
randomized double-blind placebo-controlled study. Am J Hosp Palliat Care. 2012 May;
29(3):177-82.
7. Nishihara M, Arai YC, Yamamoto Y, Nishida K, Arakawa M, Ushida T, Ikeuchi M.
Combinations of low-dose antidepressants and low-dose pregabalin as useful adjuvants
to opioids for intractable, painful bone metastases. Pain Physician. 2013 Sep-Oct;
16(5):E547-52.

Version History: First published March 2015.
20

A COMPARISON OF PREGABALIN AND GABAPENTIN IN PALLIATIVE CARE
Background Gabapentin (Neurontin®) and pregabalin (Lyrica®) share a similar mechanism of
action; however the compounds differ in their pharmacokinetic and pharmacodynamic
characteristics. See Fast Fact #049 for more information regarding gabapentin and Fast Fact
#299 for pregabalin. This Fast Fact will compare and contrast these two agents.
Pharmacokinetic Profile Comparison The major pharmacokinetic difference between

gabapentin and pregabalin is their absorption from the GI tract. The absolute bioavailability of
gabapentin drops from 60-33% as the dosage increases from 900-3600mg/day(1), while
pregabalin remains ≥90% irrespective of dosage. This suggests that dose escalations of
gabapentin are accompanied by a therapeutic ceiling effect, although this has not been proven in
studies. Neither medication binds to plasma proteins, both undergo negligible metabolism, and
both are renally excreted with terminal half-lives of 5-6 hours. Overall, literature suggests that
pregabalin has a small pharmacokinetic advantage over gabapentin, although there is little
evidence-based literature to support its clinical superiority in patient care (2).
Pharmacodynamic Profile Comparison The onset of pregabalin is approximately 25

minutes, compared to 1-3 hours for gabapentin. Equally important, pregabalin can be more
rapidly titrated to an effective dose range than gabapentin (1-2 days for pregabalin versus
approximately 9 days for gabapentin) (3).
Other Differences Research suggests a target dose of at least 900-1,800mg/day (in divided
doses) of gabapentin to maintain analgesia for persistent pain (4), although doses as high as
6,000mg/day have been taken for cancer pain (5). With pregabalin, it appears analgesia can be
achieved and maintained at any dose (6). The side effects of both drugs are dose dependent,
reversible, and relatively similar in nature (e.g., dizziness and somnolence). There is no
significant difference in the number of drug interactions. Gabapentin is not a controlled
substance, while pregabalin is designated as a Schedule V drug.
Use in Palliative Care Gabapentin is FDA-approved for post-herpetic neuralgia, and adjunctive
therapy in the treatment of partial onset of seizures, while pregabalin is approved for diabetic
peripheral neuropathy, post-herpetic neuralgia, fibromyalgia, and neuropathic pain associated
with spinal cord injury, as well as an adjunctive therapy for adult patients with partial onset
seizures. Research suggests the number need to treat (NNT; i.e. the number of patients needed
to be treated in order for one patient to benefit) in diabetic neuropathy for pregabalin is 4 (for a
50% reduction at 600 mg/day); while gabapentin had only a small effect on pain reduction
(therefore the NNT was not reported) (7). Although gabapentin is frequently given to patients with
chemotherapy-induced peripheral neuropathy, few controlled trials have been conducted and
investigations have shown conflicting results. There has been only one study comparing the
efficacy of gabapentin and pregabalin in neuropathic cancer pain. In this double-blind,
randomized, placebo-controlled trial, patients were given amitriptyline, gabapentin, pregabalin, or
placebo. There were statistically lower VAS scores in the pregabalin group when compared to the
others. The authors also noted a statistically and clinically significant morphine-sparing effect of
pregabalin as well (8). This single, mid-quality trial has not been replicated
Cost Pregabalin is approximately three times more expensive than gabapentin, which is
available as a generic. 
 
Summary Pregabalin has some pharmacokinetic advantages over gabapentin, but is much
more costly. There are no clear data demonstrating improved clinical outcomes of one agent over
21
the other.  
References
1. Twycross R, Wilcock A, Charlesworth S, et al. Palliativedrugs.com therapeutic highlights:
gabapentin. Indian J Palliat Care. 2003;9(2):71-74.
2. Bockbrader HN, Wesche D, Miller R, Chapel S, Janiczek N, Burger P. A comparison of

the pharmacokinetics and pharmacodynamics of pregabalin and gabapentin. Clin
Pharmacokinet. 2010 Oct;49(10):661-9.
3. McCaffery M, Pasero C, editors. Pain: clinical manual. 2nd ed. St Louis, (MO): Mosby;
1999.
4. Backonja MM, Serra J. Pharmacologic management part 1: better-studied neuropathic

pain diseases. Pain Med. 2004 Mar;5 Suppl 1:S28-47.
5. Farrar JT, Portenoy RK. Neuropathic cancer pain: the role of adjuvant analgesics.
Oncology (Williston Park). 2001 Nov;15(11):1435-42, 1445; discussion 1445, 1450-3.
6. Pasero C, McCaffery M. Pain assessment and pharmacological management 1e. St

Louis, MO: Mosby; 1991.
7. Bril V, England J, Franklin GM, Backonja M, Cohen J, Del Toro D, Feldman E, Iverson
DJ, Perkins B, Russell JW, Zochodne D; American Academy of Neurology; American
Association of Neuromuscular and Electrodiagnostic Medicine; American Academy of
Physical Medicine and Rehabilitation. Evidence-based guideline: Treatment of painful
diabetic neuropathy: report of the American Academy of Neurology, the American
Association of Neuromuscular and Electrodiagnostic Medicine, and the American
Academy of Physical Medicine and Rehabilitation. Neurology. 2011 May 17;76(20):
1758-65
8. Mishra S, Bhatnagar S, Goyal GN, Rana SP, Upadhya SP. A comparative efficacy of
amitriptyline, gabapentin, and pregabalin in neuropathic cancer pain: a prospective
randomized double-blind placebo-controlled study. Am J Hosp Palliat Care. 2012 May;
29(3):177-82.
Authors’ Affiliations: University of Pittsburgh Medical Center, Pittsburgh, PA. UPMC Health
System, Pittsburgh PA
Version History: First published April 2015.
22

OPIOIDS FOR NEUROPATHIC PAIN
Linda Huang PharmD, Dilafruz Khakimova PharmD, Jennifer Pruskowski PharmD
Background Neuropathic pain is caused by damage of the somatosensory nervous system

leading to abnormal neural excitability (1). Patients often describe it as ‘burning’, ‘tingling’ or
‘shooting’ down a nerve distribution, and some may experience allodynia where they feel pain
from non-painful stimuli like air or light touch on skin. Approximately 10% of the general
population has neuropathic pain (2). The role of opioids for neuropathic pain is controversial and
examined in this Fast Fact.
Why Try Opioids for Neuropathic Pain? Opioids are broad-spectrum analgesics. While there
are numerous non-opioid adjuvant medications and analgesic-based interventions available to
patients with neuropathic pain, these interventions have their own associated risks and side-
effects. Besides, many who are nearing end-of-life from a progressive illness may already be on
opioids. These patients may have trouble swallowing oral medications and they often have renal
dysfunction, limiting their ability to tolerate many non-opioid adjuvants. Only a minority of patients
with neuropathic pain experience a clinical benefit from one analgesic intervention and require
multi-modal therapies (3). Therefore, the clinical question of dose-escalating or initiating an opioid
vs adding a non-opioid adjuvant arises frequently.
Opioids vs Non-Opioids for Neuropathic Pain Large systematic reviews and meta-analyses
have examined opioids as a class for neuropathic pain of any etiology. Although these studies
have led to disparate conclusions (3-8), a Cochrane review and a 2015 meta-analysis suggest
that “strong opioids” (i.e. oxycodone, methadone, and morphine) at doses ranging from 15-240
mg oral morphine equivalents (OMEs) reduce neuropathic pain by at least 33% from baseline
(3,4). These “strong opioids” were found to have a number-needed-to-treat (NNT) of 4.3 after
4-12 weeks of treatment and a number-needed-to-harm (NNH) of 11.7. For comparison, meta-
analyses noted an NNT of 3.6 for tri-cyclic antidepressants or TCAs (such as amitriptyline or
nortriptyline), 6.4 for serotonin-norepinephrine reuptake inhibitors or SNRIs (such as duloxetine or
venlafaxine), 7.2 for gabapentin, 7.7 pregabalin, and 8.7 for capsaicin for neuropathic pain. The
NNH is 13.4 for TCAs, 11.8 for SNRIs, 25.6 for gabapentin, 13.9 for pregabalin, and 8.7 for
capsaicin (see Fast Facts #49, #187, #197, #271, #288, & #289) (4). Constipation, somnolence,
delirium, dizziness, and dry mouth are the most commonly reported adverse effects of opioids.
Maximum effectiveness was associated with 180 mg OMEs/day, with no additional benefit for
higher doses (3,4). While TCAs, SNRIs, gabapentin, or pregabalin are considered by many
experts to be first-line analgesics for neuropathic pain, opioids are often considered as second or
third-line agents for many patients or as a co-analgesic when prompt pain relief during titration of
a first-line medication is required (4). There is little published evidence on NSAIDs and
acetaminophen for neuropathic pain, though commonly prescribed (9,10).
Clinical Evidence for Individual Opioids Although oxycodone, morphine, and methadone are
the most studied opioids for neuropathic pain, there are no well-designed studies to compare the
safety or efficacy of any one specific opioid over another.
• Hydromorphone: One randomized study explored its efficacy but with a high risk of bias and
incomplete outcomes data (11). Hence, there is insufficient evidence to support or refute its
role for neuropathic pain.
• Fentanyl: There is insufficient evidence to support fentanyl for neuropathic pain, based on
one randomized study of 258 participants at patch doses of 12-50 mcg/hr for 12 weeks (12).
• Methadone: Randomized control trials have shown some efficacy but it is unclear if
methadone offers any additional neuropathic pain control over other opioids (8,13) (see Fast
Fact #171).
23
• Tramadol and Tapentadol: Tramadol at doses of 100-400 mg/day has achieved 30%
neuropathic pain relief compared with placebo in study periods of 4-6 weeks, with NNT of 3.8
and NNH of 8.3 (14) (see Fast Fact #290). Tapentadol, a similar analgesic, has also improved
neuropathic pain at doses of 100-500 mg/day in 8-12-week study periods (15-18).
• Buprenorphine: experts cite its kappa receptor antagonism as a theoretical advantage for
alleviating neuropathic pain over other opioids, but no well-controlled trials have yet
confirmed this. It is considered a partial opioid agonist, as such it may be less associated with
delirium and constipation. It can be a reasonable agent for opioid-naïve patients being
initiated on an opioid. However, rotating patients to buprenorphine from other opioids be
complicated and is best done by only experienced clinicians (see Fast Fact # 268) (19).
• Other: There is no supporting evidence nor clinical rationale for the targeted selection of
codeine, hydrocodone, or oxymorphone for neuropathic pain (20,21). Although not a true
opioid agonist, dextromethorphan has been associated with significant neuropathic pain
relief, especially for diabetic neuropathy, at doses of 120-920 mg/day for up to 3 months in
duration (8). A high prevalence of intolerable side effects (drowsiness and dizziness
especially) limits its use, however.
Conclusion While opioids are not first-line agents for most patients with neuropathic pain, meta-
analyses suggest they have efficacy when prescribed as monotherapy or part of a multi-modal
regimen for patients with refractory, function-impairing neuropathies, especially when prognosis is
short. A ceiling effect has been observed when opioids are prescribed for neuropathic pain and
the benefit of increasing the opioid dose for beyond 180-240 mg/day should be pursued only on
an individual patient basis.
References
1. Raja S, Haanpaa M. Neuropathic pain. International Association for the Study of Pain.
https://www.iasp-pain.org/GlobalYear/NeuropathicPain. Published 2014; accessed May
14, 2018.
2. van Hecke O, Austin SK, Khan RA, et al. Neuropathic pain in the general population: a
systematic review of epidemiological studies. Pain 2014;155:654-62.
3. McNicol ED, Midbari A, Eisenberg E. Opioids for neuropathic pain. Cochrane Database
Syst Rev 2013. doi: 10.1002/14651858.CD006146.
4. Finnerup NB, Attal N, Haroutounian S, et al. Pharmacotherapy for neuropathic pain in
adults: a systematic review and meta-analysis. Lancet Neurol. Feb 2015; 14(2) 162-73.
5. McNicol ED, Midbari A, Eisenberg E. Opioids for neuropathic pain. Cochrane Database
Syst Rev 2013. doi: 10.1002/14651858.CD006146.
6. Cooper TE, Chen J, Wiffen PJ, et al. Morphine for chronic neuropathic in adults.
Cochrane Database Syst Rev 2017. doi: 10.1002/14651858.CD011669.
7. Gaskell H, Derry S, Stannard C, et al. Oxycodone for neuropathic pain in adults.
8. Aiyer R, Mehta N, Gungor S, et al. A systematic review of NMDA receptor antagonists for
treatment of neuropathic pain in clinical practice. Clin J Pain 2017 Sept 1. [Epub ahead of
print]
9. O'Connor AB, Dworkin RH. Treatment of neuropathic pain: an overview of recent
guidelines. The American journal of medicine. 2009; 122(10), S22-S32.
10. Moore RA, Chi CC, Wiffem PJ, et al. Oral nonsteroidal anti-inflammatory drugs for
neuropathic pain. Cochrane Database Syst Rev. 2015; 10.
11. Stannard C, Gaskell H, Derry S, et al. Hydromorphone for neuropathic pain in adults.
12. Derry S, Stannard C, Cole P, et al. Fentanyl for neuropathic pain in adults. Cochrane
Database Syst Rev 2016; 10:CD011605.
13. McNicol ED, Ferguson MC, Schumann R. Methadone for neuropathic pain in adults.
Cochrane Database Syst Rev. 2017. doi: 10.1002/14651858.CD012499.
14. Duehmke RM, Derry S, Wiffen PJ, et al. Tramadol for neuropathic pain in adults.
15. Baron R, Kern U, Muller M, et al. Effectiveness and tolerability of a moderate dose of
tapentadol prolonged release for managing severe, chronic low back pain with a
24
neuropathic component: an open-label continuation arm of a randomized phase 3b study.
Pain Pract 2015; 15(5):471-86.
16. Baron R, Martin-Mola E, Muller M, et al. Effectiveness and safety of tapentadol prolonged
release (PR) versus a combination of tapentadol PR and pregabalin for the management
of severe, chronic low back pain with a neuropathic component: a randomized, double-
blind, phase 3b study. Pain Pract2015; 15(5): 455-70.
17. Vinik A, Shapiro DY, Rauschkolb C, et al. A randomized withdrawal, placebo-controlled
study evaluating the efficacy and tolerability of tapentadol extended release in patients
with chronic painful diabetic peripheral neuropathy. Diabetes Care. 2014; 37.8:
2302-2309.
18. Schwartz S, Etropolski M, Shapiro DY, et al. Safety and efficacy of tapentadol ER in
patients with painful diabetic peripheral neuropathy: results of a randomized-withdrawal,
placebo-controlled trial. Curr Med Res Opin. 2011;27:151–162.
19. Wiffen PJ, Derry S, Moore RA, et al. Buprenorphine for neuropathic pain in adults.
20. Smith LJ, Krugner-Higby L, Clark M, et al. A single dose of liposome-encapsulated
oxymorphone or morphine provides long-term analgesia in an animal model of
neuropathic pain. Comp Med 2003; 53(3): 280-7.
21. Wiffen PJ, Knaggs R, Derry S, et al. Paracetamol (acetaminophen) with or without
codeine or dihydrocodeine for neuropathic pain in adults. Cochrane Database Syst Rev.
2016;12: CD012227.
Conflicts of Interests: None

Author Affiliations: Temple University Hospital, Philadelphia, Pennsylvania; CVS Community
Pharmacist, Seattle WA; University of Pittsburgh Medical Center, Pittsburgh, PA.
Version History: Originally edited by Sean Marks MD, first electronically published in October
2018
25
Prognosis
#3 Syndrome of Imminent Death . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . 2-3
#13 Determining Prognosis in Advanced

Cancer. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4-5
#99 Chemotherapy: Response and Survival Data. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . 6-7
#125 The Palliative Care Performance

Scale . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8-9
#141 Prognosis in End-Stage COPD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . 10-11
#143 Prognostication in Heart Failure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . 12-14
#150 Prognostication in Dementia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . .15-17
#189 Prognosis in Decompensated Chronic Liver

Failure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18-19
#191 Prognostication in Patients Receiving Dialysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . 20-21
#234 Prognosis of Anoxic-Ischemic Encephalopathy 3rd

Edition . . . . . . . . . . . . . . . . . . . . . . . . 22-23
#235 Prognostic Models in Critically Ill

Adults . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .24-25
#239 Prognostication in Severe Traumatic Brain Injury in

Adults . . . . . . . . . . . . . . . . . . . . . . . 26-28
!1
#360 The Surprise Questions as a Prognostic Tool . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . 29-31
#374 Prognosis After

Stroke . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32-34

SYNDROME OF IMMINENT DEATH
David E Weissman MD
Background Virtually all dying patients go through a stereotypical pattern of symptoms and signs in the
days prior to death. This trajectory is often referred to as “actively dying” or “imminent death”. Prompt
recognition of this trajectory is key for clinicians to provide the most appropriate interventions for both the
patient and family.
1. Stages
• Early
o Bed bound
o Loss of interest and/or ability to drink/eat
o Cognitive changes: increasing time spend sleeping and/or delirium (see Fast Fact #1)
• Middle
o Further decline in mental status to obtundation (slow to arouse with stimulation; only brief
periods of wakefulness)
• Late
o Death rattle – pooled oral sections that are not cleared due to loss of swallowing reflex
o Coma
o Fever – usually from aspiration pneumonia
o Altered respiratory pattern – periods of apnea, hyperpnea, or irregular breathing
o Mottled extremities
2. Time Course The time to traverse the various stages can be less than 24 hours or as long as ~14
days. Patients who enter the trajectory who are nutritionally intact, with no infection (e.g. acute stroke),
are apt to live longer than cachectic cancer patients
3. Common Family Concerns Family members present during the dying process often express the
following concerns/questions. Clinicians can best help families by expecting these questions, providing
education, reassurance, and responding to emotions (see also Fast Fact # 29; #149).
• Is my loved one in pain; how would we know?

• Aren’t we just starving my loved one to death?
• What should we expect; how will we know that time is short?
• Should I/we stay by the bedside?
• Can my loved one hear what we are saying?
• What do we do after death?
4. Treatment
!2
• Confirm treatment goals; recommend stopping treatments that are not contributing to comfort –
pulse oximetry, IV hydration, antibiotics, finger sticks, etc.
• Communicate clearly to others what is going on. Write in progress notes: "patient is dying," not
"prognosis is poor".
• Treat symptoms/signs as they arise: common among these are: oral secretions (see Fast Fact
#109, #158); delirium (#1, 60); dyspnea (# 27), fever (#256) and pain (# 53, 54).
• Provide excellent mouth and skin care.
• Provide daily counseling and support to families.
References
1. Rousseau P. Management of symptoms in the actively dying patient. In: Principles and Practice
of Palliative Care and Supportive Oncology. Berger AM, Portenoy RK, and Weissman DE, eds.
2nd Edition. Philadelphia, PA: Lippincott, Williams, & Wilkins; 2002.
2. Breitbart W, Alici Y. Agitation and delirium at the end of life. “We couldn’t manage him.” JAMA.
2008; 300(24):2898-2910.
July 2005; 3rd Edition May 2015. Current version re-copy-edited May 2015.
!3
DETERMINING PROGNOSIS IN ADVANCED CANCER
David E Weissman MD
Background How long do I have, Doc? is among the most common questions asked by cancer
patients, especially when informed that there are no further effective anti-neoplastic treatment options.
Although prognostication is not an exact science, there are data to help clinicians provide useful
information to patients and families – information critical to making realistic end-of-life decisions and
referrals for home hospice service (see Fast Fact #30).
Performance Status The single most important predictive factor in cancer is Performance Status
(‘functional ability,’ ‘functional status’): a measure of how much a patient can do for themselves, their
activity and energy level. Patients with solid tumors typically lose ~ 70% of their functional ability in the
last 3 months of life. The most common scales used to measure functional ability are the Karnofsky Index
(100 = normal; 0 = dead) and the ECOG scale (Eastern Cooperative Oncology Group), (0 = normal; 5 =
dead). A median survival of 3 months roughly correlates with a Karnofsky score <40 or ECOG > 3.
Newer prognostic scales have been developed to help provide prognostic information (See Fast Facts
#124, 125).
The simplest method to assess functional ability is to ask patients: How do you spend your time? How
much time do you spend in a chair or lying down? If the response is >50% of the time, and is increasing,
you can roughly estimate the prognosis at 3 months or less. Survival time tends to decrease further with
increasing numbers of physical symptoms, especially dyspnea, if secondary to the cancer.
Other Factors Several common cancer syndromes have well-documented short median survival times:
• Malignant hypercalcemia: 8 weeks, except newly diagnosed breast cancer or myeloma (see Fast
Fact #151)
• Malignant pericardial effusion: 8 weeks (see Fast Fact #209)
• Carcinomatous meningitis: 8-12 weeks (see Fast Fact #135)
• Multiple brain metastases: 1-2 months without radiation; 3-6 months with radiation.
• Malignant ascites (see Fast Fact #176), malignant pleural effusion (#209), or malignant bowel
obstruction: < 6 months.
• Modified Glasgow Prognostic Score (mGPS): multiple studies have shown that an increased
mGPS -- meaning an elevated serum c-reactive protein and a reduced serum albumin – is
associated with a reduced cancer specific survival curve irrespective of cancer type.
Other Comments In general, a patient with metastatic solid cancer, acute leukemia or high-grade
lymphoma, who will not be receiving systemic chemotherapy (for whatever reason), has a prognosis of
less than 6 months. Notable exceptions to this are patients with metastatic breast or prostate cancer with
good performance status, as these cancers may have an indolent course. In these patients additional
features suggesting short prognosis are needed (declining functional status, dyspnea, weight loss).
Discussing Prognosis When discussing prognosis with patients/families, the following four step
approach is recommended: Preparation; Content; Patient’s Response; Close. Remember to:
• Confirm that the patient/family are ready to hear prognostic information.
• Present information using a range: a few days to weeks; 2-4 months, etc.
• Allow silence after you provide information; respond to emotion (see Fast Fact #29).
• Use prognostic information for eliciting end-of-life goals (see Fast Fact #65).
References
1. Lamont EB, Christakis NA.. Complexities in prognostication in advanced cancer. JAMA. 2003;
290:98-104.
2. den Daas, N. Estimating length of survival in end-stage cancer: a review of the literature. J Pain
Symp Manage. 1995; 10:548-555.
!4
3. Lassauniere JM, Vinant P. Prognostic factors, survival and advanced cancer. J Pall Care. 1992;
8:52-54.
4. Ralston SH, et al. Cancer associated hypercalcemia. Ann Int Med. 1990; 112:499:504.
5. Reuben DB, Mor V. Clinical symptoms and length of survival in patients with terminal cancer.
Arch Int Med. 1998;148:1586-1591.
6. McMillan DC, Crozier JE, et al. Evaluation of an inflammation-based prognostic score (GPS) in
patients undergoing resection for colon and rectal cancer. Int J Colorectal Dis 2007; 22: 881-6.
7. Proctor MJ, Morrison DS, et al. An inflammation based prognostic score (mGPS) predicts cancer
survival independent of tumour site: a Glasgow inflammation outcome study. British Journal of
Cancer 2011; 104: 726-734.
!5
!

CHEMOTHERAPY: RESPONSE AND SURVIVAL DATA
Narendranath Epperla MD and David E Weissman MD
Background Key data in the decision process regarding chemotherapy include the response rate,
median duration of response, and median survival, along with toxicity and quality of life information (see
Fast Fact #14). The table below synthesizes data for several common cancers. The data were derived
by reviewing standard oncology textbooks, along with a Medline search of recent relevant articles.
Comments on the Response and Survival Data

• All data is for patients receiving first-line, commercially available, oral or IV chemotherapy and/or
biological therapy (e.g. monoclonal antibodies).
• ‘Response Rate’ is defined as the percentage of complete and partial responders in a given trial,
where ‘Partial Response’ = > 50% reduction in measurable tumor for one month.
• Response is typically determined after 2 cycles of treatment (usually one cycle every 21-28 days).
Note: patients who progress after 1 cycle will generally continue progressing after two.
• The data reflect mid-point ranges derived from the available clinical trials; most of the data
represent combination chemotherapy trials. Note: for certain cancers, the benefit of combination vs.
single agent therapy is not proven (e.g. pancreas, biliary, liver).
• This information is not representative of all cancer patients. The data represent the ‘best case’
outcome, from a population of patients who were in good enough health to participate in a clinical
trial (e.g. ambulatory, good functional status). Actual responses and response durations for a non-
clinical trial population will likely be poorer.
• Second-line chemotherapy, following disease progression from first-line treatment, can be expected
to have a lower response rate and shorter duration of response.
• Median survival data includes both responders and non-responders. Note: patients who respond to
chemotherapy typically live longer than those who do not.
Response Median Duration of Median Survival

Rate Response
Breast 25-55% 8-12 months 24-36 months
Lung (Non-Small Cell)

NSCLC, squamous 20-36% 4-6 months 6-11 months
NSCLC, non-squamous 20-35% 4-6 months 10-12 months
Esophagus 30-50% 4-6 months 6-9 months
GEJ 40-60% 6-8 months 9-12 months
Gastric
HER2 negative 20-40% 4-7 months 6-11 months
HER2 positive ~50% 6-7 months 12-14 months
Pancreas 20-32% 4-6 months 8-11 months
Liver (Hepatocellular-HCC) 25-40% 2-5 months
Non Hepatitis C related HCC 6-10 months
Hepatitis C related HCC 14 months
Biliary (Cholangiocarcinoma) 20-35% 4-8 months 9-14 months

Colon 30-45% 8-10 months 16-21 months
!6
Melanoma 15-40% 4-14 months 6-15 months
References
1. DeVita, Hellman, and Rosenberg. Cancer: Principles and Practice of Oncology. 10th Edition.
Philadelphia, PA: Lippincott Williams & Wilkins; 2014.
2. Waun Ki Hong, et al, eds. Holland-Frei Cancer Medicine. 8th Edition. Hamilton, Ontario: BC
Decker; 2010.
Version History: This Fast Fact was originally edited by David E Weissman MD. 2nd Edition was edited
by Drew A Rosielle and published November 2007. 3rd edition edited with data updates in August 2015.
!7
THE PALLIATIVE PERFORMANCE SCALE (PPS)
L Scott Wilner MD and Robert Arnold MD
Background Accurate prognostic information is important for patients, families and physicians. This
Fast Fact reviews the Palliative Performance Scale (PPS); see Fast Fact #124 The Palliative Prognostic
Score for another prognostic tool used in palliative care patients.
The PPS uses five observer-rated domains correlated to the Karnofsky Performance Scale (100-0). The
PPS is a reliable and valid tool and correlates well with actual survival and median survival time for
cancer patients in outpatient and ambulatory settings. It has been found useful for purposes of identifying
and tracking potential care needs of palliative care patients, particularly as these needs change with
disease progression. Large validation studies are still needed, as is analysis of how the PPS does, or
does not, correlate with other available prognostic tools and commonly used symptom scales.
PALLIATIVE PERFORMANCE SCALE (PPS)

Activity Estimated
Level Level of Median Survival
% Ambulation Self-Care Intake
Evidence of Consciousness in Days
Disease (a) (b) (c)
Normal
100 Full Full Normal Full
No Disease
Normal
90 Full Some Full Normal Full
Disease N/A
Normal with
Effort Normal or N/A
80 Full Full Full
Some Reduced
Disease
108
Can’t do
normal job
70 Reduced or work Full As above Full 145
Some
Disease
Can’t do
hobbies or Occasional
60 Reduced housework Assistance As above Full or Confusion 29 4
Significant Needed
Disease
Can’t do any
Considerable
work
50 Mainly sit/lie Assistance As above Full or Confusion 30 11
Extensive
Needed
Disease
41
Mainly Mainly Full or Drowsy or
40 As above As above 18 8
in Bed Assistance Confusion
30 Bed Bound As above Total Care Reduced As above 8 5

20 Bed Bound As above As above Minimal As above 4 2
6
!8
Mouth 6
10 Bed Bound As above As above Drowsy or Coma 1 1
Care Only
0 Death - - - --
(a) Survival post-admission to an inpatient palliative unit, all diagnoses (Virik 2002).
(b) Days until inpatient death following admission to an acute hospice unit, diagnoses not specified
(Anderson 1996).
(c) Survival post admission to an inpatient palliative unit, cancer patients only (Morita 1999).
References
1. Anderson F, Downing GM, Hill J. Palliative Performance Scale (PPS): a new tool. J Palliat Care.
1996; 12(1): 5-11.
2. Morita T, Tsunoda J, Inoue S, et al. Validity of the Palliative Performance Scale from a survival
perspective. J Pain Symp Manage. 1999; 18(1):2-3.
3. Virik K, Glare P. Validation of the Palliative Performance Scale for inpatients admitted to a
palliative care unit in Sydney, Australia. J Pain Symp Manage. 2002; 23(6):455-7.
4. Myers J, Kim A, Flanagan J. Palliative performance scale and survival among outpatients with
advanced cancer. Supportive Care in Cancer 2015; 23.4: 913-918.
November 2004. Version re-copy-edited in April 2009; revised again July 2015 – reference 4 added and
incorporated into text.
!9
PROGNOSIS IN END-STAGE COPD
Julie Wilson Childers MD, Robert Arnold MD, and J Randall Curtis MD
Background Prognostic variables in COPD patients are not well described, thus decision making
regarding when to move away from aggressive life-sustaining treatments is challenging. This Fast Fact
will review prognostication in patients with advanced COPD.
Ambulatory COPD Patients The forced expiratory volume in one second (FEV1) has traditionally been
used to assess COPD severity. A FEV1 of less than 35% of the predicted value represents severe
disease; 25% of these patients will die within two years and 55% by four years. A number of other studies
have shown that age, low body mass index (BMI), serum inflammatory biomarkers (such as C-reactive
protein, IL-6, and fibrinogen) and low PaO2 were independent predictors that correlated to reduced
survival time. The BODE scale, consisting of BMI, exercise capacity, and subjective estimates of
dyspnea, has been shown to help predict survival over 1-3 years (2).
Variable Points on BODE Index

0 1 2 3
FEV1 (% predicted) ≥65 50-64 36-49 ≤35
Distance walked in 6 min (meters) >350 250-349 150-249 ≤149

MMRC dyspnea scale* 0-1 2 3 4
Body-mass index (BMI) >21 ≤21
*MMRC dyspnea scale range from 0 (none) to 4 (4 dyspnea when dressing or undressing).
BODE Index Score One year mortality Two year mortality 52 month mortality
0-2 2% 6% 19%
3-4 2% 8% 32%
4-6 2% 14% 40%
7-10 5% 31% 80%
Note: these variables do not appear to help predict prognosis within six months of death.
Hospitalized COPD Patients Mortality statistics vary for patients admitted with COPD exacerbations
depending on age, functional status, co-morbidities, and physiological variables such as hypoxia and
hypercarbia. Roughly 10% of patients admitted with a PaCO2 >50 mmHg will die during the index
hospitalization, 33% will die within six months, and 43% die within one-year (3). Patients with less severe
COPD have lower in-hospital mortality rates (4). COPD patients who require mechanical ventilation have
an-hospital mortality of ~25% (5,6). Poor prognostic factors include: co-morbid illnesses, severity of
illness (APACHE II score), low serum albumin, and/or low hemoglobin. Previous mechanical ventilation,
failed extubation, or intubation for greater than 72 hours all increase mortality (5). In one study, patients
ventilated more than 48 hours had a 50% one year survival; functional status and severity of illness were
associated with short term mortality while age and co-morbidities were associated with one year mortality
(2).
National Hospice and Palliative Care Organization Criteria NHPCO guidelines for hospice admission
in COPD include factors such as cor pulmonale and pO2 <55 mmHg while on oxygen, albumin < 2.5 gm/
dl, weight loss of > 10%, progression of disease, and poor functional status. However, a study showed
when using these factors, 50% of the patients were still alive at six months, implying that the NHPCO
!10
criteria have a limited role in predicting six month mortality and thus should be used with caution in
determining hospice eligibility under the Medicare Hospice Benefit (7).
Summary COPD is a heterogeneous disease without a simple prognostic trajectory. For ambulatory
patients, age, degree of dyspnea, weight loss (BMI), functional status, and FEV1 are relevant prognostic
factors for predicting 1-3 year survival. For hospitalized patients, the same factors are relevant. In
addition, the need for prolonged or recurrent mechanical ventilation is predictive of a shorter prognosis.
References
1. Celli BR, Locantore N, et al. Inflammatory biomarkers improve clinical prediction of mortality in
chronic obstructive pulmonary disease. American Journal of Respiratory and Critical Care
Medicine. 2012; 185:1065-72.
2. Celli BR, Cote CG, Marin JM, et al. The body-mass index, airflow obstruction, dyspnea, and
exercise capacity index in chronic obstructive pulmonary disease. N Eng J Med. 2004; 350(10):
1005-12.
3. Connors AF Jr, Dawson NV, Thomas C, et al. Outcomes following acute exacerbation of severe
chronic obstructive lung disease. The SUPPORT investigators (Study to Understand Prognoses
and Preferences for Outcomes and Risks of Treatments). Am J Respir Crit Care Med. 1996;
154:959-967.
4. Patil SP, Kirshnan JA, et al. In-hospital mortality following acute exacerbations of chronic
obstructive pulmonary disease. Arch Intern Med. 2003; 163:1180-1186.
5. Nevins ML, Epstein SK. Predictors of outcome for patients with COPD requiring invasive
mechanical ventilation. Chest. 2001; 119:1840-9.
6. Seneff MG, Wagner DP, Wagner RP, et al. Hospital and 1-year survival of patients admitted to
intensive care units with acute exacerbation of chronic obstructive pulmonary disease. JAMA.
1995; 274:1852-57.
7. Fox E, Landrum-McNiff K, Zhong Z, Dawson NV, Wu AW, Lynn J. Evaluation of prognostic
criteria for determining hospice eligibility in patients with advanced lung, heart, or liver disease.
JAMA. 1999; 282(17):1638-45.
Version History: This Fast Fact was originally edited by David E Weissman MD and published in August
2005. Version re-copy-edited in April 2009; revised again July 2015 by Sean Marks MD with reference #1
!11
PROGNOSTICATION IN HEART FAILURE
Gary M Reisfield MD and George R Wilson MD
Background This Fast Fact reviews prognostication data in Heart Failure (HF). Although the
Framingham Heart Study (1990-1999) showed a 5-year mortality rate of 50% for newly identified cases,
providing accurate prognostic data for 6-12 month mortality in HF has been nearly impossible. Reasons
cited include: 1) an unpredictable disease trajectory with high incidence (25-50%) of sudden death; 2)
disparities in the application of evidence-based treatment guidelines; 3) inter-observer differences in New
York Heart Association (NYHA) classification; and 4) heterogeneous study populations
NYHA Classification The NYHA classification remains the major gauge of disease severity. Based on
data from SUPPORT, Framingham, IMPROVEMENT, and other studies, 1-year mortality estimates are:
• Class II (mild symptoms): 5-10%.
• Class III (moderate symptoms): 10-15%.
• Class IV (severe symptoms): 30-40%.
General Predictors of Shorter Prognosis:

• Cardiac hospitalization (triples 1-year mortality; nearly 1 in 10 die within 30 days of admission).
• Intolerance to neurohormonal therapy (i.e. beta-blockers or ACE-inhibitors) is associated with high
4 month mortality
• Elevated BUN (defined by upper limit of normal) and/or creatinine ≥1.4 mg/dl (120 µmol/l).
• Systolic blood pressure <100 mm Hg and/or pulse >100 bpm (each doubles 1-year mortality).
• Decreased left ventricular ejection fraction (linearly correlated with survival at LVEF ≤ 45%).
• Ventricular dysrhythmias, treatment resistant.
• Anemia (each 1 g/dl reduction in hemoglobin is associated with a 16% increase in mortality).
• Hyponatremia (serum sodium ≤135-137 mEq/l).
• Cachexia or reduced functional capacity.
• Orthopnea.
• Co-morbidities: diabetes, depression, COPD, cirrhosis, cerebrovascular disease, and cancer
Hospice Eligibility Guidelines The National Hospice and Palliative Care Organization’s 1996
guidelines for heart disease admission criteria include: a) symptoms of recurrent HF at rest (NYHA class
IV) and b) optimal treatment with ACE inhibitors, diuretics, and vasodilators (contemporary optimal
treatment now includes β-blockers, aldosterone antagonists, and device therapies). The NHPCO guide
indicates that an ejection fraction < 20% is “helpful supplemental objective evidence,” but not required.
The NHPCO guidelines also assert that each of the following further decreases survival: treatment
resistant ventricular or supraventricular arrhythmias, history of cardiac arrest in any setting, history of
unexplained syncope, cardiogenic brain embolism, and concomitant HIV disease.
Prognostic Models Since publication of the NHPCO’s guidelines, several models have been
developed for predicting short- and/or long-term mortality among HF patients. Two recent models purport
to predict mortality among patients hospitalized with acutely decompensated HF. Fonarow et al (2005),
using a model based on admission BUN (≥ 43 mg/dl), creatinine (≥ 2.75 mg/dl), and systolic BP (< 115
mmHg), identified in-hospital mortality rates ranging from about 2% (0/3 risk factors) to 20% (3/3 risk
factors). Lee et al (2003), using a model based on admission physiologic variables and co-morbidities
(almost all from above list of indicators) identified 30-day mortality and 1-year mortality rates ranging from
<1% and <10%, respectively, for the lowest risk patients to >50% and >75%, respectively, for the highest
risk patients. While both models are applicable to bedside use, neither has been applied prospectively or
in independent patient samples, nor do they address HF treatments as predictive variables. More
recently, Levy et al (2006) developed a 24-variable risk model using the PRAISE1 (n=1125) database and
!12
validated it on preexisting ELITE2, ValHeFT, UW, RENAISSANCE, and IN-CHF (n=9942) databases. The
model purports to accurately estimate mean 1-, 2-, and 3-year survival and, importantly, dynamically
incorporates clinical and laboratory variables, HF medications, and device therapies. It awaits
independent, prospective evaluation in unselected HF patients. A web-based interactive calculator can
be accessed at http://www.seattleheartfailuremodel.org.
Bottom Line Meticulous application of medication and device therapies can and will continue to change
HF prognosis. HF follows an unpredictable disease trajectory, one which is highly mutable by application
of evidence-based therapies, yet still marked by a high incidence of sudden death. The 1996 NHPCO
criteria are not accurate predictors of 6-month mortality. Several models have recently been developed to
aid in determining short- and long-term mortality in HF patients. These models await independent,
prospective validation in unselected ambulatory HF patients and will need periodic updating to control for
continually evolving standards of HF care. At present, accurate prognostication remains problematic.
References
1. Anand I, McMurray JJV, Whitmore J. Anemia and its relationship to clinical outcome in heart
failure. Circulation. 2004; 110:149-154.
2. Anker SD, Ponikowski P, Varney S, et al. Wasting as an independent risk factor for mortality in
chronic heart failure. Lancet. 1997; 349:1050-1053.
3. Curtis JP, Sokol SI, Wang Y, et al. The association of left ventricular ejection fraction, mortality,
and cause of death in stable outpatients with heart failure. J Am Coll Cardiol. 2003; 42(4):
736-742.
4. Fonarow GC, Adams KF, Abraham WT, et al. Risk stratification for in-hospital mortality in acutely
decompensated heart failure. JAMA. 2005;2 93(5):572-580.
5. Horwich TB, Fonarow GC, Hamilton MA, et al. Anemia is associated with worse symptoms,
greater impairment in functional capacity and a significant increase in mortality in patients with
advanced heart failure. J Am Coll Cardiol. 2002; 39(11):1780-1786.
6. Kearney MT, Fox KAA, Lee AJ. Predicting death due to progressive heart failure in patients with
mild-to-moderate chronic heart failure. J Am Coll Cardiol. 2002; 40(10):1801-1808.
7. Lee DS, Austin PC, Rouleau JL, et al. Predicting mortality among patients hospitalized for heart
failure. JAMA. 2003; 290(19):2581-2587.
8. Levenson JW, McCarthy EP, Lynn J, et al. The last six months of life for patients with congestive
heart failure. J Am Geriatr Soc. 2000; 48(Suppl 5):S101-S109.
9. Levy D, Kenchaiah S, Larson MG, et al. Long-term trends in the incidence of and survival with
heart failure. NEJM. 2002; 347(18):1397-1402.
10. Levy WC, Mozaffarian D, Linker DT, et al. The Seattle Heart Failure Model. Prediction of Survival
in Heart Failure. Circulation. 2006; 113:1424-1433.
11. Muntwyler J, Abetel G, Gruner C, et al. One-year mortality among unselected outpatients with
heart failure. Eur Heart J. 2002; 23:1861-1866.
12. Stuart B, et al. Medical Guidelines for determining prognosis in selected non-cancer diseases. 2nd
Edition. Alexandria, VA: National Hospice Organization; 1996.
13. Zannad F, Briancon S, Julliere Y. Incidence, clinical and etiologic features, and outcomes of
advanced chronic heart failure: the EPICAL study. J Am Coll Cardiol. 1999; 33(3):734-742.
14. Desai AS, Stevenson LW. There must be a better way: piloting alternate routes around heart
failure hospitalizations. J of Am Coll of Card. 2013; 61(2):127-30.
October 2005. It was updated in December 2006 to reflect the newly published ‘Seattle Heart Failure
Model.’ Version copy-edited in April 2009; then revised again July 2015 by Sean Marks MD – reference
#14 added and incorporated into text; orthopnea and intolerance to neurohormonal therapy added to
predictors of shorter survival.
!13
!14
!

PROGNOSTICATION IN DEMENTIA
Sing Tsai MD and Robert Arnold MD
Background Dementia is a syndrome of acquired and persistent impairment in cognition and
intellectual functioning (1). When caused by certain diseases or injury, dementia is irreversible, leading to
progressive brain failure and death. This Fast Fact reviews issues of prognostication in dementia.
Natural history of dementia Olson (2003) classifies dementia into four functionally defined categories:
mild, moderate, severe, and terminal. ‘Terminal dementia’ is defined as loss of communication,
ambulation, swallowing, and continence. Others use the term “end-stage” or “advanced” making
interpretation of prognostic data challenging. Many prognostic factors have been associated with
shortened survival: male gender, age, diabetes mellitus, CHF, COPD, cancer, cardiac dysrhythmias,
peripheral edema, aspiration, bowel incontinence, recent weight loss, dehydration, fever, pressure ulcers,
seizures, shortness of breath, low oral intake, not being awake for most of the day, low Body Mass Index,
and recent need for continuous oxygen. A 2012 systematic review found that malnutrition, feeding issues,
and dysphagia were the strongest associated factors with 6 month mortality in elderly patients with
advanced dementia. Simply being admitted to the hospital with acute illness and end-stage or terminal
dementia is associated with a particularly poor prognosis: the six month mortality after hospitalization for
pneumonia was 53% compared with 13% for cognitively intact patients. For patients with a new hip
fracture, 55% of end-stage dementia patients died within 6 months compared with 12% for cognitively
intact patients (Morrison 2000).
Prognostic Systems (see table below):

I. The National Hospice and Palliative Care Organization (NHPCO) recommends the Functional
Assessment Staging (FAST), a 7-step staging system, to determine hospice eligibility. The FAST
identifies progressive steps and sub-steps of functional decline. NHPCO guidelines state that a FAST
stage 7A is appropriate for hospice enrollment, based on an expected six month or less prognosis, if
the patient also exhibits one or more specific dementia-related co-morbidities (aspiration, upper
urinary tract infection, sepsis, multiple stage 3-4 ulcers, persistent fever, weight loss >10% within six
months). Luchins (1997) studied the relationship of FAST to survival in 47 patients enrolled in
hospice with advanced dementia and one or more dementia-related co-morbidities. The median
survival for all patients was 6.9 months; 38% survived beyond six months. Of note, 41% of patients
did not demonstrate dementia progression in a manner that allowed for assigning a FAST stage. For
those patients who could be assigned a FAST stage (n = 12), and who were at stage 7C or greater,
mean survival was 3.2 months. The generalizability and clinical relevance of this data are greatly
compromised by this very low patient number.
II. The Mortality Risk Index (MRI), a composite score based on 12 risk factor criteria obtained from using
the MDS (Minimum Data Set), has been suggested as an alternative to FAST. Mitchell (2004)
developed and then validated the MRI by examining data from over 11,000 newly admitted nursing
home patients. Among patients with a MRI score of ≥ 12, 70% died within 6 months (mean survival
time not reported). Compared to FAST Stage 7C, the MRI had greater predictive value of six month
prognosis. The MRI as only been evaluated in newly admitted nursing home residents; it has yet to
be validated in the community setting or for previously established long-term nursing home residents.
Medical Interventions Estimation of prognosis in severe/terminal dementia is in part dependent on the
goals of care and decisions regarding the level of intervention that will be provided to treat acute medical
problems such as urosepsis and malnutrition.
Summary Although many prognostic risk factors have been identified there is no gold standard to help
clinicians determine a less than six months prognosis with any degree of certainty. The criteria adopted by
NHPCO for hospice eligibility is based on very limited research and lacks important studies to determine
FAST scale reliability and validity among referring physicians and hospice staff. The MRI is a promising
new scale but more research is needed. Physicians can best help their patients by working with families
to help them establish goals of care and levels of medical intervention that are most consistent with
current medical research and family/patient preferences.
!15
Functional Assessment Staging (FAST) Mortality Risk Index Score (Mitchell)
Stages Points Risk factor
1. No difficulties 1.9 Complete dependence with ADLs

2. Subjective forgetfulness 1.9 Male gender
1. Decreased job functioning and organizational 1.7 Cancer
capacity 1.6 Congestive heart failure
4. Difficulty with complex tasks, instrumental ADLs 6. O2 therapy needed w/in 14 day
5. Requires supervision with ADLs 1.5 Shortness of breath
6. Impaired ADLs, with incontinence 1.5 <25% of food eaten at most meals
7. A. Ability to speak limited to six words 1.5 Unstable medical condition
B. Ability to speak limited to single word 1.5 Bowel incontinence
C. Loss of ambulation 1.5 Bedfast
D. Inability to sit 1.4 Age > 83 y
E. Inability to smile 1.4 Not awake most of the day
F. Inability to hold head up
Risk estimate of death within 6 months
Score Risk %
0 8.9
1-2 10.8
3-5 23.2
6-8 40.4
9-11 57.0
≥ 12 70.0
References
1. Olson E. Dementia and Neurodegenerative Disorders. In: Morrison RS, Meier DE, eds. Geriatric
Palliative Care. New York, NY: Oxford University Press; 2003.
2. Luchins DJ, Hanrahan P, Murphy K. Criteria for enrolling dementia patients in hospice. J Am
Geriatr Soc. 1997; 45:1054-1059.
3. Mitchell SL, Kiely DK, Hamel MB, et al. Estimating prognosis for nursing home residents with
advanced dementia. JAMA. 2004; 291:2734-2740.
4. Brown MA, Sampson EL, et al. Prognostic indicators of 6-month mortality in elderly people with
advanced dementia: a systematic review. Palliat Med 2013; 27: 389-400.
5. Morrison RS, Siu AL. Survival in end-stage dementia following acute illness. JAMA. 2000;
284:47-52.
6. Schonwetter RS, Han B, Small BJ, et al. Predictors of six-month survival among patients with
dementia: an evaluation of hospice Medicare guidelines. Am J Hosp Palliat Care. 2003; 20(2):
105-13.
7. Wolfson C, Wolfson DB, Asgharian M, et al. A reevaluation of the duration of survival after the
onset of dementia. N Engl J Med. 2001; 344:1111-1116.
February 2006. Version re-copy-edited in April 2009; revised again July 2015 by Sean Marks MD –
reference # 4 added and incorporated into the text.
!16
!17
!

PROGNOSIS IN DECOMPENSATED CHRONIC LIVER FAILURE
Brigid Dolan MD and Robert Arnold MD
Background In 2009, chronic liver disease and cirrhosis resulted in approximately 30,000 deaths,
making it the twelfth leading cause of death in the United States. Patients with compensated chronic liver
failure (without ascites, variceal bleeding, encephalopathy, or jaundice) have a median survival of 12
years. After decompensation, median survival drops to ~ 2 years. This Fast Fact reviews prognosis in
chronic liver failure, focusing on two validated prognostic indices. Of note, these indices predict
prognosis for patients without liver transplantation.
The Child’s-Turcotte-Pugh (CTP) score includes 5 variables, each scored 1-3:

Numerical Value
Variable 1 2 3
Ascites None Slight Moderate/Severe

Encephalopathy None Grade 1-2 Grade 3-4
Bilirubin (mg/dL) < 2.0 2.0-3.0 >3.0
Albumin (mg/L) > 3.5 2.8-3.5 <2.8
Increase in seconds from 1-3 4-6 >6.0
normal Prothrombin time
Patients are grouped into three classes based on the total CTP score, which is simply the sum of the
scores for each of the 5 variables. Patients scoring 5-6 points are considered to have ‘Class A’ failure;
their 1 and 2 year median survivals are 95% and 90%, respectively. A score of 7-9 is considered Class B
with median survivals of 80% at 1 year and 70% at two years. Class C patients (10-15) have far greater
mortality: 1-year median survival is 45% and 2-year is 38%. Variations in the timing and subjectivity
inherent in the scoring of the CTP (e.g. in grading ascites or encephalopathy) are its major limitations. In
addition, the scale does not include renal function, an important prognostic factor in liver failure.
The Model for End-stage Liver Disease (MELD) score was developed in 2000 to overcome the above-
mentioned limitations and determine survival benefit from transjugular intrahepatic portosystemic
shunting. It is currently used to help determine organ allocation for liver transplantation, and there is
increasing evidence that it can also be used generally to predict survival in patients with chronic liver
failure. The MELD score relies on laboratory values alone (serum creatinine, total bilirubin, and INR). An
additional benefit over CTP is that it can predict prognosis on the order of months with more precision –
making it helpful for determining hospice eligibility in the US. The formula to calculate MELD score is
complex, and a calculator can be found at: http://reference.medscape.com/calculator/meld-score-end-
stage-liver-disease.
MELD Score Predicted 6 Predicted 12 month Predicted 24 month

month survival survival survival
0-9 98% 93% 90%
10-19 92% 86% 80%
20-29 78% 71% 66%
30-39 40% 37% 33%
!18
Other important prognostic variables The hepatorenal syndrome (HRS) – renal failure from renal
arterial under-filling due to decompensated liver failure – portends a particularly poor prognosis. Most
patients with type-1 HRS (rapid and severe renal failure) die within 8-10 weeks even with therapy.
Median survival with type-2 HRS (chronic, less severe renal failure with serum creatinine usually 1.5-2
mg/dL) is around 6 months. Both older age and hepatocellular carcinoma also adversely affect survival.
While the CTP and MELD systems provide objective guidance to prognostication in liver failure, clinical
judgment, patient comorbidities, the rate of decompensation, and the likelihood of transplantation all
should additionally affect the assessment and communication of a patient’s prognosis in liver disease.
References
1. Heron M. Deaths: Leading causes for 2009. National Vital Statistics Reports 2012; 61(7).
2. D’Amico, et al. Natural history and prognostic indicators of survival in cirrhosis: a systematic
review of 118 studies. J Hepatology. 2006; 44:217–231.
3. Diehl A. Alcoholic and nonalcoholic steatohepatitis. In: Goldman L, Ausiello D, eds. Cecil
Textbook of Medicine. 22nd ed. Philadelphia, PA: Saunders; 2004:935–6.
4. Cholongitas, et al. Systematic review: the model for end-stage liver disease – should it replace
Child-Pugh’s classification for assessing prognosis in cirrhosis? Alimentary Pharmacol
Therapeutics. 2005; 22:1079-1089.
5. Said, et al. Model for end stage liver disease score predicts mortality across a broad spectrum of
liver disease. J Hepatology. 2004; 40:897-903.
6. Cardenas, et al. Hepatorenal Syndrome: A dreaded complication of end-stage liver disease. Am
J Gastroenterol. 2005; 100:460-467.
Version History: Originally published September 2007. Version re-copy-edited in May 2009; then again
in July 2015.
!19
!

PROGNOSTICATION IN PATIENTS RECEIVING DIALYSIS
Matthew Hudson, Steven Weisbord MD, Robert Arnold MD
Background End stage renal disease (ESRD) is a highly prevalent and rapidly increasing condition.
While dialysis prolongs life in patients with ESRD, life expectancy remains only a third to a sixth as long
as similar patients not on dialysis. The overall one and five year mortality rates are 25% and 60%,
respectively. Approximately 20% of ESRD patient deaths occur after a decision to stop dialysis,
highlighting the importance of discussions of prognosis and goals of care with this chronically ill
population. This Fast Fact reviews the current data regarding prognostication in patients receiving chronic
hemo- and peritoneal dialysis. Note: renal transplantation reduces mortality and the following data do not
consider patients with functioning kidney transplants.
Prognostic Factors Several patient-specific factors influence prognosis:

• Age: For 1-year increments beginning at age 18, there is a 3 to 4% increase in annual mortality
compared to the general population. 1 and 2 year mortality rates go from 10 and 12% at 25-29
years of age, to 25% and 42% at 65-69 years, to 39% and 61% at 80-84 years of age.
• Functional status: the relative risk of dying within 3 years of starting dialysis is 1.44 for those with
Karnofsky Performance Status scores of <70 compared to a score ³70 (see Fast Fact #13).
• Albumin: a low serum albumin level, both at baseline and during the course of dialysis treatment, is a
consistent and strong predictor of death. For example, the 1 and 2 year survival of patients with an
albumin of >3.5 g/dL is 86% and 76% respectively, compared to 50% and 17% if less than 3.5.
• Surprise question: in a multivariate analysis, the likelihood of death in 6 months was significantly
greater when nephrologists answered no to the question “would I be surprised if this patient died
within 6 months?” 
Prognostic Tools It has long been recognized that patient comorbidity is strongly correlated with
prognosis in ESRD. An age-modified Charlson Comorbidity Index (CCI), which stratifies patients based on
medical comorbidities and age, has been successfully used to predict mortality in dialysis-dependent
patients (8):
Modified Charlson Comorbidity Index: Total score is the sum of the comorbidity points
Comorbidity Points
1 point each for coronary artery disease, congestive heart failure, peripheral vascular disease,
cerebrovascular disease, dementia, chronic pulmonary disease, connective tissue disorder, peptic
ulcer disease, mild liver disease, diabetes
1 point for every decade over 40 (e.g. a 65 year old would receive 3 points).
2 points each for hemiplegia, moderate-to-severe renal disease (including being on dialysis),
diabetes with end-organ damage, cancer (including leukemia or lymphoma)
3 points for moderate-to-severe liver disease
6 points each for metastatic solid tumor or AIDS
Modified CCI Score Low score (£3) Moderate (4-5) High (6-7) Very High (³8)
Totals
Annual mortality rate 0.03 0.13 0.27 0.49
For example, a 66 year old male on dialysis with a history of CHF, COPD, and diabetes with retinopathy
would have a CCI score of 9 and a nearly 50% chance of dying within a year. Using this, a provider could
discuss with the patient his prognosis and use this to facilitate further discussion regarding planning for
!20
the future, including end-of-life decisions. The Index of Coexistent Disease (ICED), a general illness
severity index, has also shown predictive power in ESRD. The scale’s complexity and length however (it
entails asking over 100 questions) limit its clinical usefulness.
Summary The age-modified CCI, in conjunction with other prognostic factors such as serum albumin
and functional status, can be used to help facilitate discussions with dialysis-dependent patients and their
families regarding goals of care and end-of-life planning.
References:
1. United States Renal Data System. Incidence and prevalence. Annual data report, 2006.
Minneapolis, MN: USRDS Coordinating Center; 2006. Available at: http://www.usrds.org/2006/
pdf/02_incid_prev_06.pdf.
2. Cohen LM, Moss AH, Weisbord SD, Germain MJ. Renal palliative care. J Pall Med. 2006;
9:977-992.
3. Renal Physicians Association and American Society of Nephrology. Clinical Practice Guideline on
Shared Decision-Making in the Appropriate Initiation of and Withdrawal from Dialysis.
Washington, DC: Renal Physicians Association, 2000. Available at: http://jasn.asnjournals.org/
cgi/content/full/11/7/1340.
4. Ifudu O, Paul HR, Homel P, Friedman EA. Predictive value of functional status for mortality in
patients on maintenance hemodialysis. Am J Nephrol. 1998; 18:109-116.
5. Owen WF, Lew NL, Yiu Y, Lowry EG, Lazarus JM. The urea reduction ratio and serum albumin
concentration as predictors of mortality in patients undergoing hemodialysis. NEJM. 1993;
329(14):1001-1006.
6. Owen WF, Price D. African-Americans on maintenance dialysis. Adv Ren Replace Ther. 1997;
4:3-12.
7. Lowrie EG, Lew NL. Death risk in hemodialysis patients. Am J Kidney Dis. 1990; 15:458-482.
8. Cohen LM, Ruthazer R, et al. Predicting six-month mortality for patients who are on maintenance
hemodialysis. Clin J Am Soc Nephrol 2010;5:72-79.
9. Beddhu S, Bruns FJ, Saul M, Seddon P, Zeidel ML. A simple comorbidity scale predicts clinical
outcomes and costs in dialysis patients. Am J Med. 2000; 108:609-613.
10. Miskulin DC, Martin AA, Brown R, et al. Predicting 1-year mortality in an outpatient hemodialysis
population: a comparison of comorbidity instruments. Nephrol Dial Transplant. 2004; 19:413-420.
11. Moss AH. A new clinical practice guideline on initiation and withdrawal of dialysis that makes
Explicit the role of palliative medicine. J Palliat Med. 2000; 3:253-260.
12. Nicolucci A, Cubasso D, Labbrozzi D, et al. Effect of coexistent diseases on Survival of patients
undergoing dialysis. ASAIO J. 1992; 38:M291-M295.
Version History: Originally published October 2007. Version re-copy-edited in May 2009; then again in
July 2015 – references #8 and #9 were added and incorporated into the text.
!21

PROGNOSIS OF ANOXIC-ISCHEMIC ENCEPHALOPATHY 3RD EDITION
James Fausto MD
Introduction Cardiac arrest, experienced by approximately 450,000 Americans annually, has a very
poor survival rate (see Fast Fact #179). Some patients who initially survive cardiopulmonary resuscitation
remain comatose, demonstrating obvious impairments in consciousness and neurologic function. This
syndrome, called anoxic-ischemic encephalopathy (AIE, also known as ‘anoxic brain injury,’ or ‘hypoxic-
ischemic coma’), can result in outcomes ranging from full recovery to permanent unconsciousness to
death. This Fast Fact discusses prognostic factors in adults with AIE after cardiac arrest.
“Neurologic Outcome” A challenge in interpreting the literature on AIE is the use of variable or
imprecise definitions of a ‘poor neurologic outcome.’ The American Academy of Neurology practice
parameter paper defines poor outcome as: death, persistent unconsciousness (such as a vegetative
state), or severe disability requiring full nursing care after 6 months (6). This is the definition used in this
Fast Fact.
Predictors of Neurologic Outcome A review of the current literature reveals that data obtained by
careful neurologic exam, electrophysiologic studies, and biochemical markers are most predictive of
outcome (see below). Other factors not strongly predictive of outcome include: age, sex, cause of
arrest, type of arrhythmia, total arrest time, duration of CPR, geographic location of arrest, elevated body
temperature, elevated intracranial pressure, concurrent respiratory failure, and early brain imaging
findings (3,6,7,8).
Note: the data below assume patients are not receiving medications which would significantly confound
their neurologic examination such as high-dose barbiturates. In all cases, specialist neurologic
examination and input is advised.
Strong Indicators of Poor Outcome (false positive rates of 0% based on current literature):
• Absent pupillary light reflexes 24 hours after CPR, or 72 hours after CPR for those who initially
had intact papillary light reflexes (3,6,7).
• Absent corneal reflexes 72 hours post-CPR (6,7).
• Short-latency Somatosensory Evoked Potentials (SSEP, an electrophysiologic study): bilateral
absence of the N20 potentials on SSEP of the median nerve in AIE patients greater than 24 hours
post-CPR (1,6,7,8).
• Neuron-Specific Enolase (NSE, a blood test): serum NSE > 33 mcg/L on day 1 to 3 (6,7,8).
While this biomarker is promising, it has not been studied in large trials, nor is the assay itself
standardized, so its current clinical role remains undefined (7).
Moderate Predictors of Poor Outcomes (these all predict a poor outcome, but not as invariably as
the above factors based on current literature):
• Clinical exam findings: no spontaneous eye movements or absent oculocephalic reflexes at 72
hours post-arrest (3,6,7). No, or extensor-only, motor response to painful stimuli at 72 hours also
implies a very poor chance of recovery (3,6).
• Electroencephalogram findings: certain findings can be strongly associated with poor outcomes
but are highly subject to institutional/technician variability. Myoclonic status epilepticus within 1
day of cardiac arrest is the most predictive of a poor outcome (3,6,7,8).
The Therapeutic Hypothermia Protocol The majority of the evidence for prognosis in the comatose
patient after CPR predates the widespread use of therapeutic hypothermia in patients after cardiac arrest.
It remains unclear how this intervention will change prognostication. While the above factors will likely still
indicate poor prognosis, the timing of when the evaluations should be done, as well as if they will predict
a uniformly poor outcome is uncertain. One European study advises that patients have an initial
!22
neurological assessment as soon as possible, but that the second assessment occurs no earlier than
48-72 hours after the return of normal blood temperature and not 48-72 hours after the discontinuation of
active cooling (2). Zandbergen et al suggest that serum NSE >33 mcg/L occurring while hypothermic still
consistently predicts poor outcomes accurately (8). Initial data (4,8) on the predictive value of SSEPs in
patients who underwent hypothermia confirmed that bilateral absent N20 responses is highly predictive of
a poor outcome. There has been a case report of an isolated patient with absent N20 responses who
made a full recovery, highlighting the importance of ongoing investigation into the impact of the
hypothermia protocol on the prognosis of AIE (4).
References
1. Bleck TP. Prognostication and management of patients who are comatose after arrest. Neurol.
2006; 67: 556-57.
2. Friberg,H.. Neurological prognostication after cardiac arrest. Scand J Trauma Resuscitation
Emerg Med. 2008; 16:10.
3. Levy DE, Caronna JJ, Singer BH, Lapinski RH, Frydman H, Pulm F. Predicting outcome from
hypoxic-ischemic coma. JAMA. 1985; 253:1420-6.
4. Leithner C, Ploner CJ, Hasper D, Storm C. Does hypothermia influence the predictive value of
bilateral absent N20 after cardiac arrest? Neurol. 2010; 74:965-969.
5. Lloyd-Jones D, et al. Heart disease and stroke statistics 2010 update: a report from the
American Heart Association. Circulation. 2010; 121:e46-e215.
6. Wijdicks EFM, Hijdra A, Young GB, et al. Practice parameter: prediction of outcome in comatose
survivors after cardiopulmonary resuscitation (an evidence based review): report of the Quality
Standards Subcommittee of American Academy of Neurology. Neurol. 2006; 67:203-10.
7. Young GB. Neurologic prognosis after cardiac arrest. NEJM. 2009: 361:607-11.
8. Zandbergen EG, Hijdra A, Koelman JH, et al. Prediction of poor outcome within the first 3
days of postanoxic coma. Neurol. 2006; 66:62-8.
Author Affiliation: Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY.
Version History: Originally published October 2010; copy-edited August 2015 by Ann Helms MD.
!23
!

PROGNOSTIC MODELS IN CRITICALLY ILL ADULTS
René Claxton MD, Derek Angus MD, and Robert Arnold MD
Background Prognostication for ICU patients is challenging. Grieving families, trying to make
informed decisions about their loved ones care, often ask What are the chances he or she will get through
this? Several prognostic models have been developed to predict survival for groups of patients stratified
by severity of illness. These are used in outcomes research to compare patient groups, assess and
compare ICU performance and help guide resource allocation. Anecdotally, data from these models is
sometimes used in discussing prognosis with family members of critically ill patients. This Fast Fact
discusses common ICU prognostic models and their role in guiding patient care and communication.
Widely used ICU prognostic models Common models for predicting mortality in medical-surgical ICU
patients include the Acute Physiologic and Chronic Health Evaluation (APACHE) score, the Mortality
Probability Model (MPM), the Simplified Acute Physiology Score (SAPS) and the Sequential Organ
Failure Assessment (SOFA) score (1-4). The SOFA score can be calculated at the bedside based on
laboratory and physiologic data; however, this model has not been widely used in either clinical or
research practice by the critical care community to predict mortality. The APACHE, MPM, and SAPS
models are more widely used and require computer software to calculate a score based on multiple
variables including type of admission, the patient’s underlying diseases, physiologic data, and – in the
case of APACHE – laboratory data. The APACHE score is based on the worst values available during
ICU Day 1 whereas MPM and SAPS scores are calculated based on data obtained within one hour of
ICU admission. The models require re-validation over time as ICU interventions and outcomes change.
The APACHE score is currently in its fourth version. MPM and SAPS are in their third versions. Although
APACHE IV and MPM III require proprietary software to calculate a score, the SAPS3 score can be
computed using a downloadable calculator (5). Individual institutions may use a model for all ICU
admissions for purposes of quality monitoring, outcome reporting, or research, and so some clinicians
may have these scores readily available to them.
Accuracy of the prognostic models The discrimination and calibration ability of ICU prognostic
models determine their predictive accuracy (6). Discrimination is the ability of a model to predict a
mortality rate similar to the observed rate; calibration reflects a model’s ability to predict an outcome at
multiple levels (mortality rates). The most recent versions of APACHE, MPM, AND SOFA show both high
discrimination and calibration. All three models report a score based on the above variables that
correlates with a predicted in-hospital mortality rate. For example, a SAPS3 score of 73 correlates with a
hospital mortality rate of 62%. The other two models work similarly.
Clinical use of ICU prognostic models All of these models accurately predict rates of in-hospital
mortality in a population of critically ill patients. This is different than predicting survival for an individual
patient (7), let alone using them to guide individual treatment decisions. None of the models alone can,
for instance, predict 100% mortality, a standard that some families and clinicians may require in order to
limit life-sustaining treatments. Also, as these models focus solely on in-hospital mortality as the outcome
measure, a patient’s functional status, quality of life, and long-term prognosis are not predicted. These
considerations can be equally as important as short-term survival for families and clinicians in determining
appropriate treatment goals. Practically, then, the clinical use of the models is best limited to three uses:
1. As a single ‘data point’ among many to guide patient-centered decision-making. Clinicians can
use outcome data from the tools, along with patient co-morbidity, long-term prognosis, baseline
and anticipated functional status and quality of life, etc., to guide discussions (see Fast Facts
222-227). Chances are your loved one is not going to survive this illness. She might, and
currently we are doing everything we can to get her through this. However, even if she does, her
emphysema is severe enough that we will not be able to improve her breathing or ability to take
care of herself any more than before she became this ill, and it is very likely another event like
this will happen again in the near future.
2. As a screening tool to identify those ICU patients uniquely ‘in need’ of palliative care evaluation.
3. As a research tool to look at the impact of interventions on mortality, morbidity and quality of life.
References
!24
1. Zimmerman JE, Kramer AA, McNair DS, Malila FM. Acute physiology and chronic health
evaluation (APACHE) IV: hospital mortality assessment for today’s critically ill patients. Crit Care
Med. 2006; 34(5):1297-1310.
2. Higgins TL, Teres D, Copes WS, Nathanson BH, Stark M, Kramer AA. Assessing contemporary
intensive care unit outcome: an updated mortality probability admission model (MPM₀-III). Crit
Care Med. 2007; 35(3):827-835.
3. Moreno RP, Metnitz PG, Almeida E, et al. SAPS3—From evaluation for the patient to evaluation
of the intensive care unit. Part 2: Development of a prognostic model for hospital mortality at
ICU admission. Intensive Care Med. 2005; 31:1345-1355.
4. Ferreira FL, Bota DP, Bross A, Melot C, Vincent J. Serial evaluation of the SOFA score to predict
outcome in critically ill patients. JAMA. 2001; 286(14):1754-1758.
5. SAPS3 Software. The SAPS3 Outcome Research Group. Available at: http://saps3.org/
index2.html. Accessed April 21, 2010.
6. Teres D, Lemeshow S. Why severity models should be used with caution. Crit Care Clin. 1994;
10(1):93-110.
7. Rogers J, Fuller HD. Use of daily acute physiology and chronic health evaluation (APACHE) II
scores to predict individual patient survival rate. Crit Care Med. 1994; 22(9):1402-1405.
Version History: Originally published November 2010; Copy-re-edited August 2015.

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!

PROGNOSTICATION IN SEVERE TRAUMATIC BRAIN INJURY IN ADULTS
Stacy M Kessler MD and Keith M Swetz MD
Background Traumatic brain injury (TBI) is defined as brain injury caused by an external force – most
commonly falls, struck by/against events, motor vehicle collisions, and assaults. The vast majority of
patients with mild to moderate TBIs have substantial recoveries; this is not true of severe TBIs. This Fast
Fact discusses prognostication in severe TBI in adults.
Initial TBI severity TBI severity is most commonly graded by the initial Glasgow Coma Scale (GCS)
score. The GCS rates the patient’s best verbal response, best motor response and the stimulus needed
to elicit eye opening. Scores range from 3-15, with score ≤ 8 representing coma. ‘Mild’ TBI (accounting
for ~80% of cases) is manifest by a 30 minute post-injury GCS of 13-15. ‘Moderate’ TBI consists of
immediately altered or loss of consciousness for > 30 minutes and 6 hour post-injury GCS of 9-12.
‘Severe TBI’ involves immediate loss of consciousness for > 6 hours with residual GCS of 3-8.
Long-term outcomes The Glasgow Outcome Scale (GOS) is a five-point scale used widely in brain
injury research. An eight-point Extended Glasgow Outcome Scale (GOS-E) is available with more
sensitivity to change in function, but most outcome studies reference the GOS. The GOS range is (1)
death, (2) persistent vegetative state (unconscious and unable to interact), (3) severe disability
(conscious; cannot live independently; requires daily assistance due to physical or mental impairment),
(4) moderate disability (able to live independently; able to work in a supported environment), and (5) good
recovery (minimal or no deficits; able to work and socialize normally). In addition to global functional
impairments, survivors of severe TBIs often have impairments in memory, executive functioning, impulse
control, sensory processing, and communication skills. Mental health problems are common.
Predicting outcomes Overall 30-day mortality following TBI is estimated to be 20% with the highest
mortality corresponding to the worst initial GCS scores. For patients with reliable initial GCS scores of 3-5,
only 20% will survive and less half of those survivors will have what is often referred to in the research
literature as a ‘good outcome’ (GOS 4-5). Older age, lower initial GCS score, abnormal initial pupil
reactivity, longer length of coma and duration of post-traumatic amnesia, and certain computed
tomography findings all indicate a smaller chance of recovery to GOS 4-5. Kothrari proposed the
following prognostic guidelines, based on a comprehensive review of studies that looked at outcome in
adults 6 months or later after severe TBI [8]:
• Favorable outcome (GOS 4-5) likely when the time to follow commands is less than 2 weeks after
injury, and the duration of post-traumatic amnesia is less than 2 months.
• Poor outcome (GOS <4) is likely when the patient is > 65 years old, the time to follow commands
is longer than 1 month, or the duration of post-traumatic amnesia is greater than 3 months.
• Notably, 10% of patients will not have the outcome predicted by the guidelines above.
A multinational collaborative trial developed a prognostic model (referred to as the CRASH prognostic
mode) which has been validated to predict outcomes in TBI (9,10). The model is available online and
uses age, GCS, pupil reactivity, presence of major extracranial injury, and (optional) computed
tomography findings to give rates of death at 14 days post-injury and GOS at 6 months for survivors (11).
Helping families make decisions Families of patients with severe TBIs may be confronted with
decisions about medical care (e.g. gastrostomy tube placement, chronic ventilatory support, dialysis).
Such decisions often depend on a family’s understanding of a patient’s long-term functional outcome.
The above-mentioned prognostic indicators can help clinicians provide objective information for families
about the likelihood of recovery after a TBI. As with all prognostic tools, however, clinicians can only
predict what would happen to a population of patients with a similar injury (e.g. ‘only 10% of patients
would recover such that they could live independently’); this is different from predicting any particular
patient’s course. It is important to communicate the uncertainty that accompanies most prognostic
estimations. Counseling families about long-term functional prognosis, as well as the expected treatment
course (what rehabilitation would involve) is important. While the research literature often defines a ‘good
recovery’ as GOS 4-5, that may not constitute a ‘good’ recovery for an individual patient. Clinicians
!26
should avoid such language at the bedside and instead use detailed descriptive language of expected
functional and cognitive outcomes. Early and frequent family meetings can facilitate communication, built
rapport, and are vital in expectation setting and establishing goals of care. If life sustaining treatments
are initiated, framing the treatments in the context of time-limited trials is helpful. This empowers family
members to discontinue certain cares after a specified period of time if the prognosis remains unchanged
or if the treatment is not meeting the goals of care (e.g. helping to restore a patient to a functional status
which is acceptable to the patient). Interdisciplinary team members including speech, occupational, and
physical therapists, physiatrists, neurologists, palliative care clinicians, and neurosurgeons can be
important in letting family members more fully understand a patient’s likely future. See Fast Fact #226
about helping surrogates make decisions.
References
1. Centers for Disease Control and Prevention. “Get the Stats on TBI in the United States.” Available
at: http://www.cdc.gov/traumaticbraininjury/factsheets_reports.html. Accessed Aug 14, 2015.
2. Carroll LJ, Cassidy JD, Peloso PM, Borg J, von Holst H, Holm L, Paniak C, Pépin M; WHO
Collaborating Centre Task Force on Mild Traumatic Brain Injury. Prognosis for mild traumatic
brain injury: results of the WHO Collaborating Centre Task Force on Mild Traumatic Brain Injury.
J Rehabil Med. 2004; 43(Suppl):S84-S105.
3. Serio CD, Kreutzer JS, Witol AD. Family needs after traumatic brain injury: a factor analytic
study of the Family Needs Questionnaire. Brain Injury. 1997; 11:1-9.
4. Kolakowsky-Hayner SA, Miner KD, Kretuzer JS. Long-term life quality and family needs after
traumatic brain injury. J Head Trauma Rehabil. 2001; 16:374-385.
5. Cifu DX, Kreutzer JS, Slater DN, Taylor L. Rehabilitation after Traumatic Brain Injury. In:
Braddom RL, Buschbacher RM, Chan L, et al, eds. Physical Medicine and Rehabilitation.
Philadelphia, PA: Saunders Elsevier; 2007: 1133-1174.
6. National Institute of Neurological Disorders and Stroke. Traumatic brain injury: hope through
research. Bethesda (MD): National Institutes of Health; 2002. NIH Publication No. 02-158.
Available at: http://www.ninds.nih.gov/disorders/tbi/detail_tbi.htm. Accessed Aug 14, 2015.
7. Brown AW, Elovic EP, Kothari S, Flanagan SR, Kwasnica C. Congenital and acquired brain
injury. 1. Epidemiology, Pathophysiology, Prognostication, Innovative Treatments, and Prevention.
Arch Phys Med Rehabil. 2008;89 (Suppl):S3-S8.
8. Kothari S. Prognosis after severe TBI: a practical, evidence-based approach. In: Zasler ND, Katz
DI, Zafonte RD, eds. Brain Injury Medicine: Principles and Practice. New York: Demos; 2007:
169-99
9. MRC CRASH Trial Collaborators, Perel P, Arango M, Clayton T, Edwards P, Komolafe E, Poccock
S, Roberts I, Shakur H, Steyerberg E, Yutthakasemsunt S. Predicting outcome after traumatic
brain injury: practical prognostic models based on large cohort of international patients. BMJ.
2008 Feb 23; 336(7641):425-9.
10. Roozenbeek B, Lingsma HF, et al. Prediction of outcome after moderate and severe traumatic
brain injury: external validation of the IMPACT and CRASH prognostic models. Crit Care Med
2012; 40:1609-1617.
11. Prognostic model for predicting outcome after traumatic brain injury (online calculator). MRC
Crash Trial website. Available at: http://www.crash2.lshtm.ac.uk/Risk%20calculator/index.html.
Accessed Aug 14, 2015.
12. Brain Trauma Foundation-American Association of Neurological Surgeons-Joint Section on
Neurotrauma and Critical care. Early indicators of prognosis in severe traumatic brain injury. J
Neurotrauma. 2000; 17:449-627.
Author Affiliations: Mayo Clinic, Rochester, MN.
Version History: Originally published March 2011; Copy-re-edited August 2015.
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THE SURPRISE QUESTION AS A PROGNOSTIC TOOL
Kate S. Jennings, MD1, Sean Marks, MD2, and Hillary D. Lum, MD, PhD1,3
!28
Background: Clinicians have been encouraged to utilize the surprise question (SQ) -- “Would I be
surprised if this patient died within 12 months?” – to identify patients at high 1-year mortality risk. When
clinicians answer “No – I would NOT be surprised if this patient died within 12 months,” the SQ may help
clinicians identify patients with unmet palliative care needs who could benefit from advance care planning
discussions and/or a palliative care referral (1). This Fast Fact reviews the clinical utility of the SQ.
Rationale of the SQ: As difficult as it is for clinicians to prognosticate accurately, multiple studies have
shown that patients with incurable disease desire more prognostic information the sicker they get and
prognosis is a major factor in preferences for rehospitalizations, life support, and CPR (2-4). Although,
patients and surrogates often want temporal prognostic predictions (the clinician’s estimated length of
time he or she predicts the patient will live), clinicians are more accurate and willing to offer probabilistic
predictions (the clinician’s estimate, often in a percentage, of the chance of death in a set time frame,
such as 1 year) (4-6). The SQ was designed as a clinical tool that generalist clinicians would utilize
willingly and routinely to identify patients at risk of death in a year and thereby lead to more appropriate
advance care planning, goals of care discussions, symptom management, and hospice referrals.
Effectiveness of the SQ: Although variations on the SQ have been described in the published literature
including “Would I be surprised if this patient died this hospitalization?” or “Would I be surprised if this
patient died in 3 months?”, the SQ most commonly referred is “Would I be surprised if this patient died
within 12 months?” This SQ has been studied in diverse populations, including a general inpatient setting
(7), high-risk primary care clinic (8), pediatric patients (9), advanced kidney disease (10-12), cancer
(13,14), acute surgical patients (15), emergency department settings (1,16), and nursing home settings
(17). In general, the SQ has performed modestly well in identifying patients with a prognosis of < 1 year
across these various patient populations (18,19). Notable findings from these studies include:
• A meta-analysis of the SQ among 26 studies across these patient populations found that it had a
pooled accuracy of 75%, a sensitivity of 67% and specificity of 80% (18).
• “Yes” answers appear to be much more accurate than “No” answers. The predictive value of a “Yes”
answer was 93%, while only 37% for a “No” answer (18). This means that the SQ is likely better
designed to identify patients who will live more than a year vs the patients who live less a year. It also
suggests that there is “false positives” are relatively common when clinicians answer “No” to the SQ.
• The SQ may be slightly more accurate for cancer patients (pooled accuracy 79%) and renal patients
(76%) vs other disease groups (72%) (18). This may reflect a more predictable illness trajectory in
cancer and renal disease. See Fast Fact #326 for more information on illness trajectories.
• In most studies, the SQ was utilized as one aspect of a broad prognostic assessment which included
clinician gestalt and/or other prognostic tools. Hence, used in isolation, its accuracy is unclear (18).
Implementing the SQ Into Clinical Practice: The SQ can be helpful in identifying patients at risk of
medical decline and death in a certain time frame when used as part of a larger prognostic assessment
(19). Yet, considering the relatively high false positive rate of a “No” answer, it is not established if the SQ
is a cost-effective tool nor an effective way to trigger a palliative care consultation on its own. A consensus
panel of experts suggested that a “No” answer trigger generalist clinicians to perform a primary palliative
care assessment or screening for unmet palliative care needs (20). Sentinel medical events like
hospitalization, decline in performance status, or disease progression are reasonable triggers to
implement the SQ into clinical practice. Note templates, medical rounding tools, and electric medical
record prompts are potential system-based approaches to accomplish this. Reasonable components of
the primary palliative care assessment triggered by a “No” include (20):
• Assessment for distressing physical, psychological, social, or spiritual concerns.
• Identification of whether the patient completed an advance directive such as a health care power of
attorney that is available in the medical records.
• Assessment of patient, family, and/or surrogate’s understanding of the underlying illness, treatment
options, and prognostic trajectory.
• Assessment of decision-making capacity.
• Engagement in honest conversations about prognosis and medical expectations.
• Elicitation of the patient’s care preferences and values.
• Consideration of whether a hospice referral would be appropriate.
• Consideration of whether a palliative care consultation may be beneficial.
!29
References:
1. Haydar SA, Almeder L, Michalakes L, Han PKJ, Strout TD. Using the surprise question to identify
those with unmet palliative care needs in emergency and inpatient settings: what do clinicians
think J Palliat Med. 2017 doi:10.1089/jpm2016.0403
2. Weeks JC, Cook EF, et al. Relationship between cancer patients’ predictions of prognosis and
their treatment preferences. JAMA 1998;279(21):1709-1714.
3. Murphy DJ, Burrows D, et al. The influence of the probability of survival on patients'
preferences regarding cardiopulmonary resuscitation. NEJM 1994; 330:545-549.
4. Gaston CM, Mitchell G. Information giving and decision-making in patients with advanced
cancer: a systematic review. Soc Sci and Med 2005;61(10):2252-64.
5. Christakis NA, Lamont EB. Extent and determinants of error in doctors’ prognoses in terminally ill
patients: prospective cohort study. BMJ 2000; 320;469-472.
6. Hagerty RG, Butow PN, et al. Communicating prognosis in cancer care: a systematic review of
the literature. Ann of Onc 2005; 16(7):1005-53.
7. Downer J, Goldman R, Pinto R, Englesakis M, Adhikari NKJ. The “surprise question” for
predicting death in seriously ill patients: a systemic review and meta-analysis. CMAJ.
2017;189(13):484-93.
8. Larkin JR, Robinson MG, Bernacki RE, et al. Estimating 1-year mortality for high-risk primary care
patients using the “surprise” question. JAMA Intern Med. 2016;176(12):1863-1865.
9. Burke K, Coombes LH, Menezes A, Anderson AK. The ‘surprise question’ in paediatric palliative
care: a prospective cohort study. Palliative Medicine 2018; 32(2):535-42.
10. Moss AH, Ganjoo J, Sharma S, et al. Utility of the “surprise” question to identify dialysis patients
with high mortality. Clin J Am Soc Nephrol. 2008;3(5):1379-84.
11. Pang WF, Kwan BC, Chow KM, Leung CB, Li PK, Szeto CC. Predicting 12-month mortality for
peritoneal dialysis patients using the “surprise” question. Perit Dial Int. 2013;33(1):60-6.
12. Javier AD, Figueroa R, Siew ED, et al. Reliability and utility of the surprise question in CKD
stages 4 to 5. Am J Kidney Dis. 2017 doi: 10.1053/j.ajkd.2016.11.025.
13. Moss AH, Lunney JR, Culp S, et al. Prognostic significance of the “surprise” question in cancer
patients. J Palliat Med. 2010;13(7):837-40.
14. Moroni M, Zocchi D, Bolognesi D, et al. The ‘surprise’ question in advanced cancer patients: a
prospective study among general practitioners. Palliat Med. 2014;28(7):959-964.
15. Lilley EJ, Gemunden SA, Kristo G, et al. Utility of the “surprise” question in predicting survival
among older patients with acute surgical conditions. J Palliat Med. 2017;20(4):420-23.
16. Ouchi K, Jambaulikar, et al. The “surprise question” asked of emergency physicians may predict
12-month mortality among older emergency department patients. J Pall Med 2018; 21(2): 236-40.
17. Rice J, Hunter L, Hsu AT, Donskov M, Luciani T, Toal-Sullivan D, Welch V, Tanuseputro P. Using
the ‘Surprise Question’ in Nursing Homes: A Prospective Mixed-Methods Study. J Palliat Care.
2018; 33(1):9-18.
18. White N, Kupeli N, Vickerstaff V, Stone P. How accurate is the ‘Surprise Question’ at identifying
patients at the end of life? A Systematic review and meta-analysis. BMC Med. 2017; 15(1):139.
19. Romo RD and Lynn J. The utility and value of the “surprise question” for patients with serious
illness. Canadian Medical Association Journal 2017; 189(33):E1072-1073.
20. Weissman DE, Meier DE. Identifying patients in need of a palliative care assessment in the
hospital setting: a consensus report from the Center to Advance Palliative Care. J Palliat Med.
14(1):1-6.
Author Affiliations: 1University of Colorado School of Medicine, Aurora, CO, USA; 2Medical College of
Wisconsin, Milwaukee, WI; 3Veterans Affairs Eastern Colorado Geriatric Research Education and Clinical
Center, Denver, CO, USA
Conflicts of Interest: None to report
Version History: First electronically published in July 2018.
volunteer peer-review editorial board, and are made available online by the Palliative Care Network
of Wisconsin (PCNOW); the authors of each individual Fast Fact are solely responsible for that Fast
!30
Fact’s content. The full set of Fast Facts are available at Palliative Care Network of Wisconsin with
contact information, and how to reference Fast Facts.
Fast Facts can only be copied and distributed for non-commercial, educational purposes. If you adapt or

PROGNOSIS AFTER STROKE
Lily Kosminsky, Nidhi Shah MD, Philip Chang DO
Background Patients who suffer from an acute stroke often cannot make informed medical decisions
and may not have advance directives. The rapidity of its onset often means that the burden of whether to
pursue placement in a nursing home and/or life-prolonging measures such as artificial feeding, falls on
unprepared loved ones. This Fast Fact reviews clinical factors and tools which could help in
prognostication and medical-decision-making for stroke patients.
!31
Accuracy of Clinician Predictions Stroke-related morbidity and mortality improved significantly
between 1995 and 2010 (2). Still, prognostication following stroke, even when done by neurologic
specialists, remains overly optimistic (1). In general, predictions of a poor outcome (death or severe
disability meaning a life of complete dependence) remain relatively reliable (90% accurate in one study),
but <1/2 of the predictions for a good outcome were accurate (3). One unanswered and debated clinical
question is whether a clinician’s prediction of a poor outcome, especially if made early after the stroke,
increase the likelihood that families will withdraw life-sustaining treatment (4,5), and thereby becomes a
self-fulfilling prophecy. To our knowledge, there are no studies which have assessed the prognostic
accuracy of palliative care clinicians for post-stroke patients.
Early Prognostic Factors Stroke scales and other prognostic factors have been recognized to help
predict morbidity and mortality in the first few days of a hospitalization. This data is often utilized to triage
and guide immediate post-stroke decisions by neurologists, generalist clinicians, or intensive-care
clinicians. The most commonly used and studied is the National Institute of Health Stroke Scale (NIHSS)
which is also used as a gold standard (6). The Modified NIHSS (mNIHSS) and the Scandanavian Stroke
Scale (SSS) are similarly notable scales which have been shown to have comparable reliability to the
NIHSS yet may be easier to use and have better interrater reliability (7,9). Unfortunately, all these scales
(including the NIHSS) are similarly optimistic and likely less accurate than clinician gestalt (6-9). While
high scores (e.g. an NIHSS score >16) reliably predict poor outcomes at 3 months, low or intermediate
scores are of minimal value. Other “early” prognostic factors correlated with poor outcomes include age >
75, female gender, embolic stroke type, hemorrhagic conversion, onset to treatment > 2 hours, ED stay >
8 hours, failure to receive tPA, failure to receive treatment in a dedicated stroke unit, low income (except
in universal healthcare systems), and poor social support.
Late Prognostic Factors Often times palliative care specialists are not consulted until several days
after an acute stroke at which point these “later” prognostic factors take on greater importance in the
decision-making process. Dysphagia that persists 3-7 days after a stroke is associated with worse 1-year
functional outcomes (11). Additionally, data suggest that only 10-15% of post-acute stroke patients who
require a gastric feeding tube ever make it home. Post-stroke coma lasting > 3 days and an absent
response to verbal stimuli at 3 days or later have been associated with poor outcomes as well (15), while
active finger extension (at least able to resist gravity) at 7 days is correlated with a more favorable
functional outcomes at 6 months (16). For surrogates considering withdrawal of ventilatory support for
post-stroke patients and a transition to comfort as the primary goal of care, survival times generally range
between 10 minutes to 11 days with a median survival of 7.5 hours (13). Multiple studies suggest the
greatest neurologic recovery from a stroke occurs in the first 6 months (13-16).
Palliative Care Considerations For clinicians and surrogates faced with these challenging post-stroke
decision-making situations, exploring the patient’s values and identifying things that matter most to the
patient should guide treatment choices. The common dilemma surrogates face is taking a small chance
for meaningful functional recovery while a patient remains in what is often a completely dependent state
for potentially months to years vs deciding to forgo or discontinue nutritional support which will invariably
result in death. Evidence suggests that 75% of families prefer a shared or collaborative decision-making
model in stroke care vs unilateral physician or surrogate decision making (13). Decision-making tools
such as the best case-worst case scenario may be helpful methods to achieve informed and collaborative
value-based decisions for both patients and surrogates of post-stroke patients (17). Considering that
survey data suggest that clinicians may be prone to disability biases in post-stroke patients (meaning
clinicians who are not disabled predict poorer life satisfaction and poorer resiliency than is reported by
individuals disabled by the illness) (1,12), in certain circumstances it may be reasonable to give a trial of
nasogastric feedings for 3-7 days immediately after a stroke. If there is no significant neurologic recovery
at that point and surrogates are still having significant difficult deciding, a 3-6-month time-limited trial of
skilled nursing facility placement with artificial nutrition via a more permanent feeding tube could be
reasonable if there is adequate follow up to readdress goals of care if quality of life has not improved to
an acceptable level.
References
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1. Geurts, M., de Kort, F. A. S., de Kort, P. L. M., van Tuijl, J. H., Kappelle, L. J., and van der Worp,
H. B. (2017) Predictive accuracy of physicians' estimates of outcome after severe stroke, PloS
one 12, e0184894.
2. Appelros, P., Jonsson, F., Asberg, S., Asplund, K., Glader, E. L., Asberg, K. H., Norrving, B.,
Stegmayr, B., and Terent, A. (2014) Trends in stroke treatment and outcome between 1995 and
2010: observations from Riks-Stroke, the Swedish stroke register, Cerebrovascular diseases
(Basel, Switzerland) 37, 22-29.
3. Thompson, D. D., Murray, G. D., Dennis, M., Sudlow, C. L., and Whiteley, W. N. (2014) Formal
and informal prediction of recurrent stroke and myocardial infarction after stroke: a systematic
review and evaluation of clinical prediction models in a new cohort, BMC medicine 12, 58.
4. Kelly, A. G., Hoskins, K. D., and Holloway, R. G. (2012) Early stroke mortality, patient
preferences, and the withdrawal of care bias, Neurology 79, 941-944.
5. Becker, K. J., Baxter, A. B., Cohen, W. A., Bybee, H. M., Tirschwell, D. L., Newell, D. W., Winn, H.
R., and Longstreth, W. T., Jr. (2001) Withdrawal of support in intracerebral hemorrhage may lead
to self-fulfilling prophecies, Neurology 56, 766-772.
6. Inoa, V., Aron, A. W., Staff, I., Fortunato, G., and Sansing, L. H. (2014) Lower NIH stroke scale
scores are required to accurately predict a good prognosis in posterior circulation stroke,
Cerebrovascular diseases (Basel, Switzerland) 37, 251-255.
7. Meyer, B. C., and Lyden, P. D. (2009) The modified National Institutes of Health Stroke Scale: its
time has come, International journal of stroke : official journal of the International Stroke Society
4, 267-273.
8. Thaller, M., and Mitchell, N. (2017) mSOAR: an effective bedside stroke prognosis tool, Clinical
medicine (London, England) 17, 204-208.
9. Askim, T., Bernhardt, J., Churilov, L., and Indredavik, B. (2016) The Scandinavian Stroke Scale is
equally as good as The National Institutes of Health Stroke Scale in identifying 3-month outcome,
Journal of rehabilitation medicine 48, 909-912.
10. Quinn, T. J., Singh, S., Lees, K. R., Bath, P. M., and Myint, P. K. (2017) Validating and comparing
stroke prognosis scales, Neurology 89, 997-1002.
11. Terré, R., and Mearin, F. (2009) Resolution of tracheal aspiration after the acute phase of stroke-
related oropharyngeal dysphagia, The American journal of gastroenterology 104, 923.
12. El Masry, Y., Mullan, B., and Hackett, M. (2013) Psychosocial experiences and needs of
Australian caregivers of people with stroke: prognosis messages, caregiver resilience, and
relationships, Topics in stroke rehabilitation 20, 356-368
13. Mayer, Stephan A, and Sharon B Kossoff. (1999) Withdrawal of Life Support in the Neurological
Intensive Care Unit. Neurology, vol. 52, no. 8, pp. 1602–1609.
14. Meisel, Kari, et al. (2017) Survival, Functional Status, and Eating Ability After Percutaneous
Endoscopic Gastrostomy Tube Placement for Acute Stroke. Journal of the American Geriatrics
Society, vol. 65, no. 8, 27
15. Kurent, Jerome E. (2005) Palliative Care in Specific Neurological Diseases. Continuum, vol. 11,
no. 6, pp. 33–77.
16. Smania, Nicola, et al. (2007) Active Finger Extension. Stroke, vol. 38, no. 3, pp. 1088–1090.
17. Stacey D, Bennett CL, Barry MJ, et al. Decision aids for people facing health treatment or
screening decisions. Cochrane Database Syst Rev 2011;10:CD001431-CD001431
18.
Version History: First electronically published in February 2019; originally edited by Sean Marks MD.
Author Affiliations: Drexel University College of Medicine, Philadelphia, PA; Montefiore Medical Center,
New York, NY.
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!34
!
Psychosocial
#19 Taking a Spiritual History 3rd . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . 3-4
#32 Greif and

Bereavement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. 5-6
#43 Is it Grief or
Depression? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
7-8
#47 What do I Tell the

Children? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .9-10
#56 What to do When a Patient Refuses

Treatment. . . . . . . . . . . . . . . . . . . . . . . . . . 11-12
#59 Dealing with the Angry Dying

Patient . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13-14
#65 Establishing End-of-Life Goals: The Living Well

Interview. . . . . . . . . . . . . . . . . . .15-16
#120 Physicians and Prayer Requests. . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . 17-18
#156 Evaluating Requests for Hastened

Death . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19-20
#159 Responding to a Request for Hastening Death . . . . . . . . . . . . . . . . . . . .

. . . . . .21-22
#172 Professional-Patient Boundaries in Palliative Care . . . . . . . . . . . . . . . . .

. . . . . .23-24
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#186 Anxiety in Palliative Care – Causes and
Diagnosis . . . . . . . . . . . . . . . . . . . . . . . .25-26
#203 Managing One’s Emotions as a Clinician . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . 27-28
#210 Suicide Attempts in the Terminally Ill . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . 29-31
#216 Asking About Cultural Beliefs in Palliative Care . . . . . . . . . . . . . . . . . . .

. . . . . . .32-33
#219 Responding to Requests for Non-Disclosure of Medical Information . . . . . .

. . 34-35
#252 Borderline Personality

Disorder . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36-38
#254 Complicated Grief . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . . .39-41
#319 Existential Suffering Part 1: Definition and Diagnosis . . . . . . . . . . . . . . .

. . . . . . 42-44
#320 Existential Suffering Part 2: Clinical Response and

Management . . . . . . . . . . . .45-47
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!

TAKING A SPIRITUAL HISTORY 3RD
Bruce Ambuel PhD
Background Illness raises fundamental questions – For what may I hope? Why do I suffer?
Does my suffering have meaning? What happens after I die? When a physician stands with a
patient as they face death, the physician inevitably plays a role in supporting the patient’s inquiry
into these spiritual questions (see Fast Fact #31 Confronting Personal Mortality). In addition
some patients have specific preferences regarding medical care, death and dying that are based
upon their religious beliefs. The physician often plays an important role in supporting a patient’s
exploration of these issues. Taking a spiritual history is one way to support the patient in this
exploration. Maugans (1997) presents a framework for taking a spiritual history; the interview
below comes primarily from Maugans’ article with some modification based upon the other
sources cited. See Fast Fact #274 for information on the FICA Spirituality History Tool.
Taking a Spiritual History

S—Spiritual belief system
• Do you have a formal religious affiliation? Can you describe this?
• Do you have a spiritual life that is important to you?
• What is your clearest sense of the meaning of your life at this time?
P—Personal spirituality
• Describe the beliefs and practices of your religion that you personally accept.
• Describe those beliefs and practices that you do not accept or follow.
• In what ways is your spirituality/religion meaningful for you?
• How is your spirituality/religion important to you in daily life?
I—Integration with a spiritual community
• Do you belong to any religious or spiritual groups or communities?
• How do you participate in this group/community? What is your role?
• What importance does this group have for you?
• In what ways is this group a source of support for you?
!3
• What types of support and help does or could this group provide for you in dealing
with health issues?
R—Ritualized practices and restrictions
• What specific practices do you carry out as part of your religious and spiritual life
(e.g. prayer, meditation, services, etc.)
• What lifestyle activities or practices do your religion encourage, discourage or
forbid?
• What meaning do these practices and restrictions have for you? To what extent have
you followed these guidelines?
I—Implications for medical care
• Are there specific elements of medical care that your religion discourages or
forbids? To what extent have you followed these guidelines?
• What aspects of your religion/spirituality would you like to keep in mind as I care for
you?
• What knowledge or understanding would strengthen our relationship as physician
and patient?
• Are there barriers to our relationship based upon religious or spiritual issues?
• Would you like to discuss religious or spiritual implications of health care?
T—Terminal events planning
• Are there particular aspects of medical care that you wish to forgo or have withheld
because of your religion/spirituality?
• Are there religious or spiritual practices or rituals that you would like to have
available in the hospital or at home?
• Are there religious or spiritual practices that you wish to plan for at the time of death,
or following death?
• From what sources do you draw strength in order to cope with this illness?
• For what in your life do you still feel gratitude even though ill?
• When you are afraid or in pain, how do you find comfort?
• As we plan for your medical care near the end of life, in what ways will your religion
and spirituality influence your decisions?
References:
2. Ambuel B, Weissman DE. Discussing spiritual issues and maintaining hope. In:
Weissman DE, Ambuel B, eds. Improving End-of-Life Care: A Resource Guide for
Physician Education, 2nd Edition. Milwaukee, WI: Medical College of Wisconsin; 1999.
3. Griffith JL, Griffith ME. Hope in suffering/pain in health: Talking with patients about
spiritual issues. Presented at The 18th Forum for the Behavioral Sciences in Family
Medicine, Chicago, Illinois, October 1997.
published August 2005; 3rd Edition May 2015. Current version re-copy-edited May 2015.
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GRIEF AND BEREAVEMENT
James Hallenbeck MD
Introduction Grief is a normal response to loss, any loss: a job, a limb, a life. Clinicians have
an important role in facilitating healthy grieving, and observing for signs of complicated grief.
Grief experienced by dying patients and loved-ones prior to and in anticipation of death is called
anticipatory grief (or mourning); grief of loved-ones following a death is termed bereavement.
This Fast Fact provides an overview of grief and bereavement.
What is Grief? Grief is a normal response to loss that involves processes and tasks at
emotional, cognitive and behavioral levels. The initial shock of learning of impending or actual
loss evolves into a process of creating a new relationship between the grieving person and the
person (or object) of loss. Grief tends to be experienced in waves, triggered predictably by new
losses (such as a loss of functional status) or unpredictably, by seemingly trivial events. Over time
the intensity of these waves tends to decrease. Grief does not have a set schedule; individuals
progress through the grief process at different speeds. However, no progress, getting stuck in one
phase of grief, can be cause for concern.
What is Anticipatory Grief? Anticipatory grief for patients involves reviewing one's life; for
families/friends it means looking to a future without the dying person. Byock has suggested that
patients and families may wish to say to each other, in some way, "Forgive me, I forgive you,
thank you, I love you and good-bye." People from different cultural backgrounds may differ in
terms of how and what they want to say or do in preparation for death. Not knowing or
acknowledging that a person is dying will likely delay or interfere with normal anticipatory grief.
Grief reactions in dying patients may be confused with pain, depression, and even imminent
death (e.g. social withdrawal may imply pain, depression, or anticipatory grief).
Distinguishing Grief from Depression Neither pain nor depression are normal aspects of the
dying experience, they should be carefully evaluated as both are treatable (See Fast Fact #43).
Grief tends to be experienced as sadness, whereas depression is associated with lack of self-
worth. The question, "Are you sad or are you feeling depressed?" may help begin a dialog to help
you distinguish between grief and clinical depression.
What is Complicated Grief? About 10-20% of the bereaved can experience a persistent or
prolonged period of intense loss. There is debate regarding the precise diagnostic criteria for
complicated grief and duration of symptoms (see Fast Fact # 254 for further information).
However, insecure attachment styles, weak parental bonding in childhood, childhood abuse and
neglect, female gender, low perceived social support, supportive marital relationships, and low
preparation for the loss are all felt to be risk factors.
What can the physician do to facilitate normal grieving?

Be honest when discussing prognosis, goals and treatment options; nothing inhibits normal
anticipatory grief more than ambiguity from the physician. Listen; open the door to meaningful
discussion. Ask, "How are you doing with this recent news?" “Are you scared?" "Tell me what is
going through your mind?” Ask for help – you are not the only health professional available to
help with grief. Contact a nurse, social worker, chaplain or psychologist/psychiatrist if you need
assistance. Assess for and aggressively treat pain and depression.
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References
1. Byock I. The Four Things that Matter Most. New York, NY: Simon & Schuster; 2004.
2. Markowitz AJ, Rabow MW. Caring for bereaved patients: "All the doctors just suddenly
go.” JAMA. 2002; 287(7):882.
3. Rando TA. Clinical Dimensions of Anticipatory Mourning. Champaign, IL: Research
Press; 2000.
again May 2015.
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IS IT GRIEF OR DEPRESSION?
VJ Periyakoil MD
Background Distinguishing between a dying patient’s normal grief and a major depression is a
part of routine care for patients near the end-of-life. This Fast Fact will review the definitions and
clinical features that distinguish these conditions. See Fast Facts #7, #32, and #254 for further
discussions of depression, grief, and complicated grief.
Definitions
• Preparatory (or anticipatory) grief. This is the grief, "that the terminally ill patient has to
undergo in order to prepare himself for his final separation from this world" (1). Features
include rumination about the past, withdrawal from family/friends, and periods of sadness,
crying or anxiety. Preparatory Grief is a normal, not pathological, life cycle event.
• Depression. Clinically significant depression in a population of dying patients is likely
somewhat more common (25-77%) than in the general population (2). However, depression
is not an inevitable part of the dying experience and is treatable. Somatic symptoms
(anorexia, weight changes, constipation, etc.) are often present as a part of the normal dying
process and may not help to distinguish between preparatory grief and depression. Feelings
of guilt, hopelessness, worthlessness, and suicidal ideation are the key factors that
differentiate grief from depression. When in doubt, treat for depression. Utilize mental health
professionals when available. The following additional points are offered to help the clinician
distinguish between preparatory grief and depression. Distinguishing preparatory grief from
depression
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• Temporal Variation. A temporal variation of mood is normal in preparatory grief—a mixture
of “good and bad days.” In contrast, persistent flat affect or dysphoria is characteristic of
depression. Depression is a pathological state; patients can 'get stuck' in this state without
treatment.
• Self-Image. A disturbed self-esteem is not typically seen in grief; however it is a common
feature of depression. Overwhelming and persistent feelings of worthlessness to others and
of being a burden are common in depression. Distressing guilt is usually generalized to all
facets of life in depression, while in grief, the guilt is focused around specific issues (e.g. not
being able to attend a child’s wedding).
• Hope. A grieving patient's hope shifts, but is not lost. (Hope may shift from a hope for cure
to hope for life prolongation to hope for dying well). In contrast, the depressed patient will
comment on feelings of hopelessness and helplessness.
• Anhedonia. The ability to feel pleasure is not lost in preparatory grief. Note: grieving
patients often need social interaction to help them through the grief process. Anhedonia is an
important clue to underlying depression.
• Response to Support. Social support helps provide the acceptance and assistance
necessary for completion of grief work (3). While social interaction may be helpful in some
depressed patients, it will typically not provide the assistance necessary to resolve
depression.
• Active Desire for an Early Death. An active desire for an early death is not typical of
preparatory grief. A persistent, active desire for an early death in a patient, whose
symptomatic and social needs have been reasonably met, is suggestive of clinical depression
(4).
• Self-Image. A disturbed self-esteem is not typically seen in grief; however it is a common
feature of depression. Overwhelming and persistent feelings of worthlessness to others and
of being a burden are common in depression. Distressing guilt is usually generalized to all
facets of life in depression, while in grief, the guilt is focused around specific issues (e.g. not
being able to attend a child’s wedding).
References
1. Kubler-Ross E. On Death and Dying. New York, NY: Simon and Schuster; 1997: pp123-124.
2. EPEC Project Module 6: Anxiety, Delirium, Depression. In: Emanuel LL, von Gunten CF,
Ferris FF, eds. The EPEC Curriculum: Education for Physicians on End-of-life Care.
Chicago, IL: The EPEC Project; 1999. http://www.EPEC.net.
3. Education on Palliative and End-of-Life Care. http://www.epec.net. 1999.
4. Rando TA. Grief, Dying, and Death. Clinical Interventions for the Caregiver. Champaign, IL:
Research Press Company; 1984.
5. Chochinov HM, et al. Desire for death in the terminally ill. Am J of Psychiatry. 1995;
152:1185-91.
6. Billings JA, Block SD. Depression. J Pall Care. 1995; 11:48-54.
7. Block SD, for the ACP-ASIM End-of-Life Care Consensus Panel. Assessing and managing
depression in the terminally ill patient. Annals Intern Med. 2000; 132:209-218.
8. Block SD. Psychological considerations, growth, and transcendence at the end of life: the art
of the possible. JAMA. 2001; 285:2898-905.
again May 2015.
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WHAT DO I TELL THE CHILDREN?
Paula Rauch and Robert Arnold MD
Background The death of a young adult is always difficult, even more so when there are young
children survivors. A common question asked by dying adults or their family members is What
do I tell the children? Physicians and other health care providers can provide leadership and
guidance to help young families through this crisis.
I. Screening and awareness

• Ask if the ill person has children at home. Ask about their age, personality, and coping
style.
• Ask what the ill person has told the children about the illness.
• Ask if they have a specific worry about the child.
• Ask if the child has had recent problems in school, at home or with relationships.
• Ask who they would like to talk to if they have concerns?
II. Give them some words.

• Often a parent’s biggest worry is what to say if the child asks if he or she is dying. Here
are two examples of words a parent might use. Asking a parent if these words would feel
comfortable to say can begin a dialogue between patient and clinician to arrive at
language that is honest, and life affirming.
• “X” can kill people, but I am taking the best care of myself I can. I am following the
doctor’s plan so that I can live as long as possible.
• Even with trying my hardest and getting the best possible care, my ____ is getting
worse; still I plan to live every day.
III. Give adults concrete examples to guide their interactions.

• Express interest in the child’s day.
• Work to maintain normal routines (e.g. maintain family rituals: Friday night supper,
Monday night pizza, watching television together).
• Welcome all questions but do not force discussions. Make sure you understand the real
question before answering. Take your time to think about how you want to answer.
• Overhearing bad news is the worst way to hear it. Talk with children from diagnosis
onward, being sure to give updates when there are changes in prognosis or treatment.
• Avoid euphemisms (e.g. lump, boo-boo, or sickness) that may confuse children.
• Ask children to share what they are thinking, or hear from others, so they do not worry
alone.
• Prepare children for visits with the sick person. Describe what they are likely to see.
Bring along another adult who is comfortable to stay only as long as the child wants.
Bring along markers and paper, so children can leave the parent with a picture or
message.
• Talk to the child's teacher or guidance counselor to alert the teachers. Ask teachers and
the child's friends' parents to let the parent know if the child talks about worries.
IV. Refer adults to one of the popular books on the subject (Kroen, McCue)
V. Know the resources for parents and children in your hospital and community
VI. Consider referral to a child life specialist or mental health professional when any of the
following occur:
• Symptoms of depression or anxiety that interfere with school, home or with peers
• Risk taking behavior
• Significant discord between the child and the surviving parent
• Significant discord between the parents
• The child says he or she wants to talk to someone outside of the family.
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References:
1. Rauch P. Comment: Supporting the Child Within the Family. J Clin Ethics. 2000;
11:169-170.
2. Harpham,W. When a Parent Has Cancer. A Guide to Caring for Your Children. San
Francisco, CA: HarperCollins; 1997.
3. Keeley D. Telling Children About a Parent's Cancer. BMJ. 2000; 321:462-463.
4. Krementz J. How It Feels When a Parent Dies. New York, NY: Alfred Knopf; 1988.
5. Kroen WC. Helping Children Cope with the Loss of a Loved One. Minneapolis, MN: Free
Spirit Publishing; 1996.
6. McCue K. How to Help Children Through a Parent's Serious Illness. New York, NY: St.
Martins Griffin; 1994.
7. Rauch PK, Muriel AC. Raising an Emotionally Healthy Child When a Parent is Sick. New
York, NY: McGraw-Hill; 2005.
again May 2015.
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WHAT TO DO WHEN A PATIENT REFUSES TREATMENT
Robert Arnold MD
Background A core aspect of American bioethics is that a competent adult patient has a right to
refuse treatment, even when the physician believes that the treatment would be beneficial. At
such a time it is easy to either question the patient’s capacity to make the decision or try even
harder to convince them to change their mind. The empirical literature – both in decision making
and in medicine – suggest that this is a false dichotomy and that there is a third more productive
way to proceed. The method described below is applicable to all situations of conflict between
clinicians and their patients/families; the astute reader will note the similarity between this
approach and that presented in Fast Fact #26, The Explanatory Model, designed to assist
mediating conflicts that arise in cross-cultural encounters.
Clarify Decisionality Distinguish between patients who cannot understand the medical
situation (and thus may lack decision making capacity) and those who understand your viewpoint
but do not agree with it. Ask, I have talked with you about the medical problems you are facing
and possible treatments for these problems. Just to make sure we are on the same page, can
you describe for me the medical problems you are dealing with now? Can you also describe the
possible treatments we have discussed? (See Fast Fact #55 for more on decisionality.)
Understand their story Try to understand the patient/family’s story before you try to change
their mind. This means suspending your attitude toward their decision and as openly and non-
judgmentally as possible, understanding the reasons for their decision. This can be done by
asking, Tell me more about your decision – what leads you to this conclusion?
Validate concerns Often when we try to convince others of our position, we forget to
acknowledge the reality of their concerns. This makes them feel unheard and under appreciated.
More effective are responses which first let the person know they were heard (So you are
concerned that if you have surgery you will X) or that normalize their concerns (It is not that
unusual for people to be afraid of XX) before you respond to these issues.
Explore fears Fears are stronger motivators than positive inducements. Try to understand
your patient/family’s fears/concerns with your plan of action; you can only address their fears if
you understand them. Ask, Can you tell me if there is something about this decision that frightens
you?
Establish a win-win position If the patient’s concern is the lack of control in the hospital and
your concern is her/his health if s/he leaves the hospital, what can you do to provide more control
in the hospital? Negotiate so both of you can achieve what each of you care about the most.
See the related Fast Facts #16, 17, 24, 26, 29, 59.
References
1. Drane JF. The Many Faces of Competency. Hasting Center Report. 1985; 15(2):17-21
2. Stone D, Patton B, et al. Difficult Conversations: How to Discuss What Matters Most.
New York, NY: Penguin Group; 1999.
3. Appelbaum PS, Roth LH. Patients who refuse treatment in medical hospitals. JAMA.
1983; 250:1296-1301.
4. Jones RC, Holden T. A guide to assessing decision-making capacity. Cleve Clin J Med.
2004; 71:971-5.
published July 2006; 3rd Edition May 2015. Current version re-copy-edited April 2009; references
updated; copy-edited again May 2015.
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DEALING WITH THE ANGRY DYING PATIENT
Rebekah Wang-Cheng MD, FACP
Background Anger is a common emotion expressed by seriously ill patients and their families.
A typical reaction by the health professional, confronted by the angry patient or family, is to either
get angry back or to physically and psychologically withdraw; neither are particularly helpful
coping strategies. A guide to managing these situations is presented below.
Look for the underlying source of anger. Fear is probably the most common source of anger,
especially in the dying and their families – fear of the unknown, being in pain or suffering, the
future well-being of family members, abandonment, leaving unfinished business, losing control of
bodily functions or cognition, being a burden to the family, and dying alone.
Other sources of anger include: 1) a genuine insult – so called “rational anger” (e.g. waiting six
hours to see the doctor); 2) organic pathology: frontal lobe mass, dementia or delirium; and 3)
personality style/disorder – the person whose approach to much of life is via anger or mistrust.
Recognize the direction of anger. Recognizing the difference between internal and external
anger is critical to effective management, because internal anger may lead to potentially harmful
patient consequences. When the patient directs anger internally because of fear and guilt (e.g. I
didn’t take care of myself; I’m abandoning my family.), this can lead to withdrawal, self-neglect,
anxiety, depression, or a combination of these. Others direct their anger outward at physicians,
hospitals, family members or a deity. Particularly in the case of an angry parent of a dying child,
he or she may feel helpless and guilty about many things – not bringing the child for medical care
soon enough, not being a loving enough or “great” parent (1). This internal guilt and blame can
then be displaced towards health care professionals.
Engage rather than withdraw from the patient. The natural tendency for clinicians is to cut
short the office or hospital visit, find ways to avoid contact with the angry patient or family
member, or to try to mask his/her own anger in order to continue to interact with the patient.
Robert Houston MD has written a very helpful article listing 10 rules for engaging the dying
patient which will have a beneficial impact on the physician/patient relationship and the quality of
the patient’s end-of-life experience (2). One of his most important tips is to refrain from
personalizing the anger when the patient accuses you of “missing the diagnosis” or under treating
the pain. Some of his rules which are pertinent to this discussion are:
• Engage the patient, but do not enmesh with and do the emotional work for the patient.
• Maintain adult-adult communication rather than fostering the patient’s dependency.
• Do not personalize the patient’s anger.
• Adopt a patient-centered worldview by ascertaining his/her values, priorities, hopes.
• Normalize anger so that the patient can move through this stage.
Use the "BATHE" approach to create an empathic milieu (3). As with any difficult patient
situation, communication techniques are especially important so that both the patient and
physician do not become further embittered and frustrated.
• Background: Use active listening to understand the story, the context, the patient's
situation.
• Affect: Name the emotion; for instance, You seem very angry…. It is crucial to validate
feelings so the angry person feels that you are listening. Attempting to defuse it, counter
it with your own anger or ignore it, will be counter-productive. Acknowledging their right
to be angry will help start the healing process and solidify the therapeutic relationship.
• Troubles: Explore what scares or troubles them the most about their present and future.
Just asking the question Tell me what frightens you? will help them to focus on
circumstances they may not have considered.
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• Handling: Knowledge and positive action can help mitigate fears and reduce anger. How
are they handling the dying – are they making concrete plans about their finances, their
things, their family? Have they thought about formal counseling to help deal with the
depression, the anger?
• Empathy: By displaying empathy and concern you can help the person feel understood,
less abandoned and alone. Avoid trite statements such as I know what you're going
through. Paraphrasing the patient’s comments is an effective way to convey that you
heard and are seeking to understand: You feel like it's so unfair that the cancer appeared
out of nowhere after all these years.
Summary The journey from life to death almost always is accompanied by some degree of
anger. A caring, patient clinician can assist the patient and the family in recognizing, mobilizing,
and modifying the anger into positive emotional energy. Established communication approaches
are available such as BATHE which have shown improvements in self-efficacy for communicating
with angry patients.
References
1. Grossman L. Understanding anger in parents of dying children. Am Fam Physician.
1998; 58(5):1211-2.
2. Houston RE. The angry dying patient. Prim Care Companion J Clin Psychiatry. 1999;
1:5-8.
3. Stewart MR, Lieberman J, III. The Fifteen Minute Hour: Applied Psychotherapy for the
Primary Care Physician. 2nd Edition. Westport, CT: Praeger Publishing; 1993.
4. Rueth TW, Hall SE. Dealing with the anger and hostility of those who grieve. A J Hos
Pall Care. 1999; 16:743-746.
5. Bialer PA, Kissane D, et al. Responding to patient anger: Development and evaluation of
an oncology communication skills training module. 2011; 9: 359-65.
May 2015.

ESTABLISHING END-OF-LIFE GOALS: THE LIVING WELL INTERVIEW
Bruce Ambuel PhD
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Introduction “When a person faces a fatal disease that is likely incurable, he or she faces
specific decisions not only about medical treatment but also about broader, existential issues
concerning the best way in which to spend his or her remaining time.” (Hammes 1998)
Clinician-patient discussions about end-of-life treatment are often framed as a choice between
“medical treatment vs. treatment withdrawal.” When framed in this manner, treatment withdrawal
is a negative choice that often implies giving up, abandonment, not giving the doctor a chance to
do his or her job, and not caring; this option would seem to be no option at all.
Bernard Hammes PhD suggests that clinicians reframe the clinician-patient dialogue about end-
of-life treatment by starting a conversation with the patient focused on the question “How can we
help you live well?” The goal of the living well interview is to elicit the patient’s perspective
regarding how they want to spend their remaining time. Treatment decisions are then discussed
within this broader context of patient goals and hopes. Consequently, medical treatments
become tools for achieving patient goals.
The Living Well Discussion
• When: Begin soon after the diagnosis of a life-limiting condition.
• Who: Clinician (e.g. physician or advanced practice provider), members of the IDT (social
worker, chaplain, nurse, psychologist, etc.) the patient, and family and/or other support
persons.
• How: Begin by expressing a need and interest to understand the patient’s views. The
clinician’s initial goal is to develop a broad understanding of the patient’s hopes and goals,
not to develop a specific medical plan. Utilize chaplains, social workers, psychologists and
other members of the IDT in this discussion, as these professionals can draw upon their well-
developed skills in empathy, compassion, and communication to attain a broader perspective
of the patient’s views, as well as foster clinician skill development in interviewing within the
living-well framework. Specific treatment decisions are then made only after the patient and
IDT have developed an understanding of the patient’s broader goals.
• What to say: Given what we now know about your medical condition…
o How can we help you live well? What makes you happy?
o Maintaining or fulfilling what activities or experiences are most important for
you to feel your life has quality, or for you to live well?
o What fears or worries do you have about your illness or medical care?
o If you had to choose, would you want us to focus on helping you live longer even if
that made you feel worse or on feeling well even if that meant you may not live as
long?
o What needs or services would you like to discuss?
o What do you hope for your family?
o Are there any special events or activities that you are looking forward to?
o What sustains you when you face serious challenges in your life?
o Do you have religious or spiritual beliefs that are important to you?
o In what way do you feel you could make this time especially meaningful to you?
o Most medical care is about making small sacrifices in the interest of improving your
health for tomorrow. But considering your underlying illnesses, I am hoping you can
guide me in helping you make today a better day for you.
References
1.Hammes BJ, Bottner W, et al. Expanding frames…opening choices: reconsidering
conversations about medical care when cure is not possible. Illness Crisis Loss.
1998; 6(4):3252-56.
2. Hammes BJ, Rooney BL. Death and end-of-life planning in one midwestern community.
Arch Int Med. 1998; 158:383-390.
3. Guwande A. Being Mortal: Medicine and What Matters in the End. New York :
Metropolitan Books, Henry Holt and Company, 2014.
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Fast Facts and Concepts are edited by Drew A Rosielle MD, Palliative Care Center, Medical
College of Wisconsin. For more information write to: drosiell@mcw.edu. More information, as
well as the complete set of Fast Facts, are available at EPERC: www.eperc.mcw.edu.
in August 2016 with reference #3 added and communication language updated.
Facts.
official prescribing information should be consulted before any such product is used..
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PHYSICIANS AND PRAYER REQUESTS
Kate Kwiatkowski, Robert Arnold MD, David Barnard PhD
Background Physicians are commonly asked to pray for a patient or to lead a patient/family in
prayer. The physician may feel conflicted because of uncertainty about how to be supportive to
the patient, respect professional/personal boundaries, and remain true to his/her own religious
beliefs. The following options attempt to respect the integrity of the physician’s spiritual/religious
beliefs and be supportive of the patient’s emotional needs.
Options:
1. Pray with/for the patient: It is entirely appropriate for physicians to pray if they feel
comfortable doing so and such prayer is consistent with their own spirituality (see,
however, ‘Pitfalls’ below).
2. Sit with patient while patient prays: A physician who is uncomfortable praying with/for
the patient may choose instead to sit quietly in supportive company while the patient
prays. In this way, physicians lend support to the patient and his/her spiritual beliefs
without explicitly endorsing a particular belief system themselves.
3. Respectfully decline: Physicians who are uncomfortable with either of the above
options may respectfully decline to pray with/for the patient. To avoid the patient feeling
rejected, the physician may want to say: I am really sorry, I am not comfortable with that
[eg. leading a prayer]. In such cases, physicians are encouraged to make non-religious
supportive comments: You will be in my thoughts.
Note: Patients who ask for prayers may have unmet spiritual needs. A chaplain can assist
patients talk or reflect upon their spiritual issues. The physician should ask the patient about
referral: Would you like to visit with the hospital chaplain? Or – Would it be helpful for the hospital
chaplain come and spend some time with you?
Pitfalls:
1. It is inappropriate for the physician to impose his/her religious beliefs on the patient or to
offer prayer in a manner that is not respectful of the patient’s beliefs. Given the
differences in beliefs and practices, even within specific denominations, non-
denominational prayer is safest. For example, rather than referring to Jesus, Buddha or
Allah, use a more neutral and inclusive term like God. Asking God for support or that
God’s will be done is safer than asking for specific outcomes, particularly if you think the
patient is dying.
2. A physician should not promise to pray for a patient if s/he has no intention of doing so.
This has the potential to undermine trust in the physician-patient relationship.
References:
1. Cohen C, et al. Prayer as therapy: a challenge to both religious belief and professional
ethics. Hastings Center Report. 2000; May-June Issue: 40-47.
2. Cohen C, et al. Walking a fine line: physician inquiries into patients’ religious and spiritual
beliefs. Hastings Center Report. 2001; September-October Issue: 29-39.
3. Lo B, et al. Discussing religious and spiritual issues at the end of life: a practical guide
for physicians. JAMA. 2002; 287:749-754.
4. Lo B, et al. Responding to requests regarding prayer and religious ceremonies by
patients near the end of life and their families. Palliative Medicine. 2003; 6:429-31.
in September 2004. Current version re-copy-edited in April 2009; revised again July 2015.
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EVALUATING REQUESTS FOR HASTENED DEATH
Tim Quill MD and Robert Arnold MD
Background A patient’s request to a health care professional to help hasten death is not
uncommon. The motivation for this request is usually a combination of relentless physical
symptoms, progressive debility, in combination with a loss of sense of self, loss of control, fear of
the future, and fear of being a burden on others. Some physicians are frightened by these
requests, feeling that they are being asked to cross unacceptable professional boundaries.
Others may be tempted to quickly accede, imagining that they would want the same thing in the
patient’s shoes. But requests for a hastened death may provide awareness into a patient’s
experience of suffering, and may lead to opportunities for more effective treatment if fully
evaluated. In general, the clinician should clarify, explore, evaluate, intensify treatment, and
support the patient to ensure a full understanding of the request and to ensure that all alternatives
have been considered before responding. This Fast Fact provides guidance on how to evaluate
and initially respond to a patient who raises the topic of a hastened death. Fast Fact #159 will
explore how to respond when the request for a hastened death persists after a full evaluation and
search for alternatives.
1. Clarify which question is being asked before responding. Is the patient simply having
thoughts about ending his life (very common), or is he exploring the possibility of a hastened
death in the future if his condition deteriorates, or is he exploring your willingness to assist
right now (1, 2)?
2. Support the patient, and reinforce your commitment to trying to find a mutually acceptable
solution for the patient’s problem and to continue to work through the process. This does not
mean violating fundamental values, but it does mean searching in earnest with the patient
and family to find a way to approach the dilemma (3). Attend to your own support by
discussing the patient with trusted colleagues and/or with your multidisciplinary team.
3. Evaluate the patient’s decision-making capacity. Is she seeing her medical condition clearly?
Is the request proportionate to the level of unrelieved suffering? Are there dominating
aspects of anhedonia, worthlessness and guilt, or is the capacity for pleasure and joy
preserved in some small ways? Is this request consistent with the patient’s past values? Get
help from an experienced psychiatrist or psychologist if you are unsure (4).
4. Explore the many potential dimensions that may contribute to the patient’s “unbearable”
suffering to be sure you (and the patient) fully understand its underlying cause(s).
Sometimes in may be an unrelenting physical symptom, other times feelings of depression,
or a family or spiritual crisis, or perhaps a combination of many factors (1, 2).
5. Respond to the associated emotions, which may be strong and conflicted. Try to
empathically imagine what the patient is going through and asking for. Distinguish your own
feelings and reactions from those of the patient.
6. Intensify treatment of any potentially reversible elements of the patient’s suffering.
Depending on the patient’s circumstances, offer to increase treatment of pain or other
physical symptoms, consider biological or interpersonal treatment of depression; see if an
appropriate and acceptable spiritual counselor is available. Be creative and brainstorm
potential solutions with your multidisciplinary team (1, 2).
7. Respond directly to the request for hastened death only after this multidimensional
evaluation has been completed. If the patient has full decision-making capacity and all
alternative approaches to the patient’s unbearable suffering have been fully considered, then
re-explore exactly what is being requested, and look for mutually acceptable ways to
potentially respond – see Fast Fact #159 (5). Note that many patients may be looking for the
potential of an escape they will never use, but a smaller number will be looking for a way to
hasten death in the present.
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References
1. Quill TE. Doctor, I want to die. Will you help me? JAMA. 1993; 270:870-873.
2. Block SD, Billings JA. Patient requests to hasten death: Evaluation and management in
terminal care. Arch Intern Med. 1994; 154:2039-2047.
3. Quill TE, Cassel CK. Non-abandonment: A central obligation for physicians. Ann Intern
Med. 1995; 122:368-374.
4. Block SD. Assessing and managing depression in the terminally ill patient. ACP-ASIM
End-of-Life Care Consensus Panel. Ann Intern Med. 2000; 132:209-218.
5. Quill TE, Lo, Brock DW. Palliative options of last resort: A comparison of voluntarily
stopping eating and drinking, terminal sedation, physician-assisted suicide, and voluntary
active euthanasia. JAMA. 1997; 278:1099-2104.
in May 2006. Version re-copy-edited in April 2009; then again in July 2015.
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!

RESPONDING TO A REQUEST FOR HASTENING DEATH
Timothy Quill MD and Robert M Arnold MD
Background Requests for hastened death among terminally ill patients occur commonly (see
Fast Fact #156). With good symptom management, psychological and spiritual support, most
patient requests do not persist. This Fast Fact focuses on ways of responding to patients with
persistent wishes for a hastened death despite every effort to find appropriate alternatives. This
Fast Fact does not address such requests by surrogate decision makers of patients who have
lost decision-making capacity.
1. Reflect on your personal feelings about the request and discuss with other
professionals. These cases are emotionally and ethically difficult. Brainstorm options with
other members of the care team including physician colleagues, nurses, psychologists,
chaplains and others. Allow trusted colleagues to support your emotional reactions.
2. Seek out consultation/2nd Opinion. Make sure you understand the medical, legal and
ethical issues involved in responding to a particular request for hastened death. Palliative
care and/or ethics consultations are invaluable. Independent second opinions may be helpful
in clarifying the prognosis and ensuring that all potentially effective therapeutic alternatives
have been considered.
3. Learn the possibilities. Possibilities are listed below from least to most ethically
controversial. Considering these possibilities assumes that aggressive measures to control
physical, psychological and spiritual suffering have been exhausted and/or rejected by the
patient:
o Withdrawal of life-sustaining treatments. While most clinicians consider stopping
invasive treatments under these circumstances (e.g. ventilators, ICDs, feeding tubes),
simpler therapies such as insulin, antibiotics, oxygen, or steroids might also be voluntarily
discontinued if they are prolonging life against the patient’s wishes. (Unlike the other
possibilities, there is widespread legal and ethical consensus about the permissibility of
this response based on the right to bodily integrity.)
o Voluntary withdrawal of oral intake. Patients may choose to stop eating and drinking
to shorten the dying process. Completely stopping oral food and liquids will typically
result in death within two weeks.
o Sedation for severe intractable physical symptoms (see Fast Facts #106,107). The
intent of sedation is to relieve intolerable suffering by a reduction in patient
consciousness. If artificial hydration and feeding are simultaneously stopped, death will
come within 1-2 weeks.
o Assisted Suicide. Assisted suicide is defined as someone who provides the means for
another person to end their life (e.g. prescribing an overdose amount of medication), but
the patient is the one to decide if and when the medicine is actually used, and the patient
is responsible for taking the medicine. Physician-assisted suicide is illegal in the United
States except for selected states (e.g. Oregon, Washington, Vermont, and Montana).
4. Decision making process. Have a detailed conversation regarding the risk and benefits of
the different possibilities that fit the patient’s clinical circumstances, and which the patient,
family and you find ethically acceptable. Be as specific as possible, and document your
thinking process clearly. Thus, if stopping eating and drinking is being considered, be sure
everyone understands the importance of complete cessation of drinking or else the process
can take months rather than weeks.
5. Balance integrity and non-abandonment. It is not always possible to find common ground
between the patient and physician. When asked if one can support a particular act, a
physician needs to be as specific as possible about what he/she can and cannot do, and why.
While the physician should not violate personal principles to respond to a request he/she
finds unacceptable, he/she should search in earnest with the patient and family for alternative
!23
options that might be mutually acceptable. Typically, this approach will allow the physician to
maintain integrity while not abandoning the patient, even if agreement on the particular act in
question is not possible (1-4).
References
1. Quill TE, Cassel CK. Nonabandonment: A central obligation for physicians. Ann Intern
Med. 1995; 122:368-374.
2. Quill TE, Lo, Brock DW. Palliative options of last resort: A comparison of voluntarily
stopping eating and drinking, terminal sedation, physician-assisted suicide, and voluntary
active euthanasia. JAMA. 1997; 278:1099-2104.
3. Quill TE, Byock I. Responding to intractable terminal suffering: the role of terminal
sedation and voluntary refusal of food and fluids. ACP-ASIM End-of-Life Care
Consensus Panel. Ann Intern Med. 2000; 132:408-414.
4. Quill TE, Coombs-Lee B, Nunn S. Palliative options of last resort: Finding the least
harmful alternative. Ann Intern Med. 2000; 132:488-93.
in July 2006. Version re-copy-edited in April 2009; then again November 2016 (legality of
physician assisted suicide in US updated).
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!

PROFESSIONAL-PATIENT BOUNDARIES IN PALLIATIVE CARE
Lise Taylor Barbour MD
Background Boundaries in patient care are “mutually understood, unspoken, physical and
emotional limits of the relationship between the trusting patient and the caring physician or
provider” (Farber 1997). Health professional boundaries represent a set of culturally and
professionally derived rules for how health professionals and their patients interact. Boundaries
serve to establish and maintain a trusting provider-patient relationship and help clinicians
maintain “justice and equity in dealing with all of their patients”, not only a special few (Spence
2005). This Fast Fact reviews issues in health professional-patient boundaries in palliative care.
Causes of Boundary Problems In caring for seriously ill or dying patients it is common for
strong emotional bonds to develop. However, when the limits of the provider-patient/family
relationship are not clear or where normal professional boundaries are not respected, problems
are likely to arise. Common reasons for boundary problems include:
• Personality styles or psychiatric disorders in which normal boundaries are not recognized
or respected.
• Health professional stress/burnout (see Fast Facts #167-170).
• Cultural misunderstandings.
Examples Warning signs and examples of potential boundary blurring include:

• Gift giving from/to patient/family.
• Patients having or wanting access to provider’s home phone number, or other personal
information.
• Patient/family expectations that the provider will provide care or socialize outside of
clinical care settings.
• Patient/family requests that the provider participate in prayer (See Fast Facts #120).
• The health care provider revealing excessive personal information with patient/family.
Self-Monitoring Not all ‘boundary issues’ are detrimental to the provider-patient relationship –
some clearly enhance compassionate care and serve to reinforce a trusting therapeutic
relationship. However, it is important for the provider to self-reflect when boundaries are
approached.
• Am I treating this patient or family differently than I do my other patients?
• What emotions of my own does this patient/family trigger and are the emotions impacting
my clinical decision-making?
• Are my actions truly therapeutic for the patient, or am I acting in a manner to meet my
personal needs?
• Would I be comfortable if this gift/action was known to the public or my colleagues?
• Could this boundary issue represent a sign that I am experiencing professional burnout?
Managing boundary concerns

• Set clear expectations with patients and families as to your role in the context of their
care, your availability and best ways to communicate with you.
• Use professional colleagues or a mental health professional as a sounding board when
you are uncertain about your own or your patient/family behaviors.
• Address issues as they arise with the patient/family. Acknowledge importance of
feelings, emphasize the provider-patient relationship and the importance of maintaining
objectivity; emphasize that the rejection of a requested behavior does not imply a lack of
caring.
• Seek professional counseling for yourself or the patient/family when boundary issues
impact your ability to provide objective, compassionate care.
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References
1. Gabbard GO, Nadelson C. Professional boundaries in the physician-patient relationship.
JAMA. 1995; 273:1445-1449.
2. Farber N, Novak D, O’Brien M. Love, boundaries, and the physician-patient relationship.
Arch Int Med. 1997;157:2291-2294.
3. Elder W. Erotic undercurrents and boundary violations in medical care. Clin Fam Prac.
2004; 6:975-82.
4. Spence S. Patients bearing gifts: are there strings attached? BMJ. 2005; 331:1527-1529.
5. Post S, Puchalski C, Larson D. Physicians and patient spirituality: professional
boundaries, competency, and ethics. Ann Internal Med. 2000; 132:578-583.
in January 2007. Version copy-edited in April 2009; then again in July 2015.
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!

Background Anxiety is a state of apprehension and fear resulting from the perception of a
current or future threat to oneself. The term is used to describe a symptom and a variety of
psychiatric disorders in which anxiety is a salient symptom. This Fast Fact will discuss the
causes and evaluation of anxiety.
Prevalence Anxiety is commonly reported in those facing life-threatening illnesses. At least
25% and cancer patients and 50% of CHF and COPD patients experience significant anxiety. At
least 3% of patients with advanced cancer and 10% of COPD inpatients meet DSM criteria for
Generalized Anxiety Disorder (see below).
Etiologies
arrhythmias.
corticosteroids.
• Existential and psychosocial concerns about dying, disability, loss, legacy, family, finances,
and religion/spirituality.
• Generalized anxiety disorder is a psychiatric disorder characterized by pervasive and
excessive anxiety and worry about a number of events or activities (such as work or school
performance), occurring more days than not for at least 6 months. The anxiety and worry are
associated with at least 3 of the following 6 symptoms: restlessness, easy fatigue, difficulty
concentrating, irritability, muscle tension, and sleep disturbance.
• Panic disorder is characterized by recurrent panic attacks. See Fast Fact #145 for its
evaluation and management.
• Adjustment disorder occurs within 3 months of a major stressor, and causes marked distress
and functional impairment. Usually it is characterized by a depressed mood but anxiety can
also be its most prominent affective component.
• Acute- or post-traumatic stress disorders occur after an emotionally traumatic life-event
and are characterized by anxiousness and arousal, as well as by numbness, flashbacks,
intrusive thoughts, and avoidance of stimuli which remind the patient of the trauma.
Evaluation
• Seek help from a professional familiar with the psychiatric disorders when anxiety is a
prominent and functionally impairing part of a patient’s symptoms.
akathisia, an unpleasant sense of motor restlessness from dopamine-blocking medications
such as antipsychotics and some antiemetics.
• Formal screening tools exist, but there is no consensus on the benefit of their routine use.
Commonly used tools which evaluate for anxiety as a symptom include the Edmonton
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Symptom Assessment Scale, the Memorial Symptom Assessment Scale, and the Hospital
Anxiety and Depression Scale.
References
2. Mikkelsen RL, et al. Anxiety and depression in patients with chronic obstructive
pulmonary disease (COPD). A review. Nordic J Psychiatry. 2004; 58:65-70.
3. Friedmann E, et al. Relationship of depression, anxiety, and social isolation to chronic
heart failure outpatient mortality. Am Heart J. 2006; 11:152.
4. Tremblay A and Breitbart W. Psychiatric dimensions of palliative care. Neurol Clin. 2001;
19(4):949-67.
5. Bjelland I, et al. The validity of the Hospital Anxiety and Depression Scale. An updated
literature review. J Psychosom Res. 2002; 52(2):69-77.
6. Bruera E, Kuehn N, Miller MJ, Selmser P, Macmillan K. The Edmonton Symptom
Assessment System (ESAS): a simple method of the assessment of palliative care
patients. J Palliat Care. 1991; 7:6-9.
7. Portenoy RK, Thaler HT, Kornblith AB, et al. The Memorial Symptom Assessment Scale:
an instrument for the evaluation of symptom prevalence, characteristics and distress. Eur
J Cancer. 1994; 30A(9):1326-36.
Version History: Originally published August 2007. Version copy-edited in May 2009; then
again July 2015.
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!

MANAGING ONE’S EMOTIONS AS A CLINICIAN
Donna Posluszny PhD and Robert Arnold MD
Background It is normal for clinicians to experience an array of emotions when interacting with
ill patients and their families. Although positive emotions such as joy and satisfaction are rarely
problematic, negative emotions such as anger or sadness may interfere with your ability to
communicate empathically or even to provide appropriate medical care. This Fast Fact focuses
on clinicians’ emotional responses to patient care. See Fast Facts #59, 167-170, and 172 for
more on responding to anger, clinician burnout, and professional boundaries.
Sources of Emotion Some of the emotions we experience are direct reactions to what the
patient is saying or doing (e.g. an angry patient may trigger our own anger). Difficult emotions
may also arise when patients do not act in ways that we like (e.g. feeling frustrated when a
patient is not taking medication as prescribed). We may feel sad, helpless, or even guilty when
we cannot prevent a patient from further illness or death. We may also experience emotions
triggered by our own past experiences, such as a patient who reminds us of a family member
(e.g. grief, longing).
Strategies for managing difficult emotions Dealing with one’s emotions is a learned skill.
Like all skills it takes time and practice. Be patient and keep practicing – look at each experience
as a learning opportunity.
• Prior to an interaction you anticipate will be difficult specifically identify what is causing your
emotional response. Was it the patient’s health behavior, their behavior towards you, their
intense emotions, or your own sadness about their condition? If your emotional response is
based on your past, acknowledge this and put it aside during the upcoming interaction.
• Practice the interaction ahead of time. Imagine the most likely ways that the patient will react
and how you will respond.
o Clarify your goals. It is unrealistic to expect that you can prevent or control patients from
experiencing difficult emotions, especially anger and grief. Acknowledge this and focus
on realistic goals: being empathic, listening, disclosing medical information, talking
patients through options, and validating their emotions.
o Don’t go it alone. Bring along a colleague or team member who can help if you have
trouble controlling your emotions and can give you feedback on what might work better
next time.
• During the interaction recognize when your emotions are impacting your thinking/
communicating:
o Increased heart rate; feeling flushed, sweating; shallow, rapid breathing; increased
muscle tension; speaking rapidly or loudly; repeating yourself; or realizing you are not
listening.
• If you are experiencing intense negative emotions:
o Give yourself and the patient time to allow emotional intensity to subside. Listen, rather
than speak; allow silence.
o Validate the patient’s experience by naming their emotions (‘You seem frustrated’). If you
are not sure, pose it as a question (’Are you feeling frustrated?’). Besides being
empathic, simply naming what is happening may attenuate your own emotional response.
o Naming your own emotions is appropriate as long as it does not divert attention from the
patient’s needs or put blame on the patient. For example you might say, “I am feeling
frustrated that there is not more we can do to help you.”
• If you are feeling overwhelmed, it is appropriate to say, “Please excuse me for one
moment” and then step outside the room; resume your interaction once composed.
o Most patients appreciate certain displays of clinician emotion (e.g. tears), if they occur at
appropriate times and are consonant with the tenor of the interaction.
o However, losing control of one’s emotions, including grief (sobbing), is never appropriate
in front of patients and clinicians should excuse themselves prior to doing so.
!29
• Afterwards, debrief with a trusted colleague or team member about what happened, how you
responded, and how you might do it differently next time. A less emotionally involved person
can often see things in the interaction that you cannot. Students and residents might ask
faculty to come with them the next time they interact with the patient. Repeated episodes of
emotional instability may be a sign of burnout and/or need for mental health counseling.
References
1. Meier D, Back A, Morrison RS. The inner life of physicians and care of the seriously ill.
JAMA. 2001; 286(23):3007-3014.
2. Halpern, J. Empathy and patient-physician conflicts. J Gen Int Med. 2007; 22(5):696-700.
3. Back A, Arnold R, Baile W, Tulsky J, Fryer-Edwards K. Approaching difficult
communication tasks in oncology. CA, A Cancer Journal for Clinicians. 2005; 55:164-177.
Version History: Originally published May 2008. Version copy-edited in June 2009; then again
July 2015.
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!

SUICIDE ATTEMPTS IN THE TERMINALLY ILL
Background Chronic or advanced medical illness is a significant risk factor for suicidality (1).
This Fast Fact discusses evaluating and responding to suicidality in patients with life-limiting
diseases. Note: this Fast Fact does not address cases of ‘physician assisted suicide’ which
have occurred after a deliberative process including psychiatric screening such as in Oregon in
the US (2).
Ethics
• Core Principles: It is a core obligation of physicians to prevent a patient from initiating suicide
and to intervene medically to prevent a patient from dying after a suicide attempt (3). This
obligation can include detaining and restraining patients against their will and the use of
invasive medical interventions such as mechanical ventilation if needed, although such
restrictions to a patient’s liberty should be kept to the minimum necessary. Most suicidal
patients are considered impaired by depression or other mental illnesses and their actions are
not considered autonomous, thus justifying detaining patients and providing medical
interventions against their will (4). Such interventions can create further opportunities to treat
the patient’s psychiatric condition, and only 20% of people who are prevented from committing
suicide subsequently complete another attempt.
• Exceptions at life’s end: The above logic is less compelling in terminally ill patients who have
attempted suicide, particularly with short prognoses (e.g. <1 month). In these patients most
medical interventions are unlikely to restore health or significantly alter the dying process in a
way that would materially benefit the patient. Clinicians may opt to forgo certain interventions
(e.g. mechanical ventilation), particularly if family/proxy decision makers consider such
interventions inappropriate in their dying loved ones. In these situations clinicians are advised
to 1) verify the certainty of the very short prognosis, utilizing consultants liberally, 2) discuss
with proxy decision makers all possible treatment plans including, when feasible, less-invasive
supportive care options with treatment limitations (e.g. ICU monitoring, gastric lavage and
charcoal administration for an overdose, but establishing a do-not-resuscitate/do-not-intubate
order even if the patient deteriorates), and 3) seek ethics consultation.
• Advance Directives: Advance directives such as living wills stating a patient’s wish to not be
mechanically ventilated are not binding in the setting of a suicide attempt. However, they
should be honored in patients with short prognoses per the discussion above. Advanced
directives specifying treatment limitations should be re-evaluated if it is suspected those
statements were made during a period of undetected depression (5,6).
Epidemiology and Risk Factors There has been limited research into specifically ‘terminally
ill’ populations, hence the rate of suicide in the terminally ill is unknown. What is clear is that
advancing age and psychiatric comorbidity are risk factors for suicide along with male sex, AIDS
diagnosis, a family history of suicide, and uncontrolled pain (7,8). Cancer patients have nearly
twice the incidence of suicide than the general population (rate of 31.4 vs. 16.7/100,000 patient-
years) and the first year after diagnosis carries a higher risk (6,9). Lung, prostate, pancreatic,
and head and neck cancers have the highest suicide rates among all cancer types (9). Up to
8.5% of terminally ill cancer patients express a sustained and pervasive wish for an early death,
and in one survey 10% of terminally ill patients reported “seriously pursuing” physician assisted
suicide (10,11). Rates of actual suicide attempts are presumably lower.
Assessment All patients with life-limiting illnesses should be routinely assessed for depression
and mood disorders (see Fast Facts #7, 43); depressed patients should be screened for suicidal
thoughts. Patients who admit to suicidal thoughts or a desire for hastened death should be asked
about specific plans for self-harm, past history of suicide attempts, access to firearms or other
lethal means to carry out a suicidal act, and level of support/supervision available in the home
(e.g. family caregivers). Although some clinicians may be concerned that exploring suicidal
!31
thoughts may make suicide more likely, there is no evidence that this occurs. Many ill patients
who express a desire for death are simply communicating unresolved emotional and existential
concerns about dying: see Fast Facts #156 & 159.
Responding to Suicidal Intent All patients who are seriously threatening self-harm, or who
have pervasive thoughts of ending their life, should be evaluated urgently by a psychiatrist (12).
Immediate resources depend on local availability and can include prompt evaluation by an
established psychiatrist, medical or psychiatric urgent care clinics or emergency departments, or
even voluntary hospital admission. Options include voluntary psychiatric treatment, arranging 24
hour safety monitoring from the patient’s family and friends, introducing home hospice or home
nursing support, removing means to carry out a suicidal act, and imposing emergency detention.
For disabled patients close to death, removing the means of self-harm (e.g. limit access to pain
medications as long as a reliable family member can administer them) and providing close
supervision through, for instance, hospice services are often sufficient and minimally restrictive.
References
1. Hendin H. Suicide, assisted suicide and medical illness. J of Clin Psychiatry. 1999; 60
Suppl 2:46-50.
2. Death With Dignity Act Report 2007. State of Oregon Department of Human Services.
Available at: http://www.oregon.gov/DHS/ph/pas/index.shtml. Accessed November 10,
2008.
3. Lo B. Resolving ethical dilemmas: a guide for clinicians – 3rd Edition. Lippincott Williams
& Wilkins, 2005: 256-9.
4. Miller RD. Need-for-treatment criteria for involuntary civil commitment: impact in practice.
Am J Psychiatry. 1992; 149:1380-4.
5. Ganzini L, Lee MA, Heinz RT, et al. The effect of depression treatment on elderly
patients’ preferences for life sustaining medical therapy. Am J of Psychiatry. 1994;
151:1631-6.
6. Sontheimer D. Suicide by advance directive. J Med Ethics. 2008; 34:e4; doi:10.1136/
jme.2008.025619.
7. Farberow NL, Banzler S, Cutter F, Reynolds D. An eight-year survey of hospital suicides.
Suicide and Life-Threatening Behavior. 1971; 1:184-201.
8. Rabins PV. Prevention of mental disorder in the elderly: current perspectives and future
prospects. J Am Geriatric Soc. 1992; 40:727-33.
9. Anguiano L, Mayer DK, et al. A literature review of suicide in cancer patients. Cancer
Nursing 2012; 35:E14-E26.
9. Chochinov HM, Wilson KG, Enns M, Mowchun N, Lander S, Levitt M, et al. Desire for
death in the terminally ill. Am J Psychiatry. 1995; 152:1185-91.
10. Emanuel EJ, Fairclough DL, Emanuel LL. Attitudes and desires related to euthanasia and
physician-assisted suicide among terminally ill patients and their caregivers. JAMA.
2000; 284:2460-2468.
11. Block SD. Chapter 6: Assessing and managing depression in the terminally ill patient.
Physician’s Guide to End of Life Care. Snyder, Lois ACP Press; 2001.
Author Affiliations: Medical College of Wisconsin, Milwaukee, WI (SM), University of Minnesota

Medical School & Fairview Health Services, Minneapolis, MN (DAR).
Version History: Published November 2008; copy-edited June 2012; re-copy-edited July 2015
with reference #9 added and incorporated into the text.
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!33
!

ASKING ABOUT CULTURAL BELIEFS IN PALLIATIVE CARE
Hillary Lum MD, PhD and Robert Arnold MD
Background Patients’ cultural backgrounds profoundly influence their preferences and needs
regarding discussing bad news, decision-making, and the dying experience. This Fast Fact offers
a framework for taking a ‘cultural history’ to better understand a patient’s and family’s needs. See
also these related Fast Facts: #17 (illness experience), #19 (spiritual history), #26 (explanatory
model), #183/184 (conflict resolution).
C – Communication. Identify the patient’s preferences regarding how and to whom medical
information is shared. Some people want to know everything about their medical condition, and
others do not. How much would you like to know? For those who request that the physician
discuss their condition with family members: Would you like me to speak with them alone, or
would you like to be present? Identify main contacts to give information to about the patient’s
condition. Carefully explore with families requests to hide information from a patient (see
references #4 and #5; Fast Fact #219).
U – Unique cultural values. Use respectful, curious, and open-ended questions about a
patient’s cultural heritage to identify their values. Is there anything that would be helpful for me to
know about how you and your family view serious illness? Are there cultural beliefs, practices, or
preferences that affect you during times of significant illness? If the patient is open to discussing
death: What concerns do you have about dying? Are there things that are important to you or
your family that I should know about?
L – Locus of decision-making. For some patients medical decision-making is communally
driven rather than individualistic. Multiple family members or a community elder or leader may
need to be involved, often without prior official documentation because it is assumed or
understood from the patient’s perspective. Do you prefer to make medical decisions about tests
and treatments yourself, or would you prefer that others in your family or community make them
for you?
T – Translators. Language barriers are extremely challenging, especially during times of severe
illness. Utilize medical interpreters frequently and effectively. Refer to Fast Fact #154 for a
detailed discussion on using interpreters in palliative care.
U – Understanding the patient and learning as a provider. Reassess what is being heard,
understood, and agreed upon frequently, from both the patient’s and clinician’s standpoint.
Specifically confirm the patient’s understanding or agreement (beyond nodding or “yes”
responses). This is particularly important if a medical translator is involved as miscommunication
is common even when using trained medical interpreters – see reference (6). Can you tell me – in
your own words – what you have heard from me and what’s most important to you about what
I’ve said?
R – Ritualized practices and restrictions. Determine if there are specific customs the patient
desires to be followed. These must be communicated to other health care providers, especially in
the hospital setting. It may be necessary to advocate for the patient and negotiate with healthcare
facility administrators to find an agreeable way to honor a patient’s wishes. Are there specific
practices that you would like to have in the hospital or at home? Are there aspects of medical
care that you wish to forgo or have withheld because of your cultural beliefs? Is anything
discouraged or forbidden? If the patient is approaching death, and willing to discuss it: Are there
specific practices that are important to you at the time of death or afterwards that we should know
about?
E – Environment at home. Given that a majority of hospice care happens in the patient’s home
environment, respectfully explore whether there are any needs that can be met by the health care
system, and how open the patient, family or community is to receiving care at home. Recognize
that patients may be hesitant to voice needs, or resistant to accepting help from outside the
!34
community. Even if a trusting, collaborative relationship has developed between a patient/family
and clinicians in the hospital, this may not immediately translate into the home setting. With the
patient’s permission, expectations about cultural-specific aspects of a patient’s care should be
explicitly communicated to care providers outside the hospital.
References
1. Searight HR, Gafford J. Cultural Diversity at the End of Life: Issues and Guidelines for
Family Physicians. Am Fam Phys. 2005; 71 (3)
2. Crawley LM, et al. Strategies for Culturally Effective End-of-Life Care. Ann Internal Med.
2002; 136:673-679.
4. Arnold R. Palliative Care Case of the Month: The Family Says Not to Tell. University of
Pittsburgh Institute to Enhance Palliative Care. May 2006. Available at: http://
www.dgim.pitt.edu/SPC/cases/May 06.doc.
5. Hallenbeck J, Arnold R. A request for non-disclosure: don’t tell mother. J Clin Oncol.
2007; 25(31):5030-4.
6. Pham K, et al. Alterations During Medical Interpretation of ICU Family Conferences That
Interfere With or Enhance Communication. Chest. 2008; 134(1):109-116.
Author Affiliations: University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
Version History: Originally electronically published in July 2009; copy-re-edited by Mary Rhodes
MD in August 2015.
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!

RESPONDING TO REQUESTS FOR NON-DISCLOSURE OF MEDICAL INFORMATION
Elizabeth Chaitin DHCE and Drew A Rosielle MD
Background What do you do when a family member asks you not to tell your patient important
medical information such as a diagnosis or prognosis? Requests for non-disclosure can
represent a loving family’s efforts to protect a patient from emotional harm, an inaccurate
assessment by the family about a patient’s preferences or emotional resilience, or an accurate
reflection of how the patient would prefer to make decisions. This Fast Fact will introduce readers
to a practical approach to these clinical dilemmas.
The Problem Contemporary medical ethics and professional standards dictate that patients
have the right to choose the medical care that best allows them to meet their life goals. To make
such choices requires they be fully informed of their condition, prognosis, and reasonable
treatment options (see Fast Facts #164, 165). One needs to differentiate the right to such
information from the duty to hear the information, however. Patients have different preferences
for medical decision-making, ranging from individualistic, to paternalistic (doing whatever the
physician recommends), to communal (sharing, or deferring, important medical decisions to
family members or religious/community leaders). Truly respecting patient autonomy requires
clinicians to identify and respect patient wishes to share or defer decision-making, including a
patient’s preference to not be informed of key medical information.
Prevention Negotiate with the patient before the results of testing arrive as to how much
information they would like and who they would like to have present for information sharing. Are
you the kind of person who wants to know the results of the test or would you rather I talk to your
children?
Managing Requests for Non-Disclosure (adapted from Hallenbeck and Arnold, 2007):
• Stay Calm. These situations can be confusing and emotional for clinicians. The calmer
you remain the more information you will gain from the family as to why they do not want
their loved one to be informed of the bad news. Demonstrating frustration or implying that
the request is inappropriate can break trust and derail your efforts to resolve the situation.
• Try to understand the family’s viewpoint. They know the patient best and can provide
insight into the cause of the request. Politely ask questions to understand the nature of
the request. Can you tell me more about why you feel this way? How does your family
typically handle difficult information? How are important decisions made by your family?
Ask about how the patient has responded in the past to bad news and if they have made
specific statements to others about what they want to know. Is the family more worried
more about how the information is given rather than the information itself (e.g. given to
the patient when alone, use of ‘death’ or ‘dying,’ the disclosure of specific prognostic
time-frames)?
• Clarify what the patient already knows. Politely ask questions to understand what the
family believes the patient already knows. Does the family think the patient already
knows or strongly suspects what is going on and would rather not talk further about it, or
is the patient completely in the dark? Have other clinicians already told or implied to the
patient what is going on? How did the patient respond to that? Is the patient talking with
the family about their concerns? A patient’s reluctance to talk with family members may
represent an attempt to protect them.
• Respond empathically. A family’s request to not tell their loved ones usually comes from
a kind and loving place; they are often frightened for themselves and the patient.
Responding empathically (see Fast Fact #29) allows them to recognize that you care
about them. It may allow them to see your ability to give information to their loved one in
a compassionate way.
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• State your views openly, but as your own views. Disclose any discomfort you have with
the family’s request; explain your professional obligation to ensure the patient is able to
make informed decisions in the manner they prefer. Disclose this specifically in the
context of you wanting what is best for the patient, including respecting how she or he
would like to hear information.
• Be willing to brainstorm possible solutions. Rigidly informing the family that you must tell
the patient breaks trust and is inaccurate. There is no ‘one-size-fits-all’ solution to these
scenarios. Often, there are solutions neither of you have thought about that will meet
everyone’s goals. In other cases, the family may not have thought about the implications
of the request (e.g. giving Mom chemotherapy but not telling her she has cancer).
• Negotiate a solution. Recommend to the family that you, in their presence, share with the
patient a limited amount of information, and then specifically ask the patient if they would
like to hear more. Tell the family what you plan on saying, i.e. – You came to the hospital
because you were not eating well and became dehydrated. We have been trying to figure
out what is going on. Some people want to know everything about their medical
condition, others prefer the doctors talk with family members about what is happening
and the best way to help a patient. What would you prefer? Contract with the family that
they, and you, will respect the patient’s decision.
References
1. Bok S. Lying: Moral Choice in Public and Private Life. New York, NY: Vintage Books;
1989.
2. Hallenbeck J, Arnold R. A request for nondisclosure: don’t tell mother. J Clin Oncol.
2007; 25(31):5030-34.
3. Lagarde SM, Franssen SJ, van Werven JR, et al. Patient preferences for the disclosure
of prognosis after esophagectomy for cancer with curative intent. Ann Surg Oncol. 2008;
15(11):3289-3298.
Author Affiliations: University of Pittsburgh Medical Center, Pittsburgh, PA (EC); Medical

College of Wisconsin, Milwaukee, WI (DAR).
Version History: Originally published September 2009; copy-edited August 2015.

BORDERLINE PERSONALITY DISORDER IN PALLIATIVE CARE
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Laura McLafferty MD and Julie W Childers MD
Background Borderline personality disorder (BPD) is identified by a pervasive pattern of
instability of relationships, self-image, and mood, as well as marked impulsivity (1). The
prevalence of BPD in the general population is 1-2%, and, despite the impression of a female
predominance, evidence indicates that it occurs equally frequently in men and women (2). The
stresses of serious illness may bring out these patients’ most dysfunctional coping strategies,
which can be uniquely challenging for medical professionals. This Fast Fact provides strategies
for successful interactions with patients and patients’ caregivers with BPD.
Diagnosing BPD:
The diagnosis of BPD requires a skilled clinical interview conducted by a knowledgeable
examiner who has a longitudinal view of the affected patient. In the palliative care setting, certain
behaviors and interactions with other individuals are clues to a BPD diagnosis if not previously
established.
• Individuals with BPD evoke strong emotional feelings in clinicians, including both
negative emotions (anger, disgust, frustration, and anxiety) and over-identification, which
may lead to attempts to “rescue” the patient.
• Individuals with BPD have difficulty sustaining ambivalent feelings and may instead label
clinicians as either “wonderful” or “terrible”, a defense mechanism known as “splitting”.
• Individuals with BPD will go to great lengths to avoid real or imagined abandonment.
They may demand multiple provider visits per day and become angry or withdrawn when
demands for extra attention or special exceptions are not met. They are more likely to
threaten legal action against providers when they perceive that their needs have not been
met.
• Impulsive behavior, including inappropriate use of prescribed medications, signing out
against medical advice, and inconsistency in decision-making, occur commonly.
• Defects in cognitive functioning, especially decision making, conflict resolution, and
“effortful control” (the ability to inhibit or activate behavior to adapt to a situation) affect
the ability to make reasoned decisions about medical care and sustain meaningful
interactions with loved ones and medical staff.
Strategies for working individuals with BPD (4, 5, 6, 9):

• Remember that the individual with BPD is suffering. Monitor your own feelings and
refrain from responding emotionally or aggressively to verbal attacks and manipulation
(See Fast Facts #59, 172 and 203).
• Begin encounters with a tactful assessment and acknowledgment of the individual’s
distress, and focus on specific problems. Address problem behaviors directly with
statements such as “We want to continue to treat you, but if you threaten to hurt other
people we will have to have you escorted out of the clinic”.
• Recognize splitting behavior (when clinicians find themselves exuberantly praised or
labeled as the ‘only one who has ever been helpful’ to the patient). Clinicians should
avoid excessive familiarity and should instead identify themselves as part of a unified
treatment team with a common plan.
• Set explicit limits on disruptive behavior such as angry outbursts or harm to self or
property. A written treatment contract which specifies consequences may be helpful.
Expect the individual to test the limits and be prepared to respond consistently.
Clinician Self Care and Use of the Interdisciplinary Team

• Frequent debriefing with the interdisciplinary team and key clinicians (e.g., other
consultants) where you have an opportunity to share the feelings you experience in
working with a BPD patients is essential for practitioner self-care (See Fast Facts
#167-170).
• Involve the treatment team in setting limits on behaviors (e.g., angry outbursts), visit
frequency, and inappropriate use of medications. Carefully document all interactions with
the patient or family member, including specific behaviors.
• Utilize consultants. A psychiatric consult-liaison service or the patient’s own psychiatrist
or psychologist, if the patient has one, should be involved in developing a plan for
successful interaction the individual. If a patient’s prognosis is long enough, consider
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requiring participation in psychological or psychiatric care as a condition of your
continued involvement.
References
1. American Psychiatric Association. (2013). Diagnostic and statistical manual of mental
disorders (5th ed.). Washington, DC.
2. Oldham, JM. Guideline watch: practice guideline for the treatment of patients with
borderline personality disorder. American Psychiatric Association Practice Guidelines,
2005. Available at: http://focus.psychiatryonline.org/content.aspx?
bookid=28&sectionid=1682658. Accessed December 15, 2011. DOI: 10.1176/
appi.books.9780890423363.148718.
3. Presniak MD, Olson TR, MacGregor MW. The role of defense mechanisms in borderline
and antisocial personalities. J Pers Assess. 2010; 92:137-145.
4. Leichter SB, Dreelin E. Borderline personality disorder and diabetes: a potentially
ominous mix. Clin Diabetes. 2005; 23(3):101-103.
5. Meyer F, Block S. Personality disorders in the oncology setting. J Support Oncol. 2011;
9(2):44-51.
6. Saper JR, Lake AE. Borderline personality disorder and the chronic headache patient:
review and management recommendations. Headache. 2002; 42(7):663-674.
7. Haas LJ, Leiser JP, Magill MK, Sanyer ON. Management of the difficult patient. Am Fam
Phys. 2005; 72:2063-2068.
8. Ward, RK. Assessment and management of personality disorders. Am Fam Phys. 2004;
70:1505-1512.
9. Hay JL, Passik SD. The cancer patient with borderline personality disorder: suggestions
for symptom-focused management in the medical setting. Psychooncol. 2000; 9(2):
91-100.
Version History: Originally published April 2012; Copy-re-edited August 2015 with reference #1
updated and incorporated into the text.
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!

COMPLICATED GRIEF
René Claxton MD and Charles F Reynolds III, MD
Background The majority of individuals experience normal grief after the death of a loved one
(see Fast Fact #32). However, about 10-20% of bereaved individuals experience a persistent,
debilitating phenomenon referred to as complicated grief (CG) (1). Complicated grief has also
been referred to as prolonged or pathologic grief (2); and in the most recent revision of the
Diagnostic and Statistical Manual of Mental Disorders (DSM V), CG was relabeled as Persistent
Complex Bereavement Disorder (3).
Risk Factors CG is principally considered an attachment disorder (1). Insecure attachment

styles (excessive dependency, compulsive care-giving, defensive separation) are correlated with
CG. Additionally, supportive marital relationships (characterized as security-enhancing, confiding
and emotionally supportive) are correlated with CG after the loss of a spouse suggesting that the
loss of a spouse who provides emotional stability and security may lead to an exacerbated grief
reaction (4). Other risk factors include weak parental bonding in childhood, childhood abuse and
neglect, female gender, low perceived social support, and low preparation for the loss (1,5).
Impact on Health CG is associated with mental and physical health problems including
depression, hypertension, work and social impairment and reduced quality of life. Additionally, CG
increases an individual’s risk of suicide and suicidal behavior (7).
Diagnosis CG shares characteristics with major depressive disorder (suicidal ideation,

preoccupation with worthlessness) and post-traumatic stress disorder (re-experiencing intrusive
thoughts of the deceased, avoidance of reminders of the deceased and emotional numbness).
However these are separate entities differentiated by precipitating events, risk factors, course of
illness and response to intervention (2). The precise diagnostic criteria for CG are currently being
debated (5). Commonly agreed upon characteristics include:
• yearning, pining, or longing for the deceased
• trouble accepting the death
• feeling uneasy about moving on with one’s life
• inability to trust others since the death
• excessive bitterness or anger about the death
• persistent feeling of being shocked, stunned, or emotionally numb since the death
• frequent intense feelings of loneliness
• feeling that life is empty or meaningless without the deceased (refraining from doing
things/going places that remind one of the loss)
• frequent preoccupying thoughts about the person that died
Symptoms must cause marked dysfunction in social, occupational or other important domains.
The duration of symptoms required to meet criteria for CG has not been defined and varies
between six to twelve months after the death (1, 5).
Screening The following Brief Grief Questionnaire is a 5-item screening tool scored on a 0-2
Likert scale (‘not at all,’ ‘somewhat,’ ‘a lot’) which has been used to screen for CG (6).
1. How much of the time are you having trouble accepting the death of a loved one?
2. How much does your grief interfere with your life?
3. How much are you having images or thoughts of your loved one when he or she died or
other thoughts about the death that really bother you?
4. Are there things that you used to do when your loved one was alive that you don’t feel
comfortable doing more, that you avoid? How much are you avoiding these things?
5. How much are you feeling cut off or distant from other people since your loved one died,
even people you used to be close to, like family or friends?
Expert recommendation is that individuals with scores of ≥5 should undergo a diagnostic
evaluation by a mental health professional (7).
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Treatment A recent meta-analysis on the treatment of CG showed efficacy of interventions
including cognitive-behavioral and group therapy in alleviating symptoms with a duration of
benefit from 3-6 months. Limitations of the meta-analysis include under-representation of men
(average 71% female), small number of studies included (n=5), and small number of participants
(n=485, 109 lost to follow up) (8). There have been no randomized controlled trials evaluating the
pharmacologic treatment of CG and there is currently no defined role for drug therapy. A
randomized trial is currently underway to evaluate the effect of a selective serotonin reuptake
inhibitor on CG. Many hospice agencies provide bereavement services, even if the bereaved’s
loved one was not a patient of the hospice agency.
Bottom Line Most bereaved individuals experience normal grief. A minority will experience
long-term, persistent, disruptive symptoms that impair functioning and increase the risk for
negative mental and physical health states. Individuals suffering from CG benefit from referral to
a trained mental health provider who can administer therapy specific to CG.
References
1. Zhang B, et al. Update on bereavement research: evidence-based guidelines for the
diagnosis and treatment of complicated bereavement. J Pall Med. 2006; 9:1188-1203.
2. Lichtenthal WG, et al. A case for establishing complicated grief as a distinct mental
disorder in DSM-V. Clin Psych Rev. 2004; 24:637-662.
3. American Psychiatric Association (2013). Diagnostic and Statistical Manual of Mental
Disorders, ed. 5. Arlington, VA, APA Press.
4. Van Doorn C, et al. The influence of marital quality and attachment styles on traumatic
grief and depressive symptoms. J Nerv Ment Dis. 1998; 186:566-573.
5. Shear KM, et al. Complicated grief and related bereavement issues for DSM-5. Depress
Anxiety. 2001; 28:103-117.
6. Shear KM, et al. Screening for complicated grief among project liberty service recipients
18 months after September 11, 2001. Psychiatric Services. 2006; 57:1291-7.
7. Reynolds C, et al. Healing Emotions After Loss (HEAL): Diagnosis and Treatment of
Complicated Grief. UPMC Synergies. Spring 2011. Available at: http://healstudy.org/wp-
content/uploads/2010/10/S270-Synergies_GR_Spring_2011.pdf. Accessed March 22,
2012.
8. Wittouck C, et al. The prevention and treatment of complicated grief: a meta-analysis.
Clin Psych Rev. 2011; 31:69-78.
Version History: First published June 2012. Updated December 2012 with the addition of
Reference #6. Updated again in August 2015 with reference # 3 added and incorporated into the
text.
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!

EXISTENTIAL SUFFERING PART 1: DEFINITION AND DIAGNOSIS
Tony Grech MD and Adam Marks MD MPH
Background Patients with serious illnesses often wrestle with existential questions such as:
Why is this happening to me? What is the meaning of my suffering? Where is God? Typically,
these questions do not indicate psychological pathology. However, for some patients (likely
13-18% with progressive illness), these questions can evolve into clinically significant existential
suffering that can erode self-worth, correlate with suicidal ideation, and exacerbate physical
symptoms such as pain or nausea (1-3). Palliative care clinicians are often faced with the
challenging task of identifying when existential concerns are contributing to suffering in a way that
a health care team should intervene. This Fast Fact will review the definition of existential
suffering and common identification tools. Fast Fact # 320 will review suggested care approaches
for a patient with existential distress.
Definition There is no widely agreed upon definition of existential suffering, nor an agreed upon
term to describe it. Other terms seen in the published medical literature include “existential
distress”, “demoralization syndrome”, and “total pain” (4). One commonly referred to definition is
an incapacitating state of despair resulting from an inner realization that life is futile and without
meaning (1). Four existential domains have been recognized through which existential suffering
can manifest (3,5):
Existential Description Clinical Manifestation

Domain
Mortality Awareness of the inevitability of death Anxiety about dying or the afterlife;
and a wish for life to continue concern about separating from loved
ones
Freedom Reality that humans must always Regret about past choices; unresolved
choose and all choices have conflict with one’s self or others
consequences.
Meaningles Struggle to find meaning in life despite Loss of purpose; questioning the
s the universal reality of death. meaning of their illness, suffering, or
faith
Isolation Sense of isolation from part of a larger Feelings of abandonment by community
community (church, family, etc) or God; a sense of disconnectedness.
Existential and Spiritual Suffering Existential suffering and spiritual suffering are not
synonymous although these phenomena often overlap. Spiritual suffering, defined simply as
distress due to spiritual or religious concerns, can be conceptualized as a sub-type of existential
suffering. When considering the differences between existential and spiritual suffering, several
key points warrant emphasis:
• Some patients with existential suffering may not consider themselves to be spiritual and may
become upset if a clinician reflexively consults a chaplain.
• Spirituality has vastly different meanings for different individuals. See Fast Facts #19 and
274. In its broadest definition, spirituality can include involvement in a secular club or
organization (6).
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• Spirituality is part of each existential domain; however, it does not encompass all facets of
each existential domain. Therefore, all spiritual suffering is existential suffering, but not all
existential suffering is spiritual suffering.
• “Spiritual” and “existential suffering” are not terms patients/families are typically familiar or
comfortable with. At the bedside it is best to name the distress explicitly or reflect the
patient’s language characterizing the suffering. For example: “It sounds like you are trying to
make sense of how this could happen.” Or “you said you’ve felt very apart from your family
and faith community since this began. Can you tell me more about that?”
Clinical Assessment Tools Clinicians should listen for existential ‘cues’ in all patients with
serious illness, especially when symptoms seem out of proportion to their disease. Such cues
can be expressions of doubt about life’s meaning or one’s faith or expressed feelings of isolation
– e.g. “no one understands what I’m going through.” Although there are multiple validated
assessment tools available to aid healthcare providers in the diagnosis of existential suffering,
many of these tools focus on one specific existential domain and others may be too cumbersome
to implement into clinical practice. Instead one particularly useful tool involves simply asking the
patient: “Are you at peace?” (8). A no answer should prompt further exploration of signs of
distress, physical or otherwise, with follow-up questions such as “What’s keeping you from being
at peace?” or “What worries you the most about your illness?”.
Risk Factors No associations were found with existential suffering and time since diagnosis,
stage of disease, or type of treatment (1). One systematic review identified the following risk
factors (7):
• Poor social support: single patients (including divorced, separated, and widowed) or
unemployed.
• Poorly controlled physical or psychological symptoms.
• Self-blame coping factors for illness and low sense of controllability of the illness.
• Low level of physical activity.
Diagnostic Challenges A lack of a universally accepted definition, clinician knowledge deficit,

and concomitant psychological, spiritual, or social concerns make existential suffering difficult to
diagnose. Furthermore, patients may have difficulty articulating their distress or may not be
willing to disclose it if they feel their clinicians are too busy or guarded from discussing existential
concerns (4). Not all patients with existential suffering develop clinical anxiety or depression. In
general, clinical depression can be defined by a loss of interest or pleasure in the present
moment, whereas existential suffering is typically defined by a loss of hope, meaning, and
anticipatory pleasure (9,10). Despite these challenges, it is important for clinicians who care for
seriously ill patients to elicit existential concerns, as doing so can open opportunities for
empathetic connection and clarify treatment options. Collaborating with social workers,
chaplains, or psychologists is vital to better understand a patient’s suffering.
REFERENCES
1. Kissane, DW: Demoralization: A life-preserving diagnosis to make for the severely

medically ill. Journal of Palliative Care. 2014; 30(4):255-8.
2. LeMay K, Wilson KG: Treatment of existential distress in life threatening illness: A review
of manualized interventions. Clinical Psychology Review. 2008;28:472-93.
3. Strang P, Strang S, Hultborn R, Arner S: Existential pain-An entity, a provocation, or a
challenge? Journal of Pain and Symptom Management. 2004 Mar;27(3):241-50.
4. Best M, Aldridge L, Butow P, et al: Assessment of spiritual suffering in the cancer context:
A systematic literature review. Palliative and Supportive Care. 2015;13:1335-61.
5. Existential Psychotherapy. Yalom, ID. Basic Books, New York, NY 1980.
6. McCurdy DB. Personhood, Spirituality, and Hope in The Care of Human Beings with
Dementia. The Journal of Clinical Ethics. 1998;9(1):81-91.
7. Robinson S, Kissane DW, Brooker J, et al: A systematic review of the demoralization
syndrome in individuals with progressive disease and cancer: A decade of research.
Journal of Pain and Symptom Management. 2015 Mar; 49(3):595-610.
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8. Steinhauser KE, Voils CI, Clipp EC, et al: Are you at peace? Archives of Internal
Medicine. 2009 Jan 9;166:101-5.
9. Kissane DW, Clarke DM, Smith GC. Demoralization syndrome: a relevant psychiatric
diagnosis for palliative care. J Palliat Care 2001;17:12-21.
10. Clarke DM, Kissane DW. Demoralization: its phenomenology and importance. Aust N Z
J Psychiatry. 2002;36:733-742.

Authors Affiliation: University of Michigan Health System, Ann Arbor MI
Version History: Originally edited by Sean Marks MD and Drew Rosielle MD; first electronically
published August 2016.
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!

EXISTENTIAL SUFFERING PART 2: CLINICAL RESPONSE AND MANAGEMENT
Tony Grech MD and Adam Marks MD MPH
Fast Fact #319 explored the definition and risk factors of existential suffering. This Fast Fact will
offer clinical guidance on how to respond to patients exhibiting signs of existential suffering.
Reflective Listening While existential questions at the end of life are a natural and common
occurrence, for some patients these existential concerns can be associated with overt suffering
stemming from a loss of meaning or value in life. When palliative care clinicians encounter a
patient with existential distress, they may feel a clinical need to “fix” the existential distress or
manage it with clinical therapies. Instead, words communicating empathy and validation of the
existential distress may be more comforting. “I can only imagine how scary this must feel for you.
I sometimes wonder how anyone can make sense of this” is an example of reflective listening
phrase which may normalize the patient’s existential distress.
Management Pitfalls Clinicians of seriously ill patients should avoid focusing their clinical
assessment solely on physical symptoms. Since existential suffering, spiritual suffering, physical
symptoms and psychiatric symptoms may all exacerbate the other, it is important to ensure
patients are receiving excellent management of their physical, spiritual, and psychiatric domains.
Failure to do so can result in inappropriate dose escalations of analgesics, anxiolytics, or
antidepressants. Palliative sedation has been used for refractory existential suffering; however, its
use is controversial and in many cases avoidable with the proper engagement of an
interdisciplinary team that includes social workers, chaplains, psychologists, and grief counselors.
Psychotherapeutic Modalities A variety of psychotherapeutic modalities may alleviate the

multifaceted aspects of existential suffering (1-5). Many of these interventions such as dignity
therapy do not require a referral to a trained psychotherapist, as members of the interdisciplinary
team (traditionally social workers, nurses and chaplains) can be trained with relative ease (6).
Meaning Centered Group Psychotherapy (MCGP) and Individual Meaning Centered
Psychotherapy (IMCP): Founded on Viktor Frankl’s teaching regarding the human need for
meaning, MCGP/IMCP is a form of group or individual psychotherapy initially designed for
patients with advanced cancer. MCGP/IMCP strives to help patients find meaning in their
experiences with illness while exploring philosophical questions of life. The goal is to have
patients refocus on living rather than dying, and has been shown to have psychological benefit in
patients with advanced cancer (1,2).
Dignity Therapy: This is a brief form of individual psychotherapy which involves a guided interview
to allow patients to reflect on past experiences that mattered most to them and how they want to
be remembered (legacy). Sessions are often audio-recorded, transcribed, and then provided to
the patient to share or pass on to individuals of their choosing (3,4). A recent systematic review
demonstrated benefits for both patients and families that sustained after the patient’s death (5).
Supportive Expressive Group Therapy (SEGT): This form of group therapy has its foundation in
the benefits of social support and the use of coping skills to help decrease the trauma of a
terminal illness often via normalization (initially established for metastatic breast cancer patients).
The aim is to create a supportive environment for patients where they can adjust to the demands
of their illness while learning to live life fully and authentically and improve their quality of life
(4,6).Sustained responses have been demonstrated particular in patients with breast cancer (7).
Communication Pearls For those patients who are too ill to participate in formal
psychotherapy, a thoughtful, empathetic presence may relieve, to a degree, the existential
suffering many patients experience. Examples of common clinical questions which utilize the
!46
tenets of psychotherapeutic modalities to help patients explore their existential distress and seek
meaning in their illness include:
• It sounds like you have a lot on your mind. What in particular is causing you the most
concern?
• Tell me a little about your life, particularly those parts you remember most or think are most
important.
• What are the most important roles you have played in life (family roles, vocational roles,
community-service roles, etc)? Why were they so important to you? What did you
accomplished in those roles?
• Are there particular things that you feel you still need to be say to your loved ones or say
once again?
• How do you want to be remembered by your loved ones?
REFERENCES
1. Breitbart W, Rosenfield B, Pessin H, et al: Meaning-centered group psychotherapy: An

effective intervention for improving psychological well-being in patients with advanced
cancer. Journal of Clinical Oncology. 2015 Mar;33(7):749-54.
2. Breitbart W, Rosenfield B, Vickers A, et al. Pilot randomized controlled trial of individual
meaning-centered psychotherapy for patients with advanced cancer. Journal of Clinical
Oncology. 2012 April;30(12):1304-1309.
3. Chochinov HM, Kristjanson LJ, Breitbart W, et al: The effect of dignity therapy on distress
and end-of-life experience in terminally ill patients: A randomized controlled trial. Lancet
Oncology. 2011 Aug;12(8):753-62.
4. LeMay K, Wilson KG: Treatment of existential distress in life threatening illness: A review
of manualized interventions. Clinical Psychology Review. 2008;28:472-93.
5. Fitchett G, Emanuel L, Handzo G et al: Care of the human spirit and the role of dignity
therapy: A systematic review of dignity therapy research. BMC Palliative Care. 2015 May
14(8): 1-12.
6. Kissane DW, Grabsch B, Clarke DM, et al: Supportive-expressive group therapy: The
transformation of existential ambivalence into creative living while enhancing adherence
to anti-cancer therapies. Psycho-Oncology. 2004 Mar;13:755-768.
7. Reuter K, Scholl I, Sillem M, Hasenburg A, Harter M: Implementation and benefits of
psychooncological group interventions in german breast centers: A study on supportive-
expressive group therapy for women with primary breast cancer. Breast Care. 2010:5(2):
91-96

Authors Affiliation: University of Michigan Health System, Ann Arbor MI
Version History: Originally edited by Sean Marks MD and Drew Rosielle MD; first electronically
published August 2016.
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!48
Substance Abuse
#68 Is it Pain or
Addiction? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2-3
#69 Pseudoaddiction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . .4-5
#95 Opioid
Withdrawal . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6-7
#110 Urine Drug Testing for Opioids and

Marijuana. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8-9
#127 Substance Use Disorders in the Palliative Care

Patient. . . . . . . . . . . . . . . . . . . . . . . . . . . 10-11
#244 Screening for Opioid Misuse and Abuse . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . 12-14
#311 Opioids for Chronic Pain in Patients with History of Substance Abuse Disorders
Part 1: Assessment and Initiation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . 15-17
#312 Opioids for Chronic Pain in Patients with History of Substance Abuse Disorders
Part 2: Management and
Monitoring . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18-19
#328 Outpatient Use of Naloxone for Seriously Ill Patients . . . . . . . . . . . . . . . . . . . . . . . .

. . . . 20-22
1
IS IT PAIN OR ADDICTION?
David E Weissman MD
Background A very commonly requested educational pain topic by clinicians, surrounds differentiating
the patient in pain from the patient with a substance abuse disorder. The key to proper assessment lies in
understanding 1) the definitions of tolerance, physical and psychological dependence, 2) the components
of an addiction assessment, and 3) the differential diagnosis of the symptom of “pain.”
Definitions
• Tolerance: the need to increase a drug to achieve the same effect. In clinical practice, significant
opioid tolerance is uncommon. Tolerance may be present in the pain patient or the addict; by
itself it is not diagnostic of addiction.
• Physical Dependence: development of a withdrawal syndrome when a drug is suddenly
discontinued or an antagonist is administered. Most patients on chronic opioids will develop
physical dependence; its presence cannot be used to differentiate the pain patient from the
addict.
• Psychological Dependence (Addiction): overwhelming involvement with the acquisition and use of
a drug, characterized by: loss of control, compulsive drug use, and use despite harm. Research
suggests that opioids used to treat pain rarely leads to psychological dependence.
Addiction (Substance Abuse) Assessment Assess for addiction in the domains presented in the list
below (see Reference 1). Note: one positive item from the list does not establish a substance abuse
disorder. Rather, the diagnosis rests on a pattern of behavior that includes several positive findings (see
Reference 4).
• Loss of control of drug use (has no partially filled med bottles; will not bring in bottles for
verification).
• Adverse life consequences – use despite harm (legal, work, social, family).
• Indications of drug seeking behavior (reports lost/stolen meds, requests for high-street value
meds).
• Drug taking reliability (frequently takes extra doses, does not use meds as prescribed).
• Abuse of other drugs (current/past abuse of prescription or street drugs).
• Contact with drug culture (family or friends with substance abuse disorders).
• Cooperation with treatment plan (does not follow-up with referrals or use of non-drug treatments).
Differential Diagnosis The differential diagnosis for a patient reporting “pain” includes physical
causes (broken leg, sciatica, pseudoaddiction – see Fast Fact #69); psychological causes (depression,
anxiety, hypochondriasis, somatization disorder, etc.); spiritual causes (impending death, grief); substance
abuse; and secondary gain/malingering/criminal intent (desire for attention, disability benefit, or financial
gain from pain medications).
References
1. Sees KL, Clark HW. Opioid use in the treatment of chronic pain: assessment of addiction. J Pain
Symptom Manage. 1993; 8:257-264.
2
2. Savage SR. Addication in the treatment of pain: significance, recognition and management. J
Pain Symptom Manage. 1993; 8:265-278.
3. Eisendrath SJ. Psychiatric aspects of chronic pain. Neurology. 1995; 45:S26-S34.
4. Passik SD, Kirsh KL, Portenoy RK. Understanding aberrant drug-taking behavior: addiction
redefined for palliative care and pain management settings. Principles and Practice of Supportive
Oncology Updates. 1999; 2:1-12.
3
PSEUDOADDICTION
David E Weissman MD
Introduction The term pseudoaddiction was first used in 1989 to describe an iatrogenic syndrome
resulting from poorly treated cancer pain. The index case was a 17 year old man with leukemia,
pneumonia, and chest wall pain. The patient displayed behaviors (moaning, grimacing, increasing
requests for analgesics) wrongly interpreted by the physicians and nurses as indicators of addiction,
rather than of inadequately treated pain. Put simply, pseudoaddiction is something that we do to patients,
through our fears and mis-understanding of pain, pain treatment, and addiction (see also Fast Fact #68).
Diagnostic Features
• Behaviors that suggest to the health care provider the possibility of psychological dependence
(addiction):
o Moaning or other physical behaviors in which the patient is trying to demonstrate to the
provider that they are in pain.
o Clock-watching or repeated requests for medication prior to the prescribed interval.
o Pain complaints that seem “excessive” to the given pain stimulus.
• Inadequately prescribed and titrated opioids analgesics; typically the use of an opioid of
inadequate potency and/or at an excessive dosing interval (e.g. oral morphine q6 hours PRN –
see Fast Fact #18).
Assessment Anytime there is a suggestion, because of escalating pain behaviors, that a patient on
opioids may be “addicted,” pseudoaddiction should be considered. Perform a complete pain assessment
and review the recent analgesic history:
• Is this a pain syndrome that typically responds to opioids?
• Is the current opioid dose, route and schedule appropriate? If so, has a reasonable attempt at
dose escalation been made?
• Is there any past medical history to suggest a substance abuse disorder? Complete a
comprehensive addiction assessment if such a disorder is suspected.
• Pseudoaddiction improves with the provision of adequate analgesia, including opioids. In
contrast, behaviors associated with a substance abuse disorder will not change.
Management If you believe the current problem is pseudoaddiction, there are two key management
steps:
1) Establish trust. A primary issue in most cases is the loss of trust between the patient and the
health care providers. The physician and nursing staff should meet to discuss how they will
restore a trusting therapeutic relationship; outside assistance from a pain or palliative care service
can be helpful. Plan to meet with the patient and openly discuss the events leading up to the
current problem. Engage the patient in the decision-making process about the current and future
use of analgesics.
2) Prescribe opioids at pharmacologically appropriate doses and schedules. Aggressively dose
escalate until analgesia is achieved or toxicities develop (see Fast Facts #18, 20, 36).
Frequently re-evaluate progress in pain management and ask for consultation assistance.
References
1. Weissman DE, Haddox JD. Opioid pseudoaddiction. Pain. 1989; 36:363-366.
2. Sees KL, Clark HW. Opioid use in the treatment of chronic pain: assessment of addiction. J Pain
July 2006. Current version re-copy-edited April 2009.
4
5
!

OPIOID WITHDRAWAL
Debra Gordon RN and June Dahl PhD
Background Physical dependence is a normal and predictable neurophysiological response to regular

treatment with opioids for more than 1-2 weeks duration. Continuous or near continuous opioid blood
levels are required (one oxycodone-acetaminophen tablet per day will not lead to physical dependence).
Physical dependence is characterized by a withdrawal syndrome when the opioid is abruptly
discontinued, if an opioid antagonist (naloxone) is given, or when drug blood levels fall below a critical
level. Withdrawal can also be caused by administration of a mixed agonist-antagonist (e.g.,
buprenorphine, butorphanol, nalbuphine, pentazocine). Physical dependence is not a defining condition
of addiction (see below and Fast Facts #68 and #69).
Important definitions
o Tolerance: state of adaptation in which exposure to a drug induces changes that result in
diminution of one or more of the drug’s effects over time.
o Physical dependence: state of adaption manifested by a drug class-specific withdrawal
syndrome that can be produced by abrupt cessation, rapid dose reduction, decreasing blood level
of the drug and/or administration of an antagonist.
o Addiction / psychological dependence: a primary, chronic, neurobiologic disease, with genetic,
psychosocial, and environmental factors. Characterized by one or more of the following: impaired
control over drug use, compulsive use, continued use despite harm, and craving.
Signs and symptoms of the opioid withdrawal syndrome include yawning, sweating, lacrimation,
rhinorrhea, anxiety, restlessness, insomnia, dilated pupils, piloerection, chills, tachycardia, hypertension,
nausea/vomiting, cramping abdominal pains, diarrhea, and muscle aches and pains. Unlike withdrawal
from alcohol or benzodiazepines, opioid withdrawal is not life threatening. Emergence of withdrawal
symptoms varies with half-life of the particular opioid; within 6-12 hours after the last dose of a short-
acting drug or 72-96 hours following methadone (see Fast Facts #75, 86). Duration and intensity of
withdrawal are related to clearance of the drug such that withdrawal is shorter (5-10 days) and more
intense for opioids like morphine and less severe and more protracted with methadone.
Prevention Opioid withdrawal syndrome should always be prevented. Patients treated with opioids for
more than one to two weeks should be instructed to gradually reduce the opioid before discontinuing use.
In general, dose reductions of about 20-25% every day or two will allow a tapering schedule that will
prevent signs and symptoms of withdrawal. An alternative recommendation is to give half the previous
dose for the first 2 days and then reduce the dose by 25% every 2 days. When the dose reaches the
equivalent of approximately 30 mg/day of oral morphine, this dose is given for 2 days, and then the drug
is discontinued. It is important to continue to provide around-the-clock opioids to prevent withdrawal in the
patient at end-of-life who is no longer able to communicate or take oral opioids.
Treatment Clonidine 0.1-0.2 mg PO Q 4-6 hours PRN or by transdermal patch (clonidine transdermal
0.1 mg/24hour patch which provides 0.1 mg a day for 7 days) can be used to treat autonomic
hyperactivity symptoms. It will not relieve insomnia. The major drawback of clonidine therapy is the
tendency to cause hypotension in some patients. Other agents used for control of withdrawal symptoms
include: diphenoxylate/atropine (Lomotil), hydroxyzine, trazodone, and dicyclomine hydrochloride
(Bentyl). For patients still in pain who have abruptly stopped their opioids (because they ran out, lost their
prescription, or stopped because of side effects) reinstituting opioid therapy may be appropriate to treat
both their withdrawal symptoms and ongoing pain. Depending on how long a patient has been without
opioids it may not be safe to reinstate the full opioid dose immediately (especially for long-acting opioids).
In this case patients should go through a dose-titration phase with short-acting opioids to safely achieve
analgesia.
6
This Fast Fact was adapted with permission from the University of Wisconsin Hospital & Clinics,
Madison, WI Pain Patient Care Team ‘Pain Management Fast Facts – 5 Minute Inservice’ series.
References:
1. McCaffery M, Pasero C. Pain: Clinical Manual. 2nd Ed. St Louis, MO: Mosby; 1999.
2. American Academy of Pain Medicine (AAPM), American Pain Society (APS), American Society of
Addiction Medicine (ASAM). Definitions Related to the Use of Opioids for the Treatment of Pain.
Consensus Statement, 2001. Available at: http://www.ampainsoc.org/advocacy/opioids2.htm.
3. Kenna GA, Nielson DM, Mello P, Schiesl A, Swift RM. Pharmacotherapy of dual substance abuse
and dependence. CNS Drugs. 2007; 21:213-237.
by Drew A Rosielle and published October 2007; 3rd Edition June 2015. Current version re-copy-edited
April 2009; then again June 2015.

URINE DRUG TESTING FOR OPIOIDS AND MARIJAUNA
Marissa Mapa and Robert Arnold
Background Urine drug testing (UDT) is widely used for testing for opioids and illicit drugs. There are
two types of UDT: a screening test and a confirmatory test. The screening test uses an immunoassay to
look for the parent drug and/or metabolite. Most UDTs screen for marijuana, cocaine, opiates, PCP, and
amphetamines; some also test for benzodiazepines and methadone. The confirmatory urine drug test is
done by gas chromatography/mass spectrometry (GC/MS) or high-performance liquid chromatography
(HPLC); this test is highly specific and is typically used when testing for the presence of a specific drug is
needed.
UDT Interpretation A UDT cannot tell the amount of drug ingested/used or the time of use or the source
of drug (intravenous vs. oral vs. inhaled). Detection time of a substance in urine is typically 1-3 days.
The rate of excretion varies depending on differences in metabolism/ urinary function. Thus, obtaining
history as to when a suspected drug was last used needs to be correlated to the timing of the test. Lipid-
soluble drugs (e.g. marijuana) may remain in body fat and be detectable for a week or more.
Typically the screening immunoassay UDT detects the amount of drug present in urine above a
predetermined “cut-off” concentration. Thus, a substance may be present, but if the concentration of that
drug is below the cut-off, the result will be negative. If you suspect drug use or desire the confirmation of
7
this substance, ask the urine to be tested with a “no cut-off” or “no threshold testing” or ask for a
confirmatory test with GC/MS or HPLC.
If specimen tampering is suspected, ensure the urine is compatible with human physiology. The urine
temperature should be 90-100°F; pH between 4.5 – 8.0; and a spot check of urinary creatinine should be
greater than 20 mg/dL. A creatinine less than 20 mg/dL is considered dilute; less than 5 mg/dL is not
consistent with human urine and the sample should be discarded.
The screening immunoassay test has limited specificity for opiates. The test cannot differentiate
morphine from codeine (natural occurring opiates) and will not reliably detect synthetic or semi-synthetic
opioids. A confirmatory test is required to test for all opioids.
Knowledge of opiates’ metabolism is needed for UDT interpretation. For example, codeine and heroin are
both metabolized to morphine, through different pathways and different intermediary metabolites. A
prescription for codeine may yield an appropriate positive result for codeine and morphine in the urine.
However, if codeine is prescribed and only morphine is found in drug testing, the most consistent
interpretation is the unknown use of morphine or heroin. Prescribed morphine will result in only morphine
in a sample and not codeine.
The presence of marijuana is detected by the presence of tetrahydrocannabinol (THC), its active
ingredient. The screening immunoassay UDT is unable to distinguish between smoked marijuana and
the synthetic preparation dronabinol (Marinol).
False positive immunoassays are the result of cross reactivity. Quinolones, specifically levofloxacin and
ofloxacin, may give a positive result for opiates.
The cost of a UDT differs from lab to lab and especially in the number of substances tested. The
screening test costs between $69 to $148; the confirmatory test ranges from $92 to $165.
References
1. Gourlay D, Heit H, Caplan Y. Urine Drug Testing in Primary Care: Dispelling the Myths and
Designing Strategies. Monograph PharmaCom Group, Inc; 2002.
2. Heit HA, Gourlay DL. Urine drug testing in pain medicine. J Pain Symptom Manage. 2004;
27:260-7.
Version History: This Fast Fact was originally edited by David E Weissman MD and published in April
2004. Re-copy-edited in April 2009; references updated; copy-edited again June 2015.
8
!
SUBSTANCE USE DISORDERS IN THE PALLIATIVE CARE PATIENT
Gary M Reisfield MD, Gabriel D Paulian MD, and George R Wilson MD
Background The spectrum of substance use disorders (SUDs) is characterized by increasing degrees
of craving, compulsive use, loss of control, and continued use despite harm (see Fast Fact #68).
Addiction is understood to be a disease with complex genetic, neurobiological, psychosocial, and
behavioral determinants. If not properly managed an SUD can: 1) complicate the diagnosis and treatment
of psychological (e.g. depression) and physical (e.g. pain) symptoms; 2) compromise compliance with the
palliative treatment plan; 3) impair a stressed social support network; 4) weaken trust in patient-physician/
nurse relationships; and 5) promote the use of opioids to cope with emotional distress and decision-
making – “chemical coping.”
The prevalence of SUDs in palliative care is unknown, but likely reflects that of the general population in
which alcoholism and abuse of prescription and non-prescription drugs is common. Bruera reported a
prevalence of alcoholism of 27% in patients admitted to a tertiary care palliative medicine unit. Kwon
identified an 18% prevalence of chemical coping in a Palliative Medicine clinic. Far from being a source of
pleasure, SUDs are more commonly a source of suffering for affected individuals and their loved ones.
Addressing addiction may allow for: 1) preservation/restoration of damaged social supports; 2) restoration
of self-respect and dignity; 3) accomplishment of end-of-life work through recovery; and 4) improvement
in quality of life for patients and families.
Substance Use Disorders and Pain Management Patients with a current or past history of an SUD
are particularly challenging. Patients who are in recovery are often fearful of using opioids, even in the
setting of severe pain near the end-of-life. Conversely, the ability to complete a pain assessment and use
opioids effectively is challenging in patients with an active SUD. Listed below are suggested management
techniques in patients with a past or current SUD.
1. Complete a thorough substance use history. Distinguish between those who have active SUDs
from those who are at-risk or in recovery. Validated tools such as the Opioid Risk Tool are
available for risk stratification. Explain to patients why your knowledge of this information is
important for their care. Be empathic and nonjudgmental.
2. Encourage participation in recovery programs (e.g. 12-step) if the patient is willing and physically
able. Consider consultation with an addictions/mental health professional.
3. Formalize a treatment plan and coordinate it with all other involved health professionals.
4. Consider use of a written opioid agreement with carefully defined patient and provider
expectations; this may give motivated individuals a sense of control over their SUD. Components
of an opioid agreement include: establishing a single opioid prescriber, using a single pharmacy,
employing pill counts and periodic urine drug testing (see Fast Fact #110).
5. Use non-opioid analgesics and non-pharmacological measures to their full potential; poorly
controlled pain can increase substance abuse behaviors (see Fast Fact #69).
6. Use opioids at appropriate doses and at appropriate intervals. Titrate long-acting opioids to
minimize the need for short-acting opioids. Note: opioid-tolerant patients may need larger than
‘usual’ doses.
7. Address anxiety with counseling, antidepressants and, if necessary, judicious use of anxiolytics;
this has been shown to reduce illicit drug use in a hospice population (8).
8. Monitor closely; frequent contact allows for close patient observation and prescription of limited
quantities of opioids. Careful monitoring will usually distinguish whether deteriorating function is
due to substance abuse or disease progression.
9. Recognize that addiction is a chronic, relapsing illness – and respond with increasing structure
and compassion.
10. Develop system policies for identifying and appropriately treating patients with substance abuse.
References
9
1. Kwon JH. Hui D, Bruera A. A pilot study to define chemical coping in cancer patients using the
Delphi method. J Palliat Med. 2015;18. Epub ahead of print.
2. Kwon JH, Tanco K, Park JC, et al. Frequency, predictors, and medical record documentation of
chemical coping among advanced cancer patients. Oncologist. 2015; 20(6):692-697.
3. Bruera E, Moyano J, Seifert L, et al. The frequency of alcoholism among patients with pain due to
terminal cancer. J Pain Symptom Manage. 1995; 10(8):599-603.
4. Barclay JS, Owens JE, Blackhall LJ. Screening for substance abuse risk in cancer patients using
the Opioid Risk Tool and urine drug screen. Support Care Cancer, 2014;22:1883-1888.
5. Passik SD, Theobald DE. Managing addiction in advanced cancer patients: why bother? J Pain
Symptom Manage. 2000; 19(3):229-234.
6. Passik SD, Portenoy RK, Ricketts PL. Substance abuse issues in cancer patients. Part 1:
prevalence and diagnosis. Oncology. 1998; 12(4):517-521.
7. Passik SD, Portenoy RK, Ricketts PL. Substance abuse issues in cancer patients. Part 2:
evaluation and treatment. Oncology 1998; 12(5):729-734.
8. Podymow T, Turnbull J, Coyle D. Shelter-based palliative care for the homeless terminally ill.
Palliat Med. 2006; 20(2):81-86.
9. Childers JW, King LA, Arnold RM. Chronic pain and risk factors for opioid misuse in a palliative
care clinic. Am J Hospice & Palliative Med, 2014
10. 10.Blackhall LJ, Alfson ED, Barclay JS. Screening for substance abuse and diversion in Virginia
hospices. J Palliat Med, 2013;16(3):237-242. 
December 2004. 2nd edition published April 2009. It was re-edited by Mary Rhodes MD in July 2015 for
the 3rd Edition.
10
!

SCREENING FOR OPIOID MISUSE AND ABUSE
Rene Claxton MD and Robert Arnold MD
Background Opioid analgesics are often effective in relieving both cancer and chronic non-malignant
pain but can be misused and abused by patients and others (1, 2). Clinicians need to identify patients at
risk of misusing prescribed opioids in order to prescribe and monitor opioid therapy safely. This Fast Fact
discusses how clinicians can screen for risk of misuse. See Fast Facts #68, 69, 110, and 127 for further
discussions about differentiating pain complaints from abuse, urine drug testing, and substance use
disorders in palliative care patients.
Definitions Medication misuse is the intentional or unintentional use of a prescribed medication other
than as directed. Misuse can include a patient taking more pain medicine than prescribed to control
otherwise inadequately controlled pain as well as abusive and addictive behaviors. Abuse refers to the
intentional self-administration of a medication for non-medical purpose or the use of an illegal drug.
Addiction is a primary, chronic disease defined by one or more of the following behaviors: impaired
control over drug use, compulsive use, continued use despite harm, and craving (4). Aberrant behavior is
a research term defined differently by various investigators which typically includes activities of misuse
and abuse.
Benefits of Screening Opioid therapy is a safe and effective treatment for pain in many patients.
However, opioid misuse carries the risk of development of addiction, overdose, and death which require
providers to balance individual patient’s pain and risk levels. Patients with high risk for opioid misuse
should not necessarily be denied opioid therapy but should be followed under closer supervision than
those patients with lower risk estimates. In patients with short life expectancies, clinicians may be willing
to accept greater risk in prescribing opioids than in patients with chronic non-malignant pain. However,
providers should remember that opioids do not improve quality of life for patients who misuse them as a
remedy for other symptoms such as anxiety or existential suffering, and that active substance abuse is as
devastating to terminally ill patients and families as it is to others (5).
Risk Factors Risk factors for misuse can be grouped into three categories: biological, social and
psychological. Biological risk factors include family history of drug abuse and male gender. Social risk
factors include poor social support and history of convictions related to drugs or driving while impaired by
substances. Psychological risk factors include a personal history of substance abuse (including alcohol
or tobacco), pre-adolescent history of sexual abuse, and co-morbid psychiatric illness (i.e. major
depression, bipolar disorder, personality disorder) (6).
Screening for Misuse No screening tests have been developed to screen for opioid misuse
specifically in cancer patients. However, several screening tests predict the potential for opioid misuse in
patients with chronic non-malignant pain. Common instruments include the Screener and Opioid
Assessment for Pain Patients (SOAPP) and the Opioid Risk Tool (ORT). While these tools can be
applied to patients seen in palliative care settings (such as cancer patients or patients with advanced
illnesses), clinicians should be aware they have not been validated in these patient populations.
Clinicians should always keep in mind that these are screening tools used to identify high-risk patients
appropriate for close monitoring and further assessment, but are not diagnostic tools to diagnose
substance use disorders or to definitively identify patients who should not be prescribed opioids for pain.
In addition, they do not assess the risk of diversion of drugs by family or community members.
• The SOAPP predicts risk potential for aberrant drug behavior via a 14-item self-report. Items
included in the SOAPP cluster into categories of: antisocial behavior, substance abuse history,
doctor/patient relationship, medication-related behaviors, and psychiatric and neurobiologic need for
medicine. Responses are based on a 5 point Likert scale (possible score range 0-56). Using 7 as
cut off, this test had a sensitivity of 91%, specificity of 69%, positive predictive value (PPV) of 71%
and negative predictive value (NPV) of 90% (7) to predict aberrant drug behavior. It is important to
note that while a score of 7 maximizes this test’s sensitivity, i.e. identifies most patients with a risk of
11
opioid misuse, it will also result in a large number of false positive tests given the lower specificity at
this cut-off.
• The ORT is a 5-item yes/no tool which predicts the probability of opioid misuse or abuse among
patients being considered for opioid therapy for chronic pain. This measure is based on several risk
factors including: family history of substance abuse, personal history of substance abuse, age (16-45
years is a risk factor), history of pre-adolescent sexual abuse, and psychological disease. This tool
categorizes patients as low, medium or high risk for aberrant behavior. The sensitivity and specificity
for the test for patients who score at least ‘medium risk’ is 99% and 16%, respectively. For those with
‘high risk’ scores, the test sensitivity is 53% and specificity 96% (8). Because clinicians administering
the ORT could be misled by patients with a history of opioid use who downplay past behavior, it is
best to apply the tool in lower-risk clinical settings such as primary care rather than in higher risk
settings.
Which method is the best way to predict opioid misuse or abuse? In a study of 48 chronic pain
patients, the sensitivity of predicting aberrant behavior was compared using three different methods: a
trained psychologist’s clinical interview, SOAPP and ORT. The clinical interview showed highest
sensitivity (77%). SOAPP showed a sensitivity of 73% (score ≥6 as cut-off). ORT showed sensitivity of
45% (score ≥4 as cut-off) (9).
Bottom Line Given the limited number of studies comparing and validating these instruments, it is
reasonable to choose a measure based on practicality such as familiarity, ease and time of completion or
patient versus provider administration (both the SOAPP and ORT can be completed by patients in less
than 10 minutes). Regardless of whether one uses a tool, a thorough history including personal and
family history of psychiatric conditions, substance abuse, and sexual abuse is key to identifying patients
who need closer assessment and monitoring.
Additional Resources
For an electronic version of the SOAPP, click here: http://www.painedu.org/soapp.asp.
For an electronic version of the ORT, click here: http://www.opioidrisk.com/node/884.
References
1. Gordon DB, Dahl JL, Miaskowski C, et al. American Pain Society Recommendations for improving
the quality of acute and cancer pain management. Arch Intern Med. 2005; 165:1574-80.
2. Portenoy RK, Foley KM. Chronic use of opioid analgesics in non-malignant pain: report of 38
cases. Pain. 1986; 25:171-186.
3. National Drug Intelligence Center. National Prescription Drug Threat Assessment 2009. April 2009.
Available at: http://www.justice.gov/ndic/pubs33/33775/distribution.htm. Accessed March 16, 2011.
4. Katz NP, et al. Challenges in the development of prescription opioid abuse-deterrent formulations.
Clin J Pain. 2007; 23:648-660.
5. Passik SD. Theobald DE. Managing addiction in advanced cancer patients: why bother? J Pain
6. Katz NP, et al. Foundations of opioid risk management. Clin J Pain. 2007; 23:103-118.
7. Butler SF, et al. Validation of a screener and opioid assessment measure for patients with chronic
pain. Pain. 2004; 112:65-75.
8. Webster LR, Webster RM. Predicting aberrant behaviors in opioid-treated patients: preliminary
validation of the opioid risk tool. Pain Med. 2005; 6:432-442.
9. Moore TM, et al. A comparison of common screening methods for predicting aberrant behavior
among patients receiving opioids for chronic pain management. Pain Med. 2009; 10:1426-1433.
Author Affiliation: University of Pittsburgh Medical Center, Pittsburgh, PA.

Version History: Originally published August 2011; Copy-re-edited August 2015.
12
13
OPIOIDS FOR CHRONIC PAIN IN PATIENTS WITH HISTORY OF SUBSTANCE USE DISORDERS
PART 1: ASSESSMENT AND INITIATION
Amy J. Kennedy MD, Robert M. Arnold MD, Julie W. Childers MD.
When is it appropriate to use opioids in the palliative care setting for a patient with a history of a
substance use disorder (SUD)? This Fast Fact addresses strategies for initiating opioids for patients with
a history of SUD; Fast Fact #312 will address best practices for monitoring opioids for these patients.
Definitions:
SUD: a maladaptive pattern of substance use leading to clinically significant impairment or distress.
Aberrant drug behaviors: medication-related behaviors that depart from strict adherence to the prescribed
therapeutic plan of care.
Addiction: overwhelming involvement with the acquisition and use of a drug, characterized by: loss of
control, compulsive drug use, and use despite harm (see Fast Facts #68, 69).
Diversion: the illegal transfer of a pharmaceutical controlled substance from the person it was prescribed
to another person for use. Patients with SUDs are at higher risk for diversion of opioids.
Risks of Opioid Therapy in Patients with a history of SUD:

• Inability to achieve effective analgesia due to opioid tolerance.
• Adverse opioid effects when higher doses are used.
• Aberrant drug behaviors including drug diversion.
Patient Selection: The goal of analgesic therapy is to ensure that opioid prescribing is safe, effective,
and does not contribute to worsening of an SUD. Opioids for acute severe pain (such as hospitalization
for a broken bone) can be used in a closely monitored setting, no matter the history of SUD. Patient
selection for opioid use in moderate to severe chronic pain is more complex and involves the interplay of:
• Prognosis of the serious illness
• Status of the SUD: in recovery vs. active substance abuse
• Pain severity/risk of adverse opioid effects.
Except those with a limited prognosis (e.g. < 2 months) or with an acute pain problem (e.g. bone fracture),
we do not recommend starting opioids for patients who are actively using drugs to maintain a SUD
(heroin, cocaine, methamphetamine, alcohol, prescription drugs). Marijuana use should be evaluated on
a case-by-case basis. Patients with a more distant history of SUD, those who are established in a
substance abuse treatment program, and those with aberrant drug behaviors without evidence of a SUD
should be evaluated carefully in terms of risk. Long-term opioids for selected non-life-threatening
conditions are potentially harmful (e.g. chronic headaches, fibromyalgia, chronic lower back pain,
osteoarthritis) (4). The risks of initiating opioid therapy in these patients may outweigh the benefits,
especially if the patient has a longer prognosis and/or is exhibiting aberrant drug behaviors. Other pain
relieving methods such as physical therapy and non-opioid analgesics should be utilized first.
Initial Pain Assessment: The initial assessment is similar to patients without previously identified SUDs
in that a comprehensive identification of the type of pain and its etiology is pivotal. Clinicians should:
• Perform a careful history of past, present, and quantity of tobacco, alcohol, recreational drug use, and
prescription drug misuse. Use a validated screening tool to stratify risk of opioid misuse (FF #244).
• Differentiate active substance use, at-risk behaviors, recovery, and enrollment in a treatment program.
• Evaluate for potentially treatable psychiatric disorders such as depression and anxiety, which are
common both in chronic pain and those with SUDs.
• Assess for current use of sedatives (like muscle relaxants and benzodiazepines).
Initial Opioid Management

• Describe treatment expectations. Opioids will not completely eradicate pain and their effect on both
pain and function may only be short term (4).
14
• Though access can be limited, ideally patients with an active SUD and chronic pain should be referred
to an addiction medicine specialist (4). Multi-disciplinary teams engaging social workers, and mental
health professionals can enhance treatment adherence and social support (5). See Fast Fact #127.
• Use an opioid agreement at initiation of therapy to delineate safe practices and when opioids would be
discontinued. Specify the consequences related to the presence of illicit drugs on a urine drug screen
(UDS), requests for early refills, or attempts to obtain controlled substances from other clinicians.
• For patients on maintenance therapy for opioid addiction such as buprenorphine or methadone,
discuss the care plan with the addiction treatment program. If opioids are agreed to be appropriate, be
prepared that higher doses may be needed to achieve therapeutic expectations (6,7).
• Published data and expert opinion on the use of long acting opioids in SUDs offer conflicting advice
(4,5,8). One study has shown a higher rate of unintentional overdose with long-acting opioids, most
pronounced in the first 2 weeks after initiation (9). This may suggest clinicians have a difficult time
identifying patients who misuse long-acting opioids.
• A 1-2 week course of short-acting opioids with a follow up date less than 2 weeks may be the safest
initial regimen. If available, offer a rescue naloxone prescription and opioid overdose education.
• Combination opioid agonist/antagonist therapy (e.g. oxycodone/naloxone, buprenorphine/naloxone)
under the guidance of a pain specialist has shown promise in the treatment of patients with SUD.
References:
1. Tsang A, Von Korff MV, Lee S, et al. Chronic pain conditions in developed and developing
countries: gender and age differences and comorbidity with depression-anxiety disorders. Pain.
2008; 9(10): 883-891.
2. Morasco BJ, Gritzner S, Lewis L, et al. Systematic review of prevalence, correlates, and
treatment outcomes for chronic non-cancer pain in patients with comorbid substance use
disorder. Pain. 2011; 152(3):488-97.
3. Merikangas KR, McClair VL. Epidemiology of substance use disorders. Human Genetics. 2012.
131:779-789.
4. Franklin, GM. Opioids for chronic noncancer pain: A position paper of the American Academy of
Neurology. Neurology. 2014;83:1277-1283.
5. Passik SD, Kirsh KL. Opioid therapy in patients with a history of substance abuse. CNS Drugs.
2004; 18(1):13-25.
6. Compton P, Charuvastra VC, Ling W. Pain intolerance in opioid-maintained former opiate addicts:
effect of long-acting maintenance agent. Drug Alcohol Depend. 2001;63:139-146.
7. Doverty M, White JM, Somogyi AA, et al. Hyperalgesic responses in methadone maintenance
patients. Pain. 2001; 90:91-96.
8. Chang Y and Compton P. Management of chronic pain with chronic opioid therapy in patients
with substance use disorders. Addiction Science & Clinical Practice. 2013. 8:21. http://
www.ascpjournal.org/content/8/1/21.
9. Miller M, Barber CW, Letherman S, et al. Prescription opioid duration of action and the risk of
unintentional overdose among patients receiving opioid therapy. JAMA Internal Medicine. 2015;
75(4): 608-615.
Author’s Affiliations: University of Pittsburgh Medical Center

Version History: Originally edited by Sean Marks MD and electronically published in February 2016
15
16
OPIOIDS FOR CHRONIC PAIN IN PATIENTS WITH HISTORY OF SUBSTANCE USE DISORDERS
PART 2: MANAGEMENT AND MONITORING
Amy J. Kennedy MD, Robert M. Arnold MD, Julie W. Childers MD.
Fast Fact #311 discussed the assessment and initiation of opioid therapy in patients with a history of a
substance use disorder (SUD). This Fast Fact will highlight expert suggested strategies for opioid
monitoring in this patient population.
Patient Monitoring: Adherence checklists and individual/group counseling can reduce opioid abuse in
high-risk patients (1). Only one clinician and pharmacy should be utilized in providing opioids. Regular
follow up visits should be scheduled to assess the “Four A’s of Pain” before and after every intervention
(2,3): analgesia (pain relief); activities of daily living (functional status); adverse effects; aberrant
drug-taking behaviors.
Aberrant Drug Behaviors are not all the same, each behavior should be evaluated based on the specific
patient and situation. Clinicians should assess the degree of risk involved with the aberrant drug
behavior. Considerations include the extent of the aberrant behavior, including whether it has persisted
despite attempts to correct it, if the patient is actively using, the type of substance (opioids, alcohol,
methamphetamine, cocaine, cannabis), as well as level of abuse (daily intoxication, binge use).
General Strategies
• Ask patients if they are using other substances or using their opioids to get high or emotionally cope
with stressors. Remind patients that these are routine questions asked to all patients.
• Schedule more frequent visits, provide shorter-term prescriptions, and readdress opioid agreements.
• Intensify non-opiate pain strategies.
Patients who are using illegal drugs or abusing alcohol.

In addition to the general strategies, consider the type of substance:
• If cannabis or alcohol, perform a patient specific assessment: is there evidence of loss of control or
adverse consequences? Taper opioids or intensify monitoring depending on the scenario.
• If cocaine, methamphetamine, or heroin, consider patient’s prognosis. Either taper and discontinue
opioids, or negotiate use in a highly structured environment and/or ongoing addiction treatment.
Active Substance Abuse: Regardless of the type of aberrant behavior, if the patient is in need of
addiction treatment:
• Taper and then discontinue opioid therapy.
• Provide resources for treatment with an addiction specialist.
• Continue to treat pain via non-opioid and non-pharmacologic means -- “fire the opioid, not the patient”.
It is important to maintain a therapeutic relationship with the patient and assure non-abandonment.
Opioid Diversion: Opioid diversion is a serious public health threat with legal ramifications. Patients
actively using controlled substances have a higher risk for diversion.
Voluntary diversion occurs when a patient prescribed a controlled substance knowingly transfers it to
another person. This can range from “sharing” one or two pills with others to patients selling some or all
of the prescribed medications. Treatment teams should inform patients at the beginning of treatment that
sharing medication is not permitted, and lost or stolen medications will not be replaced.
• Patients who share medications in small amounts (e.g. giving a pill to a spouse who has acute pain)
should be re-educated on the dangers involved and be reminded of opioid agreements/clinic policies.
• Suspected diversion of large amounts of medication should be verified by calling the patient in for a
pill count and UDS in the middle of the prescribing period.
• Clinicians should discontinue opioid therapy in patients with whom they have a reasonable degree of
suspicion for diversion. Consideration should be given to notification of local police.
Involuntary diversion occurs when a controlled substance is stolen from a patient without their knowledge.
This happens more frequently in patients with unstable housing and/or family dynamics.
• Clinicians should discuss safety strategies with patients (e.g. lock boxes) and perform pill counts.
17
• Clinicians should utilize the help of social workers in determining if exploitation of a vulnerable adult is
occurring which could necessitate the involvement of police or adult protective services.
• Consider weaning opioids if involuntary diversion continues given negative public health effects or
placing the patient in a more supervised setting such as a nursing home or an inpatient hospice.
• Admission to the hospital to monitor pain management can be a useful management step in
situations in which clinicians are suspicious for voluntary or involuntary diversion.
References:
1. Jamison RN, Ross EL, Michna E, et al. Substance misuse treatment for high risk chronic pain
patients on opioid therapy: a randomized trial. Pain. 2010; 150(3): 390-400.
2. Passik SD, Weinreb HJ. Managing chronic nonmalignant pain: overcoming obstacles to the use of
opioids. Adv Ther. 2000;17:70-83.
3. Peppin JF, Passik SD, Couto JE, et al. Recommendations for urine drug monitoring as a component
of opioid therapy in the treatment of chronic pain. Pain Medicine. 2012; 13: 886-896.
Author’s Affiliations: University of Pittsburgh Medical Center

Version History: Originally edited by Sean Marks MD and electronically published in February 2016
18
NALOXONE FOR OUTPATIENTS AT RISK OF OPIOID OVERDOSE
Marcin Chwistek, MD FAAHPM and Matthew Wolf, RN BSN
Background: In the US, approximately 28,000 opioid overdose deaths occur annually, with at least half of
these deaths involving prescription opioids (1). This Fast Fact discusses the use of naloxone in the
outpatient setting for patients with an advanced illness on opioid therapy who may be at risk for opioid
overdose. See Fast Fact #39 for further information on naloxone use for inpatient care settings.
Opioid Overdose in Palliative Care Patients: Previous studies have suggested that opioid overdoses
are infrequent for patients receiving palliative care (2). In recent years, however, palliative care clinicians
have been more routinely involved in the outpatient treatment of cancer pain and, in some instances, may
also manage pain in long-term cancer survivors and/or non-cancer pain (2-4). Therefore, there is concern
that many palliative care patients may be at risk for opioid overdose given their co-morbidities, relatively
high doses of opioids needed to control symptoms, and, in some instances, a history of substance use
disorders (see Fast Facts #127, 310 and 311) (5). There is also an emerging awareness of inappropriate
or excessive use of opioids among patients with cancer-related pain (2).
Naloxone Co-prescribing: In the 1990s, public health and community organizations initiated naloxone
distribution programs such as the Overdose Education and Naloxone Distribution (OEND) to prevent
opioid overdose fatalities among heroin users (6). Between 1996 and 2010, naloxone was distributed to
50,000 persons, and more than 10,000 overdose reversals were documented (7). In many scenarios,
bystanders were able to recognize an overdose from a prescribed opioid and administer naloxone
effectively. Federal agencies from the US, Canada, Australia, and many European countries have
endorsed the provision of outpatient naloxone as part of a larger strategy to reduce overdose fatalities
from prescribed opioids (6). Co-prescribing of naloxone for patients on chronic opioids is currently being
implemented through the US Veterans Affairs Medical System (8).
Pharmacology: Naloxone is an opioid antagonist indicated for the emergency treatment of known or
suspected opioid overdose, as manifested by respiratory and/or central nervous system depression. A
needle-free formulation which is FDA approved for the emergency treatment of an opioid overdose is
available via a pre-filled, single dose intranasal spray. Intranasal administration of naloxone begins to
reverse opioid-induced respiratory depression and sedation in 8-13 minutes; peak effect is 20-30 min; and
the half-life is about 2 hours (9). The nasal spray is supplied in a box containing two, 4 mg single-use
nasal spray devices. A dose can be repeated every 2-3 minutes in alternating nostrils, if necessary (8). In
some states, it is available in pharmacies without a prescription. In a study of patients who received
naloxone by paramedics, intranasal naloxone was found to be noninferior to intravenous naloxone
regarding the reversal of sedation and respiratory rate (10).
Indications For Outpatient Naloxone Prescribing: Co-prescribing of naloxone with prescription opioid
medications is still the exception rather than a rule, especially in the palliative care setting. There is a
concern that bystanders may administer naloxone inappropriately in seriously ill patients when
physiological changes related to disease progression are mistakenly thought to be related to an
overdose. The final decision about co-prescribing naloxone should be individualized based on a patient’s
risk profile, prognosis, care preferences, and the availability of an informed caregiver. Establishing more
rigorous evidence-based criteria for co-prescribing is needed, but the following patients may be at risk of
an opioid-related fatality when death from their underlying illness is not imminently anticipated (6,11):
• Daily morphine equivalent doses of > 100 mg/day (12,13)
• Methadone as a prescribed analgesic (14)
• Benzodiazepines and/or antidepressants in combination with opioids (15)
• History of unintentional or intentional overdose (16)
• History of a substance use disorder including alcohol or tobacco (17)
• History of chronic pulmonary, renal, or hepatic disease (12)
• A recent history of incarceration (18)
Patient Information: Patients and their caregivers should be educated on how to properly identify an
opioid overdose and how to administer naloxone. Informational handouts are available for patients and
their family members (see reference #19). Patients and caregivers should also be advised to call 911 with
any administration of naloxone (19). Naloxone should not be administered to patients who are imminently
dying. This recommendation needs to be clearly communicated to caregivers of patients to avoid
19
inappropriate use. The adverse effects of naloxone administration are primarily opioid-withdrawal related
however precipitation of a pain crisis is of serious concern (20). Another concern is the relatively high and
raising price of Naloxone. As of 2016, estimated costs were $150 for two nasal-spray doses (21).
Gaps in Knowledge: The risks, benefits, safety, and best practices of co-prescribing in the palliative care
setting, especially among patients with advanced illness and chronic cancer pain have not been closely
examined and require further research.
References:
1. “Injury Prevention & Control: Opioid Overdose,” Centers for Disease Control and Prevention, last
updated March 16, 2016, http://www.cdc.gov/drugoverdose/index.html.
2. Bruera E, Paice JA. Cancer pain management: safe and effective use of opioids. Am Soc Clin
Oncol Educ Book. 2015;35:e593-9. doi:10.14694/EdBook_AM.2015.35.e593.
3. Bohnert ASB, Valenstein M, Bair MJ, et al. Association between opioid prescribing patterns and
opioid overdose-related deaths. JAMA. 2011;305(13):1315-1321. doi:10.1001/jama.2011.370.
4. Chwistek M, Ewerth N. Opioids and Chronic Pain in Cancer Survivors : Evolving Practice for
Palliative Care Clinics. J Palliat Med. 2016;19(3):19111. doi:10.1089/jpm.2015.0471.
5. Tan PD, Barclay JS, Blackhall LJ. Do Palliative Care Clinics Screen for Substance Abuse and
Diversion? Results of a National Survey. J Palliat Med. 2015;18(9):752-757. doi:10.1089/jpm.
2015.0098.
6. Mueller SR, et al. A Review of Opioid Overdose Prevention and Naloxone Prescribing:
Implications for Translating Community Programming Into Clinical Practice. Substance Abuse
2016; 36(2):240-253.
7. Community-based opioid overdose prevention programs providing naloxone—United States,
2010. MMWR Morb Mortal Wkly Rep. 2012;61:101–105
8. Oliva EM, Nevedal A, Lewis ET, et al. Patient perspectives on an opioid overdose education and
naloxone distribution program in the U.S. Department of Veterans Affairs. Subst Abus.
2016;37(1):118-126.
9. Naloxone (Narcan) nasal spray for opioid overdose. Medical Letter on Drugs and Therapeutics
2016; 58(1485):1-2.
10. Merlin MA, Saybolt M, Kapitanyan R, et al. Intranasal naloxone delivery is an alternative to
intravenous naloxone for opioid overdoses. Am J Emerg Med. Mar 2010;28:296–303.
11. Dowell D, Haegerich TM, Chou R. CDC Guideline for Prescribing Opioids for Chronic Pain —
United States, 2016. Jama. 2016;315(15):1624-1645. doi:10.1001/jama.2016.1464.
12. Bohnert AS, Valenstein M, Bair MJ, et al. Association between opioid prescribing patterns and
opioid overdose-related deaths. JAMA. 2011;305:1315–1321
13. Dunn KM, Saunders KW, Rutter CM, et al. Opioid prescriptions for chronic pain and overdose: a
cohort study. Ann Intern Med. 2010;152:85–92
14. Walley AY, Doe-Simkins M, Quinn E, Pierce C, Xuan Z, Ozonoff A. Opioid overdose prevention
with intranasal naloxone among people who take methadone. J Subst Abuse Treat. 2013;44:241–
247.
15. Hall AJ, Logan JE, Toblin RL, et al. Patterns of abuse among unintentional pharmaceutical
overdose fatalities. JAMA. 2008;300:2613–2620
16. Coffin PO, Tracy M, Bucciarelli A, Ompad D, Vlahov D, Galea S. Identifying injection drug users
at risk of nonfatal overdose. Acad Emerg Med. 2007;14:616–623.
17. Evans JL, Tsui JI, Hahn JA, Davidson PJ, Lum PJ, Page K. Mortality among young injection drug
users in San Francisco: a 10-year follow-up of the UFO study. Am J Epidemiol. 2012;175:302–
308.
18. Binswanger IA, Stern MF, Deyo RA, et al. Release from prison—a high risk of death for former
inmates. N Engl J Med. 2007;356:157–165.
19. Substance Abuse and Mental Health Services Administration - Opioid Overdose Toolkit. https://
store.samhsa.gov/shin/content/SMA13-4742/Overdose_Toolkit_2014_Jan.pdf Accessed
November 13, 2016
20. Buajordet I, Naess AC, Jacobsen D, Brors O. Adverse events after naloxone treatment of
episodes of suspected acute opioid overdose. Eur J Emerg Med. 2004;11:19–23
21. Gupta, R., et al. (2016). The Rising Price of Naloxone — Risks to Efforts to Stem Overdose
Deaths. New England Journal of Medicine 375(23): 2213-2215.
20
Authors’ Affiliation: Fox Chase Cancer Center; Temple University Health System; Philadelphia PA
Version History: Edited by Sean Marks MD, first electronically published January 2017
21
Wounds and Oral Care

#37
Pruritus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . .2-3
#40 Pressure Ulcer Management: Staging and Prevention . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . 4-5
#41 Pressure Ulcers: Debridement and

Dressings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .6-7
#46 Malignant Wounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . 8-9
#121 Oral Mucositis: Diagnosis and

Assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .10-11
#130 Oral Mucositis: Prevention and Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . 12-13
#147 Oropharyngeal
Candidiasis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14-15
#182 Xerostomia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . 16-17
#218 Managing Wound Odor . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . 18-20
#249 Topical Nonsteroidal Anti-Inflammatory

Drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21-22
#250 Tracheostomy Care . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . .23-25
#281 Care of the Post-Laryngectomy Stoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . .26-28
1
#327 Topical Treatments for Acute and Chronic Wound
Pain . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .29-31
2
!

PRURITUS
Charles von Gunten MD and Frank Ferris MD
Background
Pruritus (itching) is a common and often distressing symptom near the end of life. The itch
sensation may arise from stimulation of the skin itch receptor via unmyelinated C fibers, or itch
may arise as a central phenomenon without skin involvement (e.g. opioid induced pruritus).
Although histamine causes pruritus, many patients with pruritis show no signs of histamine
release. Besides histamine, serotonin, prostaglandins, kinins, proteases and physical stimuli
have all been implicated as mediators of pruritus.
Common Causes
• Dermatological (dryness, wetness, irritation, eczema, psoriasis)
• Metabolic (hepatic failure, renal failure, hypothyroidism)
• Hematologic (iron deficiency, polycythemia, thrombocytosis, leukemia, lymphoma)
• Drugs (opioids, aspirin, drug reactions)
• Infectious (scabies, lice, candida)
• Allergy (urticaria, contact dermatitis, drug reactions)
• Psychogenic
Management Management of pruritus involves eliminating the cause when possible.

Symptomatic strategies include:
• Moisturizers: Dryness (xerosis) is very common and may exacerbate other causes.
The mainstay of treatment is skin hydration. Note: Most OTC preparations only have
small amounts of moisturizer—they are mostly water. Serious dryness requires
emollients and moisturizers (such as petroleum jelly) that patients find oily or greasy.
Nevertheless, they may applied after bathing, over damp skin, with a superficial
covering.
• Cooling agents (e.g. Calamine and/or Menthol in aqueous cream, 0.5%-2%) are mildly
antipruritic. They may act as a counterirritant or anesthetic. A more direct way to
anesthetize the skin is with the eutectic mixture of local anesthetics lidocaine and
prilocaine (EMLA cream).
• Antihistamines may be helpful in relieving itch when associated with histamine release.
Morphine causes non-immune mediated histamine release from mast cells. Although
there is not much supporting research, many report benefits of combining H1 and H2
receptor subtype antihistamines. These may have central effects as well as peripheral
antihistaminergic effects. Doxepin (10-30 mg PO at bedtime), a tricyclic antidepressant,
is a very potent antihistamine and may help in more refractory cases.
• Topical steroids may be helpful in the presence of skin inflammation. These are best
applied in ointment rather than cream formulations to alleviate dryness. Systemic
steroids have been used in refractory cases.
• Newer Generation Antidepressants There are accounts of paroxetine being used
successfully to treat pruritus associated a paraneoplastic process, opioids or cholestasis.
Also mirtazapine has been shown to improve pruritus at low doses of 15 mg/day in small
case reports; this is likely due to its known antihistamine effects and its blockage of post-
synaptic 5HT2 and 5HT3 receptors.
• Opioid Antagonists Low dose, continuous infusions of IV naloxone has the largest
body of data supporting its use in adult and pediatric patients with opioid induced
pruritus. There are smaller studies suggest oral naloxone may have less favorable
3
results. Small studies suggest a potential role for methylnaltrexone in opioid induced
pruritus.
• Other: An old-fashioned but effective remedy is immersion in an oatmeal bath (e.g.
Aveeno). More recent pharmacological treatments include cholestyramine for
cholestatic pruritis; ondansetron for patients with cholestatic, opioid-induced, or renally-
induced pruritus. Since the pain sensing neurological system seems to be responsible
for pruritis, agents like gabapentin have also been reported to be helpful.
References
1. Fleisher A, Michaels JR. Pruritus. Berger A, Portenoy RK, Weissman DE, eds. In:
Principles & Practice of Supportive Oncology. Philadelphia PA: Lippincott-Raven
Publishers; 1998: pp245-250.
2. Krajnik M, Zylicz Z. Understanding pruritis in systemic disease. J Pain Symp Manage.
2001; 21:151-168.
3. Wilde MI, Markham A. Ondansetron: a review of its pharmacology and preliminary
clinical findings in novel applications. Drugs. 1996; 52:773-794.
4. Zylicz Z, Smits C, Chem D, Krajnik M. Paroxetine for pruritis in advanced cancer. J Pain
Symptom Manage. 1998; 16:121-124.
5. Davis MP, Frandsen JL, et al. Mirtazipine for pruritus. J Pain Symptom Manage 2003;
25: 288-91.
6. Wolfhagen FH, Sternieri E, et al. Oral naltrexone treatment for cholestatic pruritus: a
double blind, placebo-controlled study. Gastroenterology 1997;113: 1264-69.
7. Miller JL, Hagemann TM. Use of pure opioid antagonists of opioid induced pruritus.
American Journal of Health-System Pharmacy 2011; 68: 1419-1425.
again May 2015.
associate editor Drew A Rosielle MD (University of Minnesota Medical School), with the
generous support of a volunteer peer-review editorial board, and are made available online by
the Palliative Care Network of Wisconsin (PCNOW); the authors of each individual Fast Fact are
solely responsible for that Fast Fact’s content. The full set of Fast Facts are available at
professionals. This information is not medical advice. Fast Facts are not continually updated,
and new safety information may emerge after a Fast Fact is published. Health care providers
should always exercise their own independent clinical judgment and consult other relevant and
up-to-date experts and resources. Some Fast Facts cite the use of a product in a dosage, for an

PRESSURE ULCER MANAGEMENT: STAGING AND PREVENTION
4
Frank Ferris MD and Charles F von Gunten MD
Background This Fast Fact discusses the staging and prevention of pressure ulcers; Fast
Fact #41 discusses management. Poor attention to skin care in the dying patient will result in
pain, odor, swelling, reduced quality of life and increased care demands for family and other
caregivers. Skin can withstand 30-60 minutes of poor perfusion, but not longer. Pressure ulcers
result from ischemia due to pressure closing the microarterioles, particularly at pressure points
such as the heels, sacrum and elbows. Intrinsic risk factors for ulcer development are limited
mobility, conditions that reduce tissue oxygenation, age-related changes in skin, and cachexia.
Extrinsic factors are physical forces such as friction, moisture, and shear forces.
Prevention of ulcers is the highest level of care; bedbound patients need to be turned regularly
and/or need a pressure-reducing surface. Skin should be protected from friction, moisture and
shear. High-risk areas should have either a thin film or hydrocolloid dressings applied. Early
involvement of a wound care specialist is recommended to assist with education, on-going
assessment, and dressing choices tailored for the patient’s unique circumstances with regards
to comfort, cost, wear time, prognosis, and wound characteristics.
Ulcer Progression
• Stage I. The heralding lesion of skin ulceration is non-blanchable erythema.
• Stage II. Partial-thickness skin loss involving epidermis, dermis, or both. The ulcer is
superficial and looks like an abrasion or shallow crater or blister.
• Stage III. Full thickness skin loss involving subcutaneous tissue. The ulcer may extend
down to, but not through, the underlying fascia. The ulcer looks like a deep crater, with or
without undermining of adjacent tissue.
• Stage IV. The ulcer is deep enough to include necrosis and damage to underlying
muscle, bone, and/or other supporting structures such as tendon or joint capsule.
Undermining of adjacent skin and sinus tracts may also be present.
Pressure Reducing Surfaces There are 3 groups of support surfaces that have demonstrated
effectiveness; some need to be ordered by a physician.
1. Air or water mattress overlays (e.g. Roho)— ideal for most patients to prevent pressure
ulcers. Order for patients at risk for pressure ulcers.
2. Low-air-loss beds (e.g. Kenn-air, Dyna-Care, Sof-Care) can be used for high-risk
patients or patients with existing ulcers to prevent worsening or to help with healing.
3. Air-fluidized beds (e.g. Clinatron, Fluid-air) are reserved for patients needing maximum
pressure reduction and pressure relief. Patients, however, frequently describe them as
overly confining (even “coffin-like”) and they are very expensive (e.g. a Clinitron bed may
lease for > $100/day).
Note: Simple foam pads are often ineffective. If they are used, particularly in the home, they
should be laid one on top of the other. If a hand is placed under the pads, there should be at
least 1 inch of non-compressed foam between the hand and the patient. Never use round
cushions (a.k.a. donuts); they occlude blood flow and do not prevent ulcers. Professional
assessment and design is needed for special pressure reducing cushions (e.g. for wheelchairs).
References
1. Walker P. The pathophysiology and management of pressure ulcers. In:Topics in
Palliative Care, Volume 3. Portenoy RK, Bruera E, eds. New York, NY: Oxford University
Press; 1998: pp 253-270.
5
2. Walker P. Update on pressure ulcers. Principles & Practice of Supportive Oncology
Updates. 2000; 3(6):1-11.
3. Chrisman CA. Care of chronic wounds in palliative care and end of life. Int Wound
Journal 2010; 7: 214-35.
published August 2005; 3rd Edition June 2015. Current version re-copy-edited March 2009; then
again in May 2015.
6
PRESSURE ULCERS: DEBRIDEMENT AND DRESSINGS
Charles von Gunten, MD and Frank Ferris, MD
Background Fast Fact #40 discussed the staging and prevention of pressure ulcers; this Fast
Fact discusses their management. The first step in deciding how to manage pressure ulcers is
an assessment of whether or not the wound is likely to heal. If the patient has a prognosis of
months to years, adequate nutrition, and blood flow to the tissue, then healing is possible. If the
patient has a prognosis of days to weeks, anorexia/cachexia, and/or the wound has inadequate
perfusion, then symptom control alone is appropriate and uncomfortable/burdensome
treatments are not appropriate.
Debridement Always provide adequate analgesia! Necrotic tissue must be removed for ulcer
healing; surgical debridement is the fastest and most effective method when there is healthy
surrounding tissue. Note: If the patient is close to dying, and/or the wound will never heal, then
debridement should not be attempted. Debridement gels (such as Hypergel, Santyl, Nu-gel) are
applied onto an ulcer under an occlusive dressing (such as DuoDerm), are available for ulcers
that don’t require surgery or when surgical debridement is incomplete. These products come
with or without enzymes to encourage autolytic or enzymatic debridement. For minimally
necrotic ulcers, occlusive dressings such as DuoDerm, changed weekly, promote autolysis.
A commonly prescribed form of mechanical debridement is the use of saline, wet-dry dressings.
This treatment actually retards healing by pulling off new epithelial cells as part of healthy
granulation tissue; its use for the treatment of skin ulcers should be abandoned.
Antimicrobials Ulcer healing is delayed if there is bacterial infection within the wound bed.
Erythema, purulent exudate and fever are signs of infection. Cleansing and application of
topical antibiotics may be sufficient for superficial infection with minimal surrounding erythema.
Systemic antibiotics are indicated for deep/surrounding tissue infection, or if ulcer healing is
delayed.
Cleanse wounds that are expected to heal with non-cytotoxic fluids (e.g. saline). Cytotoxic fluids
(e.g. Betadine) will kill granulation tissue. Clinical Pearl: do not cleanse an ulcer with any fluid
you wouldn’t put in your eye if you want the ulcer to heal.
Dressings Living tissue requires moisture for transport of oxygen and nutrients. A moist ulcer
environment promotes the migration of fibroblasts and epithelial cells; growth factors are
present in the serous exudate that speed healing. In contrast, a dry environment is conducive
to necrosis and eschar.
There are 6 classes of dressings distinguished by the wear time and whether you want to add or
remove fluid in order to maintain the ideal moist, interactive ulcer-healing environment. A dry
ulcer needs to have moisture added through a hypotonic gel (donates water). With wet
exudates, a hypertonic gel or foam is used to remove water.
1. Polyurethane foams (LYOfoam, Allevyn, Nu-Derm, Flexzan): most absorptive; used
under a covering secondary dressing.
2. Alginates (Kaltostat, Sorbsan): dessicate an overly wet wound, prevent maceration of
surrounding skin from excess fluid, and are hemostatic and may reduce infection risk.
3. Hydrogels (IntraSite, Elasto-Gel, ClearSite, Aquasorb): used for wounds with larger
volumes of exudate. Require a secondary dressing to secure.
4. Hydrocolloid wafers (DuoDerm, Comfeel, Tegasorb, Restore): promote autolysis,
angiogenesis and granulation. Self-adhesive. Remain in place for 5-7 days. Often used
7
to “seal” a wound that is otherwise clean in order to promote healing. Can also be used
to seal an underlying dressing in order to maintain a moist environment in which the
wound can heal. Note: do not to use an occlusive dressing if there is a substantial risk
of infection.
5. Thin films (OpSite, Tegaderm): for skin at risk or Stage I pressure ulcers. Can also hold
another type of absorbent dressing in place.
6. Cotton Gauze: used to cover the primary dressing. Rarely an appropriate dressing for a
significant skin ulcer. Note: Saline wet-to-dry dressings are only useful for mechanical
debridement.
References
4. Walker P. The pathophysiology and management of pressure ulcers. In:Topics in
Palliative Care, Volume 3. Portenoy RK, Bruera E, eds. New York, NY: Oxford University
Press; 1998: pp 253-270.
5. Walker P. Update on pressure ulcers. Principles & Practice of Supportive Oncology
Updates. 2000; 3(6):1-11.
published August 2005; 3rd edition May 2015. Current version re-copy-edited March 2009; then
again May 2015.
8
MALIGNANT WOUNDS
Frank Ferris MD and Charles F von Gunten MD
Introduction
Few things can worsen a patient’s quality of life greater than an oozing, odorous, painful, and
bleeding malignant skin wound. The pathology of a primary or metastatic cancer to the skin
leading to an open wound is a combination of neovascularization, necrosis and inflammation,
leading to pain, bleeding, odor and exudate. As with other chronic wounds, a fundamental
decision whether the wound can eventually heal or not should be made. The choice of dressing
is generally the same as with pressure ulcers (see Fast Fact #41). However, malignant wound
management raises additional issues that deserve comment. Note: for any complex wound, it is
recommended that you seek professional consultation from a wound care expert.
Exudates
Exudates can be substantial from malignant wounds. The overall goal is to prevent exudate
macerating other normal tissues or dripping off the patient into clothes and bedclothes. This
serves both infection control as well as cosmetic goals. One can use absorbent foams to
minimize the frequency of dressing changes and maximize absorption. Typically a gauze pad
(such as an ‘ABD’ pad) is placed on top of the foam. Alginate dressings have a role in wounds
that have exudates and/or are bleeding. They are absorptive, hemostatic, and help to control
infection. They do not have to be pulled off and can be simply washed off in the shower.
Infection
Malignant wounds carry a high risk of superficial infection, especially with anaerobic or fungal
species. Odor is frequently the first sign of anaerobic infection along with a purulent exudate. If
the infection is only superficial, topical treatment (metronidazole, silver sulfadiazine) may be
sufficient. However, if there is evidence of deeper tissue infection, then systemic metronidazole
should be used. If the wound is determined to be non-healing, then topical agents like povidone
can be used; some patients find it irritating and painful, however. Povidone is cytotoxic to
bacteria and will help keep the wound clean. Povidone should not be used for wounds that are
expected to heal because it is cytotoxic to normal granulation tissue.
Odor
Managing odor can be accomplished by using odor absorbers; kitty litter or activated charcoal
can be placed on a cookie tray underneath the bed. In addition, there are charcoal dressings
that can be used to cover a particularly malodorous wound. Additional approaches include
putting a burning flame (such as a candle) in the room in an attempt to combust the chemicals
causing the odor. One can also introduce a competing odor; bowls of vinegar, vanilla, or coffee.
Fragrances and perfumes are often poorly tolerated by patients and should be avoided.
Bleeding
Bleeding is common; the surface of a malignancy may be friable and predispose to bleeding. It
may either present as oozing (microvascular fragmentation) or vascular disruption from necrosis
or sloughing leading to “a bleeder.” Any dressing that comes into contact with the surface may
adhere and tear the surface when it is pulled off (e.g. saline wet-dry dressings). This can be
prevented by using a mesh synthetic polymer, non-stick, non absorptive dressing (e.g. Mepitel).
Other options to control bleeding are alginate dressings, topical low dose (100 U/ml)
thromboplastin, silver nitrate, or cautery. In addition to systemic treatments for pain (e.g. oral or
parenteral opioids), local anesthetics can also be helpful.
9
Reference
1. Barton P, Parslow N. Malignant wounds: holistic assessment and management. In:
Krasner DL, Rodeheaver GT, Sibbald RG, eds. Chronic Wound Care: A Clinical Source
Book for Healthcare Professionals. Third Edition. Wayne, PA: HMP Communications;
2001: pp699-710.
again May 2015.
10
ORAL MUCOSITIS: DIAGNOSIS AND ASSESSMENT
Clarissa F Henson and Robert Arnold MD
Background The term mucositis refers to the inflammatory response of the oral-pharyngeal
mucosa resulting from systemic chemotherapy or from radiotherapy that includes the oral-
pharyngeal mucosa within the radiation field. The term stomatotoxicity is specific to mucositis
effecting the oral mucosa. Mucositis results from the destruction of rapidly dividing epithelial
cells of the oral-pharyngeal mucosal epithelium and the secondary release of inflammatory
mediators such as TNF-alpha and interleukin-1 beta. This Fast Fact discusses the diagnosis
and assessment of mucositis; Fast Fact #130 discusses its prevention and treatment.
The Radiation Therapy Oncology Group (RTOG) describes five grades of acute
mucositis:
Grade 1: Injection; may experience mild pain not requiring analgesics.
Grade 2: Patchy mucositis which may produce an inflammatory serosanguinitis
discharge; may experience moderate pain requiring analgesia.
Grade 3: Confluent fibrinous mucositis; may include severe pain requiring opioid
analgesics.
Grade 4: Ulceration, hemorrhage or necrosis.
Grade 5: Death resulting from mucositis.
Causes Both patient-related factors and treatment-related factors influence the severity of
mucositis. Increased total dose of radiation, fraction size, and volume of normal tissue in the
irradiated field all increase the risk of mucositis. Not all chemotherapy agents produce the same
risk of mucositis; 5-fluoruracil, doxorubicin and methotrexate commonly cause mucositis while
vincristine does not. The simultaneous combination of radiation and chemotherapy used in
head and neck cancer will cause more intense mucositis than single-modality therapy. Patient-
related factors such as the overall condition of the oral mucosa prior to therapy, pre-existing
xerostomia, pre-existing collagen-vascular disorders, the underlying nutritional status, and the
development of neutropenia during therapy all impact the development and severity of
mucositis.
In head and neck cancer, virtually all patients undergoing radiation, with or without
chemotherapy, will develop grade 1 and 2 mucositis. More severe mucositis (grade 3 or higher)
develops in approximately 41% of patients receiving combined radiation and chemotherapy to
the head and neck and in 21% of patients receiving radiation therapy alone.
Clinical Findings & Natural History Clinical signs of mucosal damage and cell death appear
after the first 1 to 2 weeks of radiation therapy and as early as 3 days after chemotherapy.
Initial mucosal damage results in patchy erythema, edema, atrophy and whitening of the
mucosal tissue with increased sensitivity—patients report a burning sensation in the mouth.
Further loss of mucosal epithelium becomes most prominent in the fourth or fifth week of
standard fractionation radiation resulting in fibrinous exudation, confluent inflammation, and
ulceration (see Fast Facts # 66, 67). The mouth sores and swelling can lead to significant oral
pain, pain with swallowing, weight loss and dehydration. Mucosal damage predisposes the
patient to oral superinfection leading to further pain and alterations in taste and appetite and
decreased quality of life. Resolution of oral mucositis occurs several weeks after the completion
of RT and chemotherapy.
11
Assessment A thorough assessment of the patient with mucositis should include:
• Pain assessment to include thorough review of analgesics used, effect and toxicities.
• Nutritional assessment.
• Quality of life assessment including screening for depression.
• Complete oral examination; assessment for local fungal (see Fast Fact #147), bacterial,
or viral infections.
References
1. Bernier J, Domenge C, Ozsahin M, et al. Postoperative irradiation with or without
concomitant chemotherapy for locally advanced head and neck cancer. N Eng J Med.
2004; 350:1945-1952.
2. Cooper JS, Pajak TF, Forastiere AA, et al. Postoperative concurrent radiotherapy and
chemotherapy for high-risk squamous-cell carcinoma of the head and neck. N Engl J
Med. 2004; 350:1937-1944.
3. Fu K, et al. A Radiation Therapy Oncology Group (RTOG) phase III randomized study
to compare hyperfractionation and two variants of accelerated fractionation to standard
fractionation radiotherapy for head and neck squamous cell carcinomas: first report of
RTOG 9003. Int J Radiat Oncol Biol Phys. 2000; 48:7-16.
in September 2004. Version re-copy-edited in April 2009; revised again July 2015.
12
ORAL MUCOSITIS: PREVENTION AND TREATMENT
Clarissa Febles Henson and Robert Arnold MD
Introduction Radiation and chemotherapy-induced mucositis causes pain, difficulty

swallowing, and decreased oral intake. Fast Fact #121 explores the diagnosis and assessment
of mucositis; this Fast Fact focuses on prevention and treatment of radiation (XRT) and
chemotherapy-induced oral mucositis.
Background There are many treatments to choose from with mucositis, but unfortunately,
there is no gold standard protocol. A systematic review of therapeutic approaches for mucositis
suggested that no intervention is proven to prevent or treat mucositis on its own. Instead, multi-
modal therapy is often best.
Prevention
• Oral care: At least two weeks prior to the start of radiation to the head and neck region,
or the use of chemotherapy that is expected to cause severe and prolonged neutropenia
(e.g. for acute leukemia), patients should undergo a thorough oral/dental exam with
appropriate dental extraction and repair or removal of dental prostheses. Patients
should be educated on maintaining good oral hygiene including daily brushing with a soft
bristle tooth brush, flossing, use of fluoride plaques, and avoiding denture use. Mouth
rinses that contain a chlorhexidine or a mixture of baking soda, salt, and water can
prevent the build-up of bacterial overgrowth and remove dead cells. Patients may also
want to consider adding povidine iodine rinses to their standard oral care regimen, as
doing so has been shown to reduce the severity, incidence, and duration of radiation-
induced mucositis. Patients should avoid caustic and drying agents: alcoholic
beverages, mouth rinses with alcohol, hot beverages, and acidic foods.
• Radiation therapy technique: Advanced radiotherapy techniques such as 3D-
conformal therapy and intensity modulated therapy decrease radiation toxicity by limiting
doses to the normal oral mucosa. Other XRT modifications that decrease toxicity
include using shields over normal tissues, decreasing the radiation fraction size, and
decreasing overall treatment time. Severe mucositis may require a 5 to 7 day radiation
treatment break to allow for tissue recovery. However, a prolonged break is associated
with inferior local control rates and survival.
Treatment
• Treatment of infection: Prophylactic use of antifungal, antibacterial or antiviral
medications does not decrease the incidence of mucositis. However, clinicians should
consider potential super-infection, and have a low threshold to obtain cultures, especially
for fungal and viral infections. Of note, viral infections such as herpes may not present
with classic physical examination findings.
13
• Pain Management: Local anesthetics such as lidocaine and diphenhydramine are
routinely used to relieve pain but do not provide mucosal protection nor hasten recovery.
Local anesthetics decrease taste and can impact oral intake. Some patients find addition
of carafate slurry or a liquid antacid to a lidocaine/diphenhydramine mixture provides
temporary analgesia. Liquid oral or parenteral opioids may be required for adequate
pain management (see Fast Fact #185). Topical application of honey may help soothe
mucositis due to radiotherapy.
• Topical agents: A number of topical agents are available to provide symptomatic relief.
These include commercial and non-commercial preparation: Gelcair, topical lidocaine,
Maalox, diphenhydramine and nystatin, etc. Benzydamine is a mouth rinse with
analgesic, anesthetic, anti-inflammatory, and antimicrobial properties and has been
shown in randomized controlled trials to reduce ulcer rate and incidence as well as
reduce need for opioids.
• Low-energy Laser Therapy: Some studies have shown pain relief with the use of low
power laser therapy delivered in a fractionated course three times a week. Its
mechanism of action is thought to be due to anti-inflammatory effects of the laser
irradiation on local tissue; however, its use remains experimental and data has been
mixed with regards to wound healing.
Reference
1. Berger AM, Kilroy TJ. Oral Complications. In: DeVita V, et al, eds. Cancer: Principles
and Practices of Oncology. 6th Edition. Philadelphia, PA: Lippincott Williams & Wilkins;
2001.
2. Rodriguez-Caballero A, Torres-Lagares D, et al. Cancer treatment-induced oral
mucositis: a critical review. Int J Oral Maxillofac Surg 2012; 41: 225-38.
3. Epstein JB, Silverman Jr S, et al. Benzydamine HCl for prophylaxis of radiation-induced
oral mucositis: results from a multicenter randomized, double-blind, placebo-controlled
clinical trial. Cancer 2001; 92: 875-80.
4. Khanal B, Baliga M, Uppal N. Effect of topical honey on limitation of radiation-induced
oral mucositis: an interventional study. Int J Oral Maxillofac Surg 2010; 39:1181-90.
5. Migliorati C, Hewson I, et al. Systematic review of laser and other light therapy for the
management of oral mucositis in cancer patients. Support Care Center 2013;
21:333-341.
in January 2005. Version re-copy-edited in April 2009; revised again July 2015 by Sean Marks
with references #2, #4, and #5 added and incorporated into the text.
14

OROPHARYNGEAL CANDIDIASIS
Drew A Rosielle MD and Ann M Hoff MD
Background Oropharyngeal candidiasis (thrush) occurs commonly in seriously ill and dying
patients.
Risk Factors Risk factors include a) either acquired (HIV-AIDS) or drug-induced

(chemotherapy, inhaled or systemic glucocorticoids) defects of cell-mediated immunity; b)
disruption of the oropharyngeal mucosa by cytotoxic chemotherapy (See Fast Fact #121) or
radiation that includes the oropharynx; c) xerostomia (dry mouth) from any cause; d) diabetes
mellitus; e) recent antibiotic use; f) dentures; g) advanced age; h) poor oral hygiene; and i) poor
nutritional status.
Diagnosis Thrush is often asymptomatic but can lead to oral pain, oropharyngeal dysphagia,
halitosis, alterations in taste, diminished appetite, and reduced oral intake. Thrush may or may
not be present in cases of esophageal candidiasis, which presents as odynophagia and
esophageal dysphagia. Most cases of thrush are caused by Candida albicans; C. krusei,
glabrata, or tropicalis are sometimes implicated in AIDS and cancer patients. Diagnosis is made
on clinical findings: white or yellow, cottage-cheese like plaques on the buccal mucosa, tongue,
or palate. The plaques are easily removed, leaving a red or bleeding and often painful base. A
less common presentation – seen in AIDS or in patients with poorly fitting dentures – involves
red, edematous, and sometimes eroded mucosal lesions, but without plaques. If diagnostic
doubt exists, confirmation can be made by KOH staining a wet-prep of a plaque scraping,
revealing pseudohyphal Candidal forms. Culture is not recommended, as Candida species are
common colonizers of the mouth.
Treatment The decision to treat thrush should be based on the patient's overall condition,
prognosis, symptoms, and goals of care. Treatments include either systemic or topical anti-
fungal drugs. All regimens should be continued for 7-14 days. Meticulous attention to denture
cleaning, if applicable, is important to prevent recurrence. If esophageal candidiasis is
suspected, systemic therapy is necessary as topical treatment is ineffective.
Topical drugs are the most commonly used but problems can occur due to patient objections to
taste and compliance with multiple daily dosing.
• Nystatin suspension (“swish and swallow”) is dosed as 200,000-500,000 Units 4 - 5
times a day. It is substantially less effective in immunocompromised patients than the
azole anti-fungals (30-50% vs 70-90% effective) and should not be used in this
population.
• Clotrimazole (10 mg troches 5 times a day) is nearly as effective as the systemic azole
anti-fungals; however, it is associated with a higher recurrence rate of thrush.
• Systemic drugs are more effective than the topicals. However they are more expensive
and have significant drug-drug interactions—especially with macrolide antibiotics,
anticonvulsants, benzodiazepines, methadone, and coumadin.
• Fluconazole is the systemic treatment of choice; it is more effective with fewer drug
interactions than ketoconazole. Many dosing regimens have been described: 200 mg
once, then 100 mg daily for 14 days total is most commonly used.
15
• Itraconazole suspension (200 mg daily) is an alternative to fluconazole. It is better
absorbed and more effective than itraconazole capsules.
• Note: Fluconazole resistant candidiasis is rare, but becoming more common.
Itraconazole, IV or oral amphotericin, voriconazole, and caspofungin have all been used
with success.
Recommendations Clotrimazole troches are a reasonable first line therapy for patients in the
palliative care setting if the troches are tolerable and 5 times a day dosing is acceptable. If not,
and/or if the patient has problems with recurrent thrush, fluconazole should be used.
References
1. Willberg P, Hjermstad MJ, Ottesen S, et al. Oral health is an important issue in end-of-
life cancer care. Support Care Cancer. 2012; 20:3115-3122.
2. Pienaar ED, Young T, Holmes H. Interventions for the prevention and management of
oropharyngeal candidiasis associated with HIV infection in adults and children.
Cochrane Database of Systemic Reviews. 2010, Issue 11. Art. No.: CD003940. DOI:
10.1002/14651858.CD003940.pub3.
3. Davies AN, Brailsford SR, Beighton D, et al. Oral Candidosis in Community-Based
Patients with Advanced Cancer. J Pain and Symptom Management. 2008; 35(5):
508-514.
4. Wiseman M. The Treatment of Oral Problems in the Palliative Patient. J Can Dent
Assoc. 2006; 72(5):453-8.
5. Davies AN, Brailsford SR, Beighton D. Oral candidosis in patients with advanced
cancer. Oral Oncology. 2006; 42:698-702.
6. Pappas PG, Kauffman CA, Andes D, et al. Clinical practice guidelines for the
management of candidiasis: 2009 update by the Infectious Disease Society of America.
Clin Infect Dis. 2009; 48:503-35.
in December 2005. Copy-edited in April 2009. In September 2015 it was re-copy-edited with
reference #6 was added and reflected in the text.
16
XEROSTOMIA
Gary M Reisfield MD, Drew A Rosielle MD, and George R Wilson MD
Background Xerostomia (dry mouth) is a common symptom at the end of life – affecting
more than 75% of hospice patients – and is a cause of significant morbidity and diminished
quality of life. This Fast Fact will review the causes and treatments of xerostomia.
Salivary Functions include hydration, lubrication, and antimicrobial defense of the oral
mucosa. Decreased salivation can lead to oral pain; accelerated dental morbidity; oral
infections, fissures, and ulcerations; halitosis; alteration in taste and enjoyment of food; chewing
and swallowing difficulties; nutritional impairment; trouble producing intelligible speech; and
denture-related problems. Xerostomia is usually—although not always—associated with
diminished salivary secretion (hyposialia).
Etiologies
• Medications with anticholinergic activity are the most common pharmacologic causes of
xerostomia; these include many antiemetics, antihistamines, antipsychotics, antispasmodics,
antidepressants (especially the tricyclics), and bronchodilators. Sympatholytics are also
common culprits, including alpha-blockers (e.g. terazosin), alpha-2 agonists (e.g. clonidine),
and beta-blockers (e.g. metoprolol). Medication-induced xerostomia may also result from
direct interference with or damage to salivary tissue (as with some cancer chemotherapies).
Opioids and benzodiazepines cause dry mouth, although the mechanisms are not known.
• Radiation for head and neck malignancies.
• Medical comorbidities such as HIV/AIDS, diabetes, renal failure, and Sjögren’s syndrome.
• Psychiatric comorbidities such as mood and anxiety disorders.
• Dehydration from any cause including drug-induced.
Treatment
• Address underlying causes. Eliminate unnecessary drugs or substitute less drying ones.
If this is not feasible, titrate to lowest effective dose or modify dosing schedule. Replacing
immediate-release with controlled-release formulations of some drugs may help (e.g. with
oxybutynin and tolterodine for overactive bladder).
• Stimulate residual gland function.
o Sugarless gums and candies can stimulate salivary reflexes. Products sweetened with
xylitol are anticariogenic; those containing vitamin C may reduce salivary viscosity.
o Cholinergic agonists such as pilocarpine and cevimeline. Therapeutic effect is rapid for
drug-related xerostomia; latency is greater (often 8-12 weeks) for xerostomia related to
radiotherapy. Pilocarpine is started at 5 mg po tid and can be titrated to 10 mg po tid.
Cevimeline is dosed at 30 mg po tid. Urinary frequency, dizziness, and sweating are
common side effects and may be attenuated with intake of dairy products. These agents
are contraindicated in asthma, acute iritis, and narrow-angle glaucoma, and should be
used with caution in COPD and cardiac disease.
• Saliva substitutes. Most have limited efficacy; many patients find frequent sips of water
more useful and convenient. Topical products containing olive oil, betaine, and xylitol have
been found effective for medication-induced xerostomia (e.g. Xerostom® products). Newer
products with enzyme systems such as lactoperoxidase, lysozyme, and glucose oxidase
(e.g. Biotène® Oralbalance Dry Mouth Gel)—offer potential antimicrobial and moisturizing
17
benefits. Due to limited duration of action, they may be particularly useful before eating,
speaking, and sleeping. Recently, custom oral appliances with artificial saliva reservoirs
have become available and may be particularly useful at night.
• Encourage oral hydration. Humidifiers, especially during sleep, may also be helpful.
• Optimize oral hygiene.
o Antimicrobial mouthwashes (alcohol-free). Chlorhexidine gluconate oral rinse, USP
0.12%, twice daily, may be effective in preventing dental caries and oral infections.
o Most toothpaste products contain the surfactant sodium lauryl sulfate (SLS), which
can irritate dry mucosa and inactivate the enzyme systems of the newer artificial
salivas. Biotène® Dry Mouth Toothpaste contains salivary enzymes and is SLS-free.
References
1. Amerongen AVN, Veernan ECI. Current therapies for xerostomia and salivary gland
hypofunction associated with cancer therapies. Support Care Cancer. 2003; 11:226-231.
2. Chambers MS, Rosenthal DI, Weber RS. Radiation-induced xerostomia. Head & Neck.
2007; 29:58-63.
3. Frost PM, Shirlaw PJ, Challacombe SJ, et al. Impact of wearing an intra-oral lubricating
device on oral health in dry mouth patients. Oral Diseases. 2006; 12:57-62.
4. Jensen SB, Pederson AM, Reibel J, Nauntofte B. Xerostomia and hypofunction of the
salivary glands in cancer therapy. Support Care Cancer. 2003; 11:207-225.
5. Miller M, Kearney N. Oral care for patients with cancer: a review of the literature. Cancer
Nurs. 2001; 24:241-254.
6. Scully C. Drug effects on salivary glands: dry mouth. Oral Diseases. 2003; 9:165-176.
7. Shiboski CH, Hodgson TA, Ship JA, Schiodt M. Management of salivary hypofunction
during and after radiotherapy. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2007;
103(suppl 1):S66.e1-S66.e.19.
8. Ship JA, McCutcheon JA, Spivakovsky S, Kerr AR. Safety and effectiveness of topical
dry mouth products containing olive oil, betaine, and xylitol in reducing xerostomia for
polypharmacy-induced dry mouth. J Oral Rehabil. 2007; 34(10):724-734.
Version History: Originally published June 2007. Revised, and 2nd edition published,
December 2008. Version re-copy-edited in May 2009; then again July 2015.
18
MANAGING WOUND ODOR
Bansari Patel APN and Deon Cox-Hayley DO
Background Foul-smelling non-healing wounds are common in patients nearing the end-of-
life, whether from pressure ulcers, vascular disease, or tumors. Strong wound odors can lead to
social and physical isolation, altered patient body image and self-worth, and can challenge
caregivers. This Fast Fact will discuss a practical approach to ameliorating wound odors. See
also Fast Facts #40 and #41 (pressure ulcers), #46 (malignant wounds), and #185 (topical
opioids).
Pathophysiology Foul odors from wounds result from the metabolic by-products of
anaerobic and certain gram negative organisms. Deeper infection (e.g. cellulitis, necrotizing
infections) are not necessary for significant odor generation.
Management While it should be addressed, treatment of the underlying cause of the wound is
often limited in patients with advanced illnesses. In all circumstances, attempts at ameliorating
wound odor are important – whether by treating the cause of the odor or hiding the odor.
• Addressing the cause of the odor:
o Remove the wound bed contaminants (e.g. debride the wound of necrotic tissue).
o Control infection. There are several approaches, all aimed at controlling anaerobic growth.
• Topical Metronidazole is available as a commercially produced gel. Metronidazole
functions as an anti-inflammatory as well as anti-infective agent against anaerobes
which reduces odors. Metronidazole gel is applied directly to the wound once or twice
daily. Studies have shown decreases in wound odor in 2-3 days, and application is
usually continued for up to 2 weeks. Courses can be repeated if needed. In one study,
63% of patients had complete eradication of odor after a course of metronidazole gel,
with the remainder reporting improvements. Costs can range from a few dollars for
compounded gels to ~$90-150 for 45 gm of commercial gel. Metronidazole tablets can
also be broken and the powder contents sprinkled into the wound. Applying dressings
soaked in a mixture of normal saline and intravenous metronidazole solution has also
been reported as helpful for controlling odor.
• Systemic Metronidazole can be used if there is evidence of deep tissue infection
causing foul odor. 500 mg 3 or 4 times daily IV or orally is used, instead of or in
addition to topical metronidazole. Systemic side effects such as nausea and diarrhea
can occur.
• Topical Silver Sulfadiazine ($4-$20) has been shown to be helpful in controlling odors
of superficial wounds. In several studies, silver containing dressings were more
effective than nonsilver dressings in reducing odors.
• Cadexomer Iodine is an antimicrobial agent containing slow release iodine and has
been shown to decrease bacterial counts and odor from venous ulcers. Ointment,
powder and impregnated bandage forms are available. Cadexomer iodine has the
added benefit of absorbing exudate and can be particularly helpful when exudate
absorption and odor control are both needed. It can cause a burning sensation upon
application.
• Yogurt or buttermilk, applied for 15 minutes after a wound is cleaned, have been
reported to control malignant wound odor, though studies are limited. They are thought
to control bacterial proliferation by lowering a wound’s pH.
• Honey can be bactericidal, and has been increasingly studied for wound healing.
There is some evidence that it may be effective in managing odor as well as wound
pain.
• Hiding the odor:
o Aromatics: Scented candles, air freshener sprays, peppermint and other essential oils,
coffee beans or grounds, and cider vinegar in a pan are all used to hide odors.
19
o Adsorbents: Charcoal adsorbs aromatic molecules. A basket of charcoal (briquettes) can
be placed discreetly in a patient’s room. Various commercially available charcoal
dressings are also available, although expensive. These dressings are applied over the
primary dressing and may be re-used as long as they remain dry. Baking soda can be
applied between dressing layers to help absorb odor. Cat litter can also be used similarly
to charcoal briquettes.
Support and Education There can be great psychosocial distress associated with
malodorous wounds: embarrassment, shame, and isolation. In addition to wound care
specialists, psychological and spiritual support services can be important in helping patients and
families cope with a chronic wound. Educate the patient and caregivers about the management
of chronic wounds, and commit to controlling odor as much as possible. Health care providers
should be trained to avoid demonstrating distress at odors in front of or in hearing distance of
patients or families.
References
1) Alvarez O, Meehan M, Ennis W, et al. Chronic Wounds: Palliative Management for the
Frail Population Part III. Wounds. 2002; 14(8S):13-18.
2) Bates-Jensen B, Seaman S, Early L. Skin Disorders: Tumor Necrosis, Fistulas, and
Stomas. In: Ferrel B, Coyle N,
eds. Textbook of Palliative Nursing. New York, NY: Oxford University Press; 2006:
pp330-333.
3) Cooper RA, Jenkins L. A comparison between medical grade honey and table honeys in
relation to antimicrobial efficacy. Wounds. 2009; 29(2):29-36.
4) Fonder M, Lazurus G, Cowan D, et al. Treating the chronic wound: A practical approach to
the care of nonhealing wounds and wound care dressings. J Am Acad Dermatol. 2008;
58:185-206.
5) Kalinski C, Schneph M, Laboy D, et al. Effectiveness of a Topical Formulation Containing
Metronidazole for Wound Odor and Exudate Control. Wounds. 2005; 17(4):84-90.
6) McDonald A, Lesage P. Palliative Management of Pressure Ulcers and Malignant Wounds
in Patients with Advanced Illness. J Palliat Med. 2006; 9(2):285-295.
7) Sussman C, Jensen-Bates B. Wound Care: A Collaborative Practice Manuel. Philadelphia,
PA: Lippincott Williams & Wilkins; 2006.
8) Woo K, Krasner D, Kennedy, B, et al. Palliative Wound Care Management Strategies for
Palliative Patients and Their Circles of Care. Advances in Skin &Wound Care. 2015; 28(3):
130-140.
Author Affiliations: University of Chicago, Chicago, Illinois.
Version History: Originally published August 2009; copy-edited August 2015 by Krista Wiger
MD: reference #8 added and incorporated into the text.
20

TOPICAL NONSTEROIDAL ANTI-INFLAMMATORY DRUGS
Sarah Merriam MD and René Claxton MD
Background Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most commonly
prescribed drugs in the treatment of musculoskeletal pain. Two topical NSAID formulations are
commercially available in the United States: diclofenac sodium gel (Voltaren), diclofenac topical
solution (PENNSAID) and diclofenac epolamine topical patch (Flector) (1). This Fast Fact
reviews the pharmacology, clinical efficacy and adverse effects of topical NSAIDs for the
treatment of musculoskeletal pain.
21
Pharmacology High plasma concentrations of oral NSAIDs are required to achieve effective
tissue concentrations at the site of pain and inflammation. Topical NSAIDs are believed to
deliver adequate local tissue concentrations with minimal systemic absorption. Plasma
concentrations following topical administration of diclofenac sodium gel and the diclofenac
epolamine patch are far lower than levels found following oral administration of diclofenac
(0.6%-2.2%, and less than 1%, of oral systemic levels, respectively). Time to peak serum
concentration for both topical formulations is approximately 10-20 hours (2).
Clinical evidence NSAIDs are often recommended as first-line treatment for mild-to-
moderate musculoskeletal pain (3). A Cochrane review of the efficacy of topical NSAIDS in the
treatment of acute musculoskeletal pain (sprains, strains, contusions) found that compared to
placebo, the number needed to treat (NNT) was 4.5 to achieve 50% pain relief over treatment
periods of 6-14 days (4). The effectiveness of topical NSAIDs for the treatment of acute low
back pain or chronic conditions including chronic back pain is unknown (5). Several systematic
reviews report trials of poor quality with most trial lengths lasting less than 4 weeks and
demonstrating inconclusive results (6). Head-to-head trials comparing oral NSAIDs and their
topical equivalents show conflicting results with regards to efficacy and there are insufficient
data to perform meta-analysis (4). There are virtually no data about topical NSAID use in patient
populations commonly seen in palliative care settings. A literature review in June 2011 identified
a single study which showed no benefit from a topical NSAID cream over placebo in the relief of
pain related to pressure ulcers (7).
Adverse Effects Patients taking oral NSAIDs for ≥5 days at least twice annually have a 4.21
relative risk of gastrointestinal events compared to those who do not (8). Conversely, topical
NSAIDs have a high margin of safety and have not been associated with acute renal failure or
upper GI adverse events. Mild local adverse effects occur at approximately the same rate (6%)
in patients treated with topical NSAIDs or topical placebo (5).
Summary In the treatment of acute musculoskeletal pain, excluding low back pain, topical
NSAIDS are more effective than placebo and are associated with fewer adverse events than
oral NSAIDs (although this has not been demonstrated in head-to-head trials with oral NSAIDs).
Current data suggest topical NSAIDs are appropriate for patients with a flare of single joint
arthritis or acute musculoskeletal injury. Given the expense of topical NSAIDS (approximately
$36 for one 100 gm tube of diclofenac gel and $170 for thirty diclofenac epolamine patches),
unclear clinical benefit over prolonged time periods, and unknown efficacy compared to oral
preparations, they are not recommended for chronic musculoskeletal pain. Their use for
cancer-related pain syndromes and other indications is entirely empiric.
References
1. McPherson ML, Cimino NM. Topical NSAID formulations. Pain Med. 2013; 14(Supp
1):S35-9
2. Micromedex® Healthcare Series [Internet database]. Greenwood Village, Colo:
Thomson Reuters (Healthcare) Inc. Updated periodically.
3. Chou R, Qaseem A, Snow V, et al. Diagnosis and treatment of low back pain: a Joint
Clinical Practice Guideline from the American College of Physicians and the American
Pain Society. Ann Intern Med. 2007; 7:478-91.
4. Massey T, Derry S, Moore RA, McQuay HJ. Topical NSAIDs for acute pain in adults.
Cochrane Database Syst Rev. 2010; 6: CD007402.
5. Roelofs PD, Deyo RA, Koes BW, Scholten RJ, van Tulder MW. Nonsteroidal anti-
inflammatory drugs for low back pain: An updated Cochrane review. Spine. 2008;
33:1766-74.
6. Gotzsche P. NSAIDs. Clinical Evidence. 2009; 6(1108).
7. Prentice WM, Roth LJ, Kelly P. Topical benzydamine cream and the relief of pressure
pain. Palliat Med. 2004; 18:520-4.
22
8. Singh G, Triadafilopoulus G. Epidemiology of NSAID-induced GI complications. J
Rheumatol. 1999; 26:18-24.
Version History: Originally published January 2012; Copy-re-edited August 2015 with reference
#1 added and incorporated into the text.
23
!

TRACHEOSTOMY CARE
Elliott Kozin MD, Joseph Straton MD, and Jennifer Kapo MD
Background Many patients with advanced illness have tracheostomies, which require careful
observation and specialized management. Common indications for tracheostomies in patients
being seen in palliative care and hospice settings include chronic long-term ventilation, aid with
ventilation weaning, and upper airway obstruction (from, for instance, head and neck cancer). A
working knowledge of tracheostomy equipment and the basic handling procedures can avoid
complications and improve a patient’s comfort.
Tracheostomy Equipment 101 At its most basic level, a tracheostomy appliance consists of
a cannula (or tube), cuff, obturator, and ties. The cannula maintains the patency of the stoma
and airway, and it facilitates movement of air into the trachea. Tracheostomy cannulas can be
cuffed or uncuffed. The inflatable cuff, typically filled with air by a syringe, surrounds a portion of
the cannula inside the trachea. The inflated cuff occludes the trachea around the cannula, which
allows for increased protection against aspiration and also for greater degrees of positive
pressure ventilation. Cuffs require monitoring to maintain a pressure of 20-25 mmHg. Higher
pressures can produce tracheal ischemia, mucosal injury, and difficulty swallowing; lower
pressures can potentially aggravate aspiration around the cannula (1,2,3). Obturators, usually
packaged with new tracheostomy tubes, are inserted into the lumen of the cannula and provide
for increased rigidity during placement of the tracheostomy tube. Tracheostomy ties secure the
tracheostomy tube to the patient and typically wrap around the back of the patient’s neck.
Complications of Tracheostomy Placement Short-term complications include bleeding from

surgical site (~5%), wound infection, subcutaneous emphysema, pneumothorax, tracheostomy
tube obstruction, recurrent laryngeal nerve damage, and posterior tracheal wall injury (4, 5).
Long-term complications include dysphagia, airway obstruction from secretions, infection,
rupture of the innominate artery, tracheo-innominate artery fistula (<0.7%), tracheosophageal
fistula, tracheal dilation, tracheal stenosis (1-2%), granuloma formation, and tracheal ischemia
and necrosis (4, 5).
Approach to Complications and Emergencies

• Acute Dyspnea. If a patient with a tracheostomy becomes acutely dyspneic, it may be due
to partial or complete blockage by retained secretions. Ask the patient to cough and then
attempt to suction the tracheostomy in place with a flexible suction catheter. If the
tracheostomy stoma and tract is not fully matured, do not attempt to remove the cannula as
it may be difficult to re-insert. (3)
• Bleeding. Bleeding from the surgical site is among the most common early complications.
Treatments include packing around the edges of the stoma with gauze, correction of
coagulopathies, and cautery or suturing of site of bleeding (3,5). Massive pulsatile bleeding
may indicate erosion of the innominate artery, which can occur days to weeks after a
tracheostomy procedure. This can rapidly lead to airway compromise and/or exsanguination.
To minimize bleeding, place a gloved finger in the stoma, feel for a pulsatile mass, and apply
forward motion on the backside of the upper border of the sternum thereby compressing the
pulsatile artery against the posterior surface of the sternum (6). Other techniques include
overinflating the cuff. If the patient’s goals of care allow this, the patient should be
transported emergently to the operating room for management (3). See Fast Fact #251for
further details about caring for hemorrhaging patients who do not want further invasive
treatments.
24
• Accidental Decannulation. Don’t panic. Reassure the patient. If the tube has been in place
less than 5 days, consider endotracheal intubation if a tracheostomy tract cannot be
immediately re-established (5). If the tube has been in place for 5-10 days, the tract should
be well formed and should not suddenly close (2). To reinsert the tracheostomy tube, insert
the obturator (if applicable) into the cannula. Slowly insert the cannula with obturator into the
tracheostomy, following the path of the airway. When reinserting, be mindful of any
resistance. If met with resistance, it is possible to create a false passage, and one should
reevaluate the entry approach. After insertion, remove the obturator while keeping the
cannula in place. Listen for and feel for air movement through the tracheostomy tube and
ensure that there is no subcutaneous emphysema, which may indicate improper placement.
If you cannot insert a new cannula and the patient cannot breathe comfortably on their own
through the stoma, use a bag-valve mask to ventilate the patient through the upper airway.
Ventilate gently to prevent air from escaping through the stoma or carefully occlude the
stoma with a gloved hand to maximize oxygenation. Next steps depend on the patient’s
current indication for a tracheostomy (airway patency vs. ventilation vs. secretion
management) and goals of care. If the patient has a patent airway and is not on a ventilator
there may be time to have the patient evaluated by a specialist to replace the cannula. If the
patient is ventilator dependent or has an upper airway obstruction, endotracheal intubation
and/or emergency transport is indicated.
• Resuscitation via Tracheostomy Tube. Treat the patient like patients without tracheostomy,
with the following exceptions. Do not remove the tracheostomy. Check that the cannula is
patent. Ventilate by using a manual resuscitation bag attached directly to tracheostomy tube.
If unable to ventilate, try suctioning. If still unable to ventilate, try to change tracheostomy
tube. The last resort is oral intubation.
Conclusion Careful discussions with dying patients and their families about options and
preferences if there are tracheostomy complications can help prevent chaotic, emergency
decisions about urgent transportation, surgeries, or oral intubation.
References
1. Heffner JE, Hess D. Tracheostomy management in the chronically ventilated patient. Clin
Chest Med. 2001; 22:55-69.
2. Hess DR. Tracheostomy tubes and related appliances. Respir Care. 2005; 50:497-510.
3. St. John RE and Malen JF. Contemporary issues in adult tracheostomy management. Crit
Care Nurs Clin N Am. 2004; 16:413-430.
4. Conlan AA, Kopec, SE. Tracheostomy in the ICU. J Int Care Med. 2000; 15:1-13.
5. De Leyn P, Bedert L, Delcroix M, et al. Review. Tracheotomy: clinical review and
guidelines. Eu J Cardiothoracic Surg. 2007; 32:412-21.
Author Affiliations: University of Pennsylvania School of Medicine, Philadelphia, PA.
Version History: Originally published February 2012; Copy-re-edited August 2015.
25
26
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CARE OF THE POST-LARYNGECTOMY STOMA
Shweta Garg PA-C, Elliott Kozin MD, Daniel Deschler MD
Background Many patients with laryngeal cancer require a laryngectomy. While
laryngectomies are typically done as a curative cancer surgery, some patients will have
recurrences and be seen in palliative care and hospice settings. Laryngectomy stomas differ
from tracheostomies (see Fast Fact #250) in important ways, which can profoundly impact a
patient’s well being. A working knowledge of the basic management and equipment used in
patients with a stoma after laryngectomy can avoid complications and improve a patient’s
comfort and safety (1).
Laryngectomy Stoma versus Tracheostomy There are a few key differences between a post-
laryngectomy stoma and tracheostomy. At the most basic level, a post-laryngectomy stoma is
created after a patient undergoes a total laryngectomy, which involves the removal of the larynx,
including vocal cords and associated structures. A permanent, direct connection between the
trachea and the skin of the neck is made sewing the open end of the trachea to the neck skin
forming an opening through which the patient breathes. After a laryngectomy, the patient no
longer has a communication between the lungs and oral cavity or nose. These patients are
casually referred to as “neck breathers” (2). In contrast, a tracheostomy, also referred to as a
tracheotomy, is surgical opening into the trachea to bypass the upper airway, which is not
necessarily permanent. A tracheostomy tube is inserted and stents the tracheostomy open,
thereby facilitating air exchange. In patients with tracheostomies, the larynx remains present
and there is still a connection between the oral cavity and nose to the lungs.
One can differentiate a post-laryngectomy stoma from a tracheostomy based on physical exam
(Reference 6 has helpful illustrations available online). A post-laryngectomy stoma does not
typically require any stenting and appears as a circular opening above the clavicles directly
midline in the neck. Although similar in position to a tracheostomy, a post-laryngectomy stoma
will only track inferiorly into the chest and have no connection superiorly to the throat and mouth
as a tracheotomy will. Post-laryngectomy stomas, however, may have a moisture exchange
device (see below) and may be confused for a tracheostomy. In contrast, tracheostomies have a
tracheostomy tube in place and will readily close without a supportive stenting mechanism. If
there is any question about a patient’s airway anatomy, consultation with an otolaryngologist is
warranted.
Routine / Preventive Care The basic equipment for a laryngectomy stoma includes 1) a
suction device, 2) a humidified air device, 3) a personal mirror and, in some cases, 4) a soft
laryngectomy tube. Although most post-laryngectomy stomas do not require a tube to keep
them patent, some patients use a laryngectomy tube to assist with hygiene and minimize
stenosis. Suctioning is performed to remove excess mucus or crusting near the opening of the
stoma and to facilitate clearance of mucus from the lungs. Stomas require warm humidification
to prevent buildup of thick mucus, and humidification can be achieved with saline nebulizers or
a portable heat and moisture exchange (HME) device. The HME is a disposable small, round
filter device, which inserts into the opening of the laryngectomy tube. Patients generally replace
the HME every 24 hours (2). Patients with post-laryngectomy stomas will often use a small
personal mirror to assist with crust removal at the stoma site. Other patients may have a
tracheoesophageal puncture (TEP) prosthesis, which is a small circular device that is placed at
the back wall of the stoma to allow for speech (3, illustrations in Reference 6).
27
Approach to Complications and Emergencies As with all clinical situations, decision-
making at the time of emergency will depend on a patient’s overall health status, goals of care,
and code status.
• Acute Dyspnea. If a patient with a post-laryngectomy stoma becomes acutely dyspneic this
may be due to a partial or complete blockage of the trachea by retained secretions, such as
a mucus plug. Ask the patient to cough, instill 3 mL normal saline, and then attempt to
suction the stoma in place with a flexible suction catheter.
• Resuscitation via laryngectomy stoma. In a patient with a post-laryngectomy stoma, there is
no connection to the airway from the oral or nasal cavity to the trachea. Bag mask, oral, and
nasal intubation should never be attempted. Instead, a cuffed endotracheal tube (ETT)
should be directly inserted into the stoma. Ventilate by using a manual resuscitation bag
attached to the ETT tube. The ETT should be placed such that the balloon is nearly visible
under the skin. If an ETT is not available then an anesthesia facemask can be placed over
the stoma, creating a seal.
• Pharyngocutaneous fistula. In the first few weeks after a laryngectomy it is relatively
common for their to be breakdown of the mucosal lining resulting in salivary leakage to
surrounding tissue. Initial clinical signs include neck erythema, facial and neck edema, and
tenderness. Recognition is important to prevent wound complications and potential
breakdown of nearby vessels (2,4).
• Bleeding. Bleeding from a laryngeal stoma is an airway emergency. While it may be due to
dry air irritating the lining of the trachea, it could also be due to a fistula formation. Bleeding
may result in airway compromise. An otolaryngologist should evaluate the patient urgently
(5).
References
1. Darr A, Dhanji K, Doshi J. Tracheostomy and laryngectomy survey: do front-line
emergency staff appreciate the difference? J Laryngol Otol. 2012; 126(6):605-8.
2. Townsley RB, Baring DE,et al. Emergency department care of a patient after a total
laryngectomy. Eur J Emerg Med. 2013 Feb 17.
3. Deschler DG, Bunting GW, Lin DT, et al. Evaluation of voice prosthesis placement at the
time of primary tracheoesophageal puncture with total laryngectomy. Laryngoscope.
2009;119(7):1353-7.
4. White HN, Golden B, Sweeny L, et al. Assessment and incidence of salivary leak following
laryngectomy. Laryngoscope. 2012;122(8):1796-9.
5. St. John RE, Malen JF. Contemporary issues in adult tracheostomy management. Crit
Care Nurs Clin N Am. 2004;16:413-430.
6. Blom ED. Current status of voice restoration following total laryngectomy. Oncology.
2000; 14:915-922. Available at: http://www.cancernetwork.com/head-neck-cancer/current-
status-voice-restoration-following-total-laryngectomy/. Accessed Sept 25, 2015.
Authors’ Affiliations: Division of Head and Neck Surgery, Department of Otolaryngology,

Massachusetts Eye and Ear Infirmary, Boston, MA.
Conflicts of Interest Statement: The authors have disclosed no relevant conflicts of interest.
Version History: First published May 2014. Re-copy-edited in September 2015.
28
29
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TOPICAL TREATMENTS FOR ACUTE AND CHRONIC WOUND PAIN
Katherine Steele, DO
Acute and chronic wounds can be a significant source of pain in advanced illness. Systemic
opioids have been predominantly utilized for wound-related pain, however, for many patients,
dose-limiting side effects can hinder their effectiveness. This Fast Fact will discuss topical
options for acute and chronic wound pain. See Fast Facts #46 & #218 for guidance on
malignant wounds and wound odor.
Pain Classification Painful wounds can arise from many sources. Often wound pain is a
combination of nociceptive or neuropathic pain (1).
• Nociceptive pain: Typically caused by damage to body tissue. Common wound-related
etiologies include decubitus ulcers, mucositis, and procedures such as debridement,
dressing changes or radiation treatments (2,3). This pain is often described as sharp,
aching, or throbbing.
• Neuropathic pain: Typically, chronic in nature due to long-term inflammation or injury to
nerve fibers (1). This may be seen in certain malignant wounds or refractory mucositis (2,4).
This pain is usually described as burning, stabbing, or sharp (4).
Topical Drug Treatment Options

Local anesthetics: A Cochrane review found adequate evidence supporting the use of Eutetic
Mixture of Local Anesthetics (EMLA) cream (which is a combination of lidocaine and prilocaine)
for pain associated with dressing changes or debridement of a wound (5,6). It is recommended
that the cream be applied 20 minutes before the dressing change or debridement procedure to
minimize discomfort; open wounds should be avoided (5). As long as no more than 10 grams of
5% EMLA cream are applied, there is little concern for CNS toxicity. Only minor side effects like
a burning sensation, local erythema, or pallor have been documented (7). There is some
controversy whether local anesthetics negatively impact the first two stages of wound healing at
a clinically significant degree (8). A 30 g container of EMLA cream costs approximately $53.
Ketamine: While there are no high quality controlled trials on the use of topical ketamine for
wound pain, anecdotal accounts of the effective use of topical ketamine as a gel, cream,
ointment, or spray has been documented with few side effects at concentrations up to 20% (9).
Often, ketamine is compounded with other analgesics such as baclofen, amitriptyline, or
pregabalin. Coverage by insurance is variable. A 30 gram jar of a 15% ketamine/15% lidocaine
cream or a 30 mL bottle of 5-10% ketamine spray mixed with 1% lidocaine and 5% morphine
costs about $70 to $100 without insurance (10). The spray is typically applied to an entire
wound bed prior to dressing changes 4 times per day as needed. Use of the spray has also
been described for post-operative pain relief in children (9,10).
Anti-inflammatory foam dressings (Available in Canada but not in the US): These treatments
commonly utilize diclofenac or ibuprofen as their active ingredient to inhibit synthesis of
prostaglandins in body tissues and decrease proinflammatory cytokine activity. In some studies,
anti-inflammatory foam dressings have been found to be more effective in treating nociceptive
wound pain, such as chronic leg ulcers, than the local best practice (moist healing and
antimicrobial dressings) (9).
Tricyclic Antidepressants: Amitriptyline has shown effectiveness for acute nociceptive and
chronic neuropathic wound pain (11,12). Similar to ketamine, its topical use requires the
30
assistance of an experienced compounding pharmacist. The cost of a 30 gram jar of 2.5%
amitriptyline cream compounded with 2-4% baclofen and 2-5% gabapentin is estimated to be
about $70 to $90 per month when used 2-4 times per day as needed.
Topical Opioids: See Fast Facts #185 and #325. Applying opioids topically to painful wounds like
skin ulcers or calciphylaxis-related wounds has the theoretical advantage of offering a more
localized effect with less systemic absorption and side effects. While morphine infused into a
gel form is most frequently used in this manner, the use of topical methadone and
buprenorphine has also been described (13,14). In several case studies and many, but not all,
controlled trials, most patients were able to reduce their systemic analgesic doses when 10 mg
diamorphine per 10 mL gel was applied to the entire surface of a wound and covered with gauze
twice daily (9). Morphine has also been utilized as a mouthwash to reduce mucositis pain
associated with cancer or cancer treatment (15)
Other: Topical aspirin, capsaicin (0.025 to 0.075%), clonidine 0.1% gel, and menthol have all
been described to reduce wound pain, but evidence regarding safety and efficacy are lacking.
Although the analgesic effect of topical capsaicin is dose dependent, burning associated with
the application at higher concentrations (e.g. 2.5 to 7.5%) often limits patient adherence (13).
Summary Complete healing of wounds is often an unrealistic goal in palliative settings.

Dose-limiting side effects of systemic opioids can limit their efficacy. Hence, clinicians may turn
to empiric options, including topical analgesics. Clinicians should be aware that most of these
formulations are not standardized and are poorly researched.
References
1. Langemo, D.K. and J. Black. Pressure ulcers in individuals receiving palliative care: a
National Pressure Ulcer Advisory Panel White Paper. Advances in Skin and Wound
Care, 2010. Feb
2. Epstein, J.B., et al., Neuropathic and nociceptive pain in head and neck cancer patients
receiving radiation therapy. Head & Neck Oncology. 2009; 1:26.
3. Pieper, B., et al., Pressure ulcer pain: a systematic literature review and national
pressure ulcer advisory panel white paper. Ostomy Wound Management, 2009; 55(2):
16-31.
4. Seaman, S, Management of malignant fungating wounds in advanced cancer. Seminars
in Oncology Nursing, 2006; 22(3): 185-193.
5. Briggs M, Nelson EA. The Cochrane Database of Systematic Reviews. Topical agents
or dressings for pain in venous leg ulcers. Review 2003. The Cochrane Library.
6. Dever A, Galer B. Topical lidocaine patch relieves a variety of neuropathic pain
conditions: an open-label study. Clin J Pain 2000; 16:205-208.
7. Evans E, Gray M. Do topical analgesics reduce pain associated with wound dressing
changes or debridement of chronic wounds? J WOCN 2005;Sept/Oct 287-290
8. Brower M.C., Johnson M.E., Adverse effects of local anesthetic infiltration on wound
healing. Regional Anesthesia and Pain Medicine, 2003; 28(3): 233-240
9. Argoff, C.E., Topical analgesics in the management of acute and chronic pain. Mayo
Clinic Proceedings, 2013; 88(2): 195-205.
10. Kopsky, D.J., et al., Analgesic effects of topical ketamine. Minerva Anestesiol, 2015;
81(4):440-9.
11. Hoffman, K, Samaritan Evergreen Hospice House: Nurse Practitioner Case Study
Review. www.oregonhospice.org
12. Peppin, J.F., et al., Skin matters: a review of topical treatments for chronic pain. Part two:
treatments and applications. Pain Ther, 2015; 4(1): 33-50.
13. Woo, K.Y., et al., Evidence-based approach to manage persistent wound-related pain.
Current Opinion in Supportive and Palliative Care, 2013; 7(1): 86-94
31
14. He L, Kim J, Ou C, et al. Methadone antinociception is dependent on peripheral opioid
receptors. J Pain. 2009;10:369–79.
15. Cerchietti LC, Navigante AH, Bonomi MR, et al.Effect of topical morphine for mucositis-
associated pain following concomitant chemoradiotherapy for head and neck
carcinoma.Cancer.2002;95:2230–6.
Author’s Affiliations: Saint Alphonsus Health System, Boise, ID

Version History: Originally edited by Sean Marks MD; first electronically published in
December 2016.
32
!
Cardiac All
#111 Cardiac Pacemakers at End-of-Life . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . 2-3
#112 Implantable Cardioverter-Defibrillators at End-of-

Life. . . . . . . . . . . . . . . . . . . . . . . . . . . 4-5
#144 Palliative Care Issues in Heart Failure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . .6-8
#143 Prognostication in Heart

Failure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .9-11
#205 Mechanical Circulatory Support in Advanced Heart Failure . . . . . . . . . . . . . . . .

. . . . . .12-14
#209 Malignant Pericardial

Effusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .15-17
#283 Use of Home Inotropes in Patients Near the End of Life . . . . . . . . . . . . . . . . . .

. . . . . . . 18-21
#296 Total Artificial

Heart . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
22-23
#339 Extracorporeal Membrane Oxygenation in

Adults . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24-26
#353 Subcutaneous Diuretics for End of Life Management of Heart

Failure . . . . . . . . . . . . . 27-29
!1
!

CARDIAC PACEMAKERS AT END-OF-LIFE
Harrington MD, Luebke DL, Lewis WR, Aulisio MP, Johnson NJ
Introduction
This Fast Fact discusses management of cardiac pacemakers at life’s end. Fast Fact #112
discusses implantable cardioverter-defibrillators.
Background
Worldwide there are about 3 million people with pacemakers. Each year 600,000 new
pacemakers are implanted, with the majority of these devices in patients over the age of 60. The
primary function of pacemakers is to treat bradyarrhythmias (e.g. heart block). More recently,
patients with heart failure, subvalvular stenosis and treatment resistant atrial fibrillation may
qualify for pacemakers. Additionally, patients with congestive heart failure may receive
biventricular pacemakers to improve symptoms.
Pacemaker Function at Time of Death

Patients and their families often make assumptions that pacemakers prolong the dying process
and thus prolong suffering. However, a pacemaker is not a resuscitative device. In general,
pacemakers do not keep dying patients alive, as terminal events are often due to sepsis,
hemorrhage, pulmonary emboli, or arrhythmias from metabolic abnormalities associated with
end-stage cancer, liver, or renal failure. At the time of death, the myocardium is usually too sick
to respond to the pacemaker generated signals.
When is Pacemaker Deactivation indicated?

In patients with irreversible cognitive failure, where continued pacemaker activity is not meeting
the goals of care, it may be appropriate to discuss the option of deactivation. In most other
situations, deactivation is not indicated since the result is likely to be a symptomatic bradycardia,
producing signs and symptoms of worsening heart failure (fatigue, dizziness, dyspnea). In
contrast to popular belief, it is rare that disabling the pacemaker will result in a swift and painless
death as few patients are 100% pacemaker dependant, particularly during the period of imminent
death (Fast Fact # 3), where tachycardia is the most common rhythm. When questions arise
concerning dependency on the pacemaker, consult the cardiology/pacemaker service.
Ethical/Legal issues
A patient’s/surrogate’s right to request withdrawal of life sustaining medical interventions,
including pacemakers, is both legal and ethical. Withdrawal of a life sustaining medical
intervention with the informed consent of a patient or legal surrogate is not physician-assisted
suicide or euthanasia. While there may be more agreement about the deactivation of implantable
cardioverter-defibrillators than of pacemakers amongst practicing clinicians, the Heart Rhythm
Society issued a consensus statement in collaboration with many professional groups (including
the American College of Cardiology, the American Academy of Hospice and Palliative Medicine,
and the American Heart Association) which effectively erased any ethical distinction between
types of implanted devices being deactivated and endorsed a patient’s right to have one’s
pacemaker deactivated.
!2
Summary 
Initiate a discussion about pacemaker deactivation only if there is potential for patient benefit;
consider the potential negative effects of deactivation before disabling the pacemaker.
References
1. Braun TC, Hagen NA, Hatfield RE, Wyse DG. Cardiac pacemakers and implantable
defibrillators in terminal care. J Pain Symptom Manage. 1999; 18:126-131.
2. Kolarik RC, Arnold RM, Fischer GS, Tulsky, JA. Objectives for advance care planning. J
Palliative Med. 2002; 5(5):697-704.
3. Mueller PS, Hook CC, Hayes, DL. Ethical analysis of withdrawal of pacemaker or
implantable cardioverter-defibrillator support at the end of life. Mayo Clin Proc. 2003;
78:959-963.
4. Wood MA, Ellenbogen KA. Cardiac pacemakers from the patient’s perspective.
Circulation. 2002; 105:1022-1024.
5. R. Lampert, D.L. Hayes, G.J. Annas, et al. HRS expert consensus statement on the
management of cardiovascular implantable electronic devices (CIEDs) in patients nearing
end of life or requesting withdrawal of therapy. Heart Rhythm 2010 (7), 1008-1026.
in April 2004. Re-copy-edited in April 2009; then again in June 2015 – reference 5 added and
incorporated into text.
!3
!

IMPLANTABLE CARDIOVERTER-DEFIBRILLATORS AT END-OF-LIFE
Harrington MD, Luebke DL, Lewis WR, Aulisio MP, Johnson NJ
Background Recent clinical trials and advances in device technology have expanded the
indications for implantable cardioverter-defibrillators (ICDs). At least 12,000 ICDs are implanted
per month in the US and over 3 million patients in North America are eligible for an ICD. Near the
end of life, however, ICD decision-making can be the source of anguish for patients, families and
palliative care/hospice staff.
Current Devices ICDs are somewhat larger than pacemakers and are usually implanted in the
upper chest under the clavicle. They monitor cardiac rhythm and can either cardiovert or
defibrillate (electrically ‘shock’ a heart) when certain rapid abnormal cardiac rhythms are
identified. These shocks can be painful and are inconsistent with comfort care in a dying patient.
ICDs can also deliver pacing therapy. Pacing increases heart rate when slow heart rhythms are
detected and can promote comfort as slow heart rhythms can cause heart failure symptoms.
Finally, certain pacemakers or cardiac resynchronization therapy devices may include an ICD
function all in one device. For these devices, the shocking functions of an ICD can be
independently turned off and a decision to discontinue a device’s ICD function should be
considered separately from a decision to discontinue its pacing functions (see Fast Fact #111).
Indications for deactivation of ICD therapy
• Continued use of an ICD is inconsistent with patient goals.
• Withdrawal of anti-arrhythmic medications: if anti-arrhythmic medications are withdrawn
consider turning off the ICD to avoid frequent shocks.
• When a patient’s condition is worsening and death is anticipated.
• The patient has a DNR order. The functioning of an ICD is generally inconsistent with a
‘Do-Not-Resuscitate’ order since ICDs attempt to resuscitate the patient by shocking their
hearts back into a life-sustaining rhythm.
Discussing deactivation of the ICD
1. Consult the clinician who manages the ICD (usually a cardiologist or associated
clinician); that individual is often the person to assume responsibility for deactivation.
Patients are usually followed in a device clinic and probably have an established
relationship with the physician and staff. The involvement of these professionals can
provide a sense of comfort and closure for the patient and family. Note: The device
manufacturers will not send representatives to patient’s homes for deactivation by simple
reprogramming of the device.
2. Discuss expectations of “turning off” the ICD. The following should be made clear:
a. Turning off the ICD means that the device will no long provide life-saving therapy
in the event of a ventricular tachyarrhythmia.
b. Turning off the ICD will not cause death.
c. Turning off the ICD will not be painful, nor will its failure to function cause pain.
3. Establish a plan of care that will ensure availability for addressing new questions or
concerns that might arise (patient/family should not feel abandoned once the device is
turned off).
4. If there are conflicts among providers or family members, consultation with a palliative
care expert or ethics team can be helpful.
Emergency ICD Deactivation When patients are imminently dying, there may not be enough
time for a cardiac physiologist to prevent painful shocks via ICD reprogramming. Any health care
professional can temporarily deactivate the device by placing a special magnet, which are usually
available at electro-physiology clinics, directly over the implant site. This stops the defibrillation
function of the device, but would not disable the pacing functionality. Of note, once the magnet is
!4
removed, the ICD will resume functionality. Hence, reprogramming of the device by a cardiac
physiologist would still be required.
Ethical/Legal issues A patient’s right to request withdrawal of life sustaining medical
interventions, including ICDs, is both legal and ethical. Withdrawal of a life sustaining medical
intervention with the informed consent of a patient or legal surrogate is not physician-assisted
suicide or euthanasia.
References
1. Groh WJ, Foreman LD, Zipes DP. Advances in the treatment of arrhythmias: Impantable
cardioverter-defibrillators. Am Fam Phys. 1998; 57(2):297-307, 310-12.
2. Kolarik RC, Arnold RM, Fischer GS, Tulsky JA. Objectives for advance care planning. J
of Palliative Med. 2002; 5(5):697-704.
3. Moss AJ, Zareba W, Hall WJ, et al. Prophylactic implantation of a defibrillator in patients
with myocardial infaction and reduced ejection fraction. NEJM. 2002; 346(12):877-883.
4. Mueller PS. Ethical analysis of withdrawal of pacemaker or implantable cardioverter-
defibrillator support at the end of life. Mayo Clinic Proceedings. 2003; 78(8):959-963.
5. Kremers MS, et al. The national ICD registry report: version 2.1 including leads and
pediatrics for years 2010 and 2011. Heart Rhythm 2013;10: e59-e65.
in April 2004. Re-copy-edited in April 2009; June 2015 with reference #5 added and incorporated
into the text; and then again in November 2017 to include a discussion about cardiac
resynchronization therapy devices.
!5
PALLIATIVE CARE ISSUES IN HEART FAILURE
Background The physical and psychological symptom burden in the dying heart failure (HF)
patient is similar to that in the dying cancer patient. Symptom prevalence data in HF includes:
pain (78%), dyspnea (61%), depression (59%), insomnia (45%), anorexia, (43%), anxiety (30%),
constipation (37%), nausea/vomiting (32%), fatigue, difficulty ambulating, and edema. This Fast
Fact reviews domains of medical management common to most end-stage HF patients.
General Symptom Management

• Pain. Common causes include: peripheral edema, arthritis, diabetic neuropathy, and
post-herpetic neuralgia. NSAIDs are generally contraindicated because they antagonize
the effects of diuretics and ACE inhibitors, promoting fluid retention while decreasing
glomerular filtration and impairing renal function. Opioids are the agents of choice for
nociceptive and neuropathic pain because of efficacy, rapidity of onset and potential to
relieve dyspnea. See Fast Facts #18, 28, 53, 54, and 72.
• Dyspnea. Reassess/optimize HF medications and assess for reversible causes, e.g.
pleural/pericardial effusions, dysrhythmias, COPD exacerbation. See Fast Fact #27.
• Depression. Short-term psychotherapy can be helpful for mild-moderate depression, but
patient participation and logistical issues can be problematic. Selective serotonin
reuptake inhibitors (SSRIs) are the antidepressants of choice because they preserve
ejection fraction, lack hypotensive/dysrhythmogenic effects, and have few drug
interactions. Sertraline in particular may be the agent of choice in HF patients.
Psychostimulants (see Fast Fact #61) may accelerate the treatment response to SSRIs.
Note: as there exists no data on the safety of psychostimulants in HF, therapy should be
initiated with caution.
Heart Failure Pharmacotherapy Optimal drug use can improve symptoms and should be
continued until the burden of administration outweighs benefits. Diuretic therapy can be crucial,
but diuretic resistance is common. The following strategy can help overcome diuretic resistance:
• Optimize dose of oral loop diuretic (e.g. furosemide). Doses of up to 4000 mg/day have
been found to be safe and effective.
• Change to intravenous or subcutaneous routes. IV boluses can produce symptom relief
within minutes. Continuous infusions (3-200 mg/hr; 10-20 mg/hr in most patients) provide
increased efficacy.
• Add a PRN oral thiazide diuretic (e.g. hydrochlorothiazide 25-100 mg/day or metolazone
5-20 mg/day. This can reestablish diuresis in a loop diuretic-resistant patient. Note: high
dose and combination diuretics can result in electrolyte imbalances; consider electrolyte
monitoring if death is not imminent.
Inotropes Intravenous inotrope therapy (dobutamine, milrinone, dopamine) has a substantial

record of use but a paucity of data in the home setting. Data suggest these agents may improve
symptoms, but with an increased risk of dysrhythmic death. In hospitalized inotrope-dependent
HF patients, discharge on inotropes may provide the opportunity for death to occur at home if
desired by patient/family.
Device therapies Decisions regarding previously implanted device therapies should be made
in the context of goals of care. See Fast Facts #111,112 for a discussion of implantable devices
and issues surrounding deactivation; Fast Fact #205 discusses ventricular assist devices.
Prognostic Uncertainty Accurate prognostication is virtually impossible in HF (see Fast Fact

#143). While this uncertainty is frustrating for physicians, it provides a basis for initiating end-of-
!6
life discussions. The American Heart Association released a scientific statement to help
Clinicians best guide their patients:
• Initiate yearly “heart failure reviews” or advance care planning discussions.
• Utilize a HF hospitalization (which triples one-year mortality) as a bridge to either
optimizing medical therapy or palliative care.
• Educate patients and families about the unpredictable, but usually terminal nature of HF,
and the ever present danger of sudden cardiac death (even when feeling well).
• Ascertain specific goals of care (e.g. quality of life vs. length of life, living/dying at home
vs. hospital)
• Assess options for achieving these goals (e.g. initiating/handling device therapies
including when and how to deactivate, hospice vs. serial hospital/critical care unit
admissions).
• Assess resuscitation preferences.
Patient Resources A free advance care planning packet for HF patients is available through
the Heart Failure Society of America website at: http://www.hfsa.org/pdf/module9.pdf.
References
1. Albert NM, Davis M, Young J. Improving the care of patients dying of heart failure. Cleve
Clin J Med. 2002; 69(4):321-328.
2. Alvarez W, Pickworth KK. Safety of antidepressant drugs in the patient with cardiac
disease: a review of the literature. Pharmacotherapy. 2003; 23(6):754-771.
3. Berger JT. The ethics of deactivating implanted cardioverter defibrillators. An Intern Med.
2005; 142(8):631-634.
4. DeBruyne LKM. Mechanisms and management of diuretic resistance in congestive heart
failure. Postgrad Med J. 2003; 79:268-271.
5. Ward C. The need for palliative care in the management of heart failure. Heart. 2002;
87:294-298.
6. Braun TC, Hagen NA, Hatfield RE. Cardiac pacemakers and implantable defibrillators in
terminal care. J Pain Symptom Manage. 1999; 18(2):126-131.
7. Allen LA, Stevenson LW, et al. Decision making in advanced heart failure: a scientific
statement from the American Heart Association. Circulation. 2012; 125:1928-1952.
in October 2005. Version re-copy-edited in April 2009; revised again in July 2015 by Sean Marks
MD – reference #7 added and incorporated into the text..
!7
!

PROGNOSTICATION IN HEART FAILURE
Background This Fast Fact reviews prognostication data in Heart Failure (HF). Although the
Framingham Heart Study (1990-1999) showed a 5-year mortality rate of 50% for newly identified
cases, providing accurate prognostic data for 6-12 month mortality in HF has been nearly
impossible. Reasons cited include: 1) an unpredictable disease trajectory with high incidence
(25-50%) of sudden death; 2) disparities in the application of evidence-based treatment
guidelines; 3) inter-observer differences in New York Heart Association (NYHA) classification; and
4) heterogeneous study populations
NYHA Classification The NYHA classification remains the major gauge of disease severity.
Based on data from SUPPORT, Framingham, IMPROVEMENT, and other studies, 1-year
mortality estimates are:
• Class II (mild symptoms): 5-10%.
• Class III (moderate symptoms): 10-15%.
• Class IV (severe symptoms): 30-40%.
General Predictors of Shorter Prognosis:

• Cardiac hospitalization (triples 1-year mortality; nearly 1 in 10 die within 30 days of
admission).
• Intolerance to neurohormonal therapy (i.e. beta-blockers or ACE-inhibitors) is associated
with high 4 month mortality
• Elevated BUN (defined by upper limit of normal) and/or creatinine ≥1.4 mg/dl (120 µmol/l).
• Systolic blood pressure <100 mm Hg and/or pulse >100 bpm (each doubles 1-year
mortality).
• Decreased left ventricular ejection fraction (linearly correlated with survival at LVEF ≤
45%).
• Ventricular dysrhythmias, treatment resistant.
• Anemia (each 1 g/dl reduction in hemoglobin is associated with a 16% increase in
mortality).
• Hyponatremia (serum sodium ≤135-137 mEq/l).
• Cachexia or reduced functional capacity.
• Orthopnea.
• Co-morbidities: diabetes, depression, COPD, cirrhosis, cerebrovascular disease, and
cancer
Hospice Eligibility Guidelines The National Hospice and Palliative Care Organization’s 1996
guidelines for heart disease admission criteria include: a) symptoms of recurrent HF at rest
(NYHA class IV) and b) optimal treatment with ACE inhibitors, diuretics, and vasodilators
(contemporary optimal treatment now includes β-blockers, aldosterone antagonists, and device
therapies). The NHPCO guide indicates that an ejection fraction < 20% is “helpful supplemental
objective evidence,” but not required. The NHPCO guidelines also assert that each of the
following further decreases survival: treatment resistant ventricular or supraventricular
arrhythmias, history of cardiac arrest in any setting, history of unexplained syncope, cardiogenic
brain embolism, and concomitant HIV disease.
Prognostic Models Since publication of the NHPCO’s guidelines, several models have been
developed for predicting short- and/or long-term mortality among HF patients. Two recent models
purport to predict mortality among patients hospitalized with acutely decompensated HF.
Fonarow et al (2005), using a model based on admission BUN (≥ 43 mg/dl), creatinine (≥ 2.75
mg/dl), and systolic BP (< 115 mmHg), identified in-hospital mortality rates ranging from about 2%
!8
(0/3 risk factors) to 20% (3/3 risk factors). Lee et al (2003), using a model based on admission
physiologic variables and co-morbidities (almost all from above list of indicators) identified 30-day
mortality and 1-year mortality rates ranging from <1% and <10%, respectively, for the lowest risk
patients to >50% and >75%, respectively, for the highest risk patients. While both models are
applicable to bedside use, neither has been applied prospectively or in independent patient
samples, nor do they address HF treatments as predictive variables. More recently, Levy et al
(2006) developed a 24-variable risk model using the PRAISE1 (n=1125) database and validated it
on preexisting ELITE2, ValHeFT, UW, RENAISSANCE, and IN-CHF (n=9942) databases. The
model purports to accurately estimate mean 1-, 2-, and 3-year survival and, importantly,
dynamically incorporates clinical and laboratory variables, HF medications, and device therapies.
It awaits independent, prospective evaluation in unselected HF patients. A web-based interactive
calculator can be accessed at http://www.seattleheartfailuremodel.org.
Bottom Line Meticulous application of medication and device therapies can and will continue to
change HF prognosis. HF follows an unpredictable disease trajectory, one which is highly
mutable by application of evidence-based therapies, yet still marked by a high incidence of
sudden death. The 1996 NHPCO criteria are not accurate predictors of 6-month mortality.
Several models have recently been developed to aid in determining short- and long-term mortality
in HF patients. These models await independent, prospective validation in unselected
ambulatory HF patients and will need periodic updating to control for continually evolving
standards of HF care. At present, accurate prognostication remains problematic.
References
1. Anand I, McMurray JJV, Whitmore J. Anemia and its relationship to clinical outcome in
heart failure. Circulation. 2004; 110:149-154.
2. Anker SD, Ponikowski P, Varney S, et al. Wasting as an independent risk factor for
mortality in chronic heart failure. Lancet. 1997; 349:1050-1053.
3. Curtis JP, Sokol SI, Wang Y, et al. The association of left ventricular ejection fraction,
mortality, and cause of death in stable outpatients with heart failure. J Am Coll Cardiol.
2003; 42(4):736-742.
4. Fonarow GC, Adams KF, Abraham WT, et al. Risk stratification for in-hospital mortality in
acutely decompensated heart failure. JAMA. 2005;2 93(5):572-580.
5. Horwich TB, Fonarow GC, Hamilton MA, et al. Anemia is associated with worse
symptoms, greater impairment in functional capacity and a significant increase in
mortality in patients with advanced heart failure. J Am Coll Cardiol. 2002; 39(11):
1780-1786.
6. Kearney MT, Fox KAA, Lee AJ. Predicting death due to progressive heart failure in
patients with mild-to-moderate chronic heart failure. J Am Coll Cardiol. 2002; 40(10):
1801-1808.
7. Lee DS, Austin PC, Rouleau JL, et al. Predicting mortality among patients hospitalized for
heart failure. JAMA. 2003; 290(19):2581-2587.
8. Levenson JW, McCarthy EP, Lynn J, et al. The last six months of life for patients with
congestive heart failure. J Am Geriatr Soc. 2000; 48(Suppl 5):S101-S109.
9. Levy D, Kenchaiah S, Larson MG, et al. Long-term trends in the incidence of and survival
with heart failure. NEJM. 2002; 347(18):1397-1402.
10. Levy WC, Mozaffarian D, Linker DT, et al. The Seattle Heart Failure Model. Prediction of
Survival in Heart Failure. Circulation. 2006; 113:1424-1433.
11. Muntwyler J, Abetel G, Gruner C, et al. One-year mortality among unselected outpatients
with heart failure. Eur Heart J. 2002; 23:1861-1866.
diseases. 2nd Edition. Alexandria, VA: National Hospice Organization; 1996.
13. Zannad F, Briancon S, Julliere Y. Incidence, clinical and etiologic features, and outcomes
of advanced chronic heart failure: the EPICAL study. J Am Coll Cardiol. 1999; 33(3):
734-742.
14. Desai AS, Stevenson LW. There must be a better way: piloting alternate routes around
heart failure hospitalizations. J of Am Coll of Card. 2013; 61(2):127-30.
!9
in October 2005. It was updated in December 2006 to reflect the newly published ‘Seattle Heart
Failure Model.’ Version copy-edited in April 2009; then revised again July 2015 by Sean Marks
MD – reference #14 added and incorporated into text; orthopnea and intolerance to
neurohormonal therapy added to predictors of shorter survival.
!10
!

MECHANICAL CIRCULATORY SUPPORT IN ADVANCED HEART FAILURE
Keith M Swetz MD, MA, Daniel D Matlock MD, MPH, Heather Ferris MD, and Susan Hunt MD
Editor’s Note: Due to rapid changes with these technologies, this Fast Fact is meant to fully
replace the first edition of #205 (‘Destination Ventricular Assist Devices for Heart Failure’ by
Heather Ferris MD and Susan Hunt MD, published August 2008).
Introduction About 250,000 Americans have end-stage heart failure, meaning they cannot
carry out any physical activities without discomfort (dyspnea or angina) and are potentially eligible
for advanced therapy such as transplantation. Less than 1% of patients, however, will receive a
heart transplant. The left ventricular assist device (LVAD) was initially designed as an implanted
mechanical circulatory support (MCS) to extend the life of patients awaiting heart transplants
(“bridge-to-transplantation” (BTT)). In 2002, the FDA approved the LVAD not only as BTT, but also
as “destination therapy” (DT) where the patient would keep the device for life, with no expectation
of heart transplantation.
The Technology Rapid growth in the types and numbers of MCS has occurred, including the
development of the total artificial heart (see Fast Fact # 296) and biventricular support. Basically,
an LVAD involves surgical implantation of a pump to support cardiac output. Most often, this
includes a conduit implanted in the left ventricle, and another into the aorta. Blood is pulled from
the left ventricle, and mechanically moved into the aorta, increasing cardiac output and reducing
heart failure symptoms. First generation LVADs did this with a pumping motion (pulsatile flow),
but second generation LVADs move the blood continuously (continuous or axial flow). A third
conduit (the driveline) passes from the pump through the abdominal wall, and attaches to the
device’s battery and control system. This is of particular importance as serious life-threatening
infections can result via the driveline.
Right and biventricular assist devices also exist, but are not currently approved for DT. DT
patients can go home with their assist devices using a wearable battery system. Previously, to
qualify for destination LVAD therapy, a patient needed to have severe, refractory Class IV heart
failure including severe systolic dysfunction (ejection fraction <25%), inotrope dependence or
very low peak oxygen consumption (<12 ml/kg/min), and sufficient body surface area to
accommodate the LVAD. Now, patients with other situations are being considered (e.g., heart
failure with preserved ejection fraction, congenital heart disease). Also, some advocate for
expanding into patients who are less sick (Class IIIB) arguing that waiting to their heart failure is
severe and refractory is too late, and raises their operative risk to unacceptably high levels. This
hypothesis is currently being investigated.
Outcomes and Considerations

• In randomized studies, LVADs have shown significant mortality benefits, with a 2-year
survival of 58% for the newer continuous-flow devices compared to 24% with pulsatile flow
LVADs and 8% with optimal medical therapy alone (1,2). Observational studies
demonstrate 2-year survivals of 72%, but these databases are heterogeneous and patients
may be healthier than the patients enrolled in the original randomized trials (3).
• Poorer survival is predicted by poor nutritional status (hypoalbuminemia), coagulopathy,
baseline renal dysfunction, right heart dysfunction, and care at a less experienced MCS
center (3,4).
• Of those patients who are alive at 2 years, 79% will improve their NYHA functional class
from class IV to class I, and health-related quality of life will improve by 178% (5).
Readmission rates have reduced significantly as well (6).
!11
• While markedly improved, continuous-flow LVADs have many potential complications
including stroke (lifetime risk of 18%), infection (49%), sepsis (36%), bleeding requiring
transfusion (81%), bleeding requiring surgery (30%), malfunctioning or thrombosed pump
requiring pump replacement (10%), and readmission (94%) (2). Perioperative mortality has
improved dramatically (often less than 10%) with improved patient selection and
technology; however, palliative medicine providers and ICU staff often see MCS patients at
their worst when critically ill or with a protracted, complicated recovery. This can be a
source of moral distress, nevertheless many patients go on to perform all activities of daily
living and have improved quality of life.
• MCS require a high degree of ongoing device care including daily self-care (e.g. controller
self-tests, changing and maintaining power sources, and driveline exit site dressing
changes), safety precautions (e.g. no emersion in water, showering with a shower kit,
precautions while driving and traveling, need for a trained caregiver), and the ability to
troubleshoot emergent MCS-related malfunction. Due to this, social stability and patient/
family responsibility are key selection criteria when considering MCS implantation.
Discontinuing MCS and Advanced Care Planning MCS may be implanted as BTT, but later
become DT if patients are no longer transplant candidates. In the rare instance of myocardial
recovery, some devices can be explanted. More often, MCS is removed at cardiac transplantation
or, in the case of DT, when severe complications arise (such as pump thrombosis, mechanical
pump failure etc).
MCS is a surgical therapy which can prolong life and improve function in appropriately selected
patients, but can associated with significant morbidity, treatment burden, and mortality.
Discussions with patients and surrogates to clarify prognosis, goals, and endpoints for MCS
therapy should take place before implantation. These discussions should address the quality of
life below which a patient would no longer want to continue MCS, and would want to initiate
comfort focused only. Having open and honest discussion regarding goals of care prior to MCS is
encouraged, and a suggested process for these discussions will be in a future Fast Fact.
Practical aspects of discontinuing an LVAD in a dying patient are discussed in Fast Fact #269.
References
1. Rose EA, et al. Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive
Heart Failure (REMATCH) Study Group: long-term use of a left ventricular assist device for end-
stage heart failure. N Engl J Med. 2001; 345:1435-1443.
2. Slaughter MS, et al. Advanced heart failure treated with continuous-flow left ventricular assist
device. N Engl J Med. 2009; 361:2241-2251.
3. Kirklin JK, et al. Fifth INTERMACS annual report: risk factor analysis from more than 6,000
mechanical circulatory support patients. J Heart Lung Transplant. 2013; 32:141-56.
4. Cowger J, et al. Predicting survival in patients receiving continuous flow left ventricular assist
devices: The HeartMate II Risk Score. J Am Coll Cardiol. 2013; 61: 313-21. Rogers JG, et al.
Continuous flow left ventricular assist device improves functional capacity and quality of life of
advanced heart failure patients. J Am Coll Cardiol. 2010; 55:1826-1834.
5. Rogers JG, et al. Continuous flow left ventricular assist device improves functional capacity and
quality of life of advanced heart failure patients. J Am Coll Cardiol. 2010; 55:1826-1834.
6. Hasin T, et al. Readmissions after implantation of axial flow left ventricular assist device. J Am Coll
Cardiol. 2013; 61:153-63.
Author Affiliations: Mayo Clinic, Rochester, MN (KMS); University of Colorado-Denver, Aurora, CO (DDM),
University of Pittsburgh Medical Center, Pittsburgh, PA (HF); Health East Care System, St Paul, MN (SH).
!12
Version History: Originally written by Heather Ferris MD and Susan Hunt MD, and published August 2008.
Re-copy-edited in June 2009. Heavily rewritten to reflect new data, and republished in May 2013 as the 2nd
Edition; copy-edited again in July 2015.
used.
!13
!

Vincent Thai MD
Introduction Malignant pericardial effusions (MPEs) are a rare complication of advanced
cancer, but are associated with high morbidity and mortality. This Fast Fact discusses the
diagnosis and management of MPEs.
metastases, with ~75% of these affecting the epicardium (1, 2). Only a third of these, however,
will develop clinically significant MPEs (1). Lung and breast cancers are the most common
causes. MPEs are associated with a poor prognosis. Studies suggest a median survival of 2-3
months after a MPE is diagnosed, with a mean survival of 5 months for solid tumors and 20
months for hematologic malignancies (3, 4).
Physiology and Symptoms The pericardial space is normally filled with <50 ml of serous fluid.
As this volume increases due to epicardial or pericardial metastases or lymphatic obstruction,
both right and left ventricular failure can occur due to inadequate filling. Signs and symptoms
include peripheral and pulmonary edema, chest discomfort, cough, shortness of breath, and
orthopnea. Severity of symptoms depends on the volume of the MPE as well as the rapidity of its
accumulation; severe cases can present with cardiac tamponade and shock. An echocardiogram
is indicated whenever a MPE is suspected. Not only does it confirm the presence of an effusion,
but its findings can dictate whether or not urgent treatment is indicated (e.g. if signs of tamponade
are evident). A diagnostic pericardiocentesis or pericardial biopsy is sometimes needed to
confirm the cause of the effusion.
Treatment Options
• Systemic chemotherapy or radiotherapy are effective for chemo- or radio-sensitive tumors
such as previously untreated breast cancer and many lymphomas. Reaccumulation rates for
both modalities are about 1/3 overall, depending on the patient’s overall course and response
to therapy (5).
• Pericardiocentesis results in immediate symptom relief in most patients, however the effusion
may re-accumulate, requiring repeat pericardiocentesis (within 1-2 weeks in some series) (6).
• Pericardial sclerosis involves instilling a sclerosing agent with the intention of scarring the
pericardium to the epicardium, preventing reaccumulation of the MPE (similar to pleural
effusions – see Fast Fact #157). Multiple agents have been studied including doxyclycline,
minocycline, and bleomycin. Success rates (no reaccumulation at 30 days) are about
70-90% (7, 8). Longer term success rates are undefined due to the poor survival of study
patients. The major side effect is chest pain (50-70%), cardiac arrhythmias, and fever (8, 9,
10). In head to head comparisons with doxycycline, bleomycin has been shown to have
fewer side effects and to lead to shorter hospitalizations (10, 11, 12).
• Surgical decompression therapies range from less invasive (balloon pericardiotomy,
subxiphoid or thorascopic pericardiostomy) to more extensive (open thoracotomy with
pericardial stripping). A pericardial ‘window’ (which allows ongoing drainage of fluid externally
or internally such as into the pleural cavity) is often created. Case series have suggested
reaccumulation rates with surgical therapies are low (less than 15% up to 10 months out) (13,
14, 15).
Decision-Making The treatment of MPEs depends on how urgently treatment is needed, the
likelihood of the tumor responding to anti-neoplastic treatments, and the anticipated survival of
the patient. A multidisciplinary approach to decision-making, involving input from medical and
radiation oncology, cardiology, and thoracic surgery is recommended. Simple pericardiocentesis
may be appropriate for patients with short prognoses (<1 month), particularly if their MPE is not
expected to re-accumulate in their remaining life-span. A symptomatic patient with no signs of
tamponade and a chemotherapy-sensitive tumor such as untreated breast cancer may receive a
!14
durable response from a pericardiocentesis for symptom relief, followed by chemotherapy.
Patients with longer prognoses (>1 month) who are expected to re-accumulate their MPEs will
likely benefit most from sclerosis or surgical decompression; there is no clear evidence currently
suggesting one strategy is superior to the other. Symptom directed care without specific
intervention for the MPE is an appropriate option for patients with very short prognoses and for
those who decline more invasive treatments.
References
2. Abraham KP, Reddy V, Gattuso P. Neoplasms metastatic to the heart: review of 3314 consecutive
autopsies. Am.J.Cardiovasc.Pathol. 1990; 3:195-198.
3. Moores, D.W, Allen K.B, Faber L.P, Dziuban S.W, Gillman D.J, Warren W.H., Ilves R, Lininger L,
Subxiphoid pericardial drainage for pericardial tamponade, J Thoracic Cardiovascular Surg. 1995;
109:546-552.
4. Dosios T, Theaskos,N, Angouras D, et al. Risk factors affecting the survival of patients with
pericardial effusion submitted to subxiphoid pericardiostomy. Chest. 2003; 124:242
5. Lamont E, Hoffman PC. Oncologic emergencies. In: Hall JB, et al, eds. Principles of Critical Care.
3rd Edition. New York, NY: McGraw Hill; 2005.
6. Laham RJ, Cohen DJ, Kuntz RE et al. Pericardial effusion in patients with cancer: outcome with
contemporary management strategies. HEART. 1996; 75(1):67-71.
7. Lashevsky I, Ben Yosef R, Rinkevich D, Reisner S, Markiewicz W. Intrapericardial minocycline
sclerosis for malignant pericardial effusion. Chest. 1996; 109(6):1452-54.
8. Maher EA, Shepherd FA, Todd TJR. Pericardial sclerosis as the primary management of malignant
pericardial effusion and cardiac tamponade. J Thoracic Cardiovascular Surg. 1996; 112(3):637-643.
9. Ben Yosef,R, Phefer,R, Ge,A, Catane,R. Management of malignant pericardial effusion
Harefuah, 1988; 115:138-141.
10. Liu G, Crump M, Goss PE, Dancey J, Shepherd FA. Prospective comparison of the sclerosing
agents doxycycline and bleomycin for the primary management of malignant pericardial effusion
and cardiac tamponade. J Clin.Oncol. 1996; 14(12):3141-47.
11. Yano T, Yokoyama H, Inoue T, et al. A simple technique to manage malignant pericardial effusion
with a local instillation of bleomycin in non-small cell carcinoma of the lung. Oncology. 1994;
51:507-509.
12. van Belle SJ, Volckaert A, Taeymans Y, Spapen H, Block P. Treatment of malignant pericardial
tamponade with sclerosis induced by instillation of bleomycin. Int.J.Cardiol. 1987; 16(2):155-160.
13. Galli M, Politi A, Pedretti F, Castiglioni B, Zerboni S. Percutaneous balloon pericardiotomy for
malignant pericardial tamponade. Chest. 1995; 108(6):1499-1501.
14. Palacios IF, Tuzcu EM, Ziskind AA, Younger J, Block PC. Percutaneous balloon pericardial window
for patients with malignant pericardial effusion and tamponade. Cathet.Cardiovasc.Diagn. 1999;
22(4):244-49.
15. Ziskind AA, Pearce AC, Lemmon CC, et al. Percutaneous balloon pericardiotomy for the treatment
of cardiac tamponade and large pericardial effusions: description of technique and report of the first
50 cases. J.Am.Coll.Cardiol. 1993; 21(1):1-5.
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used.
!16
!

USE OF HOME INOTROPES IN PATIENTS NEAR THE END OF LIFE
Mallory Strickland Ciuksza MD, Randy Hebert MD, and George Sokos DO
Background Some patients with end-stage heart failure causing symptoms at rest are placed
on continuous infusions of cardiac inotropes in an attempt to improve symptoms and avoid
hospitalizations. Among end-stage heart failure patients who are ineligible for advanced cardiac
therapies (such as heart transplant of a ventricular assist device), mean life expectancy with
inotrope-dependent medical therapy is estimated at 9.4 months, with 26% surviving to 1 year.
Hence, the home use of continuous inotrope therapy may be commonly encountered by clinicians
who care for the seriously ill.
Pharmacology Both major classes of inotropic agents, adrenergic agonists (i.e. dopamine and
dobutamine) and phosphodiesterase inhibitors (i.e. milrinone), increase contractility by increasing
available calcium levels within myocardial tissue via cAMP regulation (2).
Patient Selection Patients on maximal medical therapy who continue to have refractory
symptoms at rest (New York Heart Association Class IV) may benefit from home IV inotrope
therapy. Eligible patients must have either failed a trial of weaning inotropic support in the
inpatient setting or been too ill to attempt weaning (3,4). Patients should not receive home
inotropic therapy if they are not maximized on their oral medications, unable or unwilling to utilize
an infusion pump and central line, unwilling to undergo appropriate monitoring, or have refractory
ventricular tachycardia or life threatening arrhythmias (5).
Outcomes and Risks Available data assess the number of hospitalizations, symptom control,
mortality, and quality of life (6-13). Unfortunately, the strength of the data is relatively weak and
the outcomes are mixed as very few studies utilize the same methods or measure the same
outcomes. The prevailing literature suggests trends of hastened death with dobutamine and
milrinone administration largely due to arrhythmias (10,11, 14-18). However, the majority of this
data is based on data from small trials on oral and intermittent IV inotropes (not continuous
therapy), and, importantly, are from an era in which prophylactic ICD implantation was not the
standard of care. The most recent guidelines advocate against the use of intermittent therapy
altogether. Despite these risks, if the patient’s goal is to be at home, there is evidence that
continuous outpatient inotrope infusion may shift the remaining survival time to a home setting
through marked improvements in symptom control and therefore may be an excellent treatment
for the well selected patient (9).
Practical Concerns Inotropes are started during an inpatient hospitalization. This typically
occurs in the setting of the intensive care unit where doses can be titrated to allow for a weaning
trial if the patient is clinically stable enough to do so. Patients will require a PICC line or Hickman
catheter for infusion with regular, high quality line care to prevent infections. Patients on home
inotropes require ongoing care by an adequately trained home care team and an experienced
physician (typically a cardiologist) so that their medications can be adjusted as needed. The most
common side effects are hypotension and arrhythmias. For this reason electrolytes should be
regularly followed, as well as renal function through regular serum creatinine monitoring in order
to anticipate dosing changes that may be necessary if changes in creatinine clearance should
occur.
Medicare Coverage Requirements: Medicare has strict coverage guidelines for home inotropes,
which greatly affect how they are used in the US. Below are the criteria that need to be met in
order for inotrope therapy to be covered (5).
● Symptoms must be uncontrolled; specifically, dyspnea at rest must be present despite
maximum tolerated doses of digoxin, loop diuretics, ACEIs, or other vasodilators.
● Hemodynamic studies must be performed within six months prior to initiation of home
!17
inotropic therapy that show both:
o Cardiac index of 2.2 L/min/m2 (maximum) and/or pulmonary capillary wedge pressure of 20
mmHg before infusions while on maximum tolerated oral medications.
o A 20% increase in cardiac index, and/or at least a 20% decrease in pulmonary capillary
wedge pressure during inotrope infusion.
● Improvement in patient “well-being” (i.e., decreased dyspnea, increased diuresis,
improved renal function, or reduction in weight) must be shown with the absence of dyspnea
at rest at the time of discharge and with outpatient follow up.
● There must be documented deterioration with attempts to discontinue/wean the patient
from inotropes while in the hospital.
● Any life-threatening arrhythmia must be controlled and addressed prior to discharge. Some
evidence suggests that oral amiodarone may benefit these patients who experience ectopy
but are still benefiting from inotrope therapy (17,19).
● Covered inotrope dosing must be within the following ranges:
o Dobutamine 2.5-10 mcg/kg/min.
o Milrinone 0.375-0.75 mcg/kg/min.
o Dopamine may also be used at a rate of 2 mcg/kg/min.
● Efforts to maintain the patient on the lowest practical dose must be made and documented
during the first three months of therapy.
Cost Cost of these therapies varies significantly depending on choice of drug and insurance
type. Milrinone cost per month ranges between $4500-$21,000 and dobutamine between $1140-
$2790 (estimates are based on a 75 kg patient with infusions of 0.5 mcg/kg/min and 5mcg/kg/min
for milrinone and dobutamine respectively) (20). Medicare will reimburse for these therapies and
for associated equipment such as infusion pumps, however nursing visits are not included in
these estimates.
Home Care and Hospice Many hospices will not accept inotrope-dependent patients given the
cost and need for advanced training (12). Some communities have specialized home-care
agencies or programs for patients on home inotropes, which may or may not be part of a hospice
program.
References
1. Long EF, Swain GW, & Mangi AA. Comparative survival and cost-effectiveness of
advanced therapies for end-stage heart failure. Circulation: Heart Failure. 2014;
7:470-478
2. Felker GM, O’Connor CM. Inotropic therapy for heart failure: an evidence-based
approach. Am. Heart J. 2001; 142(3):393–401.
3. Lewis EF. End of life care in advanced heart failure. Curr Treat Options Cardiovasc Med.
2011; 13(1):79–89.
4. Young JB, Moen EK. Outpatient parenteral inotropic therapy for advanced heart failure. J
Heart Lung Transplant. 2000; 19(8 Suppl):S49–57.
5. Gorski LA. Positive inotropic drug infusions for patients with heart failure: current
controversies and best practice. Hom Healthc Nurs. 2002; 20:244-53.
6. Oliva F, Latini R, Politi A, et al. Intermittent 6-month low-dose dobutamine infusion in
severe heart failure: DICE multicenter trial. Am. Heart J. 1999; 138(2 Pt 1):247–53.
7. Marius-Nunez AL, Heaney L, Fernandez RN, et al. Intermittent inotropic therapy in an
outpatient setting: A cost-effective therapeutic modality in patients with refractory heart
failure. American Heart Journal [Internet]. 1996; 132(4):805–8.
8. López-Candales A, Vora T, Gibbons W, Carron C, Simmons P, Schwartz J. Symptomatic
improvement in patients treated with intermittent infusion of inotropes: a double-blind
placebo controled pilot study. J Med. 2002; 33(1-4):129–46.
9. López-Candales AL, Carron C, Schwartz J. Need for hospice and palliative care services
in patients with end-stage heart failure treated with intermittent infusion of inotropes. Clin
Cardiol. 2004; 27(1):23–8.
10. Krell MJ, Kline EM, Bates ER, et al. Intermittent, ambulatory dobutamine infusions in
patients with severe congestive heart failure. Am Heart J. 1986;112(4):787–91.
11. Cesario D, Clark J, Maisel A. Beneficial effects of intermittent home administration of the
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inotrope/vasodilator milrinone in patients with end-stage congestive heart failure: a
preliminary study. Am Heart J. 1998;135(1):121–9.
12. Hershberger RE, Nauman D, Walker TL, Dutton D, Burgess D. Care processes and
clinical outcomes of continuous outpatient support with inotropes (COSI) in patients with
refractory endstage heart failure. J Card Fail. 2003; 9(3):180–7.
13. Gheorghiade M, Gattis WA, Klein L. OPTIME in CHF trial: rethinking the use of inotropes
in the management of worsening chronic heart failure resulting in hospitalization. Eur J
Heart Fail. 2003 Jan;5(1):9–12.
14. Elis A, Bental T, Kimchi O, Ravid M, Lishner M. Intermittent dobutamine treatment in
patients with chronic refractory congestive heart failure: a randomized, double-blind,
placebo-controlled study. Clin Pharmacol Ther. 1998; 63(6):682–5.
15. Amsallem E, Kasparian C, Haddour G, Boissel JP, Nony P. Phosphodiesterase III
inhibitors for heart failure. Cochrane Database of Systematic Reviews. 2005, Issue 1. Art.
No.: CD002230. DOI: 10.1002/14651858.CD002230.pub2.
16. Thackray S, Easthaugh J, Freemantle N, Cleland JGF. The effectiveness and relative
effectiveness of intravenous inotropic drugs acting through the adrenergic pathway in
patients with heart failure—a meta-regression analysis. Eur J Heart Fail. 2002; 4(4):515–
29.
17. Toma M, Starling RC. Inotropic therapy for end-stage heart failure patients. Curr Treat
Options Cardiovasc Med. 2010; 12(5):409–19.
18. Ewy GA. Inotropic infusions for chronic congestive heart failure: medical miracles or
misguided medicinals? J Am Coll Cardiol. 1999; 33(2):572–5.
19. Nanas JN, Kontoyannis DA, Alexopoulos GP, et al. Long-term intermittent dobutamine
infusion combined with oral amiodarone improves the survival of patients with severe
congestive heart failure. Chest. 2001; 119(4):1173–8.
20. Vantage Home Infusion Therapy Services. prepared by Dr. Robert Buzas. http://
www.vhcn.com/vantage-home-infusion-services/
Authors’ Affiliations: Allegheny Health Network, Pittsburgh, PA
Conflicts of Interest Statement: The authors have disclosed no relevant conflicts of interest.
Version History: First published August 2014. References updated and copy-edited in
September 2015 by Sean Marks MD.
support of a volunteer peer-review editorial board, and are made available online by the
Palliative Care Network of Wisconsin (PCNOW); the authors of each individual Fast Fact are
Palliative Care Network of Wisconsin with contact information, and how to reference Fast
Facts.
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!

TOTAL ARTIFICIAL HEART
Sara E. Wordingham MD, Rachel M. Kasten, MSN, APRN, CNP, and Keith M. Swetz MD, MA
Background With a limited supply of donor organs, mechanical circulatory support (MCS) has
played a key role in advanced heart failure (1). While left ventricular assist devices (LVADs) can
be used as a bridge to transplantation, recovery, or as destination therapy (refer to Fast Fact
#205), a total artificial heart (TAH) is only approved as a bridge to transplantation. Approximately
100 TAHs are implanted annually in the U.S (2,3). This Fast Fact explores practical and ethical
considerations with TAH therapy.
The Technology The TAH is a pulsatile pneumatic pump that orthotopically replaces both
native cardiac ventricles and all heart valves and is attached to the remnant native atria. It can
deliver a cardiac output of 9.5 L/min and is used in patients when LVAD is contraindicated --
biventricular failure or refractory arrhythmias. While a 400-lb machine was previously required to
operate a TAH, smaller “suitcase-sized” drivers are available in the hospital setting. In the U.S.,
patients with a TAH require hospital care unless part of a clinical trial. A portable “backpack-
sized” driver which can support patients outside of the hospital is under investigation in the U.S
(approved for use in Europe).
Outcomes Almost 80% of patients with a TAH go on to receive cardiac transplantion (4). For
the remaining 20% who become transplant-ineligible or die awaiting a suitable organ, data are
limited regarding best practices for the disease-directed and supportive care for when the TAH
has become de facto destination therapy. Classic symptoms of heart failure -- dyspnea, anxiety,
pain, and debility -- can remain problematic for patients with a TAH; a sense of confinement in the
hospital setting, sleep disturbance and anxiety from the sound of the pneumatic pump can
negatively impact quality of life. The longest reported time a patient has been supported with a
TAH prior to receiving a transplant is 3.5 years (2). Bleeding in the immediate postoperative
period and infection are the most common complications. When infections occur, they are unlikely
to cause death or delay transplantation. TAHs have a low risk of device malfunction or
thromboembolic events (5). In a small cohort, mortality with TAH in situ was usually from
multiorgan failure followed by procedural or technical complications (6).
Ethical/Legal Issues It is ethically permissible to discontinue life-sustaining treatments as

patients maintain a right to refuse intervention. Legal rulings have asserted no difference between
withholding or withdrawing such therapies (See Fast Fact #56,#111,#112,#159). Some raise
concern as to whether the considerations are different with TAH compared with an LVAD since
the native heart’s valves and ventricles are surgically removed (7). Regardless, many ethicists,
cardiologists, and palliative care clinicians support TAH deactivation if it no longer meets a
patient’s goals of care or if the burdens of the TAH outweighs its benefits (8). Considering that
20% who receive a TAH do not go on to transplantation, informing patients prior to TAH
implantation that an iatrogenic condition is being created that can alter their end-of-life experience
is prudent (8).
Palliative Care Specialist Services Supportive care and symptom management of patients can
be provided in parallel, similar to LVADs (See Fast Fact #269). Palliative care teams are often
instrumental in assuring symptom management, and providing psychosocial support to patients
and families when transplantation is no longer an option. Common palliative medications which
can prolong the QT interval (i.e. haloperidol or ondansetron) are acceptable as the ventricles are
surgically absent and hence ventricular arrhythmias are not an issue.
Discontinuing TAHs Most TAH deactivations take place in the hospital setting, although
deactivation elsewhere has been reported. Following informed consent from the patient or
surrogate and discussion with key stakeholders—including cardiothoracic surgery, cardiology,
MCS coordinators, and social work—deactivation can be planned. Unlike discontinuation of other
!20
cardiac therapies where survival can be variable, death after TAH deactivation occurs within
minutes due to absence of cardiac output and is confirmed by apnea. Care should be taken to
ensure that effective symptom management and that loved ones are fully supported during this
time; see related Fast Facts that explore discontinuation of other life-sustaining therapies (See
Fast Fact #33,#34,#35,#269). Patients may also progress to clinical death (i.e. respiratory arrest
or brain death) with the TAH functioning, necessitating post-mortem pump deactivation.
Providers can be trained by perfusionists to deactivate the TAH in a manner with minimal alarms.
TAHs, like LVADs, do not require explantation prior to cremation whereas pacemakers and
defibrillators do as they have an internal battery (See Fast Fact #111,#112,#269).
References:
1. Miller LW, Guglin M. Patient selection for ventricular assist devices: a moving target. J Am
Coll Cardiol. 2013;61(12):1209-1221.
2. http://www.syncardia.com/medical-professionals, Accessed 4/24/15
3. Kirklin JK et al. Sixth INTERMACS annual report: A 10,000-patient database. J Heart

Lung Transplant. 2014; 33:555-64.
4. Copeland JG et al. Cardiac Replacement with a Total Artificial Heart as a Bridge to

Transplantation. N Engl J Med 2004; 351:859-67.
5. Copeland JG et al. Total artificial heart bridge to transplantation: a 9-year experience with
62 patients. J Heart Lung Transplant. 2004; 23:823-31.
6. Leprince P et al. Bridge to transplantation with the Jarvik-7 (CardioWest) total artificial
heart: a single center 15-year experience. J Heart Lung Transplant. 2003; 22:1296-1303.
7. Rady MY, Verheijde JL. Ethical challenges with deactivation of durable mechanical
circulatory support at the end of life: left ventricular assist devices and total artificial
hearts [published online ahead of print March 6, 2012]. J Intensive Care Med. doi:
10.1177/0885066611432415.
8. Bruce CR et al. Challenges in Deactivating a Total Artificial Heart for a Patient with
Capacity. Chest. 2014;145(3):625-631.
9. Mueller PS et al. Ethical analysis of withdrawing ventricular assist device support. Mayo
Clin Proc. 2010;85(9):791-797.
Author Affiliations: Mayo Clinic Arizona; Mayo Clinic Rochester

Version History: This Fast Fact was originally edited by Sean Marks MD. First electronically
published May 2015
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used.

EXTRACORPOREAL MEMBRANE OXYGENATION IN ADULTS
Edward Feinstein MD, Jeffrey Rubins MD, Drew A Rosielle MD
Introduction Use of extracorporeal membrane oxygenation (ECMO) (sometimes called

extracorporeal life-support) is increasing in many countries. This Fast Fact will review the role of
palliative care teams in caring for adults on ECMO, and their families.
The Technology The technology is fundamentally the same as a ‘heart-lung bypass machine’
used in some cardiac surgeries, although ECMO can be used for weeks instead of hours. Central
venous blood is removed from the patient and pumped through a gas exchange membrane
where it is oxygenated and carbon dioxide is removed. In venovenous (VV) ECMO the blood is
then reinfused into the right-sided circulation where the patient’s own heart circulates it. In
venoarterial (VA) ECMO, the oxygenated blood is reinfused under arterial pressure into the aorta
for circulation. Therefore, VV ECMO ‘replaces’ lung function (gas exchange); VA ECMO ‘replaces’
both heart (pump) and lung function. Initiating and providing ECMO requires specialized teams
and currently is only offered at specific referral centers.
VV ECMO: VV ECMO is used for severe hypoxemic respiratory failure; typically the acute
respiratory distress syndrome – ARDS.
• The best available data comes from the CESAR Trial (2009) – a randomized study showing
improved disability-free survival at 6 months with ECMO (63%) vs. usual ICU care (47%) (1).
There are also observational data suggesting improved survival from ARDS during influenza
pandemics (2).
• In the Extracorporeal Life Support Organization’s (ELSO) international ECMO database, 57%
of patients receiving VV ECMO survive to hospital discharge (disability rates unknown) (3).
• VV ECMO has seen a 10-fold increase between 2005 and 2015 from ~150 cases to ~1900
cases (4).
VA ECMO: VA ECMO is used for severe cardiogenic shock such as after a massive pulmonary
embolus, ST- elevation myocardial infarction, or cardiac surgery.
• Data supporting VA ECMO are less clear than VV ECMO on whether it improves outcomes
compared with other advanced technologies for cardiogenic shock (e.g. ventricular-assist
devices, intra-aortic balloon pumps, etc.) (5).
• The ELSO database reports hospital survival for VA ECMO is ~40% (disability rates
unknown) (3).
• VA ECMO is also used for sudden cardiac death patients who do not have return of
spontaneous circulation after CPR. This use is called “E-CPR”. Patients are rapidly
transported to an ECMO center where ECMO is initiated in an attempt to perfuse the brain
and other organs while the cause of the arrest is treated. The efficacy of E-CPR has not been
evaluated yet in high quality trials.
Patient Experience & Complications ECMO requires large caliber vascular catheters, placed
in the groin or neck. Initially patients are intubated, sedated, and paralyzed. Patients who are on
ECMO for many days sometimes can be awoken, and even have limited mobility such sitting up
in a chair or engaging in physical therapy (6,7). Continuous anticoagulation is required during
ECMO to prevent thrombus formation in the circuit. Bleeding (including intracranial,
gastrointestinal, and pulmonary) is the most serious complication (30-50%) and can be life-
threatening (4,8). Other complications include thromboembolism, infections, acute kidney injury,
and limb ischemia.
!22
Patient Trajectories Apart from the survival statistics above, little has been written about what
happens to patients receiving ECMO. Our experience is that most patients fall into 1 of 6
categories.
1. The underlying illness recovers sufficiently for ECMO to be discontinued. These patients can
have a full recovery or remain chronically critically ill, albeit off ECMO.
2. No recovery occurs, but an alternative intervention is available such as heart or lung
transplantation or ventricular assist device, allowing ECMO to be discontinued.
3. The patient dies while receiving ECMO, for instance from massive intracranial bleeding.
4. ECMO is discontinued with the intent of allowing the patient to die, due to the identification of
a poor functional or survival prognosis (e.g. anoxic brain injury).
5. The ECMO circuit fails (for instance, it clots off). This can lead to urgent intervention to
replace the catheters and ECMO devices versus a decision to allow the patient to die. For
patients with a poor underlying chance of recovery, ECMO circuit failure should trigger frank
conversations about prognosis and goals, and if it is in the patient’s best interest to replace
the failing ECMO system.
6. A patient becomes “stuck” on ECMO, without recovery of the underlying illness or available
alternative intervention, and little chance of ever surviving without ECMO. This can cause
ethical and resource utilization dilemmas if the patient/family do not agree to discontinue
ECMO. There is no arbitrary time-limit to ECMO use, however its use in one patient may
prevent it being used in another due to the limitation on the number of ECMO machines and
personnel (9).
Palliative and End-of-Life Care Fundamentally, palliative care teams can support ECMO
patients/families as they would any other critically ill patient at high risk of dying: assess and
clarify patient/family understanding, provide emotional and spiritual care, support patient-centered
goals of care discussions, and help provide comfort care to dying patients. Educating families and
preparing them early on for the possibility that a patient will not recover and ECMO will need to be
discontinued is advisable. Clinicians should be prepared that most families will have no
knowledge of ECMO, unlike other ICU treatments such as mechanical ventilation. Different
institutions will have different protocols for discontinuing ECMO in a patient who is expected to
die. The approach to symptom management in patients expected to die after ECMO
discontinuation is similar to the removal of any other advanced life-support technology such as a
ventilator or LVAD. It is particularly important to ensure patients are comfortable and have
adequate circulating levels of symptom medications prior to discontinuing ECMO due to the
probability of rapid circulatory collapse (see Fast Facts #33, 34, 269).
References
1. Peek GJ, Mugford M, Tiruvoipati R, et al. CESAR Trial Collaboration. Efficacy and
economic assessment of conventional ventilatory support versus extracorporeal
membrane oxygenation for severe adult respiratory failure (CESAR): a multicenter
randomized controlled trial. Lancet. 2009;374(9698):1351-1363.
2. Noah MA, Peek GJ, Finney SJ, et al. Referral to an extracorporeal membrane
oxygenation center and mortality among patients with severe 2009 influenza A (H1N1).
[published online October 5, 2011]. JAMA. 2011;306(15):1659-1668.
3. Extracorporeal Life Support Organization. ECLS Registry Report 2016. https://
www.elso.org/Registry/Statistics/InternationalSummary.aspx. Accessed April 16, 2017.
4. Thiagarajan RR, Barbaro RP, Rycus PT, et al. Extracorporeal life support organization
registry international report 2016. ASAIO Journal. 2017;63:60-67.
5. Ouweneel DM, Schotborgh VJ, Limpens J, et al. Extracorporeal life support during
cardiac arrest and cardiogenic shock: a systematic review and meta-analysis. Intensive
Care Med. 2016;42:1922-1934.
6. Bharat A, Pham DT, Prasad SM. Ambulatory extracorporeal membrane oxygenation a
surgical innovation for adult respiratory distress syndrome [published online March 9,
2016]. JAMA Surgery. Doi:10.1001/jamasurg.2015.4951
7. Abrams D, Javidfar J, Farrand E et al. Early mobilization of patients receiving
extracorporeal membrane oxygenation: a retrospective cohort study. Critical Care
2014;18:R38
8. Mazzeffi M, Greenwood J, Tanaka K, et al. Bleeding, transfusion, and mortality on
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extracorporeal life support: ECLS working group on thrombosis and hemostasis. Ann
Thorac Surg. 2016;101:682-9.
9. Abrams DC, Prager K, Blinderman CD, Burkart KM, Brodie D. Ethical dilemmas
encountered with the use of extracorporeal membrane oxygenation in adults. Chest.
2014;145(4):876-882

Authors’ Affiliations: University of Minnesota Medical School, Minneapolis, MN (EF, JR, DAR);
Methodist Hospital, St Louis Park, MN (EF); Hennepin County Medical Center, Minneapolis, MN
(JR).
Version History: Originally edited by Dr. Christopher Lawton MD; first electronically published in
August 2017

SUBCUTANEOUS DIURETICS FOR END-OF-LIFE MANAGEMENT OF HEART FAILURE
!24
Ryan Jozwiak MD and Sean Marks MD
Background Diuretics are a mainstay of treating symptomatic volume overload in heart failure
(HF), including at the end-of-life. For some patients, bowel edema from HF-related congestion
can diminish the absorption and effectiveness of oral diuretics. Intravenous diuretics, however,
are difficult to administer in an outpatient or hospice setting, which likely contributes to the
frequent emergency department visits and hospitalizations in HF, even near the end-of-life (1). In
this context, subcutaneous (SC) furosemide can be helpful. This Fast Fact reviews its use.
Clinical Context Although thiazide diuretics (e.g. hydrochlorothiazide, chlorthalidone, or

metolazone) and potassium sparing diuretics (e.g. spironolactone) are established therapies for
chronic HF, loop diuretics such as furosemide or bumetanide are the mainstay for acute or severe
HF (2,3). Loop diuretics work via two mechanisms: an immediate veno-dilator effect as well as
diuresis of fluid and electrolytes (2). Some HF patients enrolled in hospice develop refractory
dyspnea, and swelling with resultant anxiety despite the use of opioids or benzodiazepines (4-6).
SC furosemide, which is more easily administered at home than IV, has been proposed to help
these patients.
Pharmacology Bumetanide has not been established as safe and/or effective subcutaneously,
thus furosemide is the preferred SC diuretic. Typically, the IV furosemide formulation is given via
a SC clysis line for continuous subcutaneous infusions (CSCI) or a SC butterfly needle for
intermittent dosing. Hence, SC and IV costs are essentially equivalent. For patients with an
indwelling IV catheter, there is little rationale to utilize SC over IV. Furosemide formulations come
in 20 to 50 mL syringes with concentrations of 10 mg/ml. Current daily dose limits are based on
available commercial syringes and are approximately 200-300 mg daily. This may change as the
market for SC medications change (7).
• Onset of diuresis is 1-1.5 hours for oral; 30 minutes for SC; 5 minutes for IV furosemide.
Therefore, if there is minimal urine output 1-2 hours after oral administration of furosemide, it
is reasonable to consider a dose of parenteral furosemide in the setting of symptomatic
dyspnea from HF (8).
• Diuretic effect is 6-8 hours for oral; 4 hours for SC; 2 hours for IV furosemide (9).
• For intermittent SC dosing, many experts recommend starting with an equivalent oral dose.
For CSCI dosing, calculate the initial hourly dose from the previous daily oral dose (10, 11).
E.g., someone receiving 100 mg/day of oral furosemide should receive 100 mg SC in 24
hours or 4 mg/hr CSCI.
Outcomes A human, pre-clinical, placebo-controlled trial demonstrated that furosemide has

diuretic activity when administered SC (9). The clinical evidence for SC furosemide otherwise is in
a handful of case reports and series. In a series of 43 consecutive end-stage HF patients
prescribed CSCI by palliative care or hospice clinicians, CSCI was associated with a median
weight loss of 5.6 kg and most patients avoided hospital admission and terminal breathlessness
(10). A case series of HF patients who received intermittent SC furosemide demonstrated a
prompt resolution of weight gain, breathlessness, and peripheral edema (4).
Side Effects & Safety Diuretics can cause intravascular volume depletion and kidney injury.
Furosemide promotes diuresis of sodium, potassium, magnesium, and chloride which can lead to
significant electrolyte abnormalities and subsequent risk for cardiac arrhythmia (7).
Furosemide infusions have been associated with ototoxicity when used at doses >1600 mg daily
or when used concurrently with a medication associated with ototoxicity (e.g. vancomycin) (7,12).
Self-resolving dermatologic site reactions involving stinging/burning at the site of injection may
occur in up to 23% receiving CSCI (9).
Controversies Clinicians should be cognizant of several unresolved clinical questions regarding

the appropriate use of SC furosemide (11).
• In general, the data supporting the efficacy of SC furosemide is less robust than other SC
palliative-based medications, e.g. SC use of opioids (11).
!25
• Clinical debate remains regarding the need for serum monitoring of renal function and
electrolyte abnormalities for dying HF patients receiving SC furosemide to prevent sentinel
iatrogenic events such as renal failure or cardiac arrhythmias. When prognosis is anticipated
to be less than a month and goals of care are comfort, the rationale for serum lab monitoring
may be less compelling.
• For patients who can still safely swallow oral medications, adjuvant oral diuretics such as
chlorthalidone and metolazone may augment the effectiveness of SC furosemide (5,13).
• While empiric oral potassium supplementation has been associated with prolonged survival in
those initiating furosemide use (14), there is no current literature supporting or arguing
against the use of oral potassium in standard end-of-life diuretic use and supplementation
may depend on goals of care.
• It remains unclear whether the optimal approach to utilizing SC is as a rescue therapy when
clear signs of acute HF are apparent – e.g. breathlessness, peripheral edema – versus a
preventative approach wherein intermittent SC furosemide doses are given in response to
weight gain.
Conclusion In the setting of end-of-life HF management, there appears to be a role for the use
of SC furosemide when oral treatment fails. While further research is needed, small clinical
investigations have demonstrated effective diuresis and prevention of hospital admissions and
hospice de-enrollment without significant adverse effects from SC furosemide.
References
1. Felker GM, O’Connor CM, Braunwald E. Loop diuretics in acute decompensated heart
failure: Necessary? Evil? A necessary evil? Circ Heart Fail. 2009; 2:56-62.
2. McMurray JJV, Adamopoulos S, et al. ESC Guidelines for the diagnosis and treatment of
acute and chronic heart failure 2012. Eu J Heart Failure. 2012; 14:803-69.
3. Hunt SA, Baker DW, et al. ACC/AHA Guidelines for the evaluation and management of
chronic heart failure in the adult: executive summary. Circulation. 2001; 104:2996-3007.
4. Farless, LB, et al. Intermittent subcutaneous furosemide: parenteral diuretic rescue for
hospice patients with congestive heart failure resistant to oral diuretic. Am J Hosp Palliative
Medicine. 2013; 30(8): 791-2.
5. Gadoud A, Jenkins SM, Hogg KJ. Palliative care for people with heart failure: summary of
current evidence and future direction. Palliative Med. 2018; 27(9): 822-8.
6. Lum HD, et al. Availability of heart failure medications in hospice care. Am J Hosp Pall
Med. 2016; 33(10) 924-8.
7. Carone L, et al . Furosemide. J Pain Symptom Management. 2016; 52(1)):144-150.
8. Oh SW, Han SY. Loop diuretics in clinical practice. Electrolytes & Blood Pressure. 2015;
13(1):17-21.
9. Verma AA. Diuretic effects of subcutaneous furosemide in human volunteers: a randomized

pilot study. Pharmacotherapy. 2004; 38:544-9.
10. Zacharias H, et al. Is there a role for subcutaneous furosemide in the community and hospice
management of end-stage heart failure? Palliative Med. 2011; 25(6):658-63.
11. Beattie JM, Johnson MJ. Subcutaneous furosemide in advanced heart failure: has clinical
practice run ahead of the evidence base? BMJ Supportive & Palliative Care. 2012; 2:5-6.
12. Schwartz GH, et al. Ototoxicity induced by furosemide. New Engl J Med. 1970; 282(25):
1413-14.
!26
13. Cheng HWB, Sham MK, et al. Combination therapy with low-dose metolazone and
furosemide: a “needleless” approach in managing refractory fluid in elderly renal failure
patients under palliative care. Intl Nephrol Urol. 2014; 46(9):1809-13.
14. Leonard CE, et al. Empiric potassium supplementation and increased survival in users of
loop diuretics. PloS One. 2014; 9(7):e102279.
Authors’ Affiliation: Medical College of Wisconsin, Milwaukee, WI.

Conflicts of Interest: None reported
Version History: Originally edited by Drew A Rosielle MD; first electronically published in April
2018.
!27
!
Emergency Medicine
#4 Death Pronouncement in the
Hospital . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-3
#64 Informing Significant Others of a Patient’s Death . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . 4-5
#76 Telephone Notification of Death – Part

I . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6-7
#77 Telephone Notification of Death – Part II . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . .8-9
#155 Completing a Death Certificate . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . . 10-12
#246 Emergency Department Management of Hospice Patients . . . . . . . . . . . . . . . . .

. . . . . 13-14
#247 Initiating a Hospice Referral from the Emergency Department. . . . . . . . . . . . . .

. . . . . .15-17
#298 Palliative Care Consultation in the Emergency

Department . . . . . . . . . . . . . . . . . . . . . .18-20
#305 Death Disclosure and Delivery of Difficult New in Trauma . . . . . . . . . . . . . . . . .

. . . . . . 21-23
!1
!

DEATH PRONOUNCEMENT IN THE HOSPITAL
David E Weissman MD and Charlotte A Heidenreich MD
Background Physicians traditionally have little formal training in examining patients to

determine death, notifying families, and in recording proper documentation. This Fast Fact
reviews key steps in the death pronouncement and notification process. See also Fast Facts
#76, 77 on telephone notification of death.
The Phone Call: “Please come and pronounce this patient”

• Find out the circumstances of the death from the nurse – expected or sudden? Is the
family present?
Preparation Before You Enter the Room

• For residents, find out if the attending physician has been called. In general, see the
patient before calling the attending, unless there are unusual family dynamics or details
surrounding the death that you should discuss with the attending.
• Determine if the family has requested or if you believe there is value in requesting an
autopsy. Some institutions have specific policies about autopsy requests.
• Determine if the patient/family has already been contacted by the Organ Donor Network
(see Fast Fact #79 Discussing Organ Donation).
• Review the chart for important medical (length of admission, cause of death) and family
issues (Who is family? Faith? Is there a clergy contact?).
In the Room
• You may want to ask the nurse or chaplain to accompany you; he/she can give you
support and introduce you to the family.
• Introduce yourself (including your relationship to the patient) to the family. Ask each
person their name and relationship to the patient.
• Empathetic statements are appropriate: “I’m sorry for your loss...” Or – “This must be
very difficult for you....”
• Explain what you are there to do. Tell the family they are welcome to stay while you
examine their loved one.
• Ask if family members have any questions or if they wish to speak with a chaplain.
The Pronouncement
• Identify the patient by the hospital ID tag. Note the general appearance of the body.
• Ascertain that the patient does not rouse to verbal or tactile stimuli. Avoid overtly painful
stimuli especially if family members are present. Nipple or testicle twisting, or deep
sternal pressure are inappropriate.
• Listen for the absence of heart sounds; feel for the absence of carotid pulse.
• Look and listen for the absence of spontaneous respirations.
• Record the position of the pupils and the absence of pupillary light reflex.
• Record the time at which your assessment was completed.
Documentation in the Medical Record

• Called to pronounce (name); Chart the findings of physical examination.
• Note date and time of death; Note if family and attending physician were notified.
!2
• Document if family declines or accepts autopsy
• Document if the death was natural and if the coroner was notified.
• For the purposes of filling out the death certificate (see FF #155): document cause of
death; length of time between onset of condition and death; and whether tobacco or
alcohol may have contributed to the death.
References:
1. Marshall SA, Ruedy J. On Call: Principles and protocols. 4th Ed. Philadelphia, PA:
Saunders; 2004.
2. Marchand LR, Kushner KP. Death Pronouncement: survival tips for residents. American
Family Physician. July 1998. Available at : http://www.aafp.org/afp/980700ap/
rsvoice.html.
3. Magrane BP, Gilliland MGF, King D. Certification of Death by Family Physicians.
American Family Physician. 1997; 56:1433-8.
!3
!

INFORMING SIGNIFICANT OTHERS OF A PATIENT'S DEATH
Diane Midland BSW, MS
Introduction This Fast Fact reviews the components of a sensitive notification of loved ones
when a patient dies. The physician is a key figure in the death notification process. Family and
friends who are present at the time of death look to the physician for information, reassurance
and direction regarding the weeks and months ahead. The lasting impression and memories that
family members have regarding the manner in which they received word that their loved one died
may affect the grief process and eventual integration of the loss within the survivors' world.
Research has demonstrated that the skills of compassion and sensitivity can be learned and must
be incorporated into the practice of all physicians.
Preparation
1. Confer with nursing and other staff working with the family/significant others. Review the
medical record (including any advance directive).
2. Examine the patient; confirm death (see Fast Fact #4).
3. Find a private place to meet with family/significant others.
4. Involve other members of the interdisciplinary team (e.g. nurse or chaplain) in the
notification process.
5. If possible, learn the names of those you will be talking with and their relationship to the
deceased.
Meeting with the Family/Significant Others
1. Introduce yourself and identify those present. In situations where there are family and
friends present, ask the next-of-kin who they would like with them during the
conversation.
2. Identify and respect ethnic, cultural or religious traditions (see Fast Fact #26).
3. Invite those present to sit down with you. Use body language, eye contact and touch
(introductory hand shake or clasp), if appropriate and accepted by family/significant
others.
4. Express your condolence (e.g. I’m sorry for your loss; My condolences to you and your
family.)
5. Talk openly about the death. Use "died" or "dead" during the initial conversation. Listen
for the words used by the family/significant others to describe death and use their term(s)
throughout the remaining discussion. Refer to the deceased by name.
6. If requested, explain the cause of death in non-medical terms. Allow time for questions;
be open to acknowledging that there may be things you don't know. Offer assurance that
everything possible was done to keep the patient comfortable.
7. Be prepared for a range of emotional expression. Do not offer sedation as a way to deal
with expressions of emotion. (Mild sedation for a brief time period may be considered to
assist with insomnia.)
8. Offer the opportunity to view the deceased. Prepare family/significant others for how the
deceased will appear; model touching and talking to the deceased. Offer time alone with
the deceased and assurance that survivors will not be rushed.
9. Provide time for the family/significant others to process the reality of the death before
discussing autopsy or tissue/organ donation.
10. Let family/significant others know that you will return, should questions arise or they
desire additional information. Provide information about how the family can reach you
after they leave the facility.
Follow-up
1. Personalize and sign a sympathy card to the bereaved (see Fast Fact #22).
2. Consider attending the wake, funeral, or memorial service.
3. Consider referral to a bereavement support service or agency, particularly if children are
involved.
!4
4. Encourage the bereaved to schedule a physical exam four to six months after the death.
5. Invite the bereaved to meet with you regarding autopsy results or to discuss unresolved
questions.
References
1. Schaefer C, Quesenbery CP Jr, Wi S. (1995). Mortality following conjugal bereavement
and the effects of a shared environment. Am J Epidemiology. 1995; 144(12):1142-52.
2. Shively P, Midland D, eds. The Art of Compassionate Death Notification. La Crosse, WI:
Gundersen Lutheran Medical Foundation; 1999.
3. Tolle SW, Bascom PB, Hickman DH, Benson JA. Communication between physician and
surviving spouses following patient deaths. J Gen Int Med. 1986; 1:309- 314.
4. Witter DM, Tolle SW, Moseley JR. A bereavement program: good care, quality assurance,
and risk management. Hosp Health Services Admin. 1990; 35(2):263-275.
5. Zunin HS, Zunin LM. The Art of Condolence, What to Write, What to Say, What to do at a
Time of Loss. New York, NY: Harpers Collins; 1991.
May 2015.
!5
!

TELEPHONE NOTIFICATION OF DEATH – Part I
Background Telephone notification to family members about a death is one of the most
challenging and stressful communication skills, especially for cross-covering housestaff who may
have had no direct interactions with the patient or family. Unpredictable variables are involved;
telephone notification does not allow the same level of interaction possible with direct personal
contact. This Fast Fact offers some guidelines when telephone notification is unavoidable; Fast
Fact #77 discusses issues surrounding whether or not to delay notification of death until loved
ones arrive at the hospital.
I. Preparing for the Call
1. Review death pronouncement protocol (See Fast Facts # 4 and 64).
2. Positively identify the patient (hospital ID tag) and confirm death.
3. Obtain relevant information; e.g. patient's name, age, gender, identification numbers.
4. Obtain the full name, address, phone number(s) of the person/s you are calling. Try to
establish from the chart and nursing staff the relationship of the contact to the deceased
patient.
5. Establish the circumstances of death; expected or sudden. Write down the key
information you need and thoroughly review what you will say.
6. Find a quiet or private area with a phone.
II. Timing
The call should be made as soon as possible following the death. Whenever possible, inform
the family of a grave turn of events prior to the patient dying. When substantial delay is likely,
the responsibility for informing the family should be taken by the covering doctor (or the
resident).
III. The Actual Notification
1. Identify yourself. Ask the identity of the person you are talking to and their relationship to
the patient. Ask to speak to the person closest to the patient (ideally, the health care
proxy or the contact person indicated in the chart). Avoid responding to any direct
question until you have verified the identity of the person to whom you are speaking. Ask
if the contact person is alone. Do not give death notification to minor children.
2. If you do not have a prior relationship with the person you are speaking to, ask what they
know about the patient’s condition: What have the doctors told you about _____’s
condition?
3. Provide a warning shot: I’m afraid I have some bad news.
4. Use clear and direct language, no medical jargon: I’m sorry, _____ has just died. Words
like "dead" or "died" should be used. “Expired”, “passed away” or "didn't make it" can be
misinterpreted.
5. Speak clearly and slowly, allow time for questions. Be empathetic. A perceptive family
can easily tell whether the notifier cares or is merely "going through the motions.”
6. If the family chooses to come to see the body, arrange to meet them personally.
7. Provide contact information for the physician or hospital official who can meet with them
and answer questions about the patient's death and other administrative issues.
8. Ask if you can contact anyone for them. Assess their emotional reaction (see Fast Fact
#77).
9. If you feel uncomfortable about telephone notification, ask for help.
10. Never deliver the news of death to an answering machine or voice mail. Instead, leave
specific contact information. If you are unable to make contact within 1-2 hours, contact a
hospital representative (e.g. social worker) to assist you in locating family or others.
References:
!6
Emerg Med. 2000; 36:75-77.
again May 2015.
!7
!

TELEPHONE NOTIFICATION OF DEATH – PART II
Introduction In Part I (Fast Fact # 76), the basic steps and precautions of telephone notication
of death were outlined. This Fast Fact discusses the dilemma of whether to provide telephone
information versus asking family members to first come to hospital before telling them that death
has occurred.
Delay vs. Disclose Immediately Few would disagree that it is always preferable to present
death notification in person. However, when families live at a great distance, or are physically
unable to travel, telephone discussion will be necessary. In other situations, clinicians must
weigh the benefits of truthfulness against the risk of potential harm resulting from abrupt
disclosure of the bad news. Factors to consider in making this decision include:
• Whether death was expected or not, including the nature and chronicity of the illness.
• How well the death notifier knows the patient and the patient’s family.
• The relationship of the contact person to the patient.
• The anticipated emotional reaction of the contact person based on prior information.
• Whether the contact person will be alone when receiving the information
• The contact person's level of understanding.
• Distance, availability of transport, and time of day.
For example, when death is expected due to progressive cancer and the notifier knows both the
patient and the contact person, telephone notification is very acceptable. In fact, you
should have prepared for this moment ahead of time by asking the contact how he or she
wishes to be contacted at the time of death. In contrast, if the death is sudden, especially
of a minor, notification in person is always preferred, although time and distance issues
may make this impractical.
The notifier must be prepared to quickly integrate all these factors to decide whether to reveal
that the patient is dead, or whether to describe the patient as gravely ill and request that
the contact person come to the hospital immediately. If you decide to delay disclosure of
the death, be prepared to make immediate admission of such nondisclosure as soon as
you meet the family (e.g. I'm sorry for not telling you the whole thing right away over the
phone; then give your reason for doing so).
Responding to Emotions Whether in person or by telephone, you should expect an

emotional reaction to the death notification (see Fast Fact #29). Responding to emotions via
telephone is especially difficult. Some tips include:
• Ensure that the contact has someone else with them. Offer to contact family members,
friends, clergy or others.
• Offer to meet with the contact in person.
• Contact your hospital social worker for advice on contacting other local resources such
as the Red Cross, local police, or other service agencies.
References:
Emerg Med. 2000; 36:75-77.
again June 2015.
!8
!9
!

COMPLETING A DEATH CERTIFICATE
Nikkisha Prentice and Robert Arnold MD
Background Physicians are responsible for providing proper documentation of death. This
Fast Fact reviews key steps in the completion of a death certificate.
Importance of Proper Completion Death certificate information is a permanent record of
death. It is usually necessary for burial and settlement of the deceased’s estate. Documentation
of the cause of death, in addition to direct communication, may provide family members with
closure and peace of mind. Death certificates are also used to 1) evaluate the general health of
the population, 2) assess the prevalence of medical problems among specific groups, 3) triage
medical research needs, and 4) apportion health services, grants, and other resources to
common illnesses.
Basic Guidelines Death certificates are governed by state statutes; variations exist in who can
complete a death certificate and how they should be filled out. Certification and completion of
death certificates is usually the primary responsibility of the attending physician. However, in
some states, death may be certified by the attending advanced practice nurse.
• Verify the correct spelling of names.

• Personally sign the death certificate; stamps are unacceptable.
• Complete all required items. If necessary, write “unknown” or “pending further study.”
• Common Errors
o Do not delay completion of the certificate. Some states have specific time periods
and civil and/or criminal penalties for non-completion. Moreover, funeral homes will
typically not proceed with burial without the death certificate.
o Do not use abbreviations.
o Some state forms require you spell out the month.
o Use 24 hour clock rather than 12:00 midnight.
o Some state forms do not allow alteration of the document; avoid erasing or using
white-out.
o Avoid cursive writing; print clearly or type using black ink.
Causality of Death This section of the certificate often consists of two parts. The first part asks
for a sequential chain of events that led to death and the time interval between onset of a
condition and death. The most immediate cause of death is stated on line a and the underlying
causes follow on lines b, and so on. In assessing the approximate interval between onset and
time of death, terms such as “unknown” or “approximately” may be used and general terms such
as “minutes,” “hours,” and “days” are acceptable. The second part asks about other significant
conditions that contributed to death, but that did not result in the underlying cause stated
previously.
Mechanism vs. Cause of Death It is important not to write the mechanism of death (i.e.
cardiac arrest, respiratory arrest) as the cause of death. The mechanism of death is the
physiologic derangement or biochemical disturbance by which the cause of death exerts its lethal
effect. For accurate public health records, the cause of death (e.g. chronic obstructive pulmonary
disease) is more helpful than the mechanism of death (e.g. respiratory failure). When there is
doubt as to the cause of death, it is acceptable to enter “unknown” or “pending further study.” In
some states, a condition may also be listed as “probable.” As additional medical information,
such as an autopsy report, becomes available, the certifying physician should report amendments
to the state vital records office or local registrar.
Note: Listed below are common terms and definitions that are generally interchangeable
between states. The table presents some examples.
• Immediate (or Principle) Cause = Final complication resulting in death.
!10
• Intermediate (or Antecedent or Underlying) Cause = Disease or condition causing the
immediate cause of death.
• Underlying (or Contributory) Cause = The condition present before and leading to the
intermediate or immediate cause of death.
Example 1 Example 2 Example 3 Example 4

Line A Acute Myocardial Acute Pulmonary Pneumocystis
Infarction Exacerbation of Embolism jiroveci
Obstructive pneumonia
Airway Disease
Line B Coronary Artery Chronic Deep Venous Acquired
Disease Bronchitis Thrombosis Immunodeficienc
y Syndrome
Line C Chronic Ischemic Metastatic Non- Human

Heart Disease Small Cell Lung Immunodeficienc
Cancer y Virus
Mechanism Cardiac Arrest Respiratory Respiratory Arrest Septic Shock
of death Arrest
Other Diabetes Smoking Stroke,
Significant Hemiparesis
Conditions
References
1. Campos-Outcalt D. Cause-of-death certification: Not as easy as it seems. J Fam
Practice. 2005. 54(2):134-138
2. Herring ME. The Death Certificate. AAHPM Bulletin (reprinted with permission of the
Camden Medical Society). Winter 2005; 8-9.
3. Lakkireddy DR, Gowda MS, Murray CW, Basarakodu KR, Vacek JL. Death Certificate
Completion: How well are physicians trained and are cardiovascular causes overstated?
Am J Med. 2004; 117:492-498.
4. Magrane BP, Gilliland MG, King DE. Certification of death by family physicians. Am Fam
Physician. 1997; 56:1433-8.
5. Myers KA, Farquhar DE. Improving the accuracy of death certification. CMAJ. 1998;
158:1317-23.
6. Nowels D. Curbside consultation: completing and signing the Death Certificate. Am Fam
Physician. 2004; 70(9):1873.
7. Physicians’ Handbook on Certification of Death. Department of Health and Human
Resources, Centers for Disease Control and Prevention, National Center for Health
Statistics; April 2003. DHHS Publication No. (PHS) 2003-1108.
in May 2006. Version copy-edited in April 2009; then again July 2015.
!11
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!

EMERGENCY DEPARTMENT MANAGEMENT OF HOSPICE PATIENTS
Background Patients enrolled in hospice programs will occasionally be transported to the
Emergency Department (ED). Emergency medicine training focuses on life-prolonging measures
and may fail to address hospice as a system of care. This Fast Fact provides information for
clinicians practicing in EDs on management issues when a hospice patient arrives. Fast Fact
#247 discusses initiating hospice care from the ED and #298 addresses Palliative Care
Consultation in the ED.
Why do Hospice Patients come to the ED? ED providers should never assume that arrival in
the ED equates a desire for aggressive/life-prolonging treatment. Even when a patient/family
requests such services, an assessment is needed to understand the concerns that prompted a
shift in care goals. Frequently such requests arise from fear about the dying process or guilt
about prior medical decisions to limit life-prolonging treatments. Common triggers for an ED visit
include:
• Stress/inability to cope with impending loss of life. This may be expressed as a request to
start a life-prolonging treatment previously used and discontinued (e.g. chemotherapy) or
never begun (e.g. renal dialysis).
• Poor symptom control.
• Malfunction/loss of a support device such as a gastrostomy tube.
• Failure of the hospice program to provide timely patient support and communication.
Management Guidelines
1. Notify hospice staff as soon as possible. Under the Medicare Hospice Benefit, hospice
agencies are legally/financially responsible for the patient’s plan of care and all medical
costs related to the terminal illness. See Fast Facts # 82, 87, 90.
2. Determine the trigger for the ED visit. Pay attention not only to distressing physical signs
and symptoms but also emotional and psycho-social issues. Involve social services,
chaplaincy, and Palliative Care consultative services early if needs are identified.
3. Treat distressing symptoms. See Fast Facts for specific symptom treatment guidelines.
4. If deterioration is imminent and rapid decisions are needed regarding the use of life-
sustaining treatments (e.g. intubation for respiratory failure) a focused discussion around
goals of care must occur in the ED
• Determine the legal decision maker if available and review any completed advance
directives.
• Complete a rapid goals of care discussion (see Fast Facts #223-227).
• Make recommendations. For example, ‘According to what you want for [the patient], I
would/would not recommend….’
5. If the patient is actively dying (see Fast Fact #3) assess for cultural/spiritual needs;
assure privacy and endeavor to identify if there are any preferred locations a patient can be
safely transferred to to die (e.g. back home; to a private hospital room).
6. Laboratory tests/diagnostics should be limited or withheld until discussion with the
patient’s hospice care team. Testing should be based on patient-defined goals of care.
Generally, low burden, non-invasive methods which may reveal reversible pathology or
clarify prognosis should be used first.
7. Therapeutic modalities should be based on patient-defined goals of care rather than
automatic ‘ED indications’ (e.g. antibiotics for pneumonia should only be used if they meet
a patient or surrogate defined goal of care).
8. Disposition should be planned after discussion with hospice staff based on the patient’s
goals. Returning home or a direct admission to an inpatient hospice facility may be the
best disposition rather than hospital admission. At times, hospices can arrange 24h
professional support in the home for patients with difficult to manage symptoms who wish
to remain home (‘continuous care’ – see Fast Fact #87).
!13
9. Notify the inpatient palliative care service if the patient is to be admitted to the hospital.
Hospice agencies may revoke a patient’s enrollment in hospice care if care goals have
changed, or may continue a patient under hospice care during an admission for palliation
(see Fast Fact #87).
Summary Patient-centered care for hospice patients may be enhanced by emergency
clinicians who acquire skills to quickly adapt to a supportive role in the care of a terminally-ill
patient. Recognizing common triggers for the ED visit, using a multi-disciplinary approach with
early involvement of hospice, social services and palliative team consults may assist in providing
optimal care for ED patients under hospice care.
References
1. Chan GK. End-of-life and palliative care in the emergency department: a call for research,
education, policy and improved practice in this frontier area. J Emerg Nurs. 2006. 32(1):
101-3.
2. Smith AK, Fisher J, Schonberg MA, et al. Am I doing the right thing? Provider perspectives
on improving palliative care in the emergency department. Ann Emerg Med. 2009. 54(1):
86-93.
3. Reeves K. Hospice care in the emergency department. J Emerg Nurs. 2008. 34(4):350-1.
4. Lamba S, Quest TE. Hospice care and the Emergency Department: rules, regulations and
Version History: Originally published October 2011; Copy-re-edited August 2015.

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!

INITIATING A HOSPICE REFERRAL FROM THE EMERGENCY DEPARTMENT
Background Patients with an end-stage illness often present to the Emergency Department
(ED) with a crisis event (1). This Fast Fact provides information for ED providers on how to refer
a patient to hospice care directly from the ED (2). Fast Fact #246 suggests strategies for caring
for patients receiving hospice care who present to the ED; Fast Fact #298 covers Palliative Care
consultation in the ED.
1. Assess Medicare Hospice Benefit eligibility (see Fast Fact #82). Fundamentally, this
means the patient has a prognosis that is 6 months or less if his/her disease runs its expected
course, and the patient’s care goals are compatible with hospice (see #3 below). Broad
guidelines for many cancer and non-cancer related conditions exist (3, 4, 5, 6). A useful starting
point is to ask yourself, Would I be surprised if this patient died within the next 6 months? For
disease specific prognostic information, see Fast Facts #13, 99, 124, 125, 141, 143, 150, 189,
191, 213.
2. Discuss hospice as a disposition plan with the patient’s physician. Contact the
patient’s personal physician: discuss the current condition, prognosis, and prior goals of care
conversations. If you are considering hospice care, ask if the physician is willing to be the
following physician for hospice services.
3. Assess whether the patient‘s goals are consistent with hospice care. Generally this
means a patient wants medical treatments and other support aimed at alleviating symptoms and
maintaining quality of life, without life-prolongation. Patients may enroll in hospice care if their
preeminent care goal is symptom relief, even if they are not entirely sure they want to completely
discontinue life-prolonging therapies, as long as the hospice agency indicates they can
accommodate those wishes. These four questions will help you get the discussion started to
elicit if the patient and family are psychologically ready to accept hospice care (see also Fast
Facts #222-227).
• “What have you been told about the status of your illness and what the future holds?”
• “Has anyone talked to you about your prognosis; how much time you likely have?”
• “Are there plans for new treatments designed to help you extend your life?”
• “Has anyone discussed with you hospice services? What do you know about Hospice?”
4. Introduce hospice to the patient and family/surrogates.

• Discuss the core aspects of hospice care and how these features can help the patient
and family (e.g. 24/7 on-call assistance, home visits for symptom management,
coordinated care with the patient’s physician, emotional and chaplaincy support).
• Address concerns and clarify misconceptions.
• Phrase your recommendation for hospice care in positive language, grounded in the
patient’s own care goals. “I think the best way to help you stay at home, avoid the
hospital, and stay as fit as possible for whatever time you have left is to receive hospice
care at your home….”
• Discuss location of hospice care: usually this is the patient’s residence such as a private
home or long-term care facility. Direct admissions to hospice facilities can occur
depending on bed availability and ability of local hospice agencies to arrange an
immediate, direct facility admission. This is not available in all communities and requires
a discussion with the hospice agency.
5. Make a referral and write orders (see Fast Fact #139).

Call a hospice agency; anticipate these questions:
• What is the terminal illness? Who will be the following physician? (Step 2)
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• What equipment will be needed immediately (e.g. home oxygen)? Is there a caregiver at
home?
• Code status (patients cannot be denied hospice enrollment if ‘full code’, however the
hospice team will need to know if code status needs to be addressed further.)
Questions you may need to ask the hospice agency:
• How soon can you make an intake visit to the patient’s home? Can you visit the patient
immediately, even in the ED (this is available in some communities)?
• How should I coordinate filling of new prescriptions I want the patient to have?
Example of ED Initiated Hospice Referral Orders:
o Evaluate and Admit/Enroll in hospice care
o Terminal Diagnosis: __________.
o Expected Prognosis: Terminal illness with less than 6 month survival likely if disease runs
its normal expected course [or more specific if indicated].
o Physician who will follow patient: _________.
6. Ensure patient/surrogate understanding and secure the plan. Communicate the plan
following ED discharge; provide the name and contact number for the hospice agency.
7. What if hospice enrollment is appropriate, but cannot be arranged in a timely manner?

If the patient can be cared for at home safely for 1-2 days without extra services, send her or him
home with appropriate prescriptions and care instructions. In most communities, patients can be
enrolled in hospice care within 24-48 hours, even on weekends. If they cannot be cared for
safely at home, observation vs inpatient admission is likely necessary until a safe discharge plan
can be established.
Summary Patient-centered care for hospice-eligible, terminally-ill patients may be enhanced
by emergency clinicians who acquire skills to make early appropriate hospice referrals from the
ED.
References
1. Lamba S, Quest TE. Hospice care and the emergency department: rules, regulations and
2. Education in Palliative and End-of-Life Care-Emergency Medicine Project, Trainers
Guide. Module 5. Emanuel LL, Quest TE, eds. Chicago, IL: Northwestern University;
2008.
diseases. 2nd ed. Alexandria, VA: National Hospice Organization; 1996.
4. Centers for Medicare and Medicaid Services, Medicare Coverage Database. LCD (Local
Coverage Determination) for hospice: determining terminal status (L25678). Available at:
http://www.cms.gov/medicare-coverage-database/details/lcd-details.aspx?LCDId=25678
5. Gazelle G. Understanding hospice – an underutilized option for life's final chapter. New
Engl J Med. 2007; 357(4):321-4.
6. Lynn J. Perspectives on care at the close of life. Serving patients who may die soon and
their families: the role of hospice and other services. JAMA. 2001; 285(7):925-32.
Version History: Originally published September 2011; Copy-re-edited August 2015.

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PALLIATIVE CARE CONSULTATION IN THE EMERGENCY DEPARTMENT
Sangeeta Lamba MD, MS HPEd, Tammie E Quest, MD, David E Weissman, MD
Background Adults with chronic illnesses visit the emergency department (ED) several times in
their last months of life, with over half of older Americans presenting in their last month and many
dying in the ED. Hence, the ED serves many patients with unmet palliative care needs. Initial care
decisions made in the ED also set the future hospital trajectory of care. Early palliative care (PC)
engagement in the ED has the potential to impact these decisions. In this Fast Fact we discuss
the opportunities and challenges of the PC consultations in the ED.
Indications for Palliative Care consultation in the Emergency Department
• Difficult-to-manage pain or other symptoms
• Symptom management for an actively dying patient
• Rapid consensus for goals of care (e.g. intubation decision) or complex decision making
• Clarify provisions in an advance directive
• Withdrawal of non-beneficial treatments (e.g. help with terminal extubation)
• Bereavement support (e.g. after sudden deaths in victims of trauma or death of a child)
• Challenging dispositions requiring care coordination (e.g. home hospice)
Consultation Etiquette ED clinicians are charged to provide excellent and efficient patient
care, with a mandate to keep patient encounters as expedient as possible. ED providers often
expect in-person consultation time within 30-60 minutes. Palliative programs should proactively
discuss the consultation processes with the ED leadership to clarify when and how palliative care
team members will be available for an ED consult, by phone or person. To best serve the ED
staff, palliative care clinicians are encouraged to follow these principles of consultation etiquette:
1. Determine the question: What is needed from the ED team? Orders for symptom control,
dialogue with family, guidance with disposition planning? Certain issues, such as symptom
control, may be initiated or handled over the phone whereas more complex issues such as urgent
goals of care discussions may need in-person support.
2. Establish urgency: Be explicit in asking the ED team for the timeline of expectations.
• Emergent (e.g. clinical status unstable; decision to intubate, decision to withdraw
ventilator)
• Urgent (e.g. patient relatively stable; help needed for disposition planning)
• Routine (e.g. patient is being admitted, has non-urgent needs, can be seen as inpatient).
3. Who is needed and when? Clarify care issues to determine which IDT member is best suited
to address the ED query. Be honest about timelines for in-person support and initiate telephone
support as soon as feasible.
4. Personal contact: discuss your findings and/or recommendations with the appropriate
member of the ED staff before initiating any definitive patient/family communication or
intervention. Recognize that this ED clinician may not be the one who initiated the palliative team
consult due to shift schedules.
5. Gather additional data: To offer high quality care, the consultant will need to gather data
independently.
6. Brevity: A verbal 2-4 minute summary of recommendations is useful immediately after the
consult.
7. Specificity: Be explicit in disposition and treatment directions (e.g., “begin with Morphine 5 mg
IV and repeat every 15 minutes until pain is less than 5”). Make sure your recommendations are
feasible to implement and fit the ED policies and protocols. Clarify who will be contacting other
stakeholders (home care, caregivers, etc) and what messages will be communicated.
8. Teach with tact: e.g. provide a Fast Fact, a protocol for pain, or an opioid equivalency table.
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9. Provide continuity: Communicate the established plan of care to the patient, family, ED
clinician and the provider for the patient’s next place of disposition (e.g. the hospitalist for a
patient being admitted).
10. Honor the ED environment: Appreciate the patient load and competing emergency care
demands of the ED staff. Expect and anticipate shift changes and the need to orient new staff to
your role and plans.
Summary Often a consult initiated in the ED does not have ample time to fully address patient
needs or change immediate outcomes. PC collaboration still serves a vital role in the ED as initial
discussions begun in the ED (clinician discussions about poor prognosis and introducing palliative
team as part of the next steps of care) can help prepare the patient and family for future care
discussions with the palliative team. PC clinicians are encouraged to learn about the ED culture
and develop positive relationships by joining in ED care rounds, serving as educational
resources, and working collaboratively on institutional protocols.
References:
1. Meier DE, Beresford L: Fast response is key to partnering with the emergency
department. Journal of Palliat Med 2007; 10(3):641-5.
2. Lamba S, Nagurka R, Walther S, Murphy P Emergency-Department-Initiated Palliative
Care Consults: A Descriptive Analysis. Journal of Palliative Medicine 2012; 5(6):633-636.
3. Kessler C, Kutka BM, Badillo C. Consultation in the Emergency Department; A Qualitative
Analysis and Review. J Emerg Med. 2012; 42(6):704-711
4. Hexter DA. Working with consultants. ACEP: Foresight 2002; 53.
5. Lee RS, Woods R, Bullard M, Holroyd BR, Rowe BH. Consultations in the emergency
department: a systematic review of the literature. Emerg Med J. 2008; 25(1):4–9.
6. Salerno SM, Hurst FP, Halvorson S, Mercado DL. Principles of effective consultation: an
update for the 21st-century consultant. Arch Intern Med. 2007;167(3):271–75.
7. Weissman DE. Consultation in palliative medicine. Arch Intern Med. 1997;157(7):733–37.
8. Choosing Wisely Campaign- American College of Emergency Physicians. Available at
https://www.acep.org/Clinical---Practice-Management/ACEP-Announces-List-of-Tests-As-
Part-of-Choosing-Wisely-Campaign.
Authors’ Affiliations: Rutgers New Jersey School of Medicine; Emory University School of
Medicine; Medical College of Wisconsin
Version History: First electronically published June 2015
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!
DEATH DISCLOSURE AND DELIVERY OF DIFFICULT NEWS IN TRAUMA
S Lamba, S Bryczowski, L Tyrie, DE Weissman, AC Mosenthal
Background: Traumatic injury is an ‘out of time and out of place’ event affecting people of all
ages including the young and previously healthy. Disclosure of a traumatic injury or death is often
performed by a clinician who has little relationship with the patient and who is compressed for
time in a chaotic environment with rapidly evolving clinical factors. Mass casualties may make this
even more challenging and require clinicians to manage multiple families while preserving privacy
and patient integrity. Intense emotional reactions from families may range from shock to anger
and clinicians must have to manage their own emotions perhaps after completing an intense and
unsuccessful resuscitation. In lieu of these special considerations we describe an ABCDE
framework for delivering difficult news in trauma settings. See Fast Facts #6, #11, and #222 for
guidance on delivering bad news in general.
A: Anticipate
Who: Know the name/identity of the patient. This may be difficult as some patient’s arrive in
extremis as “John/Jane Doe”. Ideally, have staff identify family members and their relationship to
the patient prior to your arrival. In multiple casualties, it is important to ensure you are speaking to
the right family about the right patient. Bring a team member who can stay longer to offer family
support – chaplain, social worker, ED nurse, palliative care clinician, or bereavement specialist.
What: Know the details of: a) the event: often by police report or EMS scene descriptions; b)
clinical course: extent of injuries, results of diagnostic tests and consultant opinions.
How: rehearse how you will deliver information and prepare the team. Focus on the “bottom line”
and avoid getting stuck in the details. Families want to know if the patient is dead or alive, and
deliver this news up front. For follow up conversations, mentally organize events into cause and
effect using the “ABCs” of resuscitation e.g., there was swelling to his face so a breathing tube
was placed; his lung was collapsed so we placed a chest tube; he had low blood pressure, so we
gave fluids intravenously.
B: Be Aware of Self and Surroundings
Appearance: Change and remove any blood-splattered clothing/shoe covers; wear a white coat.
Location: Find a quiet room; place your cell phone/pager on vibrate.
Safety: Plan to break the news with a partner; have a safety strategy to exit the physical space in
case of a violent response from family. This may mean keeping the door to the room open and
unblocked when delivering news to a large group. Have security available and aware; however
the presence of police or security in the room may escalate the situation.
C: Conversation/Concerns
Ask family to identify themselves and establish their relationship to the patient. Introduce yourself
and your role in the patient’s care and then introduce other team members.
Begin with a “warning shot” (I’m afraid I have some bad news, or I am so sorry…)
Concise summary of events
For patients who DIE in the trauma bay:
• Deliver news of the death first after a brief narrative (one sentence) that provides context
that the family can understand. Recognize that there is no way to soften the impact and
use the word dead/dying up front. “Your son was in a car crash with major injuries to his
heart, brain and other organs. We tried everything we could; he died a few minutes
ago…”
For patients who SURVIVE resuscitative efforts:
• Begin by outlining the most serious injury and how it will impact the patient’s “big picture”
condition. Meaningful information usually falls into several categories: does he have
brain damage? Is he paralyzed? Will he survive? “She has multiple injuries but we are
most concerned about the serious brain damage from the injury to her head.”
• Resist the tendency to catalog and list every injury/procedure in the initial meeting. Keep
information sharing brief. Families will need time to digest the key facts.
• Anticipate next steps and prepare the family for what will happen next. Outline those
injuries that will impact clinical decision making the most in the coming hours, especially
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if there are associated medical interventions which will require family consent in the near
future.
• Prepare family for what they will see at the bedside (e.g. splints, ventilator, wounds).
Do not speak. Allow for silence and expressions of grief, emotional or physical. Avoid giving more
clinical information unless requested. Recognize diverse cultural responses to grief which may
involve dramatic displays of emotion (falling on floor, wailing). As long as these do not represent a
danger to staff or family, allow the space necessary for this to occur.
Empathy/Explain
• Validate emotions via verbal and nonverbal expressions of empathy
• Specify what will be happening prior to the next update as well as when and where it will
occur.
• Provide an opportunity for family to see the patient. Even if injuries are disfiguring or
mutilating, bereavement outcomes are improved if the family has been able to see and
touch their loved one. Ensure that devastating injuries and wounds are covered prior to
visitation.
D: Debrief, Document and Dictate
• Document conversation in chart using the ABCDE Outline.
• Debrief with team. Are they emotionally okay? Validate common emotions generated by
death and failed attempts at resuscitation (e.g., child, young adult, expectant mother).
• Decide who will provide follow-up information to family and when.
• Death - Notify medical examiner and organ sharing network as per institutional protocols.
E: End the Encounter
• Engage the chaplain, social worker, Palliative Care team, or bereavement support as
appropriate for the trauma team and family.
• Reflect. What went well? What did not? How could you do this better in the future?
References
1. Weissman DE, Quill TE, Arnold RM., Preparing for the family meeting. Fast Facts and
Concepts #222 https://drive.google.com/file/d/0BylFEWCSwGsUQW1xNXltVjBlVkE/view
2. Tyrie L, Mosenthal AC, Bryczkowski S, Laboy C, Lamba S. Difficult Conversations After
Resuscitation in Trauma: Video Education E-Module. MedEdPORTAL Publications; 2015.
Available from:https://www.mededportal.org/publication/10092 http://dx.doi.org/10.15766/
mep_2374-8265.10092
3. Lamba, S., Nagurka, R., Offin, M. and Scott, S. R., Structured communication: teaching
delivery of difficult news with simulated resuscitations in an emergency medicine
clerkship. West J Emerg Med, 2015, 16(2):344-352.
4. Ambuel B, Weissman DE. Delivering Bad news Part 1. Fast Facts and Concepts #6.
https://drive.google.com/file/d/0BylFEWCSwGsUM0N6a0pqYTZTTVk/view.
5. Jurkovich GJ, Pierce B, Pananen L, Rivara FP. Giving Bad News: The family Perspective.
J Trauma. 2000 May;48(5):865-70
Authors Affiliations: Rutgers New Jersey Medical School; Medical College of Wisconsin.
Version History: Copy edited by Sean Marks MD. First electronically published October 2015.
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!22
!
GI
#10 Tube Feed or Not Tube Feed? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . . 3-4
#15
Constipation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . 5-6
#25 Opioids and

Nausea . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . 7-8
#45 Medical Management of Bowel

Obstructions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9-10
#81 Management of Hiccups . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . 11-12
#84 Swallow Studies, Tube Feeding, and the Death

Spiral . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13-14
#91 Interventional Options for Malignant Upper GI

Obstruction . . . . . . . . . . . . . . . . . . . . . . .15-16
#96 Diarrhea in Palliative Care . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . .17-18
#119 Invasive Treatment Options for Malignant Bowel

Obstruction . . . . . . . . . . . . . . . . . . . .19-20
#128 The Speech Pathologist and Swallowing

Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21-22
#137 Carcinoid Syndrome: Symptom

Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23-24
#176 Evaluation of Malignant Ascites . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . .25-26
#177 Palliative Treatment of Malignant

Ascites . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .27-28
#188 Hepatic Encephalopathy in

ESLD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29-31
!1
#189 Prognosis in Decompensated Chronic Liver
Failure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32-33
#260 Opioid Use in Liver Failure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . 34-36
#294 Opioid Included Constipation Part I: Established Management Strategies . . . . . . .

. . 37-39
#295 Opioid Included Constipation Part II: Newer Therapies . . . . . . . . . . . . . . . . . . .

. . . . . . 40-42
#304
Dysgeusia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . 43-45
#308 Tunneled Indwelling Catheters for Malignant

Ascites . . . . . . . . . . . . . . . . . . . . . . . . . . . 46-47
#317 Palliation of Neurogenic

Bowel . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48-50
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!

James Hallenbeck MD
advanced illness.
!3
sepsis).
demonstrated.
GI obstruction).
Summary
References
247: 39-42.
JAMA. 1999; 282:1365-1369.
1996; 348:1421-1424.
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!

CONSTIPATION
James Hallenbeck MD
Constipation – it's not fun to have or to treat. As with other symptoms, rational therapy should be
based on a sound understanding of underlying physiology. Our goal in treating constipation is
generally not to "cure" something, but to help the patient return to the best possible balance that
will allow a normal bowel movement to be passed. Four major components affect the production
of a normal BM: solid waste, water, motility and lubrication.
Solid Waste – Too much or too little is a problem. The intestine is most efficient pushing
intermediate volumes. Patients on fiber-poor diets may improve if fiber is added. Note: In patients
on opioids or patients with minimal fluid intake or poor gut motility (e.g. the dying patient)
additional fiber can worsen the situation, causing a 'soft impaction'.
Water Content – Stool water content depends on how much water we drink, our general
hydration status, how much water is absorbed from and secreted into the intestine and how fast
stool moves through the bowel. Any of these variables can be manipulated. It is easiest to limit
absorption (and increase secretion into the gut) by adding osmotically active particles that retain
water (e.g. Magnesium salts, non-absorbable sugars such as sorbitol and lactulose, or
polyethylene glycol [PEG]). Note: Magnesium and phosphorus salts are contraindicated in renal
failure. Hyperosmolar solutions may worsen dehydration by drawing body water into the gut
lumen. Sickly-sweet sorbitol and lactulose may be difficult to for patients to tolerate. PEG is
flavorless and may be better tolerated.
Motility – Patients with low-activity levels (bed-ridden, dying patients and patients with advanced
neurodegenerative disorders) and use of certain drugs (see below) lead to motility problems.
Senna preparations, which stimulate the myenteric plexus are generally favored. Use senna
tablets (or granules, liquid, or tea), starting with 1 tab QHS, may be gradually increased to 4 tabs
BID if needed. Before increasing motility, evacuate existing constipated stool with an enema or
cramping can result.
Lubrication simply eases passage and minimizes pain that can interfere with excretion. Most
commonly used is dioctyl sodium sulfosuccinate (DSS, or docusate), which decreases stool
surface tension much like soap. Usual dosage is 240 mg PO daily or BID. DSS also tastes like
soap, so liquid DSS should never be given PO, but may be given to tube-fed patients. Note: DSS
is commonly used in combination with senna in opioid-induced constipation, but is generally
inadequate as a sole agent. Mineral oil can be used as an enema but should not be given PO, as
pneumonitis can result if aspirated. Glycerin suppositories can provide lubrication and draw-in
water due to osmotically active particles.
Medications that can cause/exacerbate constipation: Opioids, anticholinergics (tricyclic

antidepressants, scopolamine, oxybutinin, promethazine, diphenhydramine), lithium, verapamil,
bismuth, iron, aluminum, aalcium salts. See Fast Facts #294 and #295 for more information on
opioid induced constipation.
References
1. Klaschik E, Nauck F, Ostgathe C. Constipation--modern laxative therapy. Support Care
Cancer. 2003; 11(11):679-685.
2. Mancini I, Bruera E. Constipation in advanced cancer patients. Support Care Cancer.
1998; 6(4):356-364.
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!

OPIOIDS AND NAUSEA
David E Weissman MD
Background Why do patients get nauseated and vomit after receiving an opioid? Commonly
described as an “allergy”, opioid-induced nausea/vomiting is not an allergic reaction. In fact,
rather than indicating a pathologic reaction, nausea indicates normal functioning of the brain.
Opioid-induced nausea occurs through the following mechanisms:
• At the base of the 4th ventricle lies the chemoreceptor trigger zone (CTZ), a “sampling
port”, to detect substances that do not belong in the blood. Adjacent to the CTZ lies the
medullary vomiting center which controls the complex muscular sequence of vomiting.
When the CTZ detects a noxious chemical in the blood, a signal is sent to the VC and the
vomiting reflex is initiated. Of note, this is the same mechanism when patients vomit after
receiving chemotherapy.
• Opioids can directly stimulate the vestibular apparatus—patients note a spinning
sensation with their nausea.
• Opioids cause constipation which can lead to nausea via stimulation of afferent
cholinergic pathways.
Do all opioids produce the same degree of nausea? There is little research data on this topic.
In clinical practice, morphine and codeine are often mentioned as the worst offenders. Some
clinical studies along with preclinical data in rats suggest that the transdermal fentanyl patch may
have less nausea and constipation than morphine.
Why are some patients more sensitive to the emetic effects of opioids than others?
Unknown
What is the natural history of opioid-induced nausea? Most patients develop tolerance to the
emetic effects, so that within 3-7 days, at a constant opioid dose, the emetic effect will abate.
What are management approaches?

• Dose adjustment—if good pain relief is achieved but associated with nausea, it may be
possible to lower the opioid dose, still retain good analgesia, but eliminate the nausea.
• Switching opioids—there is variability in emetic reaction to different opioids. Note: since
tolerance to nausea develops, one never knows if a reduction in nausea is from the
change of drug or tolerance.
• Anti-emetics— Whenever possible, choose a drug directed at the most likely cause of
nausea (see Fast Fact # 5). There are little published data to guide physicians in specific
choice of anti-emetic for opioid-induced nausea.
• Start with low-cost dopamine antagonists (e.g. prochlorperazine, haloperidol, or
metoclopromide) or anti-cholinergics (e.g. scopolamine);
• Anti-histamines may be helpful for patients who note a spinning sensation.
• 5HT3 antagonists (e.g. ondansetron) can be used for more refractory cases. Two
multi-center randomized trials have examined control of emesis associated with
opioids not used for anesthesia. In one, 16 mg of ondansetron was more effective
than 8 mg or placebo. In the other trial, stopped early due to lack of patient accrual,
24 mg ondansetron was no better than placebo or metoclopramide.
• Non-pharmacological approaches: there is little evidence to support non-pharmacological
treatments for nausea outside of chemotherapy associated nausea; suggested
approaches include acupressure and behavioral treatments.
References
1. Hardman JG, Limbird LE, et al, eds. Goodman and Gillman’s The Pharmacological Basis
of Therapeutics. 9th Ed. New York, NY: McGraw-Hill; 1996.
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2. Herndon CM, et al. Management of opioid-induced gastrointestinal effects in patients
receiving palliative care. Pharmacotherapy. 2002; 22:240-250.
4. Hardy J, et al. A double-blind, randomised, parallel group, multinational, multicentre study
comparing a single dose of ondansetron 24 mg p.o. with placebo and metoclopramide 10
mg t.d.s. p.o. in the treatment of opioid-induced nausea and emesis in cancer patients.
Support Care Cancer. 2002; 10:231-236.
5. Pan CX, et al. Complementary and aternative medicine in the management of pain,
dyspnea nd nausea and vomiting near the end-of-life: a systematic review. J Pain Sym
Manage. 2000; 20:374-387.
6. Megens AHP, Artois K, et al. Comparison of the analgesic and intestinal effects of
fentanyl and morphine in rats. Journal of Pain and Symptom Management 1998; 15:
253-7.
7. Ahmedzai S, Allan E, et al. The TTS-fentanyl multicenter study group: transdermal
fentanyl in cancer pain J Drug Dev 1994;6: 93-7.
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!

MEDICAL MANAGEMENT OF BOWEL OBSTRUCTIONS
Charles F von Gunten MD, PhD, J Cameron Muir MD, Sean Marks MD
Background Malignant bowel obstruction is a common oncologic complication; most common

in ovarian and colon cancer. Symptoms include nausea, vomiting, and abdominal pain which can
be colicky or continuous. Treatment options include surgical correction, placement of a venting
gastrostomy tube, stent placement across the obstructed site, or medical management (see Fast
Fact #119 for a discussion of interventional options). Total parenteral nutrition may be beneficial
in select patients with longer prognoses who may die of starvation rather than the cancer itself
(see Fast Fact #190). Still, the need to rely on medical management is common, especially when
the patient’s functional status is poor and expected survival is short. There has been significant
advances in the medical management of this problem, so that many patients can avoid dying with
the traditional approach of intravenous fluids and nasogastric tubes ("drip and suck”).
Major Drugs
• Opioids and anti-emetics: usually dopamine antagonists (e.g. haloperidol) can be
administered (intravenously or subcutaneously) to relieve pain and nausea.
• Antimuscarinic/anticholinergic drugs (e.g. atropine, scopolamine): are used to manage
colicky pain due to smooth muscle spasm and bowel wall distension. In the US,
scopolamine can be administered by parenteral (10 mcg/hr IV/SQ continuous infusion) or
transdermal (10 mcg/hr) routes, but is only available as the hydrobromide salt. This
penetrates the CNS and can lead to delirium. Glycopyrrolate, a quaternary ammonium
antimuscarinic with similar clinical effects to scopolamine, but without the CNS side-effects
(dosed at 0.2-0.4 mg IV/SQ q2-4h), may be a viable alternative.
• Somatostatin analogs: inhibit the secretion of GH, TSH, ACTH and prolactin, and decrease
the release of gastrin, CCK, insulin, glucagon, gastric acid and pancreatic enzymes. They
also inhibit neurotransmission in peripheral nerves of the gastrointestional tract leading to
decreased peristalsis and a decrease in splanchnic blood flow. Octreotide (Sandostatin) is
administered as a SQ injection (starting at 50-100 mcg q 8 hours) or as continuous IV or SQ
infusion, beginning at 10-20 mcg/hr. Small randomized controlled trials suggest it may be
more successful in improving nausea, vomiting, and colic than antimuscarinics for patients
with a NG tube. One case report suggested it may help in partial bowel obstruction as well.
The drug is titrated every 24 hours until nausea, vomiting, and abdominal pain are
controlled. A once monthly injection of a long-acting formulation can be used for patients on
a stable dose. A more recent randomized controlled trial suggested that dexamethasone
with ranitidine may be a more cost-effective alternative to octreotide 600 mcg/day for MBO
however.
• Corticosteroids: have been recommended to decrease the inflammatory response and
resultant edema, as well as relieve nausea, through both central and peripheral antiemetic
effects. A meta-analysis found that 6-16 mg of IV dexamethasone/day decreased symptoms
and improved bowel function in 60% of patients. In fact, a phase III trial suggested little
benefit from octreotide in patients already on intravenous ranitidine 200 mg/day and
intravenous dexamethasone 8 mg/day.
Minor Drugs
Prokinetic drugs (e.g. metoclopramide) may be beneficial if there is a partial obstruction.
However, if there is total obstruction some advocate the discontinuation of prokinetic agents as
they may exacerbate crampy abdominal pain. On the other hand metoclopramide may inhibit the
reverse peristalsis from obstruction and decrease nausea. Olanzapine, an atypical anti-psychotic,
blocks multiple neurotransmitters associated with nausea. It is available in a sublingual route with
some published accounts of utility in refractory cases of nausea in cancer.
Care Plan Often medications must be used in combination to achieve clinical goals in
malignant bowel obstruction. The goal of medical management is to decrease pain, nausea and
!10
secretions into the bowel in order eliminate the need for a nasogastric tube and IV hydration.
During the medication titration phase, IV fluids should be restricted to 50 ml/hr. When NG output
is less than 100 cc/day, the NG tube can be clamped for 12 hours and then removed. Once out,
patients are instructed that they may drink and even eat, although vomiting may occur. If a
venting gastrostomy tube is already in place, oral intake can be normal without fear of vomiting.
Supplemental parenteral hydration is only indicated if a) patients remain dehydrated despite oral
intake, and b) use of hydration to extend life is consistent with the patients’ goals (see Fast Facts
#133, 134).
References
1. Jatoi A, Podratz KC, Gill P, Hartmann LC. Pathophysiology and palliation of inoperable
bowel obstruction in patients with ovarian cancer. J Support Oncol. 2004; 2(4):323-34.
PMID: 15357517.
2. Adler DG. Management of malignant colonic obstruction. Curr Treat Options
Gastroenterol. 2005; 8(3):231-237. PMID: 15913512.
3. Ripamonti C, Mercadante S. How to use octreotide for malignant bowel obstruction. J
Support Oncol. 2004; 2(4):357-64. PMID: 15357519.
4. Mercadante S, Casuccio A, Mangione S. Medical treatment for inoperable malignant
bowel obstruction: a qualitative systematic review. J Pain Symptom Manage 2007;
33:217–223.
5. Myers J, Tamber A, Farhadian M. Management of treatment-related intermittent partial
small bowel obstruction: the use of octreotide. J Pain Symptom Manage 2010; 39:e1–e3.
6. Currow DC, et al. Double-blind, placebo-controlled randomized trial of octreotide in
malignant bowel obstruction. J Pain Symptom Manage 2015; 49: 814-21.
7. Srivastava M, Brito-Dellan N, Davis MP, Leach M, Lagman R. Olanzapine as an
antiemetic in refractory nausea and vomiting in advanced cancer. J Pain Symptom
Manage 2003; 25:578–582.
8. Soriano A, Davis MP, et al. Malignant bowel obstruction: individualized treatment near
the end of life. CCJM 2011 Mar;78(3):197-206
published August 2005; 3rd Edition May 2015. Current version re-copy-edited September 2009.
Dosing corrected/updated June 2011 for IV scopolamine; re-edited in May 2015.
Facts.
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!

MANAGEMENT OF HICCUPS
Chad Farmer MD
Background Hiccups (singultus) are distressing to patients and families; when chronic, they
diminish quality of life. A hiccup is an involuntary reflex involving the respiratory muscles of the
chest and diaphragm, mediated by the phrenic and vagus nerves and a central (brainstem) reflex
center. A single episode can last for a few seconds to as long as several days. If they last longer
than 48 hours hiccups are termed persistent; longer than one month, intractable. Etiologies
range from stress/excitement to cancer, myocardial infarction, esophageal or gastric distension,
liver disease, uremia, IV steroids, CNS lesions, chemotherapy, and idiopathic. Irritation of the
vagus nerve or diaphragm is a common pathophysiologic mechanism.
Management Once hiccups have lasted beyond a time-limited annoyance, deciding on
therapeutic intervention should be based on a thorough clinical assessment and, if possible,
treatment directed at the underlying cause. A thorough history, review of medications, focused
review of systems, and physical exam may help guide initial choice of treatment. Many drug and
non-drug treatments have been used, but there is little evidence of any one superior approach to
management; virtually all current data are anecdotal. The patient’s prognosis, current level of
function, and potential adverse effects from any proposed treatment should be considered.
Pharmacologic Therapy
• Anti-Psychotics: Chlorpromazine – the only FDA approved drug for hiccups. Dose: 25-50
mg PO TID or QID. Can also be given by slow IV infusion (25-50 mg in 500-1000 ml of NS
over several hours). Haloperidol – a useful alternative to chlorpromazine; give a 2-5 mg
(SubQ/PO) loading dose followed by 1-4 mg PO TID.
• Anti-Convulsants: Gabapentin – at doses of 300-400 TID has been described as effective
in multiple case reports. Its dual role as an analgesic may make it an especially attractive
therapeutic agent. Phenytoin – reportedly effective in patients with a CNS etiology of their
hiccups. Dose: 200 mg slow IV push followed by 300 mg PO daily. Others: Valproic Acid and
Carbamazepine have been reported to work for selected patients.
• Miscellaneous: Baclofen – the only drug studied in a double blind randomized controlled
study for treatment of hiccups. 5 mg PO q8 hours did not eliminate hiccups but did provide
symptomatic relief in some patients. Metoclopramide – 10 mg PO QID is an option,
especially if stomach distension is the etiology. Nifedipine – 10 mg BID with gradual increase
up to 20 mg TID has been suggested as a relatively safe alternative if other interventions
have failed. Other drugs that have been tried with very limited success include: amitriptyline,
sertraline, inhaled lidocaine, ketamine, edrophonium, methylphenidate, and amantidine.
Non-Pharmacologic Therapy There are many well known, time-honored home remedies:
gargling with water, biting a lemon, swallowing sugar, or producing a fright response. Other
approaches are directed at a) vagal stimulation such as carotid massage or valsalva
maneuver; b) interruption of phrenic nerve transmission via rubbing over the 5th cervical
vertebrae; or c) interrupting the respiratory cycle through sneezing, coughing, breath holding,
hyperventilation, or breathing into a paper bag. Other interventions such as acupuncture,
diaphragmatic pacing electrodes, or surgical ablation of the reflex arc can be considered
when other treatments fail.
References
1. Kolodzik PW, Eilers, MA. Hiccups (singultus): review and approach to management.
Ann Emerg Med. 1991; 20:565-573.
2. Lewis J. Hiccups: causes and cures. J Clin Gastro. 1985; 7:539-552.
3. Rousseau, P. Hiccups. Southern Med J. 1995; 2:175-181.
4. Bondi N, Bettelli, A. Treatment of hiccup by acupuncture in patients under anesthesia
and in conscious patients. Minerva Med. 1981; 72:2231-2234.
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5. Ramirez FC, Graham DY. Treatment of intractable hiccup with baclofen: results of a
double-blind, randomized, controlled, cross-over study. A J Gastro. 1992; 87:1789-91.
6. Physicians’ Desk Reference. 61st Edition. Thomson PDR; 2007. Available at http://
pdr.net.
7. Smith HS, Busracamwongs A. Management of hiccups in the palliative care population.
Am J Hosp Pall Care. 2003; 20:149-54.
8. Vaidya V. Sertraline in the treatment of hiccups. Psychosomat. 2000; 41:353-355.
9. Hernandez JL, et al. Gabapentin for intractable hiccup. Am J Med. 2004; 117:279-81.
10. Marinella, Mark A. "Diagnosis and management of hiccups in the patient with advanced
cancer." J support Oncol 7.4 (2009): 122-7.
11. Wilcox SK, Garry A, Johnson MJ. Novel use of amantadine to treat hiccups. Journal of
Pain and Symptom Management 2009; 38: 460-5. Volume 38, Issue 3, September 2009,
Pages 460–465.
edited by Drew A Rosielle and published October 2007; 3rd Edition June 2015. Current version re-
copy-edited April 2009; then again June 2015.
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!

SWALLOW STUDIES, TUBE FEEDING, AND THE DEATH SPIRAL
David E Weissman MD
Introduction The reflex by families and doctors to provide nutrition for the patient who cannot
swallow is overwhelming. It is now common practice for such patients to undergo a swallowing
evaluation and if there is significant impairment to move forward with feeding tube placement
(either nasogastric or gastrostomy) – see Fast Fact #128. Data suggest that in-hospital mortality
for hospitalizations in which a feeding tube is places is 15-25%, and one year mortality after
feeding tube placement is 60%. Predictors of early mortality include: advanced age, CNS
pathology (stroke, dementia), cancer (except early stage head/neck cancer), disorientation, and
low serum albumin.
The Tube Feeding Death Spiral The clinical scenario, the tube feeding death spiral, typically
goes like this:
1. Hospital admission for complication of “brain failure” or other predictable end organ
failure due to primary illnesses (e.g. urosepsis in setting of advanced dementia).
2. Inability to swallow and/or direct evidence of aspiration and/or weight loss with little oral
intake.
3. Swallowing evaluation followed by a recommendation for non-oral feeding either due to
aspiration or inadequate intake.
4. Feeding tube placed leading to increasing “agitation” leading to patient-removal or
dislodgement of feeding tube.
5. Re-insertion of feeding tube; hand and/or chest restraints placed.
6. Aspiration pneumonia.
7. Intravenous antibiotics and pulse oximetry.
8. Repeat 4 – 6 one or more times.
9. Family conference.
10. Death.
Note: at my institution, the finding of a dying patient with a feeding tube, restraints, and pulse
oximetry is known as Weissman’s triad.
Suggestions
• Recognize that the inability to maintain nutrition through the oral route, in the setting of a
chronic life-limiting illness and declining function, is usually a marker of the dying
process. Discuss this with families as a means to a larger discussion of overall end of life
goals.
• Ensure that your colleagues are aware of the key data and recommendations on tube
feedings (see Fast Fact #10).
• Ensure there is true informed consent prior to feeding tube insertion—families must be
given alternatives (e.g. hand feeding, comfort measures) along with discussion of goals
and prognosis.
• Assist families by providing information and a clear recommendation for or against the
use of a feeding tube. Families who decide against feeding tube placement can be
expected to second guess their decision and will need continued team support.
• If a feeding tube is placed establish clear goals (e.g. improved function) and establish a
timeline for re-evaluation to determine if goals are being met (typically 2-4 weeks).
References
1. Finucane TE, et al. Tube feeding in patients with advanced dementia. JAMA. 1999;
282:1365-1369.
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2. Finucane TE, Bynum JP. Use of tube feeding to prevent aspiration pneumonia. Lancet.
1996; 348:1421-24.
3. Cowen ME et al. Survival estimates for patients with abnormal swallowing studies. JGIM.
1997; 12:88-94.
4. Rabeneck L, et al. Long term outcomes of patients receiving percutaneous endoscopic
gastrostomy tubes. JGIM. 1996; 11:287-293.
5. Grant MD, et al. Gastrostomy placement and mortality among hospitalized Medicare
beneficiaries. JAMA. 1998; 279:1973-1976.
6. Mitchell SL. Clinical Crossroads: a 93-year-old man with advanced dementia and eating
problems. JAMA. 2007; 298:2527-2536.
7. Cervo FA, Bryan L, Farber S. To PEG or not to PEG. A review of evidence for placing
feeding tubes in advanced dementia and the decision-making process. Geriatrics. 2006;
61:30-35.
edited by Drew A Rosielle MD and published October 2007; 3rd Edition June 2015.
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!

INTERVENTIONAL OPTIONS FOR MALIGNANT UPPER GI OBSTRUCTION
James Ouellette DO, Lisa Patterson MD, and Paula Termuhlen MD
Background Patients with unresectable cancers of the upper gastrointestinal tract often suffer
severe symptoms due to pain, nausea and vomiting, weight loss, cachexia, and poor food
tolerance. This can be related to gastric and duodenal cancers causing intrinsic obstruction of the
intestinal lumen or pancreatic and biliary cancers causing extrinsic biliary compression.
Management options vary depending on the site of obstruction, the patient’s functional status, the
patient-defined goals of care, and estimated prognosis. Fast Fact #45 discussed medical
management options. This Fact Fact reviews interventional approaches for upper GI
obstructions, especially when further radiation, chemotherapy, medical management, or curative
surgical options are longer helpful. Listed below are treatment options for managing different
sites of obstruction (listed from least invasive to most invasive). Management decisions for these
problems are complex, requiring a multi-disciplinary approach (involving surgery,
gastroenterology, medical and radiation oncology, radiology, and palliative care) to achieve the
best possible outcome with minimum morbidity.
Esophageal obstruction
1) External beam radiation therapy (successful in 40% of patients).
2) Endoscopic laser therapy (can be repeated every 4-6 weeks).
3) Endoscopic/fluoroscopic stenting (different stent materials are available for different
situations).
Gastric or Duodenal obstruction
1) Nasogastric tube decompression (poor long-term solution due to patient discomfort).
2) Venting gastrostomy tube, which allows for drainage of intestinal contents (can be placed
endoscopically, laparoscopically, or with open surgery).
3) Janeway gastrostomy (surgically created gastrocutaneous fistula).
4) Endoscopically/fluoroscopically placed stent across the site of obstruction (e.g. pylorus).
5) Laparoscopic gastrojejunostomy.
6) Open gastrojejunostomy.
If unable to restore continuity of the gastrointestinal tract with a surgical procedure to bypass the
obstruction, a combination of a gastrostomy tube with a separate jejunostomy tube can be used.
This can provide enteral nutrition to the small intestine while venting the stomach. Patients can
enjoy the pleasure of eating, even if the food is drained through the G-tube.
Pancreaticobiliary obstructions
1) Stent placement (plastic or metal) across obstruction through an endoscopic procedure
(ERCP).
2) Stent/drain placement across obstruction by a radiologic procedure (transhepatic).
3) Laparoscopic cholecystojejunostomy (after gallstone absence is confirmed).
4) Open choledochojejunostomy, cholecystojejunostomy or hepaticojejunostomy.
Adjuvant medications may augment the efficacy of these interventions.
• Proton pump inhibitor to reduce gastric secretions.
• Sucralfate (Carafate) slurry, 1 gram q6 hours, for patients with ulcerated esophageal or
gastric lesions.
• Metoclopramide (Reglan) 10 mg tid to qid, as a prokinetic drug.
• Octreotide (Sandostatin) 50-100 micrograms q6-8 h for high volume output conditions.
• Dexamethasone 4-8 mg per day.
References
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1. Harris G, Senagore A, et al. The management of neoplastic colorectal obstruction with
colonic endoluminal stenting devices. Am J Surg. 2001; 181:499-506.
2. Acunas B, Poyanli A, Rozanes I. Intervention in gastrointestinal tract: the treatment of
esophageal, gastroduodenal and colorectal obstructions with metallic stents. Eur J Rad.
2002; 42:240-248.
3. Choi Y. Laparoscopic gastrojejunostomy for palliation of gastric outlet obstruction in
unresectable gastric cancer. Surg Endoscop. 2002; 16:1620-1626.
4. Tang CN, Siu WT, et al. Laparoscopic biliary bypass – a single centre experience.
Hepatogastroenterology. 2007; 54:503-7.
5. Jeurnink SM, Steyerberg EW, et al. Gastrojejunostomy versus stent placement in patients
with malignant gastric outlet obstruction: a comparison in 95 patients. J Surg Oncol. 2007;
96:389-96.
6. Frech EJ, Douglas AG. Endoscopic therapy for malignant bowel obstruction. J Supp Oncol.
2007; 5:303-310,319.
7. Laval G, Arvieux C, et al. Protocol for the treatment of malignant inoperable bowel
obstruction: a prospective study of 80 cases at Grenoble University Hospital Center. J
edited by Drew A Rosielle and published December 2007; 3rd Edition June 2015. Current version
!17
!
DIARRHEA IN PALLIATIVE CARE
Jeffrey Alderman MD
Diarrhea is a debilitating and embarrassing problem, defined as an abnormal looseness of the
stools (increased liquidity or decreased consistency). Patients with uncontrolled diarrhea are at
increased risk for dehydration, electrolyte imbalance, skin breakdown, and fatigue.
Common Causes Diarrhea can usually be divided into different types and treatment will vary
depending on cause: secretory, osmotic, mechanical, or disordered motility. In palliative care, the
overuse of laxatives, typically seen when the management of constipation is suddenly ‘stepped-
up,’ is a common cause. Other causes include partial intestinal obstruction, pancreatic
insufficiency, Clostridium difficile infection, and radiation enteritis. Chemotherapeutics are another
common cause, especially in advanced cancer where the incidence can be up to 60% (diarrhea
may be even more common with chemotherapy regimens with 5 flourouracil boluses or
combination of irinotecan and fluoropyrimidines). Infectious diarrhea is especially common in HIV
infection (Cryptosporidia, Giardia lambila, E. histolytica, and Cytomegalovirus). Severe
constipation and fecal impaction can also cause diarrhea as backed-up, liquefied stool may be all
that the patient can pass (‘overflow diarrhea’).
Evaluation Review diet, medications, laxatives, procedures, timing of movements in relation to
ingestion of food or liquids, and a description of quantity and quality of stool. When performing a
physical exam, make sure to palpate the abdomen and do a rectal exam. Radiographs are often
not necessary, but may help clarify a partial bowel obstruction or overflow diarrhea. Keep in mind
that patients at the end-of-life are also at risk for developing the same diarrheal illnesses that
occur in the general population (viral/bacterial gastroenteritis, adverse effects of medications).
Treatment
• General Ensure adequate hydration; encourage sips of clear liquids; parenteral hydration
should be considered for severe dehydration. Simple carbohydrates, toast or crackers, will
add back small amounts of electrolytes and glucose; milk and other lactose-containing
products should be avoided.
• Medications include bulk forming agents, antimicrobials, adsorbents, and opioids.
o Kaolin and Pectin (Kaopectate®) is a suspension of adsorbent and bulk-forming agents,
which can provide modest relief from diarrhea. However, kaolin-pectin may take up to 48
hours to produce an effect and can interfere with the absorption of certain medications.
o Antibiotics: infectious diarrhea should be identified and treated with appropriate
antibiotics, particularly C. difficile enteritis.
o Bismuth has an additional antimicrobial effect, and can be added for increased
symptomatic control against organisms such as enterotoxigenic E. Coli.
o Loperamide (Imodium®), an opioid, reduces peristalsis in the gut, increases water
reabsorption, and promotes fecal continence, making it a potent anti-diarrheal agent.
Because it only weakly crosses the blood-brain barrier, loperamide’s side effect profile is
more favorable than other opioids (e.g. codeine or diphenoxylate [Lomotil®]). The initial
dose of loperamide is 4 mg, with titration to 2 mg after each loose stool, with the typical
dose being 4 – 8 mg per day. Although the package insert recommends a maximum of
16 mg in a 24-hour period, up to 54 mg per day of loperamide has been used in palliative
care settings with few adverse effects. Note: loperamide should be used with caution if
an infectious diarrhea is suspected.
o Aspirin and Cholestyramine can reduce the diarrhea in radiation-induced enteritis, as
can addition of a stool bulking agent such as psyllium (Metamucil™).
o Mesalamine and other antiinflammatories are used for inflammatory bowel disease.
o Pancreatic Enzymes such as pancrelipase are used for pancreatic insufficiency.
o Octreotide, although costly, is effective with profuse secretory diarrhea seen in HIV
disease, chemotherapy induced diarrhea, and those with high effluent volume from a
stoma. It may be given via continuous subcutaneous infusion at a rate of 10 – 80 mcg
every hour until symptoms improve.
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o Budesonide, probiotics and activated charcoal have been described in the literature
for use in chemotherapy induced diarrhea, but there role in the clinical setting is not yet
established.
References
1. Doyle D, et al, eds. Oxford Textbook of Palliative Medicine. 3rd ed. New York, NY: Oxford
2. Fallon M, O'Neill B. ABC of palliative care. Constipation and diarrhoea. BMJ. 1997;
315:1293-6.
3. Saunders DC. Principles of symptom control in terminal care. Med Clin North Amer. 1982;
6: 1175.
4. Berger A, et al, eds. Principles and Practice of Palliative Care and Supportive Oncology. 3nd
ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2006.
5. McEvoy GK, ed. AHFS Drug Information 2003. Bethesda, MD: American Society of Health-
System Pharmacists; 2003: pp2740-41.
6. Ruppin H. Review: loperamide--a potent antidiarrhoeal drug with actions along the
alimentary tract. Alimentary Pharmacology & Therapeutics. 1987; 1(3):179-90.
7. Stein A, Voigt W, and Jordan K. Chemotherapy-induced diarrhea: pathophysiology,
frequency and guideline-based management. Therapeutic advances in medical oncology
2010; 2: 1 51-63
re-copy-edited April 2009; then again by Sean Marks MD June 2015.
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!

INVASIVE TREATMENT OPTIONS FOR MALIGNANT BOWEL OBSTRUCTION
Robert S Krouse MD
Background
Malignant bowel obstruction (MBO) is a common problem in patients with ovarian and colorectal
cancers. MBO also occurs with other abdominal (e.g. gastric and pancreatic) and non-abdominal
malignancies. MBO may be related to cancer (intraluminal or extraluminal tumor growth), its
treatment (e.g. radiation enteritis), or benign etiologies (e.g. adhesions or internal hernias).
Invasive treatment options should be considered for all patients except those who are actively
dying (see Fast Fact #3). In cases where surgical management is not feasible, medical
management can be very effective at relieving symptoms (see Fast Fact #45).
Goals of Treatment
The goals of treatment include relieving nausea and vomiting, allowing oral intake, alleviating
pain, and permitting the patient to return to their chosen care setting. Although it is recognized
that improvement in quality of life after surgery is variable (42-85%), there is no consistent
parameter used to determine this clinical outcome. Operations may offer an advantage of an
increased survival.
Surgical Approaches
The optimal procedure is that which offers the quickest, safest, and most efficacious ability to
alleviate the obstruction and improve symptoms. Options include bowel resection (which may
lead to the best overall outcome), bypass, or a gastrostomy. An intestinal stoma may be
necessary after resection or to adequately bypass the blockage. Laparoscopic procedures may
be attempted, although this approach may be difficult due to adhesions, carcinomatosis, or bowel
dilatation. Cytoreductive procedures (resection of intraperitoneal tumor) frequently carry a high
morbidity and usually are only considered with very low grade tumors, such as psuedomyxoma
peritonii. Many patients are deemed inoperable (6.2-50%), with the most frequent reasons being
extensive tumor spread, multiple partial obstructions, and inability to correct obstructions
surgically.
Surgical risks must be carefully considered prior to an operation, as morbidity (42%) and mortality
(5-32%) are common, and the re-obstruction rate is high (10-50%). Poor prognostic indicators for
surgical intervention include ascites, carcinomatosis, palpable intra-abdominal masses, multiple
bowel obstructions, prior obstructions and very advanced disease with poor performance status.
Endoscopic Approaches
Endoscopic procedures are suited for patients who are poor operative candidates or who decline
an open operative intervention. The major approaches include stenting and percutaneous
endoscopic gastrostomy (PEG) tube placement. Stenting may include procedures to initially
canalize the lumen (e.g. laser or balloon dilatation). Endoluminal wall stents have a high
success rate for relief of symptoms (64-100%) in complete and incomplete colorectal
obstructions, and in over 70% of upper intestinal malignant obstructions including gastric outlet,
duodenal and jejunal obstructions. While risks include perforation (0-15%), stent migration
(0-40%), or re-occlusion (0-33%), stents can frequently lead to adequate palliation for long
periods of time. Stent occlusion by tumor in-growth is usually amenable to another endoscopic
intervention.
PEG tubes are generally well tolerated “venting” procedures that can alleviate symptoms of
intractable vomiting and nausea for upper GI obstructions. In combination with other medical
techniques, both open and percutaneous gastrostomy offer the possibility of intermittent oral
intake. Complications are rare, even when puncturing other organs. The presence of significant
ascites is a relative contraindication.
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References:
1. Feuer DJ, Broadley, KE, Shepherd JH, Barton DP. Systematic review of surgery in
malignant bowel obstruction in advanced gynecological and gastrointestinal cancer.
Gynecol Oncol. 1999; 75:313-322.
2. Harris GJC, Senagore AJ, Lavery IC, Fazio VW. The management of neoplastic
colorectal obstruction with colonic endoluminal stenting devices. Am J Surg. 2001;
181:499-506.
3. Soetikno RM, Carr-Locke DL. Expandable metal stents for gastric outlet, duodenal, and
small intestinal obstruction. Gastrointestinal Endoscopy Clinics of North America. 1999;
9:447-458.
4. Campagnutta E, Cannizzaro R. Percutaneous endoscopic gastrostomy (PEG) in
palliative treatment of non-operable intestinal obstruction due to gynecologic cancer: a
review. Eur J Gynaecol Oncol. 2000; 21:397-402.
in August 2004. Current version re-copy-edited in April 2009; web-sites updated; revised again
July 2015.
!21
!

THE SPEECH PATHOLOGIST AND SWALLOWING STUDIES
Carol Monteleoni MS, CCC-SLP
Background Speech pathologists can facilitate communication among members of the

medical team, and between the team and the patient/family, to make treatment decisions that
honor patient wishes. Speech pathology services for symptom control to enable the individual to
maintain activities of daily living and basic functional skills are reimbursable under the Medicare
Hospice Benefit (see Fast Facts #82, 87, 90). Swallowing studies are used to evaluate a patient’s
ability to safely ingest oral food and oral secretions, yet the role of swallowing studies to facilitate
optimal care near the end of life is not clear. This Fast Fact will review the indications and
contraindications for a swallowing study and the role of the speech pathologist.
Potential Indications for a swallowing evaluation (Bedside or Instrumental)
• Acute stroke or other neurological condition affecting oral motor function (see Fast Facts
#201, 300).
• Tracheostomy or recent endotracheal extubation.
• Changes to oropharyngeal anatomy secondary to tumor, surgery, trauma, etc.
• Observed difficulty swallowing food or liquid.
• Recurrent upper respiratory infections or pneumonias.
• Reduced oral food intake; unexplained weight loss or fever.
Contra-indications for swallowing evaluation (Instrumental only)
• Imminent death—death expected within 2 weeks (See Fast Fact #3).
• Death expected within weeks from any progressive terminal illness.
• Reduced level of arousal (e.g. coma/obtundation).
Types of swallowing studies
• Bedside dysphagia evaluation involves an in-depth feeding/swallowing history, oral
peripheral examination, and trial swallows of various food consistencies. Bedside
evaluation cannot rule out silent aspiration.
• Instrumental swallowing evaluation is performed via modified barium swallow
(videofluoroscopy), fiber-endoscopic evaluation of swallowing (FEES), or fiber-
endoscopic evaluation of swallowing with sensory testing (FEEST). All of these
instrumental assessments require the patient to be alert, cooperative, and able to follow
simple commands.
Speech Pathologist Role The decision to perform a swallowing evaluation should be made
based on the overall goals of care and expected prognosis. Consultation with your
speech pathologist prior to ordering an evaluation can help clarify how you will use any
new information to improve patient comfort and satisfaction. If performed, the speech
pathologist will evaluate the patient’s swallowing and recommend feeding strategies
which may include:
• Appropriate food consistencies.
• Positioning of the head and neck.
• Timing of meals
• Promoting family involvement.
Using the Speech Pathologist’s Assessment Decisions regarding feeding management

should not be made based solely upon the speech pathologist’s assessment of swallowing
dysfunction, which may be a sign of the final stage of life in many terminal conditions. In addition,
feeding tube placement decisions in this population should not be based on the likelihood of
aspiration. In patients with advanced dementia and other terminal conditions, feeding tubes have
not been found to reduce the incidence of aspiration and can significantly impair the dying
patient’s quality of life (see Fast Facts #10, 84).
!22
References:
1. Finucane TE, Christmas C, Travis K. Tube feeding in patients with advanced dementia.
JAMA. 1999; 282:1365-1369.
2. Levy A, Dominguez-Gasson L, Brown E, Frederick C. Technology at End of Life
Questioned. The ASHA Leader. 2004; July 20: pages 1, 14.
3. Ahronheim JC. Nutrition and hydration in the terminal patient. Clinics in Geriatrics. 1996:
12(2):379-391.
4. Monteleoni C, Clark E. Using rapid-cycle quality improvement methodology to reduce
feeding tubes in patients with advanced dementia: before and after study. BMJ. 2004;
329:491-494.
5. Pollens R. Role of the speech-language pathologist in palliative hospice care. J Palliat
Med. 2004; 7(5):694-702.
in December 2004. Version re-copy-edited in April 2009; revised again July 2015 by Mary Rhodes
MD.
!23
!

CARCINOID SYNDROME: SYMPTOM MANAGEMENT
Stacey Shaffer and Robert Arnold MD
Background The carcinoid syndrome (CS) is a symptom complex resulting from hormone
secretion in patients with carcinoid tumors. Carcinoid tumors typically grow slowly, and patients
may live for many years following diagnosis. CS becomes manifest only when sufficient
concentration of hormones reach the systemic circulation, most commonly in the presence of liver
metastases. This Fast Fact will focus on managing the symptoms of CS.
Symptoms and Causes The CS includes the complex of: flushing, diarrhea, abdominal
cramping, cyanosis, bronchoconstriction, and symptoms of right heart failure. Compared with the
general population and other cancer patients, CS sufferers may also be at increased risk for
cognitive impairment. Other specific symptoms depend on the hormones the tumor secretes.
Serotonin-secreting tumors cause diarrhea and cramping; bradykinin and histamine secretion
lead to flushing and cyanosis. Carcinoid tumors may also produce somatostatin, norepinephrine,
dopamine, gastrin, vasoactive intestinal peptide, and other hormones. Drugs that block the
hormonal secretion can help to control the symptoms of carcinoid syndrome.
Somatostatin Analogs These drugs are the treatment of choice for CS. Three formulations
are available: short-acting octreotide (continuous infusion or 50-500 mcg TID, IV or
subcutaneously); depot octreotide (standard dose is 30 mg intramuscularly every 4 weeks;
however, doses up to 40 to 60 mg every 4 weeks may offer added benefit); and lanreotide
(standard dosing is 30 mg every other week intramuscularly). 50-70% of patients experience a
significant reduction of diarrhea and flushing episodes within seven days. Efficacy and side effect
profiles for the three preparations are similar. Side effects include pain at the injection site,
abdominal bloating, fatigue, transient fever, elevated serum glucose, and asymptomatic biliary
lithiasis.
Interferon Interferon alpha is effective in controlling both diarrhea and flushing, although it is
inferior to the somatostatin analogs. The dose is 3-9 mU subcuteneously three to seven
times per week. Interferon alpha therapy is often limited by its side effects: fever,
anemia, thrombocytopenia, neutropenia, fatigue, depression, and flu-like symptoms.
Other Drugs & Symptom-Specific Treatments

• Diarrhea: Cyproheptadine is an alternative treatment for carcinoid-associated diarrhea.
60% of patients report improvement within one week. The dosage is 4 mg TID given
orally as a tablet; it can be titrated up to 0.5 mg/kg per day. Side effects include sedation,
dry mouth, dizziness, mild blurring of vision, nausea, and vomiting. Loperamide and
opioids are non-specific anti-diarrheal agents that can be used for mild symptoms.
• Wheezing: bronchodilators.
• Heart failure: diuretics; tricuspid valve replacement.
Non-Drug Treatments Patients should be counseled to identify and eliminate stressors that
reproducibly cause symptoms—this may include specific stressful situations, foods, or alcohol.
Other Other treatments for refractory symptoms include systemic chemotherapy, hepatic artery
embolization, hepatic chemoembolization, or debulking surgery of hepatic metastases.
References
1. Kulke, MH, Mayer, RJ. Medical progress: carcinoid tumors. N Engl J Med. 1999;
340:858-68.
2. Pasieka JL, Longman RS, et al. Cognitive impairment associated with carcinoid
syndrome. Annals of Surgery 2014; 259:355-359.
!24
3. di Bartololmeo M, Bajetta E, Buzzoni R, et al. Clinical efficacy of octreotide in the
treatment of metastatic neuroendocrine tumors. A study by the Italian Trials in Medical
Oncology Group. Cancer. 1996; 77:402-8.
4. Ruszniewski P, Ducreux M, Chayvialle J, et al. Treatment of carcinoid syndrome with the
longacting somatostatin analogue lanreotide: a prospective study in 39 patients. Gut.
1996; 39:279-83.
5. Garland J, Buscombe JR, Bouvier C, et al. Sandostatin LAR (long-acting octreotide
acetate) for malignant carcinoid syndrome: a 3-year experience. Aliment Pharmacol Ther.
2003; 17:437-44.
6. Strosberg JR, Benson AB, et al. Clinical benefits of above-standard dose of octreotide
LAR in patients with neuroendocrine tumors for control of carcinoid syndrome symptoms:
a multicenter retrospective chart review study. The Oncologist 2014; 19:930-936.
7. Moertel CG, Kvols LK, Rubin J. A study of cyproheptadine in the treatment of metastatic
carcinoid tumor and the malignant carcinoid syndrome. Cancer. 1991; 67:33-6.
8. Oberg K, Funa K, Alm G. Effects of leukocyte interferon on clinical symptoms and
hormone levels in patients with mid-gut carcinoid tumors and carcinoid syndrome. N Engl
J Med. 1983; 309:129-33.
9. Sitaraman SV, Goldfinger SE. Treatment of carcinoid tumors and the carcinoid syndrome.
In: Basow DS, ed. UpToDate. Waltham, MA; UpToDate; 2004.
in May 2005. Version re-copy-edited in April 2009; revised again July 2015 by Sean Marks MD
with references #2 and #6 added and incorporated into the text.
!25
!

Background Malignant ascites is the accumulation of abdominal fluid due to the direct effects
of cancer. This Fast Fact reviews the causes and diagnosis of malignant ascites. Fast Fact #177
will review its treatment.
Pathophysiology The pathophysiology of malignant ascites is incompletely understood.
Contributing mechanisms include tumor-related obstruction of lymphatic drainage, increased
vascular permeability, over-activation of the renin-angiotensin-aldosterone system, neoplastic
fluid production, and production of metalloproteinases that degrade the extracellular matrix.
Portal venous compression can also occur from metastatic invasion of the liver, leading to
peritoneal fluid accumulation.
Natural History The most common cancers associated with ascites are adenocarcinomas of
the ovary, breast, colon, stomach and pancreas. Median survival after diagnosis of malignant
ascites is in the range of 1-4 months; survival is apt to be longer for ovarian and breast cancers if
systemic anti-cancer treatments are available.
Presentation and Diagnostics Symptoms include abdominal distension, nausea, vomiting,
early satiety, dyspnea, lower extremity edema, weight gain, and reduced mobility. Physical exam
findings may include abdominal distention, bulging flanks, shifting dullness, and a fluid wave.
Plain abdominal x-rays are not specific, but may show a hazy or a “ground glass” appearance.
Ultrasound or CT scanning can confirm the presence of ascites and also demonstrate if the fluid
is loculated in discrete areas of the peritoneal cavity.
There are many potential causes of ascites in the cancer patient: peritoneal carcinomatosis,
malignant obstruction of draining lymphatics, portal vein thrombosis, elevated portal venous
pressure from cirrhosis, congestive heart failure, constrictive pericarditis, nephrotic syndrome,
and peritoneal infections.
Depending on the clinical presentation and expected survival, a diagnostic evaluation is usually
indicated as it will impact both prognosis and treatment approach. Key tests include the serum
albumin and protein level and a simultaneous diagnostic paracentesis, checking ascitic fluid white
blood cell count, albumin, protein, and cytology.
A SAAG > 1.1 g/dl indicates ascites due to, at least in part, increased portal pressures, with an
accuracy of 97%. This is most commonly seen in patients with cirrhosis, hepatic congestion,
CHF, or portal vein thrombosis.
A SAAG < 1.1 g/dl indicates no portal hypertension, with an accuracy of 97%; most commonly
seen in peritoneal carcinomatosis, an infectious process of the peritoneum, nephrotic syndrome,
or malnutrition/hypoalbuminemia.
Cytological evaluation is approximately 97% sensitive in cases of peritoneal carcinomatosis, but
is not helpful in the detection of other types of malignant ascites due to massive hepatic
metastasis or malignant obstruction of lymph vessels.
References
1. Thomas J, von Gunten CF. Diagnosis and Management of Ascites. In: Berger AM, Von
Roenn J, Schuster J, eds. Principles and Practice of Palliative Care and Supportive
Oncology. 3rd edition. Philadelphia, PA: Lippincott, Williams & Wilkins; 2006.
!26
198:999-1011.
4. Becker G. Galandi D. Blum HE. Malignant ascites: systematic review and guideline for
treatment. Eu J Cancer. 2006; 42:589-97.
!27
!

Background The natural history, presenting signs/symptoms, and diagnostic approach to the
patient with malignant ascites are discussed in Fast Fact #176; readers are encouraged to read
this Fast Fact to review the important role of determining the Serum Ascites-Albumin Gradient as
a diagnostic and treatment aid. This Fast Fact will review treatment approaches.
although no randomized trials have been completed. Patients with evidence of portal
hypertension (SAAG > 1.1) are more likely to respond to diuretics.
2. Paracentesis: Paracentesis can provide immediate relief of symptoms in up to 90% of

patients. Drainage of uncomplicated large-volume ascites (4-6 L/session) can be done
safely and quickly in the outpatient setting—including the home—or at the hospital bedside;
ultrasound guidance is necessary only when there is loculated fluid.
3. Drainage catheters: For patients who require frequent paracentesis, external drainage
catheters placed through the abdominal wall allow frequent or continuous drainage of ascites
fluid without repetitive needle insertions. Patients or caretakers may perform the drainage,
reducing visits to medical clinics. Several types of catheters are available:
a. Pigtail Catheter: A simple, temporary all-purpose catheter; they are prone to
complications when used over an extended duration (peritonitis, accidental removal,
leakage, occlusion), hence are rarely used now.
b. Tunneled Catheter: A catheter that prevents infection by promoting scarring around an
antibiotic-impregnated Dacron cuff in subcutaneous tissue. Used conventionally for
peritoneal dialysis, it is placed with ultrasound or fluoroscopic guidance and has lower
risks of infection and leakage than the pigtail catheter. Complications are reduced by
daily drainage for the first two weeks of cuff healing. The PleurX catheter is FDA
approved for malignant ascites and features a one-way rubber valve to prevent leaks
between draining sessions. Tunneled catheters are used in patients with life expectancy
of at least one month.
4. Vascular Shunts:
a. Peritovenous shunt (PVS) systems are designed to channel peritoneal fluid and proteins
in benign ascites back into the circulation via the superior vena cava. PVS has not been
shown to have clinically significant risk of disseminating tumor cells in malignant ascites.
A PVS is placed by interventional radiology under conscious sedation, and patients
typically require 24 hours of monitoring with a central venous line after the procedure.
The best response to PVS (only about 50%) is in ovarian and breast cancers. PVS is
recommended only in patients with a life expectancy of one to four months, considering
that eventual occlusion rate is up to 24%.
b. Transjugular Intrahepatic Portosystemic Shunt (TIPS) is a shunt between the portal vein
and hepatic vein, designed to reduce portal hypertension and improve sodium balance.
Most patients with malignant ascites do not have portal hypertension although TIPS
might be helpful in the occasional cancer with evidence of increased portal pressures
(SAAG > 1.1).
5. Hyperthermic Intraperitoneal Chemotherapy (HIPEC): This procedure is performed by

surgical oncology specialists and entails warmed chemotherapy being infused into the
peritoneal cavity for a short period of time. Most commonly this procedure is done along
with tumor debulking or cyto-reductive surgery (CRS). However, considering that recovery
from HIPEC with CRS can take 3 to 6 months, CRS-HIPEC is typically reserved for low-
!28
grade appendiceal primary cancers seeing that these cancers are associated with a longer
survival. For patients with anticipated shorter survivals, HIPEC without CRS can be done
laparoscopically (and is therefore associated with less morbidity) with high rates of ascites
control.
References
Roenn J, Schuster J. Principles and Practice of Palliative Care and Supportive Oncology.
3rd edition. Philadelphia, PA: Lippincott, Williams & Wilkins; 2006.
2. Adam RA, Adam YG. Malignant ascites: past, present, and future. J Am Coll Surg.
2004; 198:999-1011.
4. Becker G, Galandi D, Blum HE. Malignant ascites: systematic review and guideline for
5. Aslam N, Marino CR. Malignant ascites: new concepts in pathophysiology, diagnosis,
and management. Arch Int Med 2001;161:2733-7.
6. Smith EM, Jayson GC. The current and future management of malignant ascites.
Clinical Oncology. 2003; 15:59-72.
7. Pockros PJ, Esrason KT, Nguyen C, Duque J, Woods S. Mobilization of malignant
ascites with diuretics is dependent on ascitic fluid characteristics. Gastroenterology.
1992; 103:1302-1306.
8. Abeloff M, Armitage J, Niederhuber J, Kastan M, McKenna WG, eds. Clinical Oncology.
3rd edition. New York, NY: Churchill Livingstone; 2004: 1199-1205.
9. Covey AM. Management of malignant pleural effusions and ascites. J Support Oncol..
2005; 3:169-73.
10. White MA, Agle SC, et al. Denver peritoneovenous shunts for the management of
malignant ascites: a review of the literature in the post-LeVeen era. The American
Surgeon 2011;77: 1070-1075.
11. Randle RW, Swett KR, et al. Efficacy of cytoreductive surgery with hyperthermic
intraperitoneal chemotherapy in the management of malignant ascites. Ann of Surg Onc
2014;21: 1474-1479.
Version History: Current version copy-edited in May 2009; then again July 2015 by Sean Marks
MD: references #10 and #11 were added and incorporated into the text.
!29
HEPATIC ENCEPHALOPATHY IN ESLD
Julie Wilson Childers MD and Robert Arnold MD
Background Hepatic encephalopathy (HE) is a neuropsychiatric syndrome with a fluctuating

course associated with end stage liver disease (ESLD). HE symptoms, which are graded from 0
to IV, range from subtle personality or sleep disturbances to confusion and coma. Severe HE
(grade III or IV) is manifested by gross disorientation, bizarre behavior, stupor, or coma (1).
Without transplantation, severe HE signifies a poor prognosis (58% 1 year and 77% 3 year
mortality in one case series) (2). In addition, 15% of patients awaiting liver transplantation die
before receiving an organ (3).
Etiology The cause of HE is uncertain, but may be related to the accumulation of neurotoxic
substances normally metabolized by the liver; these include ammonia and endogenous
benzodiazepine-like substances that activate GABA-receptors to cause neurotoxicity.
Evaluation HE is a diagnosis of exclusion, and in one study 80% of cases were associated
with an identifiable secondary cause such as gastrointestinal bleeding, infection (including
spontaneous bacterial peritonitis), renal failure, alcohol withdrawal, excessive dietary protein,
volume depletion, or drugs (particularly benzodiazepines) (4). Because of its association with
coagulopathy, brain imaging often via a CT scan without contrast, may be needed to rule out
intracranial hemorrhage. Serum ammonia levels are usually elevated in HE, although the utility of
following ammonia levels has not been established.
Therapy begins with correction of the underlying causes if this is consistent with the goals of
care. Specific therapy of HE is aimed at limiting production of and increasing excretion of
intestinally derived toxins, particularly ammonia.
• Nonabsorbable disaccharides such as lactulose and lactitol are the mainstay of
treatment though there is a lack of controlled evidence supporting their use (5). These
agents not only cause increased transit time through the gut and less absorption of
toxins, but also promote bacterial fermentation, leading to a hostile environment for
ammonia-producing bacteria. The daily dose of lactulose should be titrated to result in
two to four soft stools daily. For most patients the daily dose is between 30 and 60 grams.
Side effects include gastrointestinal cramping, diarrhea, and flatulence.
• Nonabsorbable antibiotics such as neomycin and vancomycin were the first treatments
for HE. They lower ammonia by combating urea-producing bacteria in the gut.
Neomycin likely produces more rapid improvement than lactulose but its use is limited by
its nephro- and oto-toxic effects (5). Rifaximin is a nonabsorbable derivative of rifampin
which received orphan drug status from the FDA in 2005 for treatment of HE. Rifaximin,
given at 400 mg orally three times a day, is as effective as neomycin or lactitol and better
tolerated than other nonabsorbable antibiotics (6). Rifaximin costs $4.00 a pill (average
wholesale price). Because of this and its lack of clear superiority to disaccharides
rifaximin is considered a second-line agent for patients who cannot tolerate or who are
not responding to disaccharide therapy.
• Other therapies have limited efficacy in treating HE and play no clear role in its
management. These include branched chain amino acids (7), the benzodiazepine
antagonist flumazenil (8, 9), zinc, L-ornithine–L-aspartate and limitation of dietary protein
(10).
Advance care planning The patient's values, goals of care, and treatment options should be
discussed in the context of HE’s poor prognosis. A health care proxy should be established in
patients with cirrhosis before cognitive impairment prevents this.
Supportive care The patient and family must be educated to recognize HE’s symptoms,
understand its fluctuating course, and avoid precipitating factors when possible. They should also
be counseled about the risk of motor vehicle accidents. Patients who are confused should be
reoriented and measures should be taken to prevent falls, skin breakdown, and aspiration.
Intravenous fluids, nasogastric feeding, and airway protection are sometimes appropriate. Dose-
adjusted acetaminophen (<2 gm/day) is the first line analgesic. Opioids can worsen HE but are
!30
sometimes necessary to adequately treat pain; their use should be closely monitored and
balanced with the patient’s degree of suffering and goals of care (11). Dying patients should
receive attentive comfort care. Besides pain – dyspnea, restlessness, edema, and secretion
management are common challenges in dying ESLD patients.
References
1. Blei AT, Cordoba J. Practice guidelines: Hepatic encephalopathy. Am J
Gastroenterology. 2001; 96(7):1968-1976.
2. Bustamante J, Rimola A, Ventura PJ, Navasa M, Cirera I, Reggiardo V, et al. Prognostic
significance of hepatic encephalopathy in patients with cirrhosis. J Hepatol. 1999;
30:890–895.
3. Russo MW, LaPointe-Rudow D, Kinkhabwaa M, Emond J, Brown RS. Impact of adult
living donor liver transplantation on waiting time survival in candidates listed for liver
transplantation. Am J Transplantation. 2004; 4(3):427–431.
4. Fessel JM, Conn HO. An analysis of the causes and prevention of hepatic coma.
Gastroenterology. 1972; 62:191.
5. Als-Nielsen B, Gluud LL, Gluud C. Nonabsorbable disaccharides for hepatic
encephalopathy. Cochrane Database of Systematic Reviews 2004, Issue 2. Art. No.:
CD003044. DOI: 10.1002/14651858.CD003044.pub2.
6. Mas A, Rodes J, Sunyer L, et al. Comparison of rifaximin and lactitol in the treatment of
acute hepatic encephalopathy: results of a randomized, double-blinded, double-dummy,
controlled clinical trial. J Hepatol. 2003; 38(1):51-8.
7. Als-Nielsen B, Koretz RL, Kjaergard LL, Gluud C. Branched-chain amino acids for
hepatic encephalopathy. Cochrane Database of Systematic Reviews 2003, Issue 1. Art.
No.: CD001939. DOI: 10.1002/14651858.CD001939.
8. Barbaro G, Di Lorenzo G, Soldini M, et al. Flumazenil for hepatic encephalopathy grade
III and IVa in patients with cirrhosis: an Italian multicenter double-blind, placebo-
controlled, cross-over study. Hepatology. 1998; 28(2):374-8.
9. Als-Nielsen B, Gluud LL, Gluud C. Benzodiazepine receptor antagonists for hepatic
encephalopathy. Cochrane Database of Systematic Reviews 2004, Issue 2. Art. No.:
CD002798. DOI: 10.1002/14651858.CD002798.pub2.
10. Cordoba J, Lopez-Hellin J and Planas M, et al. Normal protein diet for episodic hepatic
encephalopathy. J Hepatol. 2004; 41:38–43.
11. Larson AM and Curtis JR. Integrating palliative care for liver transplant candidates: "Too
well for transplant, too sick for life". JAMA. 2006; 295(18):2168-76.
12. Leise, MD, Poterucha JJ, et al. Management of hepatic encephalopathy in the hospital.
Mayo Clinic Proceedings. 2014; 89:241-253.
then again July 2015 with reference #12 added and incorporated into the text.
!31
!32
!

PROGNOSIS IN DECOMPENSATED CHRONIC LIVER FAILURE
Brigid Dolan MD and Robert Arnold MD
Background In 2009, chronic liver disease and cirrhosis resulted in approximately 30,000
deaths, making it the twelfth leading cause of death in the United States. Patients with
compensated chronic liver failure (without ascites, variceal bleeding, encephalopathy, or jaundice)
have a median survival of 12 years. After decompensation, median survival drops to ~ 2 years.
This Fast Fact reviews prognosis in chronic liver failure, focusing on two validated prognostic
indices. Of note, these indices predict prognosis for patients without liver transplantation.
The Child’s-Turcotte-Pugh (CTP) score includes 5 variables, each scored 1-3:

Numerical Value
Variable 1 2 3
Ascites None Slight Moderate/Severe

Encephalopathy None Grade 1-2 Grade 3-4
Bilirubin (mg/dL) < 2.0 2.0-3.0 >3.0
Albumin (mg/L) > 3.5 2.8-3.5 <2.8
Increase in seconds from 1-3 4-6 >6.0
normal Prothrombin time
Patients are grouped into three classes based on the total CTP score, which is simply the sum of
the scores for each of the 5 variables. Patients scoring 5-6 points are considered to have ‘Class
A’ failure; their 1 and 2 year median survivals are 95% and 90%, respectively. A score of 7-9 is
considered Class B with median survivals of 80% at 1 year and 70% at two years. Class C
patients (10-15) have far greater mortality: 1-year median survival is 45% and 2-year is 38%.
Variations in the timing and subjectivity inherent in the scoring of the CTP (e.g. in grading ascites
or encephalopathy) are its major limitations. In addition, the scale does not include renal function,
an important prognostic factor in liver failure.
The Model for End-stage Liver Disease (MELD) score was developed in 2000 to overcome the
above-mentioned limitations and determine survival benefit from transjugular intrahepatic
portosystemic shunting. It is currently used to help determine organ allocation for liver
transplantation, and there is increasing evidence that it can also be used generally to predict
survival in patients with chronic liver failure. The MELD score relies on laboratory values alone
(serum creatinine, total bilirubin, and INR). An additional benefit over CTP is that it can predict
prognosis on the order of months with more precision – making it helpful for determining hospice
eligibility in the US. The formula to calculate MELD score is complex, and a calculator can be
found at: http://reference.medscape.com/calculator/meld-score-end-stage-liver-disease.
MELD Score Predicted 6 Predicted 12 month Predicted 24 month

month survival survival survival
0-9 98% 93% 90%
10-19 92% 86% 80%
20-29 78% 71% 66%
30-39 40% 37% 33%
!33
Other important prognostic variables The hepatorenal syndrome (HRS) – renal failure from
renal arterial under-filling due to decompensated liver failure – portends a particularly poor
prognosis. Most patients with type-1 HRS (rapid and severe renal failure) die within 8-10 weeks
even with therapy. Median survival with type-2 HRS (chronic, less severe renal failure with serum
creatinine usually 1.5-2 mg/dL) is around 6 months. Both older age and hepatocellular carcinoma
also adversely affect survival. While the CTP and MELD systems provide objective guidance to
prognostication in liver failure, clinical judgment, patient comorbidities, the rate of
decompensation, and the likelihood of transplantation all should additionally affect the
assessment and communication of a patient’s prognosis in liver disease.
References
1. Heron M. Deaths: Leading causes for 2009. National Vital Statistics Reports 2012; 61(7).
2. D’Amico, et al. Natural history and prognostic indicators of survival in cirrhosis: a
systematic review of 118 studies. J Hepatology. 2006; 44:217–231.
3. Diehl A. Alcoholic and nonalcoholic steatohepatitis. In: Goldman L, Ausiello D, eds. Cecil
Textbook of Medicine. 22nd ed. Philadelphia, PA: Saunders; 2004:935–6.
4. Cholongitas, et al. Systematic review: the model for end-stage liver disease – should it
replace Child-Pugh’s classification for assessing prognosis in cirrhosis? Alimentary
Pharmacol Therapeutics. 2005; 22:1079-1089.
5. Said, et al. Model for end stage liver disease score predicts mortality across a broad
spectrum of liver disease. J Hepatology. 2004; 40:897-903.
6. Cardenas, et al. Hepatorenal Syndrome: A dreaded complication of end-stage liver
disease. Am J Gastroenterol. 2005; 100:460-467.
then again in July 2015.
!34
!

OPIOID USE IN LIVER FAILURE
Carlene Oliverio PharmD, BCPS, Natalie Malone PharmD, Drew A Rosielle MD
Background Most opioids are at least partially metabolized by the liver, complicating their use
in liver failure. This Fast Fact discusses the use of opioids in patients with liver failure (see also
Fast Facts #161 about opioid use in renal failure, #176 and #177 about managing ascites and
#189 about prognostication in end-stage liver disease). Note: while there are plenty of
pharmacokinetic data about opioids & liver failure, all the clinical recommendations below are
empiric and not based on clinical outcomes research.
Hepatic Opioid Metabolism There are two different types of chemical reactions involved in
hepatic drug metabolism. The first, oxidation/reduction reactions, occurs through the cytochrome
(CYP) P450 enzyme system. The CYP450 enzymes most relevant in palliative medicine include
CYP1A2, 2D6, 2C9, 2C19, 3A3 and 3A4; most opioids are metabolized by these enzymes. In
hepatic failure, opioid clearance is reduced and drug bioavailability is increased. These changes
can be secondary to reduced hepatic blood flow (limiting first-pass metabolism) or decreased
CYP450 enzyme levels in these patients. Conjugation and glucuronidation comprise the second
group of chemical reactions in the liver. These reactions are less affected in hepatic disease due
to glucuronidation enzyme preservation and also because of extrahepatic glucuronidation
processes. Glucuronidated opioid metabolites are generally renally excreted. Changes such as
decreased serum albumin and ascites can also alter opioid volume of distribution which can lead
to either increased or decreased drug concentrations, although there is no practical way to ‘test’
for or predict this apart from close clinical observation.
Morphine Morphine is metabolized by glucuronidation to two major metabolites, morphine-3-

glucuronide (M3G) and morphine-6-glucuronide (M6G). M6G is an active analgesic that is more
potent than morphine, while M3G has no analgesic effect but contributes to neurotoxic side
effects such as confusion. Morphine accumulation has been reported in liver disease which can
result from decreased plasma clearance and/or increased elimination half-life of the parent drug.
In patients with early liver disease, initial lower doses should be used, but at normal dosing
intervals. However, as the disease progresses to advanced hepatic failure, longer dosing intervals
may be necessary.
Oxycodone Oxycodone is metabolized to two different metabolites by CYP2D6 and 3A4.

However, neither metabolite contributes significantly to analgesia. In advanced liver failure,
oxycodone’s maximum concentration increases 40%, and immediate-release oxycodone’s half-
life increases to 4.6-24.4 hours (average 14 hours; its usual half-life is ~3.5 hours). Initial
oxycodone dosing in patients with severe hepatic failure should be reduced to 30%-50% of the
recommended starting dose.
Codeine & Meperidine Both these drugs should be avoided entirely in patients with liver failure.
Codeine is a prodrug that is hepatically converted to morphine by CYP2D6. In patients with liver
dysfunction, pain control can be compromised if codeine is not metabolized. Meperidine is
metabolized by CYP3A4 to normeperidine and also by hydrolysis. In hepatic disease, meperidine
clearance is reduced and its half-life is prolonged. Seizures, a major side effect of meperidine and
normeperidine, can occur at reduced doses in patients with hepatic failure (see Fast Fact #71).
Hydromorphone & Hydrocodone Hydromorphone is glucuronidated to metabolites which

have no analgesic properties but can be neurotoxic (see Fast Facts #57, 58, 142).
Hydrocodone is a prodrug metabolized by CYP2D6 to hydromorphone and other metabolites,
and is only available in combination with non-opioids such as acetaminophen. Hydrocodone
dose titrations are limited by the non-opioid component, and overconsumption of acetaminophen-
containing products is hepatotoxic. In patients with severe liver disease, initial starting doses of
!35
each drug should be reduced to 50% of normal and as the disease progresses, prolonged dosing
intervals may also be necessary.
Fentanyl Fentanyl is primarily metabolized by CYP3A4 and quickly redistributes to muscle

and fat upon administration. In single-bolus studies, intravenous fentanyl’s pharmacokinetics
were unchanged by liver failure, however its half-life is prolonged in liver failure with repeated
dosing or high dose therapy. Transdermal fentanyl has not been adequately studied in liver
failure. Hepatic failure can alter skin permeability and drug absorption; the clinical relevance of
this, if any, has not been determined. Some experts suggest fentanyl is a preferred opioid in liver
failure (1, 4), although this judgment appears to be entirely empiric.
Methadone Methadone is metabolized by CYP3A4, 2D6 and 1A2. Methadone’s clearance is

reduced in severe liver disease. Notably, however, hepatitis C infection stimulates CYP3A4
activity and may actually increase methadone clearance, particularly early on (before overt liver
failure occurs).
Clinical Management Pearls As in any clinical setting, the ‘right dose’ of an opioid analgesic
medication is that which provides adequate pain relief in conjunction with an acceptable side
effect profile. This statement is especially true in end stage liver disease (ESLD). Opioid doses
should not be decreased solely out of concern for hepatic disease (e.g., if a patient with ESLD
appears to tolerate and require q3 hour dosing of oxycodone, that dosage should continue). In
general, lower doses of most opioids should be initiated in patients with ESLD, and clinicians
should be cautious prescribing opioids at ‘regular’ dosing intervals until patients have
demonstrated an ability to tolerate them. Patients with deteriorating liver function should be
closely monitored for signs of drug accumulation and need for dose reductions, assuming the
level of analgesia remains acceptable. Finally, potential drug interactions involving the CYP450
enzyme system must always be considered as there is potential for non-opioid medications to
either induce or inhibit the metabolism of any opioid that is a CYP450 enzyme substrate.
References
1. Rhee C, Broadbent AM. Palliation and liver failure: palliative medications dosing
guidelines. J Pall Med. 2007; 10:677-685.
2. Zichterman A. Opioid pharmacology and considerations in pain management. May 2007.
US Pharmacist (Web). Available at: http://www.uspharmacist.com/continuing_education/
ceviewtest/lessonid/105473/. Accessed July 19, 2012.
3. Davis M. Cholestasis and endogenous opioids: liver disease and exogenous opioid
pharmacokinetics. Clin Pharmacokinet 2007; 46:825-850.
4. Johnson SJ. Opioid safety in patients with renal or hepatic dysfunction. June 2007. Pain
Treatment Topics (Web). Available at: http://pain-topics.org/pdf/Opioids-Renal-Hepatic-
Dysfunction.pdf#search="opioids and liver failure". Accessed July 3, 2012.
5. Tegeder I, Lotsch J, Geisslinger G. Pharmacokinetics of opioids in liver disease. Clin
Pharmacokinet. 1999; 37:17-40.
Authors’ Affiliations: Lake Health System & Ohio Northern University, Concord, OH (CO);
Mount Carmel St. Ann’s Hospital, Westerville, OH (NM); University of Minnesota Medical School
& Fairview Health Services, Minneapolis, MN (DAR).
Version History: First published August 2012. Copy-edited by Sean Marks in September 2015.
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!37
!

OPIOID INDUCED CONSTIPATION PART 1: ESTABLISHED MANAGEMENT STRATEGIES
Background Opioid induced constipation (OIC) affects 45-90% of patients (1, 2) and can cause
significant morbidity. It is the most common reason patients avoid and/or discontinue opioids (3,
4) and can often result in an increase in hospital length of stay (5) and overall healthcare costs
(6). This Fast Fact will describe the physiology of OIC and describe established treatment
strategies. Fast Fact # 295 will discuss newer management strategies.
Physiology OIC is mediated through several different mechanisms including ineffective GI

motility, inhibition of mucosal transport of electrolytes and fluids, and interference with the
defecation reflex (7). The greatest risk factor for developing OIC is duration of opioid therapy.
Route of delivery or increased opioid dosing does not appear to affect the risk of developing OIC
(2). While patients usually develop tolerance to most other side effects from opioids, they do not
develop tolerance to OIC (1).
Non-pharmacologic Therapies Physical activity, scheduled toileting, fiber, and adequate fluid
intake have been traditional non-pharmacologic mainstays for preserving GI regularity in
constipation (8). However, there is no specific evidence in favor for any of these interventions to
treat OIC and adherence may be challenging for chronically ill patients.
Pharmacologic Therapies In general, patients with regular opioid exposure will require
pharmacologic therapy to appropriately manage OIC. Both stimulant and osmotic laxatives have
shown to be effective in treating OIC and are considered the cornerstone of treatment. Failure of
oral pharmacologic therapy usually requires more invasive rectal based interventions or one of
the newer treatment modalities (see Fast Fact #295).
• Stimulant Laxatives: Senna and bisacodyl are the main stimulant laxatives available in the
US and work by increasing enteric muscle contraction and GI motility. The onset of action for
oral senna and bisacodyl is around 6-12 hours. Starting dose for senna is two 8.6 mg tabs;
bisacodyl is one 10mg tab. However, higher doses are usually needed for OIC. Senna can be
safely dosed up to 12 tabs daily and bisacodyl up to 30 mg (9). Both medications are
relatively inexpensive. Because stimulant laxatives cause intestinal contractions their use can
be limited by abdominal cramps and pain. This can sometimes be avoided by dividing the
total dose into smaller more frequent doses (9).
• Osmotic Laxatives: These include non-absorbable sugar molecules such as polyethelyne
glycol (PEG), lactulose, and sorbitol, as well as poorly absorbed salt-based molecules like
milk of magnesia and magnesium citrate. Osmotic laxatives have limited intestinal absorption
leading to an increase in colonic intraluminal water through oncotic pressure. With increased
intraluminal volume and distension, reflex peristalsis subsequently occurs. Additionally, the
increase in intraluminal water also leads to softer stool and allows for easier intestinal transit.
The starting daily dose for PEG is 17 g, for lactulose is 15 ml, and 30 ml for 70% sorbitol
solution. Osmotic laxatives will have a linear effect on bowel function with dose increases; the
maximum effective daily dose of PEG is 68 g (10), lactulose is 60 ml, and for sorbitol is 150
ml. The onset of action for osmotic laxatives tends to be variable ranging from 12 to 48 hours,
but when used regularly patients will have a more consistent effect. Osmotic laxatives
generally do not lead to a loss of fluids or electrolytes as they only bind to orally taken fluid.
With this, PEG requires 125 ml of fluid per 17 g dose (11) and similarly ~200 ml is
recommended with every 30 ml of lactulose (12). Major side effects from osmotic laxatives
include abdominal cramping, pain, and flatulence. Lactulose and sorbitol tend to have more
of these side effects than PEG (11). While sorbitol and lactulose have shown similar efficacy,
sorbitol tends to be more cost effective (13). Magnesium based compounds (milk of
magnesia and magnesium citrate) are also effective, but the magnesium load can be
dangerous for patients with renal insufficiency.
!38
• Rectal Based Laxatives: Unfortunately, there is a lack of clinical research to support rectal
based laxatives, but anecdotally they are often used for refractory constipation. Stimulant
suppositories such as bisacodyl and rectal vault lubricants such as glycerin are inexpensive.
Their onset is usually within 10-15 minutes and can be dosed daily (9). Warm tap water and
milk of molasses enemas (12) can be dosed more frequently (up to every two hours). They
work by causing rectal distension and reflex defecation. Other enema formulations, such as
phosphate or saline enemas, should be used with caution in renal insufficiency due to
concern for electrolyte shifts.
• Manual Evacuation: Digital stimulation and manual disimpaction may be necessary if fecal
impaction is suspected. Due to the discomfort associated with manual evacuations, these are
often interventions of last resort and may require pre-medication with pain medications and/or
anxiolytics.
• Ineffective Therapies: Docusate sodium not demonstrated efficacy in randomized controlled
studies for OIC compared with placebo (14). Bulk forming laxatives (psyllium or fiber) require
at least 1.5 L of water to be effective and can actually lead to worsened constipation with
inadequate fluid intake. Consequently, most guidelines do not routinely recommend their use
(11,15,16).
Practical Advice A consistent bowel regimen is essential in preventing constipation in patients

on chronic opioid therapy. Providers should educate their patients about the signs and symptoms
of OIC and seek appropriate consultation in a timely manner. A scheduled stimulant laxative
regimen such as Senna 2 tabs twice daily should be prescribed at the onset of regular opioid use
regardless of opioid dosing. The goal for the bowel regimen should be an unforced bowel
movement at least every other day. If a patient has not had a bowel movement in 48 hours,
increasing stimulant laxative dose and/or adding an osmotic laxative is appropriate. Failure of oral
laxative therapy usually requires rectal based interventions and/or one of the newer treatment
modalities (see Fast Fact #295).
References
1. Bell TJ, Panchal SJ, Miaskowski C, Bolge SC, Milanova T, Williamson R. The Prevalence,
Severity, and Impact of Opioid-Induced Bowel Dysfunction: Results of a US and European
Patient Survey (PROBE 1). Pain Medicine. 2009; 10(1):35–42.
2. Tuteja AK, Biskupiak J, Stoddard GJ, Lipman AG. Opioid-Induced Bowel Disorders and
Narcotic Bowel Syndrome in Patients with Chronic Non-Cancer Pain. Neurogastroenterology
and Motility: The Official Journal of the European Gastrointestinal Motility Society. 2010;
22(4): 424–30, e96.
3. Poulsen J, Lykke CB, Olesen AE, Nilsson M, Drewes AM. Clinical Potential of Naloxegol in
the Management of Opioid-Induced Bowel Dysfunction. Clinical and Experimental
Gastroenterology. 2014; 7:345–58.
4. Tamayo AC, Diaz-Zuluaga PA. Management of Opioid-Induced Bowel Dysfunction in Cancer
Patients. Supportive Care in Cancer: Official Journal of the Multinational Association of
Supportive Care in Cancer 2004; 12(9):613–18.
5. Pappagallo, M. Incidence, Prevalence, and Management of Opioid Bowel Dysfunction.
American Journal of Surgery. 2001; 182 (5A Suppl): 11S – 18S.
6. Hjalte F, Berggren AC, Bergendahl H, Hjortsberg C. The Direct and Indirect Costs of Opioid-
Induced Constipation. Journal of Pain and Symptom Management. 2010; 40(5): 696–703.
7. Kumar L, Barker C, Emmanuel A. Opioid-Induced Constipation: Pathophysiology, Clinical
Consequences, and Management. Gastroenterology Research and Practice. 2014: 141737.
8. Librach S, Bouvette LM, De Angelis C, Farley J, Oneschuk D, Pereira JP, Syme A.
Consensus Recommendations for the Management of Constipation in Patients with
Advanced, Progressive Illness. Journal of Pain and Symptom Management 2010; 40(5): 761–
73.
9. Twycross R, Sykes N, Mihalyo M, Wilcock, A. Stimulant Laxatives and Opioid-Induced
Constipation. Journal of Pain and Symptom Management 2012; 43(2): 306-13.
10. Di Palma, Jack A., Julie R. Smith, and Mark vb Cleveland. Overnight Efficacy of Polyethylene
Glycol Laxative. The American Journal of Gastroenterology 97, no. 7 (July 2002): 1776–79.
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11. Klaschik, E., F. Nauck, and C. Ostgathe. Constipation--Modern Laxative Therapy. Supportive
Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
11, no. 11 (November 2003): 679–85.
12. Bisanz, Annette. Self-Help for Severe Constipation. MD Anderson Cancer Center: Patient
Education 2007: 1-4, retrieved from http://www.fredonc.com/pdfs/constipation.pdf. 4/15/2015.
13. Volicer L, Lane P, Panke J, Lyman P. Management of Constipation in Residents with
Dementia: Sorbitol Effectiveness and Cost. Journal of the American Medical Directors
Association 2005; 6(3): S32–34.
14. Tarumi Y, Wilson MP, Szafran O, and Spooner GR. Randomized, Double-Blind, Placebo-
Controlled Trial of Oral Docusate in the Management of Constipation in Hospice Patients.
Journal of Pain and Symptom Management 2013; 45(1): 2–13.
15. Kyle, G. Constipation and Palliative Care - Where Are We Now? International Journal of
Palliative Nursing 2007; 13(1): 6–16.
16. Larkin PJ, Sykes NP, Centeno C, Ellershaw JE, Elsner F, Eugene B, Gootjes JRG, et al. The
Management of Constipation in Palliative Care: Clinical Practice Recommendations.
Palliative Medicine. 2008; 22(7): 796–807.
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!

OPIOID INDUCED CONSTIPATION PART II: NEWER THERAPIES
Background Fast Fact #294 introduces OIC and discusses well-established treatments. This
Fast Fact discusses emerging management approaches. In general, these agents are used for
refractory OIC, which implies persistent and distressing symptoms despite exposure to typically
effective doses of stimulant and osmotic laxatives. When exactly to use these emerging
therapies remains largely empiric.
Opioid Antagonists Since the majority of symptoms associated with OIC are secondary to
stimulation of µ-opioid receptors in the gut, opioid antagonists offer an attractive pharmacologic
rationale for OIC (1).
Naloxone: Until recently, naloxone was the only available opioid antagonist for OIC treatment.
Typically, patients orally ingest the contents of IV ampules. Naloxone has a high first pass
metabolism, so it is possible for patients who take it orally to have peripheral µ-opioid receptor
antagonism without significant impact on central receptors which could lead to opioid withdrawal
and loss of analgesia (2). In a small, non-controlled study, 80% of chronic opioid users had bowel
evacuation in 1-4 hours after naloxone administration. Unfortunately, over two-thirds reported a
10-15% loss of analgesia and nearly one-third had withdrawal symptoms (3). Therefore, if used, it
is recommended to start at a low dose of 0.8 mg twice daily. Effective doses typically need to be
at least 10% of equivalent daily morphine dose, so naloxone usually requires slow up-titration
with max dosing of 12 mg daily (2).
Methylnaltrexone bromide: Methylnaltrexone is a peripherally-acting µ-opioid receptor antagonist.

It is a methylated form of naltrexone and formulated as a subcutaneous injection. It is less able to
cross the blood brain barrier, reducing the risk of altering analgesia or inducing central opioid
withdrawal. An industry-funded randomized controlled trial of chronic opioid users showed that
weight based methylnatrexone dosing led to laxation in nearly half of subjects within 4 hours as
opposed to 15% of placebo (4). A subsequent meta-analysis of 6 separate trials with
methylnaltrexone demonstrated the number needed to treat (NNT) is 3 for OIC patients that have
failed to respond to standard laxative therapy (5). Its use is limited by cost which averages $55
per dose, and it is also contraindicated when bowel obstruction is suspected or for patients with
compromised bowel integrity. The most common side effects are nausea, diarrhea, and cramping
– which can be severely painful.
Naloxegol: Two oral peripheral acting µ-opioid receptor antagonists are available in the US:
alvimopam, which is only approved for post-operative ileus, and naloxegol (pegylated naloxone),
which has recently been approved for OIC in non-cancer patients. Two separate phase-three
clinical trials showed an increase from 1 to >3 bowel movements per week in non-cancer patients
on chronic opioids with daily dosed naloxegol compared to placebo. There was also a significant
improvement in a subset of patients who had failed traditional laxative therapy as well (7). Both
12.5 mg and 25 mg have been studied; the 25 mg dose has a higher success rate but is
associated with more abdominal pain, nausea, vomiting and diarrhea (7). Its current price is
approximately $300 for 30 pills.
Other Agents
Lubiprostone: Lubiprostone is a selective chloride channel-2 activator that acts locally on the
small intestine to increase fluid secretion and GI motility. It is FDA approved for OIC. Two
randomized controlled trials in non-cancer chronic opioid users demonstrated an increase in
frequency of spontaneous bowel movements by week 8. Moreover, approximately 40% of
subjects had a bowel movement at 24 hours, 60% within 48 hours, and 27% of subjects had > 3
bowel movements per week (8,9). The most studied dose is 24 mcg orally twice per day.
!41
Common side effects included nausea, diarrhea and abdominal distension. Curiously,
lubiprostone does not appear to be effective for methadone induced constipation (10).
Linactolide has a different mechanism than lubiprostone, but is also a small intestinal
secretogogue. It currently is approved for irritable bowel syndrome. Though there is interest in its
efficacy in OIC, it has yet to be specifically studied in this population.
Prucalopride is a serotonin receptor type-4 agonist which is available in Canada and parts of
Europe and Asia to treat chronic constipation. It is a prokinetic agent which has shown promise
for treating OIC in a phase 2 study (5). It is unclear if or when it will be released in the US.
Practical Advice Traditional oral and rectal laxatives have been the mainstay of treatment in
OIC for many years. However, recent development of novel approaches to treat OIC show
promise for the future. Of the pharmacologic interventions described above, methylnatrexone has
been the best studied and shown to be the most efficacious. It is reasonable to give
methylnaltrexone after failure of oral laxatives (see Fast Facts #294) in OIC, and potentially can
be used prior to using more invasive rectal based interventions. With time and more clinical trials,
other oral formulations targeting OIC may become more standard of care. Patient and caregiver
education about the importance of adherence to recommended therapy and guidance about signs
and symptoms of OIC is essential to ensure effective treatment.
References
17. Holzer, Peter. Opioids and Opioid Receptors in the Enteric Nervous System: From a
Problem in Opioid Analgesia to a Possible New Prokinetic Therapy in Humans.
Neuroscience Letters. 2004; 361(1–3): 192–95.
18. Choi YS, Billings JA. Opioid Antagonists: A Review of Their Role in Palliative Care, Focusing
on Use in Opioid-Related Constipation. Journal of Pain and Symptom Management. 2002;
24(1): 71–90.
19. Latasch L, Zimmermann M, Eberhardt B, Jurna I. Treament of morphine-induced
constipation with oral naloxone. Der Anaesthesist. 1997; 46 (3): 191–94.
20. Thomas J, Karver S, Cooney GA, Chamberlain BH, Watt CK, Slatkin NE, Stambler N,
Kremer AB, Israel RJ. Methylnaltrexone for Opioid-Induced Constipation in Advanced
Illness. The New England Journal of Medicine. 2008; 358 (22): 2332–43.
21. Ford AC, Brenner DM, Schoenfeld PS. Efficacy of Pharmacological Therapies for the
Treatment of Opioid-Induced Constipation: Systematic Review and Meta-Analysis. The
American Journal of Gastroenterology. 2013; 108(10): 1566–74.
22. Twycross R, Sykes N, Mihalyo M, Wilcock A. Stimulant Laxatives and Opioid-Induced

Constipation. Journal of Pain and Symptom Management. 2012; 43(2): 306–13. doi:
10.1016/j.jpainsymman.2011.12.002.
23. Chey WD, Webster L, Sostek M, Lappalainen J, Barker PN, Tack J. Naloxegol for Opioid-
Induced Constipation in Patients with Noncancer Pain. The New England Journal of
Medicine. 2014; 370(25): 2387–96.
24. Cryer B, Katz S, Vallejo R, Popescu A, Ueno R. A Randomized Study of Lubiprostone for
Opioid-Induced Constipation in Patients with Chronic Noncancer Pain. Pain Medicine. 2014;
15(11): 1825–34.
25. Jamal M, Mazen, Mareya SM, Woldegeorgis F, Joswick TR, Ueno R. 848a Lubiprostone
Significantly Improves Treatment Response in Non-Methadone Opioid-Induced Bowel
Dysfunction Patients with Chronic, Non-Cancer Pain: Results from a Phase 3, Randomized,
Double-Blind, Placebo-Controlled Clinical Trial. Gastroenterology 2012; 142(5):144 –145S.
26. Brenner DM, Chey DM. An Evidence-Based Review of Novel and Emerging Therapies for
Constipation in Patients Taking Opioid Analgesics. The American Journal of
Gastroenterology Supplements 2014; 2(1): 38–46.
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!

DYSGEUSIA
Rafael Bloise MD, Mellar P Davis MD FCCP FAAHPM
Background Taste warns us of danger and is a stimulus for appetite. The most common taste
disorder is dysgeusia, commonly defined as a qualitative distortion of the sense of taste. Though
taste acuity declines with age, many patients with age-related hypogeusia are not subjectively
bothered by it. Rather patients are more often to report dysgeusia when they experience an
abrupt alteration resulting in an overly strong/weak taste as occurs in many progressive illnesses
frequently encountered by palliative care clinicians. Among the seriously ill, dysgeusia can
adversely influence nutrition and quality of life as well as lead to food aversions, distorted smells,
and loss of eating pleasure (1,2). This Fast Fact will assist clinicians caring for seriously ill
patients better identify and care for patients with dysgeusia.
Etiologies Dysgeusia is more closely associated with medical illness than age. Much of the
medical literature on dysgeusia has been focused on cancer patients, as cancer is a putative risk
factor for dysgeusia. In cancer, dysguesia is most associated with chemotherapy and radiation;
yet there is considerable intra-individual variability regarding the intensity of impact (3). Patients
with head and neck cancer and those exposed to tyrosine kinase inhibitors or taxane based
regimens are most at risk (4,5). Common non-malignancy causes of dysgeusia in the seriously ill
include, infections, zinc deficiency, hypothyroidism, Cushing’s Syndrome, liver disease, sequelae
from ENT operations, and medications such as psychotropics, opioids, and antihypertensives.
Medical Evaluation Patients often fail to volunteer symptoms of dysguesia to their clinicians
and when they do, the symptom is often ignored (6). Hence, patients with cancer or other
described risk factors should be routinely asked about distorted smell and taste.
• Do you have an altered sense of smell or taste which interferes with eating?
• Do you experience a metallic taste when eating?
• Have you developed aversions to certain foods? (7)
In addition, clinicians should evaluate for:

• Recent ear or respiratory infections, Bell’s palsy, cranial nerve deficits, or dental
procedures.
• Cheilitis -- a painful inflammation and cracking of the corners of the mouth
• Mucositis or thrush
• Gastrointestinal symptoms such as dysphagia, weight loss, appetite changes, and early
satiety
• Thyroid function testing if clinically appropriate
• The “3 drop test” is available to measure taste thresholds and identify hypogeusia by
using sugar, citric acid, sodium chloride and caffeine or quinine; however, most experts
believe such tests likely offer little guidance in the management of dysgeusia (8).
Impact on Quality of Life (QOL) Chemotherapy induced dysgeusia most often resolves within
months. However, in that time, it can have a devastating effect. Because eating habits are shaped
by life experiences and life experiences are shaped by eating habits, dysgeusia can alter customs
within the family unit and lead to a reduction in socialization around meals (9,10).
Non-Pharmacological Management Strategies Many with dysguesia try home remedies such
as lemon juice, candy before meals, sweet drinks, plastic utensils, drinking from a straw, brushing
teeth and tongue before meals, and using salt, soda or antibacterial mouthwashes before eating
even though there is little evidence to their use (11). There is weak evidence for flavor enhancers
(e.g. salt, sugar, monosodium glutamate, monopotassium glutamate) during chemotherapy (12).
Randomized trials of dietary counseling had mixed results (13). Acupuncture is likely ineffective
(14).
!44
Pharmacological Management Strategies First, clinicians should treat identified reversible
causes if consistent with goals of care and the patient’s overall medical situation. Once these are
ruled out, clinicians may consider empiric therapies. There are a multitude of ineffective drugs
which clinicians should be aware: corticosteroids, vitamin A, gabapentin, gingko biloba,
glutamine, and amifostine have all been shown to be non-beneficial (15-17). Other medications
may help, however the data are not fully convincing. A randomized trial demonstrated taste
improvement with alpha lipoic acid (available over the counter); however, other studies did not
reproduce this finding (18-20). Dronabinol at low doses such as 2.5 mg twice daily may improve
dysguesia in advanced cancer without improving appetite; however, it is not always covered by
insurance (21). Multiple randomized trials of zinc supplementation at doses between 30 to 50 mg
three times a day demonstrated a modest improvement in taste acuity and taste quality among
individuals undergoing chemotherapy and/or radiation (22,23). This benefit was not observed in a
non-cancer population (24).
Summary Although there are no guidelines for the assessment and management of dysgeusia,
clinicians should inquire about dysgeusia in at risk patients to better identify reversible causes
such as thrush, mucositis, and hypothyroidism. Much like fatigue, anorexia, or other common
constitutional symptoms in serious illness, inquiring about dysgeusia can better ennoble clinicians
to the patient experience. Zinc at doses of 100-150 mg daily has modest benefits but it can cause
adverse effects such as eczema and gastrointestinal distress. Those who do not tolerate zinc or
fail to respond after 1-2 months may benefit from dronabinol 2.5 mg twice daily or alpha lipoic
acid.
References
1. Brisbois TD, et al., Taste and smell abnormalities as an independent cause of failure of
food intake in patients with advanced cancer--an argument for the application of sensory
science. J Palliat Care, 2006. 22(2): p. 111-4.
2. Yavuzsen, T., et al., Components of the anorexia-cachexia syndrome: gastrointestinal
symptom correlates of cancer anorexia. Support Care Cancer, 2009. 17(12): p. 1531-41.
3. Bernhardson, B.M., C. Tishelman, and L.E. Rutqvist, Self-reported taste and smell
changes during cancer chemotherapy. Support Care Cancer, 2008. 16(3): p. 275-83.
4. Steinbach, S., et al., Qualitative and quantitative assessment of taste and smell changes
in patients undergoing chemotherapy for breast cancer or gynecologic malignancies. J
Clin Oncol, 2009. 27(11): p. 1899-905.
5. Baharvand, M., et al., Taste alteration and impact on quality of life after head and neck
radiotherapy. J Oral Pathol Med, 2013. 42(1): p. 106-12.
6. Hong, J.H., et al., Taste and odor abnormalities in cancer patients. J Support Oncol,
2009. 7(2): p. 58-65.
7. Allis, T.J. and D.A. Leopold, Smell and taste disorders. Facial Plast Surg Clin North Am,
2012. 20(1): p. 93-111.
8. Fark, T., et al., Characteristics of taste disorders. Eur Arch Otorhinolaryngol, 2013.
270(6): p. 1855-60.
9. Brisbois, T.D., et al., Characterization of chemosensory alterations in advanced cancer
reveals specific chemosensory phenotypes impacting dietary intake and quality of life. J
Pain Symptom Manage, 2011. 41(4): p. 673-83.
10. Bernhardson, B.M., et al., Reframing eating during chemotherapy in cancer patients with
chemosensory alterations. Eur J Oncol Nurs, 2012. 16(5): p. 483-90.
11. Speck, R.M., et al., Taste alteration in breast cancer patients treated with taxane
chemotherapy: experience, effect, and coping strategies. Support Care Cancer, 2013.
21(2): p. 549-55.
12. Wismer, W.V., Assessing alterations in taste and their impact on cancer care. Curr Opin
Support Palliat Care, 2008. 2(4): p. 282-7.
13. Ravasco, P., et al., Dietary counseling improves patient outcomes: a prospective,
randomized, controlled trial in colorectal cancer patients undergoing radiotherapy. J Clin
Oncol, 2005. 23(7): p. 1431-8.
14. Hummel, T., B.N. Landis, and K.B. Huttenbrink, Smell and taste disorders. GMS Curr Top
Otorhinolaryngol Head Neck Surg, 2011. 10: p. Doc04.
!45
15. Heckmann, S.M., et al., Gabapentin has little or no effect in the treatment of burning
mouth syndrome - results of an open-label pilot study. Eur J Neurol, 2006. 13(7): p. e6-7.
16. Strasser, F., et al., Prevention of docetaxel- or paclitaxel-associated taste alterations in
cancer patients with oral glutamine: a randomized, placebo-controlled, double-blind
study. Oncologist, 2008. 13(3): p. 337-46.
17. Buntzel, J., et al., Radiochemotherapy with amifostine cytoprotection for head and neck
cancer. Support Care Cancer, 1998. 6(2): p. 155-60.
18. Spanemberg, J.C., et al., Burning Mouth Syndrome: update. Oral Health Dent Manag,
2014. 13(2): p. 418-24.
19. Carbone, M., et al., Lack of efficacy of alpha-lipoic acid in burning mouth syndrome: a
double-blind, randomized, placebo-controlled study. Eur J Pain, 2009. 13(5): p. 492-6.
20. Lopez-Jornet, P., F. Camacho-Alonso, and S. Leon-Espinosa, Efficacy of alpha lipoic acid
in burning mouth syndrome: a randomized, placebo-treatment study. J Oral Rehabil,
2009. 36(1): p. 52-7.
21. Cannabis In Cachexia Study, G., et al., Comparison of orally administered cannabis
extract and delta-9-tetrahydrocannabinol in treating patients with cancer-related anorexia-
cachexia syndrome: a multicenter, phase III, randomized, double-blind, placebo-
controlled clinical trial from the Cannabis-In-Cachexia-Study-Group. J Clin Oncol, 2006.
24(21): p. 3394-400.
22. Najafizade, N., et al., Preventive effects of zinc sulfate on taste alterations in patients
under irradiation for head and neck cancers: A randomized placebo-controlled trial. J Res
Med Sci, 2013. 18(2): p. 123-6.
23. Halyard, M.Y., et al., Does zinc sulfate prevent therapy-induced taste alterations in head
and neck cancer patients? Results of phase III double-blind, placebo-controlled trial from
the North Central Cancer Treatment Group (N01C4). Int J Radiat Oncol Biol Phys, 2007.
67(5): p. 1318-22.
24. Matson, A., et al., Zinc supplementation at conventional doses does not improve the
disturbance of taste perception in hemodialysis patients. J Ren Nutr, 2003. 13(3): p.
224-8.
Authors’ Affiliations: Harry R Horvitz Center for Palliative Medicine, Taussig Cancer Institute,
Cleveland Clinic
Version History: First electronically published September 2015.
used.

TUNNELED INDWELLING CATHETERS FOR MALIGNANT ASCITES
James Burleigh DO, Zankhana Mehta MD, Dr. Neil Ellison MD
!46
Background Malignant ascites can develop in almost half of patients with certain cancers and
may portend a survival of one to four months (1,2). When ascites recurs after a large volume
paracentesis (LVP), physical symptoms along with the need for travel to an office for repeat
procedures, can carry significant burden (3). Tunneled indwelling peritoneal catheters are an
alternative, permanent drainage system that allows patients to control symptoms in the home
setting. This Fast Fact will review the use of tunneled indwelling catheters, including indications,
use, and associated risks. See Fast Facts 176 and 177 for further information on the diagnostic
and treatment approaches for malignant ascites.
Indication As of 2015, the FDA has approved multiple tunneled indwelling catheter systems,
such as PleurX®, Asept®, and Aspira®, for the management of malignant ascites requiring
frequent therapeutic LVPs (4). Timing of placement for malignant ascites is empiric; though
usually it is considered after a patient has had at least two prior LVPs (2,4). Placement may also
be considered in patients for whom disease burden makes frequent clinic visits difficult, and when
post-procedural symptoms, such as discomfort, fatigue, and dizziness, are troublesome (3,4).
The same considerations are relevant for non-malignant ascites; however, due to survival and
infection concerns many clinicians limit the off-label use for non-malignant ascites to patients with
an anticipated survival of less than two months. Due to the cost of the initial procedure, catheter
placement is often performed prior to hospice enrollment.
Contraindications Single or multifocal loculated pockets of ascites, peritonitis, and non-

correctable coagulopathy (4). While the literature does not have set guidelines for platelet counts
or safe INR levels, some experts caution against catheter placement with INR levels greater than
2.
Complications If obstruction or accidental removal occurs, replacement of a new catheter can

be pursued (4,5). Insertion site erythema, bacterial peritonitis, and exudative drainage have been
documented; associated superficial infections are often manageable with oral antibiotics (2,4).
Recent studies have shown much lower complication rates with the tunneled indwelling catheters,
with 0.12 events per 100 catheter-days, compared with non-tunneled catheter systems.
Consequently, the use of non-tunneled catheter systems for malignant ascites is essentially
archaic (3). Overall rate of procedural complications, including immediate and delayed infections,
are similar to repeat LVPs (6).
Use Using radiographic guidance, a single cuff, 15.5 French silastic catheter is tunneled under
the skin into the peritoneum (1). This is usually performed as an outpatient procedure by an
Interventional Radiology clinician (2). Technical success rates for placement are near 100%.
Catheters usually remain in place until death; a recent study found a mean length of retention of
113 days (4). Patients and their families can be trained to perform drainage at home or use home
health staff (5). Most systems utilize low-vacuum drainage bottles or bags; other alternatives are
wall or portable suction, or water seal. The one-way valve is opened with sterile technique and up
to two liters can be drained daily (2). The drainage valve is closed when flow slows to a trickle,
and fluid is disposed of in the toilet. During use, transient pain and cough may be experienced.
Once completed, the catheter is coiled against the skin, and a cover dressing is replaced (2).
Drainage frequency is determined by the rate of ascites recurrence and patient’s symptoms, with
some patients requiring daily drainage (1). Using a protective dressing, patients can shower;
however product information recommends against bathing. If wet, the catheter should be dried
immediately, and the dressing replaced. If required, sterile samples of peritoneal fluid can be
drawn directly from the catheter (7).
Cost According to Medicare’s 2015 Ambulatory Payment Classifications, including imaging

guidance and equipment, the initial outpatient placement of a tunneled indwelling catheter can
cost five to seven times that of a LVP. Even considering the cost of drainage containers plus
placement cost, tunneled indwelling catheters can have a potential financial benefit over LVPs in
as early as a week (8).
!47
Conclusion Peritoneal indwelling tunneled catheters are safe and effective for the
management of refractory malignant ascites. Patient satisfaction has been quite high, with a
relatively low complication rate (5).
References
1. Richard HM, Coldwell DM, et al: PleurX tunneled catheter in the management of
malignant ascites. J Vasc Interv Radiol 2001;12:373-375.
2. Narayanan G, Pezeshkmehr A, Venkat S, et al: Safety and efficacy of the PleurX catheter
for the treatment of malignant ascites. J Pall Med 2014;17(8):906-912.
3. Lungren MP, Kim CY, et al: Tunneled peritoneal catheter placement for refractory ascites:
single-center experience in 188 patients. J Vasc Interv Radiol 2013;24(9):1303-1308.
4. Tapping CR, Ling L, Razack A: PleurX drain use in the management of malignant ascites:
safety, complications, long-term patency and factors predictive of success. Brit J Rad
2012;85:623-628.
5. Courtney A, Nemcek AA, et al: Prospective evaluation of the PleurX catheter when used
to treat recurrent ascites associated with malignancy. J Vasc Interv Radiol 2008;19(12):
1723-31.
6. Rosenberg S, Courtney A, et al: Comparison of percutaneous management techniques
for recurrent malignant ascites. J Vasc Interv Radiol 2004;15:1129-1131.
7. Stokes LS: Percutaneous management of malignant fluid collections. Seminars Interv
Radiol 2007;24(4):398-408.
8. “Physician’s Fee Schedule Code Search & Downloads.” novitas-solutions.com. Network
Solutions, LLC. Aug. 2015. Web. 12 Oct. 2015.
Authors Affiliations: Geisinger Medical Center, Danville, Pennsylvania; Reading Health System,
West Reading, Pennsylvania
Conflicts of Interests: None reported
Version History: First electronically published in December 2015

PALLIATION OF NEUROGENIC BOWEL
Kathleen McCabe DO; Earl L Smith MD, PhD 
Background: Neurogenic bowel is the loss of normal bowel function that results from damage to
the gastrointestinal innervation (1). It occurs in many diagnoses within the scope of hospice and
!48
palliative care clinicians. This Fast Fact will focus on how to identify and manage neurogenic
bowel in the palliative care and hospice patient population.
Pathophysiology:
• Upper motor neuron (UMN) lesions: occur above the conus medullaris and are associated
with hyperreflexic bowel or an increase in tone of the intestinal wall and anal sphincter (2).
Because peristalsis remains intact, the combination of propelling stool against a tight
sphincter often presents as constipation with fecal retention and impaction. Evacuation
depends on initiating the rectal-colon reflex by stimulating the bowel wall digitally or with a
suppository.
• Lower motor neuron (LMN) lesions: are at or below the level of the conus medullaris and are
associated with an areflexic bowel, characterized by a flaccid anal sphincter, and slow
peristalsis (2). LMN lesions present as constipation with bowel incontinence. The major
therapeutic distinction is to utilize stool bulking agents like fiber to prevent bowel accidents in
LMN lesions.
Impact of Neurogenic Bowel: Neurogenic bowel rates as a significant cause of anxiety and
distress, especially for those who require greater than 15 minutes to complete bowel routines
(3,4). In the critically ill, neurogenic bowel can even be life threatening and associated with
viscous perforation, delirium, or difficulty weaning from a ventilator (5-7). Patients with non-
traumatic spinal cord injury (SCI) have shorter life expectancies whereas traumatic SCI patients,
if getting excellent care and are not ventilator dependent, have near normal life expectancies (8).
Clinical Evaluation: While the presence of neurogenic bowel is usually evident in traumatic
SCI, clinicians may overlook it in non-traumatic etiologies such as multiple sclerosis, stroke, or
cancer (see FFs # 237 & 238). In patients with an insult to the spinal cord, a digital rectal exam
should be performed to distinguish between UMN and LMN lesions. UMN lesions will result in a
tight sphincter, while LMN lesions will result in a flaccid anal sphincter with no volitional
contraction.
Management of Neurogenic Bowel: Despite data showing that patients with well-managed
neurogenic bowel have a better quality of life, there is a paucity of controlled trials examining the
best treatments (1,4,6). As a result, the following empiric recommendations arise from a
consortium of SCI experts (9):
• Non-pharmacological measures: Routine is critical. At the same time every day, ideally
about 30 minutes after a meal in order to utilize the gastro-colic reflex, the patient should sit
on a commode while a clinician applies pressures to the abdomen in a clockwise manner for
5 minutes at a time. For terminally ill patients who cannot tolerate regular meals nor a
commode, do the same with the patient on his or her side in the bed. Follow this with digital
stimulation to the rectal wall in a circular motion for 20-30 seconds and if necessary, manual
disimpaction.
• Pharmacological measures: Administer a 10 mg bisacodyl suppository at the same time
daily. Make sure the suppository contacts the bowel wall, not just the stool itself. Once the
patient is having regular bowel movements at least every other day, transition to a glycerin
suppository or a mini-enema (a commercially available 5 mL enema of docusate,
polyethylene glycol and glycerin). To time bowel movements for the morning, give 2-4 tabs of
senna at bedtime.
• Next steps: if these measures are ineffective after 2-3 days, imaging with a KUB may be
needed to evaluate for ileus or bowel obstruction. Otherwise consider lactulose 30 mL,
magnesium citrate 300 mL or sorbitol 70% solution up to 150 mL PO, or an enema.
Special Considerations
• SCI patients are susceptible to autonomic dysreflexia (AD), an abnormal sympathetic
nervous system response to a noxious stimulus below the level of the spinal cord lesion.
Typical AD symptoms are diaphoresis and a rapid rise in blood pressure that can be life
threatening. The definitive treatment is to remove the noxious stimulus (e.g. malfunctioning
Foley, TED stockings or impacted stool).
• Patients already on opioids will likely require higher doses as well as more frequent use of
cathartics. See Fast Facts #294 and 295.
!49
• Transanal irrigation, a self-administered irrigation consisting of a soft inflatable balloon to hold
a rectal catheter in place, has been shown to be effective for refractory cases in small studies
(4).
• Though more invasive, colostomy placement and electrical stimulation to the bowel have
been described in select patients with longer prognoses and refractory symptoms.  
References:
1. Coggrave, et al. Management of faecal incontinence and constipation in adults with
central neurological diseases. Cochrane Database of Systematic Reviews 2014, Issue 1.
Art. No.: CD002115. DOI: 10.1002/14651858.CD002115.pub5.
2. Lynch AC, et al. Bowel dysfunction following spinal cord injury. Spinal Cord. 2001; 39,
193-203.
3. Christensen, et al. Outcome of Transanal Irrigation for Bowel Dysfunction in Patients with
Spinal Cord Injury. The Journal of of Spinal Cord Medicine. 2008; 31(5), 560-567.
4. Glickman, Scott and Michael Kamm. Bowel Dysfunction in Spinal-Cord-Injury Patients.
Lancet. 1996; 347(9016), 1651-1654.
5. Larkin, PJ, et al. The management of constipation in palliative care: clinical practice
recommendations. Palliative Medicine. 2008; 22: 796-807.
6. Mostafa SM, et al. Constipation and its implications in the critically ill patient. British
Journal of Anaesthesia. 2003; 91(6) 815-9.
7. Roland, et al. Constipation is independently associated with delirium in critically ill
ventilated patients. Intensive Care Medicine. 2016; 42:126-127.
8. Strauss, et al. Trends in life expectancy after spinal cord injury. Archives of Physical
Medicine and Rehabilitation. 2006; 87, 1079-1085.
9. Krassioukov, et al. Neurogenic bowel management after spinal cord injury: A systematic
review of the evidence. Spinal Cord. 2010; 48(10): 718-733.

Authors Affiliations: Icahn School of Medicine; New York, NY; Emory School of Medicine,
Atlanta GA.
Version History: Originally edited by Sean Marks MD; electronically published May 2016.
!50
!
Hospitalist
#3 Syndrome of Imminent Death . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . 2-3
#10 Tube Feed or Not Tube

Feed? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4-5

Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .6-7
#23 Discussing DNR Orders – Part I . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . . 8-9
#24 Discussing DNR Orders – Part

II . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10-11
#42 Broaching the Topic of a Palliative Care

Consultation . . . . . . . . . . . . . . . . . . . . . . . . . . . . .12-13
#82 Medicare Hospice Benefit – Part I: Eligibility and Treatment Plan. . . . . . . . . . . . .

. . . . . . 14-15
#87 Medicare Hospice Benefit – Part II: Places of Care and Funding . . . . . . . . . . . . . .
. . . . . . 16-17
#90 Medicare Hospice Benefit – Part III: Special

Interventions . . . . . . . . . . . . . . . . . . . . . . . . 18-19
#222 Preparing for the Family Meeting . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . .20-21
#223 The Family Meeting: Starting the Conversation . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . .22-24
#224 Responding to Emotion in the Family Meetings . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . 25-26
#225 The Family Meeting Causes and

Conflicts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27-28
#226 Helping Surrogates Make Decisions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . 29-30
!1
#227 The Family Meeting: End of Life Goal Setting and Future Planning . . . . . . . . . . .
. . . . . 31-32
#326 Illness Trajectories: Description and Clinical

Use . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33-35
#360 The Surprise Questions as a Prognostic Tool . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . .36-38

SYNDROME OF IMMINENT DEATH
David E Weissman MD
Background Virtually all dying patients go through a stereotypical pattern of symptoms and
signs in the days prior to death. This trajectory is often referred to as “actively dying” or
“imminent death”. Prompt recognition of this trajectory is key for clinicians to provide the most
appropriate interventions for both the patient and family.
1. Stages
• Early
o Bed bound
o Loss of interest and/or ability to drink/eat
o Cognitive changes: increasing time spend sleeping and/or delirium (see Fast
Fact #1)
• Middle
o Further decline in mental status to obtundation (slow to arouse with stimulation;
only brief periods of wakefulness)
• Late
o Death rattle – pooled oral sections that are not cleared due to loss of swallowing
reflex
o Coma
o Fever – usually from aspiration pneumonia
o Altered respiratory pattern – periods of apnea, hyperpnea, or irregular breathing
o Mottled extremities
2. Time Course The time to traverse the various stages can be less than 24 hours or as long as
~14 days. Patients who enter the trajectory who are nutritionally intact, with no infection (e.g.
acute stroke), are apt to live longer than cachectic cancer patients
3. Common Family Concerns Family members present during the dying process often express
the following concerns/questions. Clinicians can best help families by expecting these questions,
providing education, reassurance, and responding to emotions (see also Fast Fact # 29; #149).
• Is my loved one in pain; how would we know?

• Aren’t we just starving my loved one to death?
• What should we expect; how will we know that time is short?
• Should I/we stay by the bedside?
• Can my loved one hear what we are saying?
• What do we do after death?
!2
4. Treatment
• Confirm treatment goals; recommend stopping treatments that are not contributing to
comfort – pulse oximetry, IV hydration, antibiotics, finger sticks, etc.
• Communicate clearly to others what is going on. Write in progress notes: "patient is
dying," not "prognosis is poor".
• Treat symptoms/signs as they arise: common among these are: oral secretions (see Fast
Fact #109, #158); delirium (#1, 60); dyspnea (# 27), fever (#256) and pain (# 53, 54).
• Provide excellent mouth and skin care.
• Provide daily counseling and support to families.
References
1. Rousseau P. Management of symptoms in the actively dying patient. In: Principles and
Practice of Palliative Care and Supportive Oncology. Berger AM, Portenoy RK, and
Weissman DE, eds. 2nd Edition. Philadelphia, PA: Lippincott, Williams, & Wilkins; 2002.
2. Breitbart W, Alici Y. Agitation and delirium at the end of life. “We couldn’t manage him.”
JAMA. 2008; 300(24):2898-2910.
!3
!

James Hallenbeck MD
advanced illness.
sepsis).
demonstrated.
GI obstruction).
Summary
!4
References
247: 39-42.
JAMA. 1999; 282:1365-1369.
1996; 348:1421-1424.
!5
!

David E Weissman MD
patients, especially when informed that there are no further effective anti-neoplastic treatment
options. Although prognostication is not an exact science, there are data to help clinicians
provide useful information to patients and families – information critical to making realistic end-of-
life decisions and referrals for home hospice service (see Fast Fact #30).
Performance Status The single most important predictive factor in cancer is Performance
Status (‘functional ability,’ ‘functional status’): a measure of how much a patient can do for
themselves, their activity and energy level. Patients with solid tumors typically lose ~ 70% of their
functional ability in the last 3 months of life. The most common scales used to measure
functional ability are the Karnofsky Index (100 = normal; 0 = dead) and the ECOG scale (Eastern
Cooperative Oncology Group), (0 = normal; 5 = dead). A median survival of 3 months roughly
correlates with a Karnofsky score <40 or ECOG > 3. Newer prognostic scales have been
developed to help provide prognostic information (See Fast Facts #124, 125).
The simplest method to assess functional ability is to ask patients: How do you spend your time?
How much time do you spend in a chair or lying down? If the response is >50% of the time, and
is increasing, you can roughly estimate the prognosis at 3 months or less. Survival time tends to
decrease further with increasing numbers of physical symptoms, especially dyspnea, if secondary
to the cancer.
Other Factors Several common cancer syndromes have well-documented short median
survival times:
• Malignant hypercalcemia: 8 weeks, except newly diagnosed breast cancer or myeloma
(see Fast Fact #151)
• Malignant ascites (see Fast Fact #176), malignant pleural effusion (#209), or malignant
bowel obstruction: < 6 months.
• Modified Glasgow Prognostic Score (mGPS): multiple studies have shown that an
increased mGPS -- meaning an elevated serum c-reactive protein and a reduced serum
albumin – is associated with a reduced cancer specific survival curve irrespective of
cancer type.
Other Comments In general, a patient with metastatic solid cancer, acute leukemia or high-
grade lymphoma, who will not be receiving systemic chemotherapy (for whatever reason), has a
prognosis of less than 6 months. Notable exceptions to this are patients with metastatic breast or
prostate cancer with good performance status, as these cancers may have an indolent course. In
these patients additional features suggesting short prognosis are needed (declining functional
status, dyspnea, weight loss).
Discussing Prognosis When discussing prognosis with patients/families, the following four
step approach is recommended: Preparation; Content; Patient’s Response; Close. Remember
to:
!6
References
1. Lamont EB, Christakis NA.. Complexities in prognostication in advanced cancer. JAMA.
2003; 290:98-104.
2. den Daas, N. Estimating length of survival in end-stage cancer: a review of the literature.
J Pain Symp Manage. 1995; 10:548-555.
3. Lassauniere JM, Vinant P. Prognostic factors, survival and advanced cancer. J Pall Care.
1992; 8:52-54.
5. Reuben DB, Mor V. Clinical symptoms and length of survival in patients with terminal
6. McMillan DC, Crozier JE, et al. Evaluation of an inflammation-based prognostic score
(GPS) in patients undergoing resection for colon and rectal cancer. Int J Colorectal Dis
2007; 22: 881-6.
7. Proctor MJ, Morrison DS, et al. An inflammation based prognostic score (mGPS)
predicts cancer survival independent of tumour site: a Glasgow inflammation outcome
study. British Journal of Cancer 2011; 104: 726-734.
!7
!

Background ‘Code status’ discussions with seriously ill patients should always take place in the
context of the larger goals of care, using a step-wise approach. This Fast Fact introduces an
approach to having these discussions; Fast Fact #24 discusses disagreements about ‘code
status.’ Prior to any discussion of a do-not-resuscitate (DNR) order, physicians must know the
data defining outcomes and morbidity of cardiopulmonary resuscitation in different patient
populations (see Fast Fact #179) and care settings (see Fast Fact #292 regarding DNR orders in
the Operating Room).
1. Establish the setting. Ensure comfort and privacy; sit down next to the patient. Ask if family
members or others should be present. Introduce the subject with a phrase such as: I’d like to talk
with you about possible health care decisions in the future.
2. What does the patient understand? An informed decision about DNR status is only possible
if the patient has a clear understanding of their illness and prognosis. Ask an open-ended
question to elicit patient understanding about their current health situation. It is important to get
the patient talking – if the doctor is doing all the talking, it is unlikely that the rest of the
conversation will go well. Consider starting with phrases such as: What do you understand about
your current health situation? What have the doctors told you about your condition? If the patient
does not know/appreciate their current status this is time to review that information.
3. What does the patient expect? Ask the patient to consider the future. Examples of ways to
start this discussion are What do you expect in the future? or What goals do you have for the time
you have left—what is important to you? This step allows you to listen while the patient describes
a real or imagined future. Many patients with advanced disease use this opening to voice their
thoughts about dying—typically mentioning comfort, family, and home, as their goals of care. If
there is a sharp discontinuity between what you expect and what the patient expects, this is the
time to clarify.
Listen carefully to the patient’s responses; most patients have thought a lot about dying, and only
need permission to talk about what they have been thinking. Setting up the conversation in this
way permits the physician to respond with clarifying and confirming comments such as:
So what you’re saying is – you want to be as comfortable as possible when the time comes? Or –
What you’ve said is – you want us to do everything we can to fight, but when the time comes, you
want to die peacefully? Whenever possible, ask patients to explain the values that underlie their
decisions: Can you explain why you feel that way?
4. Discuss a DNR order. Use language that the patient will understand; give information in small
pieces. Don’t introduce CPR in mechanistic terms (e.g. “starting the heart” or “putting on a
breathing machine”). Never say Do you want us to do everything? “Everything” is euphemistic
and easily misinterpreted. Using the word “die” helps to clarify that CPR is a treatment that tries
to reverse death. To most lay-people, when the heart and/or lungs stop, the patient dies.
If the patient and doctor mutually recognize that death is approaching and the goals of care are
comfort, then CPR is not an appropriate medical intervention and a clear recommendation
against CPR should be made. You can say: We have agreed that the goals of care are to keep
you comfortable and get you home. With this in mind, I do not recommend the use of artificial or
heroic means to keep you alive. If you agree with this, I will write an order in the chart that if you
die, no attempt to resuscitate you will be made.
!8
If the clinical situation is more ambiguous in terms of prognosis and goals of care, and you have
no clear recommendation, the issue of DNR can be raised by asking: If you should die in spite of
all of our efforts, do you want us to use heroic measures to attempt to bring you back? Or, How
do you want things to be when you die? If you are asked to explain “heroic measures”, then
describe the purpose, risks and benefits of CPR in greater detail. The clinical pearl here is to start
general and become specific later in the conversation.
5. Respond to emotions. Strong emotions are common when discussing death. Typically the
emotional response is brief. The most profound initial response a physician can make may be
silence, providing a reassuring touch, and offering facial tissues (see Fast Fact #29).
6. Establish a plan. Clarify the orders and plans that will accomplish the overall goals you have
discussed, not just the DNR order. A DNR order does not address any aspect of care other than
preventing the use of CPR. It is unwise and poor practice to use DNR status as a proxy for other
life-sustaining therapies. Consider using words: We will continue maximal medical therapy to
meet your goals. However, if you die, we won’t use CPR to bring you back. Or, It sounds like we
should move to a plan that maximizes your comfort. Therefore, in addition to a DNR order, I’d like
to talk further with you how we can best do that.
References
1. Quill TE and Brody H. Physician recommendations and patient autonomy: finding a
balance between physician power and patient choice. Ann Int Med. 1996; 125:763-769.
2. Buckman R. How to break bad news: a guide for health care professionals.
Baltimore, MD: Johns Hopkins University Press; 1992.
3. Junkerman C, Schiedermayer D. Practical Ethics for Students, Interns and Residents.
2nd Edition. Hagerstown, MD: University Publishing Group; 1998.
!9
!

Introduction The basic steps in the DNR discussion for seriously ill hospitalized patients were
described In Fast Fact # 23. If you have followed those steps, what do you do if the patient or
family/surrogate continues to want CPR and you think it is not in the patient's best interest? The
seemingly unreasonable request for CPR typically stems from one of several themes:
1. Inaccurate information about CPR. The general public has an inflated perception of CPR
success. While most people believe that CPR works 60-85% of the time, in fact the actual
survival to hospital discharge is more like 10-15% for all patients, and less than 5% for the elderly
and those with serious illnesses. This is a time to review/clarify the indications, contraindications,
potential outcomes and morbidity of CPR. Start the discussion by asking, “What do you know
about CPR?”
2. Hopes, fears, and guilt. Be aware that guilt (I haven't lived nearby to care for my dying
mother) and fear (I am afraid to make a decision that could lead to my wife's death) are common
motivating emotions for a persistent CPR request. Some patients or families need to be given an
explicit recommendation, or permission from the physician, to stop all efforts to prolong life, to be
told that that death is coming and that they no longer have to continue "fighting". Whenever
possible, try to identify the underlying emotions and offer empathic comments that open the door
to further conversation. This decision seems very hard for you. I want to give you the best
medical care possible; I know you still want CPR, can you tell me more about your decision?
Agreeing to a DNR order for many patients feels equivalent to them "choosing" to die.
Acceptance of impending death occurs over a vastly different time course for different patients/
families; for some, it never occurs. Some patients see CPR as a "last chance" for continued life.
Probe with open-ended questions: What do you expect to happen? What do you think would be
done differently, after the resuscitation, that wasn't being done before? Many patients describe
hope for a new treatment. Use the opportunity to respond by describing that you are doing
everything in your power to prolong their life before a cardiopulmonary arrest – you wouldn't be
"saving something" to do after they had died. If patients are not ready for a DNR order, don't let it
distract you from other important end-of-life care needs; emphasize the goals that you are trying
to achieve; save a repeat discussion for a future time; good care, relationship building and time
will help resolve most conflicts.
3. Distrust of the medical care system. Patients or families may give you a clue that there is
a fundamental distrust of doctors or the medical system; this should be addressed openly. What
you said makes me wonder if you may not have full trust in the doctors and nurses to do what is
best for you? Can you tell me about your concerns?
4. Managing persistent requests for CPR. Decide if you believe that CPR represents a futile
medical treatment—that is, CPR cannot be expected to either restore cardiopulmonary function or
to achieve the expressed goals of the patient (see Fast Fact #136). Physicians are not legally or
ethically obligated to participate in a futile medical treatment, and some facilities have a policy
that a physician may enter a DNR order in the chart against patient wishes. Aside from writing a
DNR order without patient or family agreement, other options at this time include:
• Transfer care to another physician chosen by the patient/family.
• Plan to perform CPR at the time of death – but don't end the discussion. Engage the
patient about her or his wishes if she or he survive the resuscitation attempt. Tell the
patient that you need guidance because it is very likely that if she or he survives CPR,
they will be on life support in the ICU, and they may not be able to make decisions for
themselves; ask them (or the family) to help you determine guidelines for deciding
!10
whether to continue life-support measures. If not already done, clarify if there is a legal
surrogate decision-maker.
References
1. Cantor MD, et al. Do-Not-Resuscitate orders and medical futility. Arch Int Med. 2003;
163:2689-2694.
2. Layson RT, OcConnell T. Must consent always be obtained for a Do-Not-Resuscitate
order? Arch Int Med. 1996; 156:2617-2620..
3. Diem SJ, Lantos JD, Tulsky JA. Cardiopulmonary resuscitation on television. Miracles
and misinformation. NEJM.1996; 334(24):1578-82.
4. Council on Ethical and Judicial Affairs. Medical futility in end-of-life care: Report of the
Council on Ethical and Judicial Affairs of the AMA. JAMA. 1999; 281:937-941. .
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!

BROACHING THE TOPIC OF A PALLIATIVE CARE CONSULTATION
WITH PATIENTS AND FAMILIES
Robert Arnold MD and David E Weissman MD
Introduction Palliative care consultative services are becoming commonplace in academic and
community hospitals and clinics. Patients and families may have negative perceptions of palliative
care and hospice – viewing such a discussion as signaling that the physician is “giving up on the
patient” and that the reality of impending death must be faced. For the attending physician, the
decision to convey to a patient and family that a consultation is needed can provoke anxiety.
Physicians may fear such a discussion will provoke anxiety, anger or a sense of hopelessness.
This Fast Fact provides tips for beginning a discussion leading to a visit by a palliative care
consultation team.
First, decide why you want assistance from the palliative care team. Typically, physicians seek
assistance in four domains: 1) pain and non-pain symptom assessment and management; 2)
assistance in making difficult decisions, usually about continued use or withdrawal of potentially
life-prolonging treatments such as feeding tubes, antibiotics, dialysis, or ventilators; 3) assistance
in planning for the most appropriate care setting to meet patient/family goals for end-of-life care;
and 4) providing psychological support to patients, families and the health care team.
Second, contact the palliative care team. Discuss your reason(s) for consultation along with
pertinent details of the patient’s history and family support structure. Describe both what your
goals are for the consultation, as well as what the family’s/patient’s goals may be. This is a good
time to discuss any concerns you have about using the term palliative care with the patient or
family.
Third, engage the patient/family in a discussion of the current medical condition and goals of
care. Introduce the topic of a consultation by saying: To best meet some of the goals we’ve been
discussing (fill in with the goals mentioned by the family/patient) I’d like to have some consultants
from the Palliative Care Team visit with you. You can follow this by saying, They are experts in
treating the symptoms you are experiencing (fill in symptom). They are also good at helping your
family deal with all the changes brought on by your illness; they can answer your questions about
(fill in previously discussed patient questions).
You should not say that the reason you are asking Palliative care to be involved is “that there is
nothing more to do” or because “I have nothing more to offer.” Talk about the positive goals
Palliative Care can help you and the patient achieve.
Finally, emphasize your continued involvement: You and I will talk about the recommendations of
the palliative care experts. I'll make sure all your questions are answered. This can help relieve
fears of abandonment. If a patient or family reacts negatively to the suggestion for a consultation,
explore their concerns. Someone may have mentioned palliative care and this may have
negative connotations to them. Ask, What experience do you have with hospice/palliative care?
What are your concerns? It may be important to discuss that palliative care is compatible with
aggressively treating the underlying disease. Emphasize the positive aspects of what palliative
care can do, rather than focusing on how the palliative care team will help them accept death and
dying. After all, the goal of palliative care is to achieve the best possible quality of life through
relief of suffering, control of symptoms and restoration of functional capacity, while remaining
sensitive to the patient and family’s values. Palliative Care guides the patient and family as they
face disease progression and changing goals of care, and helps those who wish to address
issues of life completion and life closure.
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References
1. Weissman DE. Consultation in Palliative Medicine. Arch Int Med. 1997; 157:733-737.
2. Last Acts Campaign Task Force on Palliative Care. Precepts of Palliative Care. J Pall
Med. 1998; 1:109-115.
May 2015.
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!

MEDICARE HOSPICE BENEFIT – PART I: ELIGIBILITY AND TREATMENT PLAN
Background In the United States, the Medicare Hospice Benefit (MHB) pays for 80% of all
hospice care. Established in 1983, the MHB pays for medical, nursing, counseling, and
bereavement services to terminally ill patients and their families. The original goal of the MHB
was to support families caring for a dying relative at home. Under certain circumstances, hospice
services under the MHB can also be provided in a nursing home or the acute care hospital.
Referral for hospice care is appropriate when the overall plan of care is directed toward comfort
rather than reversing the underlying disease process. Fast Facts #87, 90, 139, and 140 further
discuss the MHB.
Eligibility—Medicare Hospice Benefit
1. The patient must be entitled to Medicare Part A (hospital payments); once the patient decides
to enter hospice care, they sign off Part A and sign on (elect) the MHB. Note: this process is
reversible—patients may at a future time elect to return to Medicare Part A.
2. The patient must be certified by the Hospice Medical Director and primary physician to have
a life expectancy < 6 months “if the patient's disease runs its natural course.” Patients can
continue to be eligible if they live beyond 6 months as long as the physicians believe death is
likely within 6 months.
3. Under the MHB, DNR status cannot be used as a requirement for admission.
Covered Services (100% coverage with no co-pay)
• Case oversight by the physician Hospice Medical Director
• Nursing care: symptom assessment, skilled services/treatments and case management.
The nurse visits routinely; 24-hour/7-day per week emergency contact is also provided.
• Social work: counseling and planning (living will, DPOA).
• Counseling services including chaplaincy.
• All medications and supplies related to the terminal illness. The hospice can charge a $5
copay per medication, but most choose not to charge this. Medications for conditions not
related to the terminal condition are not covered.
• Durable medical equipment: hospital bed, commode, wheelchair, etc.
• Home health aid and homemaker services.
• Speech, nutrition, physical, and occupational therapy services as determined by the plan
of care (see below).
• Bereavement support to the family after the death of the patient.
• Short term General Inpatient Care for problems that cannot be managed at home—most
commonly intractable pain, delirium, or caregiver breakdown.
• Short term Respite Care—up to 5 days to permit family caregivers to take a break.
• Continuous care at home for short episodes of acute need.
Not Covered: Continuous nursing assistance (i.e. extended supervisory care) or nursing home
Plan of Care (POC): The hospice team and the patient’s physician work together to maximize
quality of life by jointly developing the Plan of Care. The POC is based on the patient's diagnosis,
symptoms, and other needs. The hospice program and the patient’s physician must together
approve any proposed tests, treatments, and services. In general, only those treatments that are
necessary for palliation and/or management of the terminal illness will be approved.
Physician Role: At the time of enrollment the patient indicates the primary physician who will
direct care; the patient may select a hospice physician for this role or may select their usual
primary doctor. The primary physician is responsible for working with the hospice team to
determine appropriate care.
Non-Medicare Hospice Plans: Medicaid hospice benefits closely mirror the MHB. Private
insurance plans generally emulate the MHB but occasionally depart from it dramatically (e.g.
capping the total number of days a patient may receive hospice care).
!14
References:
2. Herbst L. Hospice care at the end of life. Clin Geriatr Med. 2004; 20: 753-65.
NEJM. 2007; 357: 321-324.
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!
FAST FACT AND CONCEPT # 87

MEDICARE HOSPICE BENEFIT – PART II: PLACES OF CARE AND FUNDING
Introduction Fast Fact #82 described eligibility for the Medicare Hospice Benefit (MHB) and the
services it covers. This Fast Fact will review where services are provided and the reimbursement
system for hospice care. Fast Fact #90 reviews special interventions under the MHB, and #140
further discusses levels of care.
Places of Care
• Home: The majority (~95%) of hospice care takes place in the home. Hospice team
members visit the patient and family on an intermittent basis determined by the Plan of Care
(see Fast Fact #82), which changes based on the patient’s needs. Medicare rules do not
require a primary caregiver in the home, but as death nears, it becomes increasingly difficult
to provide care for a patient who does not have someone (family, friends, hired caregivers)
who can be present 24 hours a day in the home.
• Long-term care facility: 25% of patients in the US die in nursing homes. Medicare
recognizes that this can be the resident’s ‘home’ and that the patient’s ‘family’ frequently
includes the nursing home staff. Hospice care under the MHB can be provided to residents
in addition to usual care provided by the facility. Individual hospice programs must establish
a contract with the facility to provide hospice care. The MHB does not pay for nursing home
• Hospice inpatient unit: Dedicated units, either free-standing or within other facilities (such
as nursing homes or hospitals) are available in some regions. Patient eligibility (e.g,
whether or not a patient requires general inpatient care or not), permitted length-of-stay, and
fees for room and board vary between facilities.
• Hospital: When pain or other symptoms related to the terminal illness cannot be managed
at home, the patient may be admitted to a hospital for more intensive management, still
under the MHB. The inpatient facility must have a contract with the hospice program to
provide this service.
Payment Medicare pays for covered services using a per diem capitated arrangement in one
of four categories (see Fast Fact #140). The rates below reflect 2015 Medicare and Medicaid
reimbursements.
• Routine Home Care: care at home or nursing home (~$159/day).
• Respite Care: care in an inpatient setting (nursing home, hospice facility, or hospital) for up
to 5 days to give caregivers a rest (~$164/day).
• General Inpatient Care: acute inpatient care (at a hospital or hospice facility) for conditions
related to the terminal illness such as pain and symptom control, caregiver breakdown, or
impending death that requires inpatient-level interventions (~$709/day).
• Continuous Home Care: provides acute care at home with around-the-clock nursing for a
crisis that might otherwise lead to inpatient care (~$930/day).
The rates of reimbursement are fixed for each category of care on an annual basis, but they vary
by geographical location. Cited rates are approximate and are intended to convey general orders
of magnitude of payment. Payment is made from Medicare to the hospice agency, which then
pays the hospital or nursing home (for respite or acute care), depending on the specifics of the
contractual arrangement between the hospice agency and the facility.
Physician Services Direct patient care services by physicians, for care related to the terminal
illness, are reimbursed by Medicare, and are not included in the per diem. If the attending
physician is not associated with the hospice program via employment or similar contract, the
physician bills Medicare Part B in the usual fashion. The bill must indicate that the physician is not
associated with the hospice program or the claim may be denied. If the attending is associated
with the hospice program (e.g. as a medical director) the physician submits the bill to the hospice
!16
program, which in turn submits the claim to Medicare under Part A. The physician is then
reimbursed based on a contract with the hospice program. Patients can see consulting physicians
under the MHB if the hospice agency contracts with the consultant to do so. The hospice agency
submits the claim under Medicare Part A and reimburses the consultant per their contract.
References
1. von Gunten CF, et al. Coding and reimbursement mechanisms for physician services in
hospice and palliative care. J Pall Med. 2000; 3:157-164.
NEJM. 2007; 357:321-324.
3. Hospice Center. Centers for Medicare and Medicaid Services. Available at: http://
www.cms.hhs.gov/center/hospice.asp. Accessed November 1, 2007.
4. National Hospice and Palliative Care Organization. “The Medicare Hospice Benefit.”
January 2015. Available at: http://www.nhpco.org/sites/default/files/public/
communications/Outreach/The_Medicare_Hospice_Benefit.pdf. Accessed July 9 2015.
5. CGS Medicare. “Hospice Payment Rates.” Available at: http://www.cgsmedicare.com/
hhh/claims/fees/hospice_rates.html. Accessed July 9 2015.
edited by Drew A Rosielle MD and published November 2007. It was re-copy-edited April 2009
and then again in February 2016.
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!

MEDICARE HOSPICE BENEFIT – PART III: SPECIAL INTERVENTIONS
Introduction This Fast Fact will discuss the use of interventions in hospice care that can be
controversial due to high cost and/or uncertainty whether they constitute ‘palliative’ interventions.
When a patient elects the Medicare Hospice Benefit (MHB), the patient, the doctor, and the
hospice team develop a Plan of Care (POC) that lists a) the patient’s goals for care and b) the
services needed to achieve these goals. A hospice program is fiscally responsible for all services
outlined in the POC, and these services are paid for from the pool of money the hospice program
gets from per diem payments (physician fees are billed separately – see Fast Fact #87).
Note: since there is no Medicare regulation that specifies what treatments are deemed ’palliative,’
it is up to the individual hospice agency to determine whether or not they can financially and
philosophically provide the interventions listed below. Most hospice agencies are not able to
provide high-cost interventions due to financial limitations; patients may elect to be discharged
from hospice care if they wish to pursue these options. Hospices with a large number of enrolled
patients have greater financial resources and thus are better able to provide high-cost treatments.
Recently, some hospices have introduced ‘open-access’ programs which more freely provide
costly and even life-prolonging therapies to dying patients who would otherwise benefit from
hospice services. The hope is that the increased costs will be covered by increased revenue from
enrolling more patients earlier in the course of their illness.
Indications for use in Hospice Care In general, the interventions listed below are potentially
indicated in patients with a) a good functional status (up, out of bed > 50% of the time; Karnofsky
Performance Status >50; ECOG ≤2 – see Fast Facts #13, 124), or b) a clear goal to be met (e.g.
wedding anniversary in two weeks). These interventions are not indicated solely to assist
patients or families psychologically cope with impending death – to give the impression that
’something is being done.’
• Parenteral Fluids. Indication: symptomatic dehydration where there is a patient-defined
goal (e.g. upcoming family event). Fluids are not indicated to treat dry mouth or solely to
reverse dehydration occurring as a normal aspect of the dying process; fluids may be of
benefit to treat delirium in selected patients (see Fast Fact #133).
• Enteral feeding. Indication: patient is hungry and there is a reason oral nutrition cannot be
given (e.g. upper GI obstruction from esophageal cancer). See Fast Facts #10 and 84 for a
complete review of the indications/contraindications for tube feeding.
• Total Parenteral Nutrition. Indication: patient has short-gut syndrome or bowel obstruction
and good functional status and a functional goal. See Fast Fact #190 for further discussion.
• Radiation Therapy. Indication: symptoms of pain, bleeding, or neurological catastrophe (e.g.
acute spinal cord compression) and the patient is expected to live long enough to experience
benefit (> 4 weeks) and the potential benefits outweigh logistic burdens (e.g. travel to the
radiotherapy site, getting on and off the treatment table). See Fast Facts # 66, 67.
• Red Blood Cell Transfusions or Erythropoietin. Indication: Symptomatic anemia
(dyspnea or fatigue) in ambulatory patients who demonstrate continued functional benefit
from treatment.
• Platelet Transfusions. Indication: active bleeding and severe thrombocytopenia (Platelet
count < 10,000).
• Chemotherapy. Indication: symptoms from the cancer are causing distress; the likelihood of
effectiveness is high (expected Response Rate greater than 25% - see Fast Facts #14, 99);
patient will live long enough to benefit (> 4-8 weeks, ECOG 0-2); and benefits outweigh
burdens.
• Antibiotics. Indication: oral antibiotics are appropriate to treat simple symptomatic
infections (e.g. UTI). Parenteral antibiotics are not indicated unless there is an identified
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susceptible organism, there is a clear functional goal to be met, the likelihood of successful
treatment is high, and the patient is expected to live long enough to achieve benefit.
• Laboratory/Diagnostic services. Indication: to monitor aspects of POC (e.g. warfarin
monitoring) or as part of a diagnostic evaluation for a new symptom for which the testing is
likely to substantially alter patient management. Note: diagnosis of a new problem that does
not relate to the terminal illness can be evaluated and treated by the patient’s primary care
provider under usual Medicare billing (e.g. acute myocardial infarction).
References
2. Wright AA, Katz IT. Letting go of the rope – aggressive treatment, hospice care, and
open access. NEJM. 2007; 357:324-327.
3. Marantz Henig R. Will we ever arrive at the good death? New York Times. August 7,
2005. Available at: http://www.nytimes.com/2005/08/07/magazine/07DYINGL.html.
Accessed November 2, 2007.
edited by Drew A Rosielle MD and published November 2007; 3rd Edition June 2015. Current
version re-copy-edited April 2009; then again in June 2015.
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!

PREPARING FOR THE FAMILY MEETING
Background A cornerstone procedure in Palliative Medicine is leadership of family meetings to

establish goals of care, typically completed at a time of patient change in status, where the value
of current treatments needs to be re-evaluated. As with any procedure, preparation is essential to
ensure the best outcome. This Fast Fact reviews how to prepare for a Family Meeting. See also
Fast Fact #16 for a concise overview of family meetings, as well as Fast Facts 223-227 for
discussion of additional aspects of family conferences.
Data Review
• Review the medical history relevant to the current medical situation (e.g. history of disease
progression, symptom burden, past treatments, treatment-related toxicity, and prognosis).
• Review all current treatments (e.g. renal dialysis, artificial nutrition, antibiotics) and any
positive and/or negative treatment effects.
• Review all treatment options being proposed.
• Determine the prognosis with and without continued disease-directed treatments. Prognostic
information includes data concerning future patient function (physical/cognitive), symptom
burden, and time (longevity).
• Solicit and coordinate medical opinions about the utility of current treatments among
consultants and the primary physician. If possible, families need to hear a single medical
consensus—all relevant clinicians should be contacted and consensus reached prior to the
meeting. If the consultants do not agree, then prior to the family meeting they should meet to
negotiate these differences and attempt to reach consensus regarding the plan. If there is no
consensus, a plan should be developed for how to describe these differences to families.
• If the patient lacks capacity, review any Advance Directive(s), with special attention to
discover if the patient has named a surrogate decision maker, and if the patient has indicated
any specific wishes (e.g. DNR status, ‘no feeding tubes’).
• Seek out patient/family psychosocial data. Focus on psychological issues and family
dynamics (e.g. anger, guilt, fear) potentially impacting decision making. These issues may be
long-standing, or due to the current illness. Note: talking to the patient’s social worker,
bedside nurses, and primary and consulting physicians can help you get a better sense of the
family and how they make decisions.
o Review what transpired in prior family meetings.
o Learn about particular cultural/religious values and/or or social/financial issues that may
impact decision making.
Information Synthesis Based on your review of the medical and prognostic data, make an
independent determination of which current and potential tests/treatments will improve, worsen,
or have no impact on the patient’s function/quality of life (physical/cognitive) and time (longevity).
Meeting Leadership Leading a family meeting requires considerable flexibility to ensure that
all relevant participants have the opportunity to have their points of view expressed. Though it is
useful to have one person designated as the main orchestrator and coordinator of the meeting,
the essential skills for making a family meeting successful can come from more than one
participant. These skills include:
• Group facilitation skills.
• Counseling skills.
• Knowledge of medical and prognostic information.
• Willingness to provide leadership/guidance in decision making.
Invitations A decisional patient can be asked who he/she wants to participate from his/her
family/community, including faith leaders; in general it is wise not to set any arbitrary limits on the
number of attendees. The medical care team should likewise decide who they want to
participate. Note: it is important not to overwhelm a family with too many health professionals.
!20
On the other hand, a physician from the primary team as well as a nurse and social worker
should attend when possible; these individuals can help ensure the consistency of information as
well as help deal with complicated dynamics. If the patient has a long-time treating physician
whom he/she trusts, this person should ideally be present.
Setting The ideal setting is private and quiet, with chairs arranged in a circle or around a table.
Everyone should be able to sit down if they wish. For non-decisional patients, the clinical team
should negotiate with the surrogate whether or not to have the meeting in the presence of the
patient.
The Pre-Meeting Meeting The participating health care members should meet beforehand to
confirm: a) the goals for the meeting (e.g. information sharing, specific decisions sought), b) who
will be the meeting leader to start the meeting, and c) likely sources of conflict and initial
management strategies.
References
2009.
Med. 2006; 9:704-715.
5. Weiner JS, Roth J. Avoiding iatrogenic harm to patient and family while discussing goals
of care near the end of life. J Pall Med. 2006; 9:451-463.
292:1738-1743.


used.

THE FAMILY MEETING: STARTING THE CONVERSATION
David E Weissman MD, Timothy Quill MD, and Robert M Arnold MD
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Background Fast Fact #16 gives a concise overview of running a family meeting. Fast Fact
#222 provides a list of preparatory steps in planning for a family meeting to discuss end-of-life
goals; this Fast Fact reviews the early steps of the actual meeting.
1. Introductions & setting goals for the meeting

• The meeting leader begins the meeting by introducing him or herself, and suggesting that
each person present (medical team and family/community) introduce themselves
including their relationship to the patient.
• The meeting leader should summarize the meeting goals (e.g. We are here to discuss
next steps in the care of Mr. Jones) and ask the family to confirm these goals and/or add
other agenda items.
• Note: if you do not know the patient or family well, take a moment to build relationship.
Ask a non-medical question such as I am just getting to know you. I had a chance to look
at your chart and learn about your medical condition but it does not say much about your
life before you got sick. Can you tell us about the things you liked to do before you got
sick? Similarly, if the patient is not able to participate in the meeting, ask family to
describe the patient prior to his becoming ill: As we get started, can you describe what
Mr. Jones was like before he became ill?
2. Determine what the patient/family already knows This step is essential as it guides you in
providing a synthesis of the medical information (see below). Always invite the patient and all
family members to provide their understanding of the medical information. Examples of opening
lines:
• Tell me what the doctors have told you about your condition?
• Can you describe for me your sense of how things are going?
• For patients who have been declining from a chronic illness, you can ask: Tell me about
the past 3-6 months: what types of changes have you noted? The patient or family will
typically describe changes in terms of function (physical or cognitive) and quality of life.
3. The Medical Review Once you know what the patient/family understands, you are in a good
position to confirm their understanding, or provide new information/correct misunderstandings.
First, ask if you can bring them up-to-date about what is going on; asking shows politeness and
also signals that they should attend to what you are trying to say. The clinician most closely
aligned with the patient’s ongoing treatment should begin this discussion, supplemented with
information from consulting services if relevant. Do not provide information using medical jargon
or in an organ system approach (e.g. The creatinine is improving, but there is a new pleural
effusion and the heart rate has become irregular). A more patient-centered approach is to
provide a succinct summary of the current condition, without any medical jargon, focusing on the
issues of most importance, which are usually function/quality/time. Give a ‘bottom-line’
statement: ‘getting worse,’ ‘not going to improve,’ ‘dying and time is likely very short.’
• The worsening weakness and pain you describe is from the cancer which is growing
despite the chemotherapy.
• You are telling me that despite the recent hospitalization, you are not able to do as much
around the house; unfortunately your lung disease is getting worse despite all our best
treatments.
• Despite our best efforts, your wife’s brain injury from the car crash is getting worse. She
can no longer stay awake or move her arms/legs.
Using the ‘D word’ if relevant: when a patient is clearly deteriorating and death is likely within
the next days to weeks, or even a few months, it is appropriate to use the word dying in the
conversation. Both patients and surrogates find that saying the word dying, if done
compassionately, is helpful in clearing what is often a confusing and frightening situation. I’m
afraid we have run out of options to shrink the cancer. Based on your declining function, I believe
you are dying.
4. Silence Whether or not you use the word dying, when you have presented bad news (such
as information about disease progression), the next step is for you to allow silence, and let the
!22
family/patient respond. In truth, no matter what you might imagine the response from the patient/
family to be once the bad news is delivered, you really cannot predict their emotional reaction
(e.g. relief, anxiety, anger, regret, fear). This silence can be uncomfortable; resist the urge to fill it
with more facts as they will not be heard. Not all patients/families express emotions at this point
and instead respond practically (Well, what happens next then?). This is fine, but you need to
wait, silently, to see what response the patient/family demonstrates. In addition, even practical
questions have underlying emotions (Are you sure? Or – There must be something you can do?).
It is important to respond to both the factual aspect of the question (Yes I am sure. Or – There are
no more effective treatments available.), as well as the emotional level (I wish I had better news
for you. Or – I wish our treatments worked better than they do.).
When the patient/surrogates openly acknowledge that current treatments are no longer effective,
that death is coming, they will generally ask one or all of the following questions: How long?
What will happen? Will there be suffering? What do we do now? Your response at this point
should be to address prognosis in terms of time, function, and symptoms, as best you can (see
Fast Facts #13,141,143,149,150). This will answer the first two questions; the last questions will
require more discussion of patient-centered goals (see Fast Fact #227).
References
2009.
2. Quill TE, Townsend P. Bad news: delivery, dialogue and dilemmas. Arch Intern Med.
1991; 151:463-468.
Med. 2006; 9:704-715.

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!24
!

RESPONDING TO EMOTION IN FAMILY MEETINGS
Background Family meetings are stressful events, often provoking strong emotional reactions.
Fast Fact #29 presents a general outline on the topic of how clinicians can respond to emotions.
The Fast Fact will provide a more detailed approach to emotions that arise during family
meetings.
Consider your role. It is important to reflect on the role of clinicians in responding to patient/
family emotions at the time life-altering information is shared. The goal is not to prevent a patient/
family from having those emotions. Sadness, fear, anger, and loss are normal responses to
unwelcome news. Instead your role is: 1) to maintain a trusting therapeutic relationship and safe/
supportive environment that allows emotions to be expressed in a way that meets the patient’s/
family’s needs; and 2) not to worsen the experience for the patient/family by ignoring or
delegitimizing their responses, or confusing them with medical information when they are not
ready to hear it. Recognize that most families find clinicians’ expressions of empathy
tremendously supportive and these are associated with family satisfaction.
Acknowledge that emotion is being expressed. If you have a good sense of what the emotion
is, then it is useful to name it. If not, using more general language is preferable.
• I can see this is really affecting you.
• This information is very upsetting.
Legitimize the appropriateness and normalcy of the reaction. Medical professionals are in a
powerful position to help patients and families feel that strong emotions under these
circumstances are normal and to be expected.
• Anyone receiving this news would feel devastated.
• It is completely expected to be very distressed by this kind of news.
Explore more about what is underneath the emotion. It is tempting to try to limit the emotion,
and be prematurely reassuring. But it is generally more helpful and ultimately more time-efficient
to allow the patient and family to more deeply explore their feelings and reactions.
• Tell me what is the scariest (most difficult) part for you.
• Tell me more about that…. (Keep the exploration going until it is fully expressed and
understood.)
Empathize (if you genuinely feel it). Empathy means being able to emotionally imagine what
the patient is going through. Clinicians can initiate the prior responses (acknowledge, legitimize,
explore) without having a clear feeling for the patient’s experience. These responses can be
adequate in themselves. If the clinician cannot imagine the patient’s experience, he or she can
still sensitively explore the experience and provide caring and support. But if you have a strong
sense of what the patient is experiencing, it can be very therapeutic to express it.
• This seems really unfair.
• I can imagine that you might feel very disappointed.
Explore strengths/coping strategies. This may occur at this phase of the interview, or it may
be postponed to a later phase when planning for next steps begins.
• In past circumstances, what has helped?
• How have you adapted to difficult circumstances in the past?
References
1. Back A, Arnold R, Tulsky J. Mastering communication with seriously ill patients: balancing
honesty with empathy and hope. New York, NY: Cambridge University Press; 2009.
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2. Suchman AL, Markakis K, Beckman HB, Frankel R. A model of empathic communication in
the medical interview. JAMA. 1997; 277:678-682.
3. Hardee JT. An overview of empathy. The Permanente Journal. 2003; 7(online). Available at:
http://xnet.kp.org/permanentejournal/fall03/cpc.html. Accessed August 5, 2009.

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!

THE FAMILY MEETING: CAUSES OF CONFLICT
Background When family meetings are conducted with the goal of helping a patient/family cope
with a shift in goals from life-sustaining treatments to a more comfort focused approach,
communication can break down. This Fast Fact reviews the common causes of conflict.
Recognizing Conflict When the patient/surrogates are not psychologically ready to accept the
limits of medical interventions or the finality of the impending death, you will hear comments such
as these: There must be some mistake; I know there are other treatments available; We want a
second opinion; We believe in miracles; She is fighter, she will never give up; There must be
something (medically) you can do. Health professionals may interpret these statements as
‘denial.’ But the term denial, by itself, is insufficient to help the clinician understand what is
causing the impasse. Understanding the cause is essential in planning an effective strategy to
move beyond the conflict to meet the needs of the patient and surrogates.
Information Gaps
• Inaccurate understanding of the patient’s medical condition (e.g. overly optimistic/
pessimistic prognosis).
• Inconsistent information (One doctor tells us one thing and another something else.).
• Confusing information (e.g. use of medical jargon, multiple treatment options presented
without a clear recommendation).
• Excessive information (well-meaning family/friends/clinicians providing information
without full awareness of the problems).
• Genuine uncertainty (e.g., predicting functional outcome from a brain injury in its
immediate aftermath may be impossible).
• Language/translation/cultural issues (We never tell someone they are dying in our
culture.).
Treatment Goal Confusion
• Inconsistent treatments and unclear goals, often due to physician/patient/surrogate
emotional issues (see below):
o Clinician initiated: We will keep your husband on blood pressure raising medicine
but stop antibiotics.
o Family initiated: We want you to do CPR, but not intubate her.
• Differing priorities about disease-directed treatment and comfort-oriented treatment
between clinicians and patient/family.
• Lack of clarity about goals when several things are going on simultaneously (advanced
cancer, severe infection, respiratory failure – Isn’t the pneumonia potentially treatable?)
Emotions
• Grief (I don't know how I will live without him.)
• Fear/anxiety (I don't want to be responsible for ending my father's life. My family will be
angry at me for doing this.)
• Guilt (I haven't visited my sister in 20 years. I should have been here for her.)
• Anger (My mother was very abusive, I've never forgiven her; you are just giving up on
her.)
• Hope (I’m still hoping and praying she can pull through this.)
Family/Team dynamics
• Patient/family conflicted within themselves; may want different things at different times
• Dysfunctional family system (family members unable to put the patient's needs/values/
priorities above their own).
• Surrogate lack of ability (cognitive deficit, psychological/psychiatric trait/illness). In
pediatrics, this can be conflict between what is in the best interest of a child vs. a
caregiver or family.
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• Consulting teams disagree about the optimal approach, putting the patient/family in the
middle of the dispute.
Relationship between the Clinician and the Patient/Surrogate
• Lack of trust in the health care team/health care system.
• Past experiences where the patient has had a better outcome than predicted.
• Genuine value differences:
o Cultural/religious values concerning life, dying, and death.
o Clinician value to protect the patient from invasive, non-beneficial treatment while
the family values wanting to prolong life no matter how much suffering it might
entail.
All of these issues represent a degree of conflict and will need to be addressed before proceeding
to set end-of-life goals. See Fast Facts #183,184 for additional discussion on managing conflict.
Debriefing Conflicts are stressful for all involved health professionals. It is helpful to debrief the
process – what went well, what could have been improved, and – most importantly – addressing
the emotional reaction and needs of the care team. See Fast Fact # 203 on managing clinician
emotions.
References
1. Back AL, Arnold RM. Dealing with conflict in caring for the seriously ill. JAMA. 2005;
293:1374-1381.
2. Lazare A, Eisenthal S, Frank A. Clinician/Patient Relations II: Conflict and Negotiation.
In: Lazare A, ed. Outpatient Psychiatry. Baltimore, MD: Williams and Wilkins; 1989.
4. Quill TE. Recognizing and adjusting to barriers in doctor-patient communication. Ann
Intern Med. 1989; 111:51-57.
2009.


used.
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HELPING SURROGATES MAKE DECISIONS
Background Surrogate decision makers are often placed in the difficult position of making
what feels to them as life or death decisions. This Fast Fact reviews an approach to help
surrogates through the decision process when patients cannot participate in decision-making
themselves.
Surrogate decision making The surrogate’s role is clearly to exercise “substituted judgment” –
that is, to make decisions as the patient would make them using the patient’s values and
preferences as previously expressed. The challenge was clearly expressed by the New Jersey
Supreme Court in the Quinlan case: if (the patient) could wake up for 15 minutes, understand his
current medical situation completely, and then had to go back into it, what would he tell us to do?
In the case of children, surrogate decision makers (usually parents) are expected to make
decisions that represent the child’s ‘best interests’; depending on the age and capacity of the
child to participate in his/her own healthcare decision making, the applied ‘best interest’ judgment
by the surrogate and healthcare providers may incorporate the patient’s values and preferences
to the extent possible, or may be solely based on the decision maker’s interpretation of best
interest. If there is conflict about what is in a child’s best interest, or in cases of developmentally
disabled adults who have never had capacity, consultation from ethics and law may be
appropriate, as the rules governing decision-making vary considerably.
Helping surrogates
1. Before making a recommendation, make sure there is a common understanding of the
patient’s condition and prognosis. Following this, the next step is to try to understand the
patient’s goals in light of these medical facts.
2. Bring the patient’s “voice” into the decision process even if he/she cannot participate directly:
If your father were sitting here with us, what would he say? If available, share a copy of any
advance care planning document with the surrogate. Realize that it is common for the
surrogate never to have seen the document.
3. Whenever possible, frame the decision around the treatment goals (e.g. life prolongation,
allowing a peaceful death) in light of the patient’s current condition, rather than focusing on
very specific treatments (e.g. thoracentesis, antibiotics). The details of the medical plan
should flow from the overall goals of care.
4. Do not make the surrogate feel that they are taking full responsibility for medical decisions,
especially those which may result in the death of their loved one (We can do option a or b;
what would like me to do?). Once you have a sense of the patient’s goals in light of his/her
medical condition, offer to make a recommendation that reflects those goals. Note: Many
families are looking for support and guidance from medical professionals, especially the
physician. Given what you have told me about your mother, and what we know about her
medical condition, I would recommend…. Start with what you are going to do to achieve the
patient’s goals and then talk about what does not make sense given those goals. Remember,
however, that some families may want information but not your recommendation. It is
therefore important to offer your recommendation (Would it be helpful for me to say what
medically makes the most sense, given what you’ve told me about your Dad?).
5. Remember that we are talking about the potential death of the surrogate’s loved one.
Emotions – sadness, frustration and guilt – are appropriate and to be expected. Use
previously discussed emotion management skills to acknowledge, legitimize, empathize and
support the family’s emotional response (see Fast Facts #29 and #224).
6. Do not argue over the facts; repeating the facts over and over again is not likely to be
effective. When the surrogate says He is a fighter, acknowledge that he is and has really
fought hard. The surrogate saying I want you to do everything is as much a sign of emotional
desperation as it is a factual request. Respond with empathy: It seems this is really hard for
you. If hope for a miracle is expressed, it is appropriate to acknowledge that you hope for an
unancticipated recovery as well, but that a miracle is truly what it would take at this point.
7. Rather than reiterating what medicine cannot do, consider using “I wish” statements to keep
you in touch with the surrogate’s feelings, while simultaneously expressing medicine’s
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limitations (I wish our medicines were more effective; I wish we had more medical treatment
to offer than we do…).
8. Recognize the importance of time and support for surrogates to do their necessary grief-
work. Offer counseling services, either informal through the work of a palliative care team, or
more formal resources available at your institution. Bring together your clinical care team and
strategize potential resources for support such as chaplaincy, social services, psychology,
palliative care or ethics consultation.
Remember that time is your ally. The surrogate needs to process that their loved one is dying
and conceptualize what life will be like without him or her. This grief work takes time and
psychological support. Often, letting people think about what you have said and talking again
over subsequent days provides them the space to do grief work. It also allows them to see for
themselves that what you have advised is coming true (e.g. the patient is not getting better).
References
1. Quill TE, Brody H. Physician recommendations and patient autonomy: Finding a balance
between physician power and patient choice. Ann Intern Med. 1996; 125:763-769.
4. Quill TE, Arnold RM, Back A. Discussing treatment preferences in patients who want
"everything". Ann Intern Med. 2009; 151:345-349.


THE FAMILY MEETING: END OF LIFE GOAL SETTING AND FUTURE PLANNING
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Background End-of-life goal setting is a key palliative care skill, typically occurring as part of a
family meeting (see Fast Facts #16, 65, 222-226). This Fast Fact discusses an approach to goal
setting when the expected length of life is short.
Establishing patient-centered goals Here is an example of how to start the conversation (the
patient should be given sufficient time to respond to each of these questions):
I/we have discussed your current condition and that time may be short. With that in mind –
• What is important to you?
• What do you need to accomplish?
• Who do you need to see in the time that is left?
Common responses invoke family, home, and comfort; often surviving until a specific future family
event/date or visit with a key family member is described as an important goal. Re-state your
understanding: What I hear you saying is that you want to be home, comfortable, and survive
until your daughter gives birth – you hope to meet your next grandchild. Note: if you believe the
patient’s goal of survival to a specific event/date is not practical, it is important to say so and
discuss alternative plans.
Recommend a care plan based on the goals Once the goal(s) is/are established, you can
then review the patient’s current treatments (e.g. antibiotics, chemotherapy), monitoring (e.g.
pulse oximetry), planned tests (e.g. colonoscopy), and medications (e.g. anti-hypertensives), and
decide which will help meet, or not, the patient’s goals. Anything that will not help meet the goals
should be discussed for potential discontinuation. Depending on the specific disease/patient
condition, other issues that are naturally discussed at this point include:
• Future hospitalizations, ICU admissions, laboratory and radiology tests.
• Resuscitation orders/code status (see Fast Facts #23-24).
• Current/future use of blood products, antibiotics, artificial hydration/nutrition.
• If present, the potential continuation or stopping of dialysis or cardiac devices.
• Role of a second (or third) opinion.
• Exploration of experimental therapy.
• Exploration of treatment options the patient or family may bring into the conversation.
• Disposition options to best meet the goals (e.g. home hospice referral).
Note: There is no need to ask about each option as a yes/no question (Do you want blood
products?). Based on what you know about the patient’s goals, make a recommendation about
what should and should not be done in light of the patient’s goals, condition and prognosis. If you
are unsure, you can explore the issue with the patient/family (Given that your dad wanted to get
home as soon as possible and yet he was also willing to do easy things that might help him live
longer, I am unsure whether it makes sense to stay in the hospital an extra day or two to finish the
antibiotics. What do you think he would say?).
‘Long-shot’ goals If patients are going to pursue ‘long-shot’ or experimental therapy, perhaps
even against the recommendation of the treating team, it is useful to ensure the following:
• Reinforce the team’s respect for the decision, and desire to make sure the treatment has
the best possible chance of working.
• Simultaneously try to maximize quality of life in the present, including the best possible
pain and symptom management and support.
• Encourage the patient and family to prepare in case treatment is not successful and the
patient dies sooner rather than later. Useful language is to say, I’d encourage us all to
hope for the best, but prepare for the worst.
• Reinforce that the team will not abandon the patient and family even if the decision is not
what is being recommended.
Close the meeting Following this discussion, restate your understanding of the patient’s goals
and agreed-upon next steps to meet those goals, invite and answer questions, and close the
meeting.
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Discussion & documentation Discuss the goals with key staff not in attendance (e.g.
consulting physicians, patient’s nurse, discharge planner, primary care provider). Document the
goals, preferably using a templated family meeting note (see Reference 1): who was present,
what was discussed (e.g. treatment options, prognosis), what was decided, next steps.
Debriefing A useful step after every family meeting is to debrief the process – what went well,
what could have been improved and, most importantly, addressing the emotional reaction and
needs of the care team.
References
1. Clinical Tools. Center to Advance Palliative Care. Available at: http://www.capc.org/tools-
for-palliative-care-programs/clinical-tools/. Accessed August 4, 2009. Free registration
required.
2009.


ILLNESS TRAJECTORIES: DESCRIPTION AND CLINICAL USE
Paige Comstock Barker, MD and Jennifer S. Scherer, MD
Illness trajectories can provide a framework for addressing patient and family expectations of
what will happen with regards to their anticipated health. Distinct illness trajectories have been
recognized in the medical literature (see Figure 1). This Fast Fact will review the medical
evidence of these trajectories as well as their utility as a patient teaching tool.
General Evidence: A large observational study, described distinct illness trajectories at the end
of life for frailty/dementia, cancer, and organ failure (1). Subsequent research has cast some
!32
controversy about the validity of these
findings, particularly whether
hospitalizations may have a more
significant role on the pattern of
decline than the specific illness itself
(2-4).
Illness Trajectories:
Frailty / Dementia: A pattern of
dwindling cognitive and/or physical
disability that may progress over
several years (1). Seventy percent of
dementia patients require assistance
in ≥3 ADLs, in the last year of life,
making these patients at heightened
risk for nursing home placement and
caregiver breakdown (2). Many
clinicians and families may not
recognize that dementia by itself is a
terminal illness.
Cancer: A relatively stable period of

physical function followed by an acute
decline in the last few months of life. Multiple studies have supported this trajectory however, the
timing of steep decline ranges between 1 to 5 months before death depending on the study
(1,5-7). Cancer patients may also experience more predictable patterns of spiritual distress with
peaks at diagnosis, disease recurrence, and the terminal phase of illness (8). Because the
physical decline and psycho-spiritual distress can be better anticipated, especially in solid tumors,
more accurate prognostication and implementation of specialized palliative care services can
occur. One study of Medicare patients showed that cancer patients were more likely to utilize
hospice in comparison to other chronic illnesses because of the more predictable trajectory (9).
More research is needed to validate this trajectory in the face of new targeted treatment
modalities.
Organ failure: A more erratic trajectory with punctuated periods of decline likely correlating with
acute exacerbations (1). Each exacerbation may result in death but is often survived with gradual
deterioration in health and functional status. Timing of death is less certain than in cancer.
Perhaps as a result, patients with congestive heart failure (CHF) and chronic obstructive
pulmonary disorder are more likely to die in the hospital and less likely to receive hospice
services nor understand the likely progression of their illness (9-12). Other take home points
regarding the organ failure trajectory include:
• The functional decline for CHF has been shown to be particularly heterogeneous (2,13).
Some hypothesize this may be related to co-morbidities and/or research methodologies (13).
• Often prognosis is more centered around patient specific goals regarding acceptance or not
of repeat hospitalizations and treatment of potentially reversible complications.
• Although observational studies have shown inconsistent findings, elderly end stage renal
disease patients who forgo initiating hemodialysis may be more likely to have an illness
trajectory similar to sudden death – stable function for months with a rapid end of life
deterioration (14-16).
Sudden Death or Decline: An abrupt change from normal physical function to either death or
significant medical disability, often as a result of trauma or an acute cardiopulmonary/neurologic
event. Many times there is little or no prior interaction with the health system nor a recognizable
pattern of functional decline preceding the event (1,9). Thus, intense displays of shock or anger
are common from family members when clinicians break bad news. See Fast Fact #305. Loved
ones are at increased risk for depression and complicated grief as they adjust to the new medical
reality after the event (17,18).
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Clinical Use: Although there is no known published data assessing the effectiveness of utilizing
the illness trajectories as a clinical teaching tool, describing or even diagramming these illness
trajectories with patients and families may be a concise communication technique to set
expectations and offer guidance regarding the anticipated impact of chronic illness on daily life.
Clinicians should be aware of the significant variability in the medical literature regarding the
validity of these illness trajectories as well as the limitations in the way functional decline is
measured between studies. Therefore, it is vital that illness trajectories be reevaluated as the
condition evolves. In particular, certain patterns such as an abrupt functional decline or frequent
hospitalizations may indicate the need to readdress goals of care.
References:
1. Lunney JR, Lynn J, Foley D, et al; Patterns of Functional Decline at the End of Life.
JAMA. 2003;289(18): 2387-2392.
2. Gill TM, Gahbauer EA, Han L, et al; Trajectories of Disability in the Last Year of Life. The
New England Journal of Medicine. 2010;362(13): 1173-1180.
3. Gill TM, Gahbauer EA, Han L, et al; The role of intervening hospital admission on
trajectories of disability in the last year of life: prospective cohort study of older people.
BMJ. 2015;350:1-8.
4. Steinhauser KE, Arnold RM, Olsen MK, et al. Comparing Three Life-Limiting Diseases:
Does Diagnosis Matter or Is Sick, Sick? J Pain Symptom Manage. 2011; 42(3): 331-341.
5. Seow, H, Barbera L, Sutradhar R, et al. Trajectory of Performance Status and Symptom
Scores for Patients With Cancer During the Last Six Months of Life. Journal of Oncology.
2011; 29(9): 1151 – 1158.
6. Tang ST, Liu LN, Lin KC, et al; Trajectories of the Multidimensional Dying Experience for
Terminally Ill Cancer Patients. Journal of Pain and Symptom Management. 2014;48(5):
863-874.
7. Teno JM, Weitzen S, Fennell ML, et al. Dying Trajectory in the Last Year of Life: Does
Cancer Trajectory Fit Other Diseases? Journal of Palliative Medicine. 2001; 4(4): 457 –
464.
8. Murray SA, Kendall M, Grant E, et al; Patterns of Social, Psychological, and Spiritual
Decline Toward the End of Life in Lung Cancer and Heart Failure. Journal of Pain and
Symptom Management. 2007;34(4): 393-402.
9. Lunney JR, Lynn J, Hogan C. Profiles of Older Medicare Decendents. JAGS.
2002;50:1108-1112.
10. Gavazzi, A, De Maria R, Manzoli L, et al. Palliative needs for heart failure or chronic
obstructive pulmonary disease: Results of a multicenter observational registry.
International Journal of Cardiology. 2015;184: 552-558.
11. Kendall M, Carduff E, Lloyd A, et al; Different Experiences and Goals in Different
Advanced Diseases: Comparing Serial Interviews With Patients With Cancer, Organ
Failure, or Frailty and Their Family and Professional Carers. Journal of Pain and
Symptom Management. 2015;50(2): 216-224.
12. Levenson JW, McCarthy EP, Lynn J, et al; The Last Six Months of Life for Patients with
Congestive Heart Failure. JAGS. 2000;48(5): S101-S109.
13. Kheribek RE, Alemi F, Citron BA, et al; Trajectory of Illness for Patients with Congestive
Heart Failure. Journal of Palliative Medicine. 2013;16(5): 478-484.
14. Murtagh, FEM, Addington-Hall J, and Higginson IJ. End-Stage Renal Disease: A New
Trajectory of Functional Decline in the Last Year of Life. JAGS. 2011; 59: 304-308.
15. Schell JO, Da Silva-Gane M, and Germain MJ. Recent insights into life expectancy with
and without dialysis. Current Opin Nephrol Hypertens. 2013;22: 185-192.
16. Schell JO and O’Hare AM. Illness trajectories and their relevance to the care of adults
with kidney disease. Current Opin Nephrol Hypertens. 2013;22: 316-324.
17. Burton, AM, Haley WE, Small BJ. Bereavement after caregiving or unexpected death:
Effects on elderly spouses. Aging and Mental Health. 2006;10(3): 319-326.
18. Kristensen, P, Weisaeth L, Heir T. Bereavement and Mental Health after Sudden and
Violent Losses: A Review. Psychiatry. 2012;75(1):76-97.
Author’s Affiliations: New York University, New York, NY

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Version History: Originally edited by Sean Marks MD; first electronically published in December
2016.

Background: Clinicians have been encouraged to utilize the surprise question (SQ) -- “Would I
be surprised if this patient died within 12 months?” – to identify patients at high 1-year mortality
risk. When clinicians answer “No – I would NOT be surprised if this patient died within 12
months,” the SQ may help clinicians identify patients with unmet palliative care needs who could
benefit from advance care planning discussions and/or a palliative care referral (1). This Fast
Fact reviews the clinical utility of the SQ.
Rationale of the SQ: As difficult as it is for clinicians to prognosticate accurately, multiple

studies have shown that patients with incurable disease desire more prognostic information the
sicker they get and prognosis is a major factor in preferences for rehospitalizations, life support,
!35
and CPR (2-4). Although, patients and surrogates often want temporal prognostic predictions
(the clinician’s estimated length of time he or she predicts the patient will live), clinicians are more
accurate and willing to offer probabilistic predictions (the clinician’s estimate, often in a
percentage, of the chance of death in a set time frame, such as 1 year) (4-6). The SQ was
designed as a clinical tool that generalist clinicians would utilize willingly and routinely to identify
patients at risk of death in a year and thereby lead to more appropriate advance care planning,
goals of care discussions, symptom management, and hospice referrals.
Effectiveness of the SQ: Although variations on the SQ have been described in the published
literature including “Would I be surprised if this patient died this hospitalization?” or “Would I be
surprised if this patient died in 3 months?”, the SQ most commonly referred is “Would I be
surprised if this patient died within 12 months?” This SQ has been studied in diverse populations,
including a general inpatient setting (7), high-risk primary care clinic (8), pediatric patients (9),
advanced kidney disease (10-12), cancer (13,14), acute surgical patients (15), emergency
department settings (1,16), and nursing home settings (17). In general, the SQ has performed
modestly well in identifying patients with a prognosis of < 1 year across these various patient
populations (18,19). Notable findings from these studies include:
• A meta-analysis of the SQ among 26 studies across these patient populations found that it
had a pooled accuracy of 75%, a sensitivity of 67% and specificity of 80% (18).
• “Yes” answers appear to be much more accurate than “No” answers. The predictive value of
a “Yes” answer was 93%, while only 37% for a “No” answer (18). This means that the SQ is
likely better designed to identify patients who will live more than a year vs the patients who
live less a year. It also suggests that there is “false positives” are relatively common when
clinicians answer “No” to the SQ.
• The SQ may be slightly more accurate for cancer patients (pooled accuracy 79%) and renal
patients (76%) vs other disease groups (72%) (18). This may reflect a more predictable
illness trajectory in cancer and renal disease. See Fast Fact #326 for more information on
illness trajectories.
• In most studies, the SQ was utilized as one aspect of a broad prognostic assessment which
included clinician gestalt and/or other prognostic tools. Hence, used in isolation, its accuracy
is unclear (18).
Implementing the SQ Into Clinical Practice: The SQ can be helpful in identifying patients at
risk of medical decline and death in a certain time frame when used as part of a larger prognostic
assessment (19). Yet, considering the relatively high false positive rate of a “No” answer, it is not
established if the SQ is a cost-effective tool nor an effective way to trigger a palliative care
consultation on its own. A consensus panel of experts suggested that a “No” answer trigger
generalist clinicians to perform a primary palliative care assessment or screening for unmet
palliative care needs (20). Sentinel medical events like hospitalization, decline in performance
status, or disease progression are reasonable triggers to implement the SQ into clinical practice.
Note templates, medical rounding tools, and electric medical record prompts are potential
system-based approaches to accomplish this. Reasonable components of the primary palliative
care assessment triggered by a “No” include (20):
• Identification of whether the patient completed an advance directive such as a health care
power of attorney that is available in the medical records.
• Assessment of patient, family, and/or surrogate’s understanding of the underlying illness,
treatment options, and prognostic trajectory.
References:
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1. Haydar SA, Almeder L, Michalakes L, Han PKJ, Strout TD. Using the surprise question to
identify those with unmet palliative care needs in emergency and inpatient settings: what
do clinicians think J Palliat Med. 2017 doi:10.1089/jpm2016.0403
2. Weeks JC, Cook EF, et al. Relationship between cancer patients’ predictions of
prognosis and their treatment preferences. JAMA 1998;279(21):1709-1714.
3. Murphy DJ, Burrows D, et al. The influence of the probability of survival on patients'
preferences regarding cardiopulmonary resuscitation. NEJM 1994; 330:545-549.
4. Gaston CM, Mitchell G. Information giving and decision-making in patients with
advanced cancer: a systematic review. Soc Sci and Med 2005;61(10):2252-64.
5. Christakis NA, Lamont EB. Extent and determinants of error in doctors’ prognoses in
terminally ill patients: prospective cohort study. BMJ 2000; 320;469-472.
6. Hagerty RG, Butow PN, et al. Communicating prognosis in cancer care: a systematic
review of the literature. Ann of Onc 2005; 16(7):1005-53.
2017;189(13):484-93.
8. Larkin JR, Robinson MG, Bernacki RE, et al. Estimating 1-year mortality for high-risk
primary care patients using the “surprise” question. JAMA Intern Med. 2016;176(12):
1863-1865.
9. Burke K, Coombes LH, Menezes A, Anderson AK. The ‘surprise question’ in paediatric
palliative care: a prospective cohort study. Palliative Medicine 2018; 32(2):535-42.
10. Moss AH, Ganjoo J, Sharma S, et al. Utility of the “surprise” question to identify dialysis
patients with high mortality. Clin J Am Soc Nephrol. 2008;3(5):1379-84.
11. Pang WF, Kwan BC, Chow KM, Leung CB, Li PK, Szeto CC. Predicting 12-month
mortality for peritoneal dialysis patients using the “surprise” question. Perit Dial Int.
2013;33(1):60-6.
12. Javier AD, Figueroa R, Siew ED, et al. Reliability and utility of the surprise question in
CKD stages 4 to 5. Am J Kidney Dis. 2017 doi: 10.1053/j.ajkd.2016.11.025.
13. Moss AH, Lunney JR, Culp S, et al. Prognostic significance of the “surprise” question in
cancer patients. J Palliat Med. 2010;13(7):837-40.
14. Moroni M, Zocchi D, Bolognesi D, et al. The ‘surprise’ question in advanced cancer
patients: a prospective study among general practitioners. Palliat Med. 2014;28(7):
959-964.
15. Lilley EJ, Gemunden SA, Kristo G, et al. Utility of the “surprise” question in predicting
survival among older patients with acute surgical conditions. J Palliat Med. 2017;20(4):
420-23.
16. Ouchi K, Jambaulikar, et al. The “surprise question” asked of emergency physicians may
predict 12-month mortality among older emergency department patients. J Pall Med
2018; 21(2): 236-40.
17. Rice J, Hunter L, Hsu AT, Donskov M, Luciani T, Toal-Sullivan D, Welch V, Tanuseputro P.
Using the ‘Surprise Question’ in Nursing Homes: A Prospective Mixed-Methods Study. J
Palliat Care. 2018; 33(1):9-18.
18. White N, Kupeli N, Vickerstaff V, Stone P. How accurate is the ‘Surprise Question’ at
identifying patients at the end of life? A Systematic review and meta-analysis. BMC Med.
2017; 15(1):139.
19. Romo RD and Lynn J. The utility and value of the “surprise question” for patients with
serious illness. Canadian Medical Association Journal 2017; 189(33):E1072-1073.
20. Weissman DE, Meier DE. Identifying patients in need of a palliative care assessment in
the hospital setting: a consensus report from the Center to Advance Palliative Care. J
Palliat Med. 14(1):1-6.
Author Affiliations: 1University of Colorado School of Medicine, Aurora, CO, USA; 2Medical
College of Wisconsin, Milwaukee, WI; 3Veterans Affairs Eastern Colorado Geriatric Research
Education and Clinical Center, Denver, CO, USA
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!38
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Neurology
#115 Declaring Brain Death: The Neurologic
Criteria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2-3
#135 Neoplastics Meningitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . 4-5
#150 Prognostication in Dementia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . . 6-8
#201 Palliative Care for Patients with Huntington’s

Disease. . . . . . . . . . . . . . . . . . . . . . . . . . .9-11
#229 Seizure Management in the Dying

Patient . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .12-14
#234 Prognosis of Anoxic-Ischemic Encephalopathy 3rd Edition. . . . . . . . . . . . . . . . . .

. . . . . . 15-16
#237 Evaluation of Spinal Cord Compression . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . .17-18
#238 Management of Spinal Cord

Compression . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19-21
#239 Prognostication in Sever Traumatic Brain Injury in Adults . . . . . . . . . . . . . . . . .

. . . . . . . 22-24
#300 Non-pharmacologic Management Strategies in

ALS . . . . . . . . . . . . . . . . . . . . . . . . . . . . .25-27
#301 Pharmacologic Management Strategies in

ALS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28-30
#303 Locked-In
Syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . 31-33
#350 Palliative Care Issues in Glioblastoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . .34-36
#361 Parkinson’s Disease: Part 1 Disease

Trajectory . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27-39
!1
#362 Parkinson’s Disease: Part 2 Palliation for Common Non-Motor Symptoms . . . . . . .
. . . 40-42

DECLARING BRAIN DEATH: THE NEUROLOGIC CRITERIA
Amal Puswella, Mike DeVita, Robert M Arnold MD
Background This Fast Fact reviews the details of declaring death based on neurological
criteria. In 1980, the Uniform Determination of Death Act (UDDA) was created which stated that
“An individual who has sustained either 1) irreversible cessation of circulatory and respiratory
function, or 2) irreversible cessation of all functions of the entire brain, including the brainstem, is
dead. A determination of death must be made with accepted medical standards.” The UDDA did
not define “accepted medical standards,” and so the American Academy of Neurology published
guidelines in 1995, and updated them in 2010. Despite these national guidelines, there is still
considerable variability in local institutional guidelines.
Determining death by neurologic criteria involves two steps:
• Step 1: Rule out reversible causes of unconsciousness: sedative medication,
neuromuscular blocking agents or hypothermia.
• Step 2: Rule out the presence of cortical activity and brainstem reflexes using clinical
exams/tests. The exact tests done may vary by institution and one should check with their
own institution’s policies. Brain death exams are typically completed by neurologists,
neurosurgeons, and critical care physicians. For a person to be dead by brain death,
typically all of the following tests must show lack of brain function:
o No spontaneous movement and no movement in response to painful stimuli (movement
due to spinal reflexes are acceptable).
o No seizures, decerebrate or decorticate posturing, or dyskinetic movements.
o Absent cranial nerve reflexes including pupillary response to light, corneal reflexes,
oculocephalic reflex, caloric response, facial movement to a noxious stimulus, and
gagging and cough with suctioning.
o Caloric testing is done by first ensuring the auditory canal is clear and the tympanic
membranes are intact. The head is elevated to 300, 50 ml of ice water is slowly infused
into the canals, and the eyes are observed for one minute. The normal response in an
awake patient is tonic deviation of the eyes toward the cold stimulus followed by
nystagmus back to the midline; the normal response in a comatose patient with an intact
brainstem is tonic deviation of the eyes toward the cold stimulus without nystagmus; in
brain death, the eyes do not move. Both ears must be tested with an interval of several
minutes in between.
o Note: At some institutions other clinical tests are done before a formal apnea test (see
below). For example, some require documentation of no vagal nerve activity – an
atropine test is used. The patient is given 2 mg IV atropine. In the dead patient, the
parasympathetic outflow is non-functioning and the heart rate will not change (<10 beats/
minute).
o Absence of central respiratory drive is assessed using the apnea test to see if a rise of
CO2 provides a stimulus to breathe. The patient is ventilated with 100% oxygen for 10-20
minutes and a baseline blood gas is obtained. The ventilator is then removed while
100% oxygen is delivered; O2 saturation is continuously assessed. A follow-up ABG is
done after 5-10 minutes. If the PaCO2 rises past 60mm Hg (or >20 mm Hg above
!2
baseline), and no breathing efforts are observed, the respiratory center is not functioning.
The test should be aborted if the patient develops hypoxemia (also indicates no
respiratory drive), hypotension, or arrhythmias.
Adjunctive or confirmatory tests are needed in complex clinical situations such as uremia or
hepatic encephalopathy, when apnea testing cannot be performed, when the primary brain insult
is infratentorial, or if required by the local institutional brain death policy.
• Electroencephalogram: must be isoelectric, which is difficult in the ICU due to electrical
artifact).
• Transcranial Doppler: intracranial arteries demonstrate either absence of diastolic flow,
or small systolic peaks.
• Somatosensory Evoked Potentials: bilateral median nerve stimulation demonstrates an
absence of the N20-P22 response.
• Intracranial Pressure: sustained, elevated ICP within 10 mmHg of mean arterial
pressure.
• Tests of cerebral blood flow: if there is no cerebral blood flow then there is no brain
function and death may be determined based on this test alone. Specific tests include
cranial radionuclide angiography and conventional contrast angiography.
References
1. Wijdicks E, Varelas P, Gronseth G, et al. Evidence-Based guideline update: Determining
brain death in adults. Report of the quality standards subcommittee of the American
Academy of Neurology. Neurology 2010; 74;1911-1918.
2. Greer D, Varelas P, Haque S, et al. Variability of brain death determination guidelines in
leading US neurologic institutions. Neurology 2008; 70:284-289.
3. Plum F, Posner J. The Diagnosis of Stupor and Coma. 3rd Edition. New York, NY: Oxford
University Press; 1982: pp57-61, 313-320.
4. Van Norman G. A matter of life and death: what every anesthesiologist should know
about the medical, legal, and ethical aspects of declaring brain death. Anesthesiology.
1999; 91(1):275-287.
5. Certification of Death in Adults Policy: 5108. University of Pittsburgh Medical Center,
Pittsburgh, PA; 2000.
in May 2004. Re-copy-edited in April 2009; then it was copy-edited again by Sam Maiser MD in
June 2015 in which references 1 and 2 were added and incorporated into the text.
Sarah Friebert MD.
!3
!

Background Neoplastic meningitis (NM) – also known as leptomeningeal metastases,

meningeal carcinomatosis, or leukemic meningitis, is a common oncologic complication
representing spread of tumor cells to the subarachnoid space (SAS). It is a complication which
often portends a very short prognosis.
Epidemiology NM is found in 20% of cancer patients at autopsy. Among solid tumors, NM is
common in breast cancer, small cell lung cancer, and melanoma while rare in gastrointestinal and
gynecologic cancers. 90% of solid tumor patients with NM have widespread metastatic disease.
NM is found in 40-50% of patients with hematological malignancies, mostly commonly the acute
leukemias and high-grade lymphomas (such as large cell and Burkitt lymphomas).
Signs/Symptoms Tumor reaches the SAS by hematogenous spread via arachnoid vessels or
direct invasion along nerve roots. Cancer cells in the subarachnoid space have the potential to:
a) settle in dependent portions of the neuraxis (base of brain/cranial nerves or lower spinal canal),
b) grow into the surface of the brain and fill the sulci, and c) block normal paths of cerebral spinal
fluid (CSF) flow. Thus, the hallmark of diagnosis is neurological signs/symptoms at more than
one level of the neuraxis:
• Spinal – radicular pain, weakness (usually legs), parenthesis, bladder and bowel
dysfunction.
Diagnosis Lumbar puncture typically reveals a CSF profile of high opening pressure, low
glucose, high protein, and lymphocytic pleocytosis. Sensitivity for finding malignant cells is 50-
70% for one sample, increasing to 80-90% with three samples. MRI can identify nodular/bulky
areas of disease, hydrocephalus, and/or enhancement of the cortex/tentorium if tumor growth
along the sulci leads to neovascularization. NM commonly causes abnormal CSF flow; this can
be demonstrated by a radionucleotide cisternogram.
Prognosis and Treatment Patients with breast cancer or hematological malignancies that
have not been extensively treated with chemotherapy, have a reasonable chance at remission of
their CNS disease if their systemic cancer can also be controlled. In contrast, patients with other
cancers (e.g. lung, melanoma) typically have a dismal prognosis (1-4 months) with or without
treatment. In fact, the median survival of patients who underwent placement of an implanted
intraventricular reservoir (Ommaya reservoir) for intrathecal chemotherapy administration was
only 72 days in a multicenter retrospective analysis. Unlike spinal cord compression or brain
metastases, there is no accepted role for corticosteroids except in lymphoid malignances.
Treatment options include chemotherapy and/or radiation.
• Radiation: Either cranio-spinal irradiation (entire spinal column) or focused radiation
therapy to sites of bulky or symptomatic areas (e.g. cauda equina for radicular leg pain).
• Chemotherapy: Options include systemic high-dose chemotherapy (Ara-C or
Methotrexate) intrathecal chemotherapy (1-2 times per week) administered either by
repeated lumbar puncture or via repeated puncture of an Ommaya reservoir. Commonly
used intrathecal drugs include methotrexate or Ara-C.
!4
Summary For many patients, NM represents a pre-terminal diagnosis and no anti-neoplastic
therapy is warranted. Establishing the diagnosis in such patients may be important to help
prognosticate and to anticipate future neurological problems (e.g. seizures, headache, radicular
pain). The decision whether or not to begin anti-neoplastic treatment should be made in
consultation with a medical, radiation, or neuro-oncologist.
References
1. Wasserstrom WR, Glass JP, Posner JB. Diagnosis and treatment of leptomeningeal
metastases from solid tumors. Cancer. 1982; 49:759-772.
3. Kaplan JG, DeSouza TG, Farkash A, et al. Leptomeningeal metastases: comparison of
clinical features and laboratory data of solid tumors, lymphomas and leukemias. J
Neurooncol. 1990; 9:225-9.
4. Demopoulos A, et al. Leptomeningeal metastases: a review. Curr Neurol Neurosci Rep.
2004; 4(3):196-204.
5. Roguski M, Rughani A, et al. Survival following Ommaya reservoir placement for
neoplastic meningitis. Journal of clinical neuroscience. 2015; article in press.
in April 2005. Version re-copy-edited in April 2009; edited again by Sean Marks MD July 2015
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!

PROGNOSTICATION IN DEMENTIA
Sing Tsai MD and Robert Arnold MD
Background Dementia is a syndrome of acquired and persistent impairment in cognition and
intellectual functioning (1). When caused by certain diseases or injury, dementia is irreversible,
leading to progressive brain failure and death. This Fast Fact reviews issues of prognostication in
dementia.
Natural history of dementia Olson (2003) classifies dementia into four functionally defined
categories: mild, moderate, severe, and terminal. ‘Terminal dementia’ is defined as loss of
communication, ambulation, swallowing, and continence. Others use the term “end-stage” or
“advanced” making interpretation of prognostic data challenging. Many prognostic factors have
been associated with shortened survival: male gender, age, diabetes mellitus, CHF, COPD,
cancer, cardiac dysrhythmias, peripheral edema, aspiration, bowel incontinence, recent weight
loss, dehydration, fever, pressure ulcers, seizures, shortness of breath, low oral intake, not being
awake for most of the day, low Body Mass Index, and recent need for continuous oxygen. A 2012
systematic review found that malnutrition, feeding issues, and dysphagia were the strongest
associated factors with 6 month mortality in elderly patients with advanced dementia. Simply
being admitted to the hospital with acute illness and end-stage or terminal dementia is associated
with a particularly poor prognosis: the six month mortality after hospitalization for pneumonia was
53% compared with 13% for cognitively intact patients. For patients with a new hip fracture, 55%
of end-stage dementia patients died within 6 months compared with 12% for cognitively intact
patients (Morrison 2000).
Prognostic Systems (see table below):

I. The National Hospice and Palliative Care Organization (NHPCO) recommends the Functional
Assessment Staging (FAST), a 7-step staging system, to determine hospice eligibility. The
FAST identifies progressive steps and sub-steps of functional decline. NHPCO guidelines
state that a FAST stage 7A is appropriate for hospice enrollment, based on an expected six
month or less prognosis, if the patient also exhibits one or more specific dementia-related co-
morbidities (aspiration, upper urinary tract infection, sepsis, multiple stage 3-4 ulcers,
persistent fever, weight loss >10% within six months). Luchins (1997) studied the relationship
of FAST to survival in 47 patients enrolled in hospice with advanced dementia and one or
more dementia-related co-morbidities. The median survival for all patients was 6.9 months;
38% survived beyond six months. Of note, 41% of patients did not demonstrate dementia
progression in a manner that allowed for assigning a FAST stage. For those patients who
could be assigned a FAST stage (n = 12), and who were at stage 7C or greater, mean
survival was 3.2 months. The generalizability and clinical relevance of this data are greatly
compromised by this very low patient number.
II. The Mortality Risk Index (MRI), a composite score based on 12 risk factor criteria obtained
from using the MDS (Minimum Data Set), has been suggested as an alternative to FAST.
Mitchell (2004) developed and then validated the MRI by examining data from over 11,000
newly admitted nursing home patients. Among patients with a MRI score of ≥ 12, 70% died
within 6 months (mean survival time not reported). Compared to FAST Stage 7C, the MRI
had greater predictive value of six month prognosis. The MRI as only been evaluated in
newly admitted nursing home residents; it has yet to be validated in the community setting or
for previously established long-term nursing home residents.
Medical Interventions Estimation of prognosis in severe/terminal dementia is in part
dependent on the goals of care and decisions regarding the level of intervention that will be
provided to treat acute medical problems such as urosepsis and malnutrition.
Summary Although many prognostic risk factors have been identified there is no gold
standard to help clinicians determine a less than six months prognosis with any degree of
certainty. The criteria adopted by NHPCO for hospice eligibility is based on very limited research
!6
and lacks important studies to determine FAST scale reliability and validity among referring
physicians and hospice staff. The MRI is a promising new scale but more research is needed.
Physicians can best help their patients by working with families to help them establish goals of
care and levels of medical intervention that are most consistent with current medical research and
family/patient preferences.
Functional Assessment Staging (FAST) Mortality Risk Index Score (Mitchell)
Stages Points Risk factor
1. No difficulties 1.9 Complete dependence with ADLs

2. Subjective forgetfulness 1.9 Male gender
1. Decreased job functioning and organizational 1.7 Cancer
capacity 1.6 Congestive heart failure
4. Difficulty with complex tasks, instrumental 6. O2 therapy needed w/in 14 day
ADLs 1.5 Shortness of breath
5. Requires supervision with ADLs 1.5 <25% of food eaten at most meals
6. Impaired ADLs, with incontinence 1.5 Unstable medical condition
7. A. Ability to speak limited to six words 1.5 Bowel incontinence
B. Ability to speak limited to single word 1.5 Bedfast
C. Loss of ambulation 1.4 Age > 83 y
D. Inability to sit 1.4 Not awake most of the day
E. Inability to smile
F. Inability to hold head up
Risk estimate of death within 6 months
Score Risk %
0 8.9
1-2 10.8
3-5 23.2
6-8 40.4
9-11 57.0
≥ 12 70.0
References
1. Olson E. Dementia and Neurodegenerative Disorders. In: Morrison RS, Meier DE, eds.
Geriatric Palliative Care. New York, NY: Oxford University Press; 2003.
2. Luchins DJ, Hanrahan P, Murphy K. Criteria for enrolling dementia patients in hospice. J
Am Geriatr Soc. 1997; 45:1054-1059.
3. Mitchell SL, Kiely DK, Hamel MB, et al. Estimating prognosis for nursing home residents
with advanced dementia. JAMA. 2004; 291:2734-2740.
4. Brown MA, Sampson EL, et al. Prognostic indicators of 6-month mortality in elderly
people with advanced dementia: a systematic review. Palliat Med 2013; 27: 389-400.
5. Morrison RS, Siu AL. Survival in end-stage dementia following acute illness. JAMA.
2000; 284:47-52.
6. Schonwetter RS, Han B, Small BJ, et al. Predictors of six-month survival among patients
with dementia: an evaluation of hospice Medicare guidelines. Am J Hosp Palliat Care.
2003; 20(2):105-13.
7. Wolfson C, Wolfson DB, Asgharian M, et al. A reevaluation of the duration of survival
after the onset of dementia. N Engl J Med. 2001; 344:1111-1116.
!7
in February 2006. Version re-copy-edited in April 2009; revised again July 2015 by Sean Marks
MD – reference # 4 added and incorporated into the text.
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!

PALLIATIVE CARE FOR PATIENTS WITH HUNTINGTON’S DISEASE
Sean Marks MD, Serena Hung MD, and Drew A Rosielle MD
Background Huntington’s disease (HD) is an incurable neurodegenerative disorder inherited in

an autosomal dominant fashion. It is characterized by progressive movement disorders,
psychiatric manifestations, behavioral abnormalities, and cognitive impairment. This Fast Fact will
focus on supportive and terminal care for patients with HD and their families.
Natural History and Prognosis

• Symptom onset is usually between 33 and 44 years; subtle cognitive and motor changes may
precede diagnosis by many years. Mean duration of illness from onset to death is 15-20
years with average age of death of 60 years; there are no proven therapies which slow the
progression of HD.
• Patients show signs of progressive dementia and become unable to walk, talk, take in
nutrition, and care for themselves. Life threatening complications may result from aspiration,
chronic infections, poor nutrition, falls, or cardiovascular disease.
• ~1/3 of all patients with HD are institutionalized in long-term care facilities.
Impact on Families HD often begins during a time when family life is most complex and
therefore most disruptive to the family structure (e.g. child-rearing, career development). Children
can be particularly affected: distress is aggravated by concerns about their own genetic
susceptibility, and as many as 40% of children of HD patients describe HD as splitting their family
apart. Careful assessments of familial coping and psychosocial needs are an integral part of
ongoing care for the HD patient.
Common Symptoms and Supportive Care Patients are best served by an interdisciplinary
team familiar with caring for patients with HD.
• Motor Manifestations. Abnormal involuntary movements include: chorea, dystonia, rigidity,
bradykinesia, tremor, and myoclonus; other motor manifestations include gait and balance
problems leading to frequent falls, slurred speech and swallowing difficulties
o First-line strategies are non-pharmacologic and include gait/balance training, speech
therapy, and orthotics and leg weights to assist with upright posture.
o Chorea is the most frequently targeted symptom for pharmacologic therapy. Tetrabenazine
(a dopamine depleting agent) has been shown to reduce chorea in a well-designed placebo
controlled trial; it is undergoing approval in the US. Haloperidol and other antipsychotics
are also used for chorea, although trials evaluating their effectiveness have shown mixed
results.
• Psychiatric manifestations are present in over half of HD patients.
o Depression is a significant psychiatric problem and rates of suicide are higher in HD
patients than the general population. Case reports support using tricyclic as well as newer
antidepressants.
o Agitation is also common, and a small number of patients develop psychosis. Atypical
neuroleptics are commonly used. Emotional lability (including episodes of extreme anger)
can respond to propranolol.
o Low doses of scheduled benzodiazepines before meals or propranolol are used to control
motor manifestations and anxiety related to eating.
o Establishing strict daily and hourly routines can help lessen anxiety, short-term memory
deficits, intrusive thoughts, and fear of abandonment.
• Cognitive Deficits: gradual loss of memory and executive function are common.
Consequently, increasing impairments in initiating movements and conversation occur. Yes/
no questions may be preferable over open-ended questions when cognitive impairments
become severe.
!9
Advance Care Planning Advanced care planning should be performed as early as possible,
prior to cognitive impairment. Of particular importance is establishing a health care power of
attorney, as well as documenting guidance to families for likely decisions they will face (such as
tube feeding and mechanical ventilation). Some states require clear evidence that a patient
would want tube feeding withheld or withdrawn at the end of life and patients should be instructed
to document this if consistent with their wishes. See also Fast Facts #12, 65, 162, and 178 for
further discussion of advance care planning.
Terminal Care There are no evidence-based criteria for determining a 6 month prognosis in
HD; web-based reference 13, however, provides some guidance regarding hospice eligibility. A
retrospective, multi-centered study of over 100 HD patients, suggested that the hospice length of
stay is longer than non-HD hospice patients and only a significant minority of HD patients are
able to die at home. Labored breathing, excessive secretions, and restlessness are common
terminal symptoms – see Fast Facts #1, 60, 109, 158, and 176.
References
1. Moskowitz CB, Marder K. Palliative care for people with late-stage Huntington’s disease.
Neurologic Clinics. 2001; 9(4):849-865.
2. Bonelli RM, Wenning GK. Pharmacological management of Huntington’s disease: an
evidence-based review. Curr Pharm Design. 2006; 12(21):2701-20.
3. Huntington Study Group. Tetrabenazine as antichorea therapy in Huntington disease: a
randomized controlled trial. Neurology. 2006; 66(3):366-72.
4. Paulsen JS, Hoth KF, Nehl C, Stierman L. Critical periods of suicide risk in Huntington’s
disease. Am J Psychiatry. 2005; 162(4):725-31.
5. Folstein SE. Huntington’s disease: a disorder of families. Baltimore, MD: The Johns
Hopkins University Press; 1989.
6. Nance MA, Sanders G. Characteristics of individuals with Huntington’s disease in long-
term care. Movement Disorders. 1996; 11:542-548.
7. Sorensen SA, Fenger K. Causes of death in patients with Huntington’s disease and in
unaffected first degree relatives. J Med Genet. 1992; 29:911-914.
8. Lanska DJ, Lavine L, Lanska MJ, Schoenberg, BS. Huntington’s disease mortality in the
United States. Neurology. 1988; 38:769.
9. Myers RH, Sax DS, Koroshetz WJ, et al. Factors associated with slow disease
progression in Huntington’s disease. Arch Neurol. 1991; 448:800-804.
10. Mitchell S, Buchanan J, Littlehale S, Hamel M. Tube-feeding versus hand-feeding
nursing home residents with advanced dementia: a cost comparison. J Am Med Direct
Assn. 2003; 4(1):27-33.
11. Vamos M, Hambridge J, Edwards M, Conaghan J. The impact of Huntington’s disease on
family life. Psychosomatics. 2007; 48(5):400-404.
12. Wong MT, Chang PC, Yu YL, et al. Psychosocial impact of Huntington’s disease on
Hong Kong Chinese families. Acta Psychiatry Scand. 1994; 90:16-18.
13. Hospice Eligibility: Huntington’s Disease. Hospice of the Valley Inc. Available at: http://
www.hospiceofthevalley.net/med-pros/eligibility-guidelines. Accessed July 30, 2015.
14. Foroud T, Gray J, Ivashina J, Conneally PM. Differences in duration of Huntington’s
disease based on age at onset. J Neurol Neurosurg Psych. 1999; 66:52-56.
15. Mendlik M, Frank S, Casarett D. Utilization of Hospice Services in a Population of
Patients with Huntington's Disease (TH307-C). Journal of Pain and Symptom
Management 2015; 2: 333-334.
Version History: Originally published April 2008. Version re-copy-edited in June 2009; then
again July 2015 – reference #15 added and incorporated into text, web resources updated.
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!11
!

SEIZURE MANAGEMENT IN THE DYING PATIENT
Jennifer Connelly MD and David E Weissman MD
Background Seizure management in the dying patient without intravenous (IV) access, such
as is in the home environment, is challenging. In this population they can be due to primary or
metastatic brain cancers, strokes, toxic/metabolic causes like hypoglycemia, or pre-existing
epilepsy. The incidence of seizures in dying patients is unknown, and while likely uncommon,
they can cause tremendous distress to patients and families. This Fast Fact reviews
management strategies for seizures near the end of life.
Seizure Prophylaxis Up to 40% of patients with brain tumors have a seizure at the time of
diagnosis and another 20% eventually develop seizures. Although antiepileptic drugs (AEDs) are
commonly started as prophylaxis at the time of brain tumor diagnosis, they have not been found
to prevent seizures and the American Academy of Neurology Clinical Practice Guidelines do not
support this practice (1). Thus, prophylactic AEDs can be safely discontinued in patients with
brain tumors who have never had a seizure. For brain tumor patients with a seizure history
(especially those with a history of status epilepticus), AEDs should be continued when possible.
In one study, tapering AEDs in the last week of life was associated with seizures in 35% of
patients with high-grade gliomas. For patients who lose an enteric route and have no intravenous
access, rectal administration of prophylactic AEDs is possible. Clinical judgment should be used
as to whether to continue AEDs in this setting as it can be appropriate to simply stop them,
particularly if the patient’s prognosis is very short. Phenobarbital, pentobarbital, carbamazepine,
valproic acid, and lamotrigine can all be given rectally. Rectal absorption of other prophylactic
AEDs is undefined and they should not be administered. No AEDs need dose adjustments for
rectal administration. Carbamazepine should be divided into small doses administered 6-8 times
a day. Lamotrigone is administered rectally by crushing and suspending the chewable tablets in
10 mL of water. When clinically indicated, drug levels of lamotrigine should be monitored as
rectal absorption is erratic. There is no data for the use of rectal levetiracetam in humans.
Seizure Management
• Single self-limited seizure: Check for treatable causes such as hypoglycemia. If no reversible
cause is identified, initiation of maintenance AED therapy should be considered, particularly if
the patient is expected to survive more than a few weeks.
• Acute seizure or status epilepticus:
o Non-IV routes: Studies, mainly in the pediatric population, have shown intranasal (IN)
midazolam at a dose of 0.2 mg/kg to be an effective and convenient agent to abort an
acute seizure. It has a quick onset of action of only 4-8 minutes and a time to maximal
concentration of 15-30 minutes. Rectal diazepam (0.3 mg/kg) used to be the drug of
choice for this indication and can be considered, but it has a longer onset of action, is more
expensive, and appears to be less preferred by patients compared with IN midazolam.
Once the initial seizure is controlled, diazepam 20 mg PR nightly should be considered to
reduce the occurrence of further seizure events. Other rectal benzodiazepines are
available (clonazepam, lorazepam, and midazolam), but take longer to reach peak serum
levels. Sublingual lorazepam is also available, but is not well-studied.
o IV routes: When available, IV or subcutaneous (SC) benzodiazepines should be used to
stop a seizure in progress; IV lorazepam is preferred due to its onset of action and half-life.
SC dosing is equivalent to IV for lorazepam, midazolam, and clonazepam. If seizure
activity persists, additional anti-epileptic medication should be provided using a loading and
then maintenance dose. Patients with refractory seizures who have short prognoses and
comfort-oriented goals of care should be considered for an anti-epileptic sedative such as a
continuous midazolam or barbiturate infusion with the goal of deep sedation (see Fast
Facts #106,107).
Parenteral AED Dosing and Routes.
!12
Drug Status loading dose Maintenance dose
Diazepam 0.2 mg/kg or 10-20 mg PR 20 mg PR nightly
Lorazepam 0.1 mg/kg IV, IM, or SC
Midazolam 0.1-0.3 mg/kg IV or SC Titrate to control refractory seizures if needed
Clonazepam 1 mg IV or SC
Phenytoin 20 mg/kg IV 4-5 mg/kg/day IV divided TID
Fosphenytoin 20 mg/kg IV or IM 4-5 mg/kg/day IV or IM divided TID
Phenobarbital 10-15 mg/kg 1-3 mg/kg/day IV or IM

1200 mg/day SC (2)
* Levetiracetam: Doses up to 2,500 mg IV have been used successfully and safely when added to
standard status epilepticus regimens. A typical maintenance dose is 500-1500 mg PO or IV BID.
Family Education Family members should be counseled that all medications used to manage
seizures can cause sedation and cardiopulmonary depression. Family members who have
witnessed prior seizures often have great fear about seizure recurrence. Many hospice agencies
have established seizure protocols and medication kits which can be stored at home, and will
collaborate with physicians and families on establishing a ‘seizure plan’ for acute seizures.
Review seizure safety with families, including not putting anything in the patient’s mouth and
making sure the patient is in a safe environment.
References
1. Glantz MJ, Cole BF, Forsyth PA, et al. Practice parameter: anticonvulsant prophylaxis in
patients with newly diagnosed brain tumors: report of the Quality Standards
Subcommittee of the American Academy of Neurology. Neurol. 2000; 54:1886-1893.
2. Krouwer H, Pallagi J, Graves N. Management of seizures in brain tumor patients at the
end of life. J Palliat Med. 2000;3:465-475.
3. Davis M, Walsh D, LeGrand S, et al. Symptom control in cancer patients: the clinical
pharmacolog and therapeutic role of suppositories and rectal suspensions. Support Care
Cancer. 2002; 10:117-138.
4. Brown L, Bergen DC, Kotagal P, et al. Safety of Diastat when given at larger-than-
recommended doses for acute repetitive seizures. Neurol. 2001; 56:1112.
5. Voltz R, Borasio GD. Palliative therapy in the terminal stage of neurological disease. J
Neurol. 1997; 244[Suppl 4]:S2-S10.
6. Droney J, Hall E. Status epilepticus in a hospice inpatient setting. J Pain Symptom
Manage. 2008; 36:97-105.
7. Sizoo E, Koekkoek J, Postma T, et al. Seizures in patients with high-grade glioma: a
serious challenge in the end-of-life phase. BMJ Support and Palliat Care. 2014; 4:77-80.
8. Uges J, van Huizen M, Engelsman J, et al. Safety and pharmacokinetics of intravenous
levetiracetam infusion as add-on in status epilepticus. Epilepsia. 2009; 50(3):415-421.
9. Holsti M, Dudley N, Schunk J, et al. Intranasal midazolam vs rectal diazepam
for the home treatment of acute seizures in pediatric patients with epilepsy.
Arch Pediatr Adolesc Med. 2010;164(8):747-753.
10. Ivaturi VD, Riss JR, Kriel RL, Cloyd JC. Pharmacokinetics and tolerability of
intranasal diazepam and midazolam in healthy adult volunteers. Acta Neurol
Scand. 2009;120(5):353-357.
11. Wusthoff CJ, Shellhaas RA, Licht DJ. Management of common neurologic
symptoms in pediatric palliative care: seizures, agitation and spasticity. Pediatr
Clin North Am. 2007;54:709-733.
Author Affiliations: Medical College of Wisconsin, Milwaukee, WI.
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Version History: Originally published April 2010; copy-edited August 2015 by Sam Maiser MD –
references #7 and #8 added and incorporated into the text; updated again in June 2018 with
Facts.
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!

PROGNOSIS OF ANOXIC-ISCHEMIC ENCEPHALOPATHY 3RD EDITION
James Fausto MD
Introduction Cardiac arrest, experienced by approximately 450,000 Americans annually, has a
very poor survival rate (see Fast Fact #179). Some patients who initially survive cardiopulmonary
resuscitation remain comatose, demonstrating obvious impairments in consciousness and
neurologic function. This syndrome, called anoxic-ischemic encephalopathy (AIE, also known as
‘anoxic brain injury,’ or ‘hypoxic-ischemic coma’), can result in outcomes ranging from full
recovery to permanent unconsciousness to death. This Fast Fact discusses prognostic factors in
adults with AIE after cardiac arrest.
“Neurologic Outcome” A challenge in interpreting the literature on AIE is the use of variable or
imprecise definitions of a ‘poor neurologic outcome.’ The American Academy of Neurology
practice parameter paper defines poor outcome as: death, persistent unconsciousness (such as
a vegetative state), or severe disability requiring full nursing care after 6 months (6). This is the
definition used in this Fast Fact.
Predictors of Neurologic Outcome A review of the current literature reveals that data
obtained by careful neurologic exam, electrophysiologic studies, and biochemical markers are
most predictive of outcome (see below). Other factors not strongly predictive of outcome
include: age, sex, cause of arrest, type of arrhythmia, total arrest time, duration of CPR,
geographic location of arrest, elevated body temperature, elevated intracranial pressure,
concurrent respiratory failure, and early brain imaging findings (3,6,7,8).
Note: the data below assume patients are not receiving medications which would significantly
confound their neurologic examination such as high-dose barbiturates. In all cases, specialist
neurologic examination and input is advised.
Strong Indicators of Poor Outcome (false positive rates of 0% based on current literature):
• Absent pupillary light reflexes 24 hours after CPR, or 72 hours after CPR for those who
initially had intact papillary light reflexes (3,6,7).
• Absent corneal reflexes 72 hours post-CPR (6,7).
• Short-latency Somatosensory Evoked Potentials (SSEP, an electrophysiologic study):
bilateral absence of the N20 potentials on SSEP of the median nerve in AIE patients
greater than 24 hours post-CPR (1,6,7,8).
• Neuron-Specific Enolase (NSE, a blood test): serum NSE > 33 mcg/L on day 1 to 3
(6,7,8). While this biomarker is promising, it has not been studied in large trials, nor is
the assay itself standardized, so its current clinical role remains undefined (7).
Moderate Predictors of Poor Outcomes (these all predict a poor outcome, but not as
invariably as the above factors based on current literature):
• Clinical exam findings: no spontaneous eye movements or absent oculocephalic reflexes
at 72 hours post-arrest (3,6,7). No, or extensor-only, motor response to painful stimuli at
72 hours also implies a very poor chance of recovery (3,6).
• Electroencephalogram findings: certain findings can be strongly associated with poor
outcomes but are highly subject to institutional/technician variability. Myoclonic status
epilepticus within 1 day of cardiac arrest is the most predictive of a poor outcome
(3,6,7,8).
The Therapeutic Hypothermia Protocol The majority of the evidence for prognosis in the
comatose patient after CPR predates the widespread use of therapeutic hypothermia in patients
after cardiac arrest. It remains unclear how this intervention will change prognostication. While
the above factors will likely still indicate poor prognosis, the timing of when the evaluations should
be done, as well as if they will predict a uniformly poor outcome is uncertain. One European
!15
study advises that patients have an initial neurological assessment as soon as possible, but that
the second assessment occurs no earlier than 48-72 hours after the return of normal blood
temperature and not 48-72 hours after the discontinuation of active cooling (2). Zandbergen et al
suggest that serum NSE >33 mcg/L occurring while hypothermic still consistently predicts poor
outcomes accurately (8). Initial data (4,8) on the predictive value of SSEPs in patients who
underwent hypothermia confirmed that bilateral absent N20 responses is highly predictive of a
poor outcome. There has been a case report of an isolated patient with absent N20 responses
who made a full recovery, highlighting the importance of ongoing investigation into the impact of
the hypothermia protocol on the prognosis of AIE (4).
References
1. Bleck TP. Prognostication and management of patients who are comatose after arrest.
Neurol. 2006; 67: 556-57.
2. Friberg,H.. Neurological prognostication after cardiac arrest. Scand J Trauma
Resuscitation Emerg Med. 2008; 16:10.
3. Levy DE, Caronna JJ, Singer BH, Lapinski RH, Frydman H, Pulm F. Predicting outcome
from hypoxic-ischemic coma. JAMA. 1985; 253:1420-6.
4. Leithner C, Ploner CJ, Hasper D, Storm C. Does hypothermia influence the predictive
value of bilateral absent N20 after cardiac arrest? Neurol. 2010; 74:965-969.
5. Lloyd-Jones D, et al. Heart disease and stroke statistics 2010 update: a report from the
American Heart Association. Circulation. 2010; 121:e46-e215.
6. Wijdicks EFM, Hijdra A, Young GB, et al. Practice parameter: prediction of outcome in
comatose survivors after cardiopulmonary resuscitation (an evidence based review):
report of the Quality Standards Subcommittee of American Academy of Neurology.
Neurol. 2006; 67:203-10.
7. Young GB. Neurologic prognosis after cardiac arrest. NEJM. 2009: 361:607-11.
8. Zandbergen EG, Hijdra A, Koelman JH, et al. Prediction of poor outcome within the first
3
days of postanoxic coma. Neurol. 2006; 66:62-8.
Author Affiliation: Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY.
Version History: Originally published October 2010; copy-edited August 2015 by Ann Helms
MD.
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EVALUATION OF SPINAL CORD COMPRESSION
Background Malignant epidural spinal cord compression (SCC) is a common and devastating
complication of cancer (see Fast Fact #62). If not diagnosed and treated in a timely manner,
SCC can lead to permanent weakness, paraplegia, and loss of bowel and bladder control. This
Fast Fact discusses the clinical features and diagnosis of SCC in adults. Fast Fact #238
discusses its management.
Epidemiology Breast, lung, prostate, and multiple myeloma are the most common cancers
causing SCC. Cumulative incidence of SCC in the 5 years preceding death is roughly 8% in
multiple myeloma, 7% in prostate cancer, 5.5% in breast and 3% in lung cancer patients. The
thoracic spine (70%) is the most common site of SCC because of its narrow epidural space and
dense vascularization, followed by the lumbosacral (20%) and cervical spines (10%).
Hematogenous spread (both arterial and venous) to the vertebral bone and subsequent growth
into the epidural space is the most common mechanism of metastasis to the epidural space,
although and direct invasion through the neural foramen can also occur. Once in the epidural
space, tumor may spread in any direction, including pressing on the dura mater causing ischemia
and demyelination of the spinal cord.
Symptoms Symptoms usually present in a progressive manner from pain to neurologic deficits.
Back pain is the most common and the most sensitive symptom in SCC (>90%), but is non-
specific. It can be localized (20-80%), radicular (40-60%), or mechanical (14%), and can worsen
with recumbent position (20%) or coughing or sneezing (35-40%). Back pain that is new or
changing should raise one’s suspicion of SCC. Pain may be present for 2-3 months before
neurological symptoms develop. Motor deficits are more specific for SCC than pain, but present
late in its course. The time from the onset of weakness to frank paraplegia can range from less
than 24 hours to many weeks. Motor symptoms include progressive motor weakness
(60%-95%), ataxia, and subsequently total paralysis. Sensory deficits are less common than
motor symptoms (40%-80%). Autonomic symptoms, including bladder (50%) and bowel (75%)
complaints occur last in the disease process. These include urinary hesitancy (14%), retention
(25%), incontinence (15%), constipation (66%), and fecal incontinence.
Signs Physical examination can reveal weakness (85%) and a sensory level of deficit
(50-60%), but there is poor correlation between the level of pain and the actual level of
compression. More than half of patients with upper thoracic compression present with
lumbosacral pain and vice-versa (7). A clinically detected sensory level abnormality is also poorly
correlated (16%) with the level of compression identified on MRI.
Risk Factors In cancer patients with suspected SCC, the following factors have been
associated with an increased risk of having SCC compared to patients without these
characteristics: age less than 60 years, inability to walk, middle or upper back pain, abnormal
neurologic examination, presence of spinal metastases, radiographically diagnosed compression
fractures, bone metastases diagnosed more than 1 year earlier, and metastatic disease at initial
cancer diagnosis (3,4).
Imaging Because symptoms poorly correlate with compression level, and SCC can occur at
multiple levels simultaneously, imaging of the entire spine is recommended. MRI (without
contrast) is the imaging modality of choice because of its high sensitivity (93%) and specificity
(97%). In addition, MRI reveals if there is compression of the cord versus nerve roots and can
provide useful information about the spine’s stability. CT myelography has sensitivity and
specificity close to that of MRI, and can be used in patients who cannot get an MRI. Plain films
are not sensitive and cannot rule out either vertebral metastases or SCC. If they show vertebral
lesions in a suspected area, however, that should increase one’s suspicion of SCC and prompt
further investigation. Bone and PET scans can show the presence of vertebral metastases but
do not provide information about compression of the spinal cord. CT scans are not
recommended due to poor revelation of the epidural space and spinal cord.
Conclusion New or worsening back pain in cancer patients with or without neurological deficits
should be evaluated urgently for SCC. Clinicians should have a very low threshold to image a
patient’s entire spine with MRI. If a patient has developed any neurologic deficits, glucocorticoids
should be administered (see Fast Fact #238) and total spine MRI should be performed
emergently.
!17
References
1. Loblaw DA, Laperriere NJ, Mackillop WJ. A population-based study of malignant spinal
cord compression in Ontario. Clin Oncol (R Coll Radiol). 2003;15(4):211-7.
2. Zaikova O, Giercksky KE, et al. A population-based study of spinal metastatic disease in
South-East Norway. Clin Oncol (R Coll Radiol). 2009;21(10):753-9.
3. Talcott JA, Stomper PC, Drislane FW, et al. Assessing suspected spinal cord
compression: A multidisciplinary outcomes analysis of 342 episodes. Support Care
Cancer. 1999;7:31-38
4. Lu, C., Gonzalez, R. G., et al. Suspected spinal cord compression in cancer patients: a
multidisciplinary risk assessment. The Journal of Supportive Oncology. 2005;3:305–312.
5. Rades D, Douglas S, Veninga T, et al. Validation and simplification of a score predicting
survival in patients irradiated for metastatic spinal cord compression. Cancer. 2010 Apr
29.
6. Cole JS, Patchell RA. Metastatic epidural spinal cord compression. Lancet Neurol.
2008;7(5):459-66.
7. Levack P, Graham J, et al. Don't wait for a sensory level-listen to the symptoms: a
prospective audit of the delays in diagnosis of malignant cord compression. Clin Oncol (R
Coll Radiol). 2002;14(6):472-80.
8. White BD, Stirling AJ, Paterson E et al. Diagnosis and management of patients at risk of
or with metastatic spinal cord compression: summary of NICE guidance. BMJ.
2008;27:337.

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!

MANAGEMENT OF SPINAL CORD COMPRESSION
Background Metastatic spinal cord compression (SCC) is a medical emergency; early
treatment is associated with less functional disability. Treatment options include corticosteroids,
radiotherapy and surgery. This Fast Fact discusses management of SCC in adults. Fast Fact
#237 discusses its diagnosis.
Corticosteroids Dexamethasone is the most tested steroid in clinical trials. Studies have
shown that steroids provide analgesia and reduce vasogenic edema which may lead to better
neurological outcomes. Treatment should be started as soon as diagnosis is made; studies in
acute spinal cord injury suggest significant neurological improvement when used within 8 hours of
injury. Historically, debate existed between using high dose dexamethasone (100 mg loading,
then 96 mg daily) versus moderate dose (10 mg loading, then 16 mg daily). A randomized
controlled trial comparing the two doses found no differences in efficacy and thus most give the
lower dose. (1) Many studies give the steroids divided 4 times a day (total 16 mg daily), tapered
over 10-14 days. Most generally start IV and then switch to PO when patients are “clinically
stable” and more definitive therapy (radiation or surgery) has been initiated. Steroids should be
tapered as soon as possible to prevent long term toxicities (2). Common short term side effects
include hyperglycemia, insomnia and gastric distress. Serious acute adverse effects such as
gastrointestinal perforation or bleeding, psychosis, risk of infections and death are associated
with high doses only (17%) (3).
Radiotherapy (RT) In the absence of bony instability, RT has historically been the treatment of
choice, preferably started within 24 hours of diagnosis. Dose schedule for RT ranges from single
fraction 8 Gy to 20 fractions of 40 Gy. One or two fractions of 8 Gy may be preferable in patients
with short prognoses and, in one study, had a similar outcome to more prolonged treatment (4).
RT results in pain relief in 40-80% of patients and sphincter control in 45-90% of cases (3, 4)
when instituted in time. About 90% of ambulatory patients retain ambulation with RT alone, but
less than 30% of patients who have lost the ability to walk by the time RT is initiated regain
ambulation (3).
Surgery Until recently, surgery was reserved for cases with SCC in a previously irradiated
area, neurologic deterioration during RT, spinal instability, or bony compression. However a
recent meta-analysis (5) and a randomized controlled trial (6) found better functional outcomes
with surgery plus post-operative RT as compared to RT alone. This trial used a newer surgical
technique (circumferential decompression, reconstruction and immediate stabilization). 84% of
the patients in the surgery group were ambulatory and retained ambulation for a longer time (a
median of122 days) after treatment compared to 57% in the RT group (median 13 days). 62% of
the non-ambulatory patients regained the ability to walk after the surgery compared to 19% in the
RT groups. The surgery group also maintained continence for a significantly longer time (median
156 days vs. 17 days). A more recent retrospective matched pair analysis of cancer patients with
SCC comparing RT alone to surgery plus RT did not find any significant differences in outcome
between the two treatments (7). Prompt, interdisciplinary evaluation by radiation oncologists and
spine surgeons is indicated in order to identify the best treatment course.
Other treatments Spinal Stereotactic Radiosurgery (SRS) has an investigational role in

adult non-surgical patients with radio-resistant tumor or those with previously irradiated areas.
Studies suggest more than 80% improvement in overall neurological function (8). Transarterial
embolization is another novel investigational treatment. It is generally used preoperatively for
hypervascular spinal tumors causing compression, is safe and effective, and can make radical
tumor resection possible at times (9). In adults, chemotherapy has no role in acute management
even in chemo-sensitive cancers because of its slow effect. Although bisphosphonates reduce
!19
the incidence of skeletal complications of cancer, there are no data to suggest a benefit in treating
SCC.
Prognosis Median survival after developing SCC is between 3-6 months in adults. Poor
prognostic factors for survival include non-ambulatory status, SCC within 15 months of original
cancer diagnosis, presence of visceral or other bone metastases, cancer type (survival is worse
for lung cancer and better for myeloma/lymphoma), and rapidity of developing motor symptom
(worst if <7 days and better if more than 2 weeks after the onset of symptoms).
Conclusion A loading dose of dexamethasone 10 mg IV should be given as soon as possible

after diagnosis, followed by maintenance dose of 4 to 6 mg every 6-8 hours, and referral made for
primary surgery (if feasible) with adjuvant RT. If surgery is contraindicated, palliative RT alone is
indicated.
References
1. Vecht CJ, et al. Initial bolus of conventional versus high-dose dexamethasone in
metastatic spinal cord compression. Neurology. 1989; 39(9):1255-7.
2. Weissman DE, Dufer D, Vogel V, Abeloff MD. Corticosteroid toxicity in neuro-oncology
patients. J Neurooncol. 1987;5(2):125-8
3. George R, Jeba J, Ramkumar G, Chacko AG, Leng M, Tharyan P. Interventions for the
treatment of metastatic extradural spinal cord compression in adults. Cochrane Database
of Systematic Reviews 2008, Issue 4. Art. No.: CD006716. DOI:
10.1002/14651858.CD006716.pub2
4. Maranzano E, et al. Short-course versus split course radiotherapy in metastatic spinal
cord compression: results of a phase III, randomized, multicenter trial. J Clin Oncol. 2005;
23:3358–65
5. Klimo P, et al. A meta-analysis of surgery versus conventional radiotherapy for the
treatment of metastatic spinal epidural disease. Neuro Oncol. 2005; 7(1):64-76.
6. Rades D, et al. Validation and simplification of a score predicting survival in patients
irradiated for metastatic spinal cord compression. Cancer. 2010; 116:3670-3.
7. Rades D, Huttenlocher S. Matched pair analysis comparing surgery followed by
radiotherapy and radiotherapy alone for metastatic spinal cord compression. J Clin
Oncol. 2010; 28(22):3597-3604.
8. Ryu S, Rock J, Jain R, et al. Radiosurgical decompression of metastatic epidural
compression. Cancer. 2010; 116(9):2250-7
9. Kato S, et al. Surgical management of aggressive vertebral hemangiomas causing spinal
cord compression: long-term clinical follow-up of five cases. J Orthop Sci. 2010; 15(3):
350-6.
10. Rades D, et al. Validation and simplification of a score predicting survival in patients
irradiated for metastatic spinal cord compression. Cancer. 2010; 116:3670-3.

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!

PROGNOSTICATION IN SEVERE TRAUMATIC BRAIN INJURY IN ADULTS
Stacy M Kessler MD and Keith M Swetz MD
Background Traumatic brain injury (TBI) is defined as brain injury caused by an external
force – most commonly falls, struck by/against events, motor vehicle collisions, and assaults.
The vast majority of patients with mild to moderate TBIs have substantial recoveries; this is not
true of severe TBIs. This Fast Fact discusses prognostication in severe TBI in adults.
Initial TBI severity TBI severity is most commonly graded by the initial Glasgow Coma Scale
(GCS) score. The GCS rates the patient’s best verbal response, best motor response and the
stimulus needed to elicit eye opening. Scores range from 3-15, with score ≤ 8 representing
coma. ‘Mild’ TBI (accounting for ~80% of cases) is manifest by a 30 minute post-injury GCS of
13-15. ‘Moderate’ TBI consists of immediately altered or loss of consciousness for > 30 minutes
and 6 hour post-injury GCS of 9-12. ‘Severe TBI’ involves immediate loss of consciousness for >
6 hours with residual GCS of 3-8.
Long-term outcomes The Glasgow Outcome Scale (GOS) is a five-point scale used widely in
brain injury research. An eight-point Extended Glasgow Outcome Scale (GOS-E) is available
with more sensitivity to change in function, but most outcome studies reference the GOS. The
GOS range is (1) death, (2) persistent vegetative state (unconscious and unable to interact), (3)
severe disability (conscious; cannot live independently; requires daily assistance due to physical
or mental impairment), (4) moderate disability (able to live independently; able to work in a
supported environment), and (5) good recovery (minimal or no deficits; able to work and socialize
normally). In addition to global functional impairments, survivors of severe TBIs often have
impairments in memory, executive functioning, impulse control, sensory processing, and
communication skills. Mental health problems are common.
Predicting outcomes Overall 30-day mortality following TBI is estimated to be 20% with the
highest mortality corresponding to the worst initial GCS scores. For patients with reliable initial
GCS scores of 3-5, only 20% will survive and less half of those survivors will have what is often
referred to in the research literature as a ‘good outcome’ (GOS 4-5). Older age, lower initial GCS
score, abnormal initial pupil reactivity, longer length of coma and duration of post-traumatic
amnesia, and certain computed tomography findings all indicate a smaller chance of recovery to
GOS 4-5. Kothrari proposed the following prognostic guidelines, based on a comprehensive
review of studies that looked at outcome in adults 6 months or later after severe TBI [8]:
• Favorable outcome (GOS 4-5) likely when the time to follow commands is less than 2
weeks after injury, and the duration of post-traumatic amnesia is less than 2 months.
• Poor outcome (GOS <4) is likely when the patient is > 65 years old, the time to follow
commands is longer than 1 month, or the duration of post-traumatic amnesia is greater
than 3 months.
• Notably, 10% of patients will not have the outcome predicted by the guidelines above.
A multinational collaborative trial developed a prognostic model (referred to as the CRASH
prognostic mode) which has been validated to predict outcomes in TBI (9,10). The model is
available online and uses age, GCS, pupil reactivity, presence of major extracranial injury, and
(optional) computed tomography findings to give rates of death at 14 days post-injury and GOS at
6 months for survivors (11).
Helping families make decisions Families of patients with severe TBIs may be confronted
with decisions about medical care (e.g. gastrostomy tube placement, chronic ventilatory support,
dialysis). Such decisions often depend on a family’s understanding of a patient’s long-term
functional outcome. The above-mentioned prognostic indicators can help clinicians provide
objective information for families about the likelihood of recovery after a TBI. As with all
prognostic tools, however, clinicians can only predict what would happen to a population of
!22
patients with a similar injury (e.g. ‘only 10% of patients would recover such that they could live
independently’); this is different from predicting any particular patient’s course. It is important to
communicate the uncertainty that accompanies most prognostic estimations. Counseling families
about long-term functional prognosis, as well as the expected treatment course (what
rehabilitation would involve) is important. While the research literature often defines a ‘good
recovery’ as GOS 4-5, that may not constitute a ‘good’ recovery for an individual patient.
Clinicians should avoid such language at the bedside and instead use detailed descriptive
language of expected functional and cognitive outcomes. Early and frequent family meetings can
facilitate communication, built rapport, and are vital in expectation setting and establishing goals
of care. If life sustaining treatments are initiated, framing the treatments in the context of time-
limited trials is helpful. This empowers family members to discontinue certain cares after a
specified period of time if the prognosis remains unchanged or if the treatment is not meeting the
goals of care (e.g. helping to restore a patient to a functional status which is acceptable to the
patient). Interdisciplinary team members including speech, occupational, and physical therapists,
physiatrists, neurologists, palliative care clinicians, and neurosurgeons can be important in letting
family members more fully understand a patient’s likely future. See Fast Fact #226 about helping
surrogates make decisions.
References
1. Centers for Disease Control and Prevention. “Get the Stats on TBI in the United States.”
Available at: http://www.cdc.gov/traumaticbraininjury/factsheets_reports.html. Accessed
Aug 14, 2015.
2. Carroll LJ, Cassidy JD, Peloso PM, Borg J, von Holst H, Holm L, Paniak C, Pépin M;
WHO Collaborating Centre Task Force on Mild Traumatic Brain Injury. Prognosis for mild
traumatic brain injury: results of the WHO Collaborating Centre Task Force on Mild
Traumatic Brain Injury. J Rehabil Med. 2004; 43(Suppl):S84-S105.
3. Serio CD, Kreutzer JS, Witol AD. Family needs after traumatic brain injury: a factor
analytic study of the Family Needs Questionnaire. Brain Injury. 1997; 11:1-9.
4. Kolakowsky-Hayner SA, Miner KD, Kretuzer JS. Long-term life quality and family needs
after traumatic brain injury. J Head Trauma Rehabil. 2001; 16:374-385.
5. Cifu DX, Kreutzer JS, Slater DN, Taylor L. Rehabilitation after Traumatic Brain Injury. In:
Braddom RL, Buschbacher RM, Chan L, et al, eds. Physical Medicine and Rehabilitation.
Philadelphia, PA: Saunders Elsevier; 2007: 1133-1174.
6. National Institute of Neurological Disorders and Stroke. Traumatic brain injury: hope
through research. Bethesda (MD): National Institutes of Health; 2002. NIH Publication
No. 02-158. Available at: http://www.ninds.nih.gov/disorders/tbi/detail_tbi.htm. Accessed
Aug 14, 2015.
7. Brown AW, Elovic EP, Kothari S, Flanagan SR, Kwasnica C. Congenital and acquired
brain injury. 1. Epidemiology, Pathophysiology, Prognostication, Innovative Treatments,
and Prevention. Arch Phys Med Rehabil. 2008;89 (Suppl):S3-S8.
8. Kothari S. Prognosis after severe TBI: a practical, evidence-based approach. In: Zasler
ND, Katz DI, Zafonte RD, eds. Brain Injury Medicine: Principles and Practice. New York:
Demos; 2007: 169-99
9. MRC CRASH Trial Collaborators, Perel P, Arango M, Clayton T, Edwards P, Komolafe E,
Poccock S, Roberts I, Shakur H, Steyerberg E, Yutthakasemsunt S. Predicting outcome
after traumatic brain injury: practical prognostic models based on large cohort of
international patients. BMJ. 2008 Feb 23; 336(7641):425-9.
10. Roozenbeek B, Lingsma HF, et al. Prediction of outcome after moderate and severe
traumatic brain injury: external validation of the IMPACT and CRASH prognostic models.
Crit Care Med 2012; 40:1609-1617.
11. Prognostic model for predicting outcome after traumatic brain injury (online calculator).
MRC Crash Trial website. Available at: http://www.crash2.lshtm.ac.uk/
Risk%20calculator/index.html. Accessed Aug 14, 2015.
12. Brain Trauma Foundation-American Association of Neurological Surgeons-Joint Section
on Neurotrauma and Critical care. Early indicators of prognosis in severe traumatic brain
injury. J Neurotrauma. 2000; 17:449-627.
Author Affiliations: Mayo Clinic, Rochester, MN.
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Version History: Originally published March 2011; Copy-re-edited August 2015.

NON-PHARMACOLOGIC MANAGEMENT STRATEGIES IN ALS
Kristin Scott MD, Ugur Sener MD, Robert Shannon MD, Alva Roche-Green MD, Kevin
Boylan MD
!24
Background Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disorder
leading to weakness, spasticity, and incoordination of the muscles involved in speaking,
swallowing, breathing, and ambulation. Currently, there is no cure for ALS and the disease
progresses inexorably toward death. Despite the lack of cure, there are available treatments that
can improve quality of life. This Fast Fact will discuss non-pharmacologic therapies for common
challenges faced by ALS patients. See Fast Fact ### for pharmacologic therapies and Fast Fact
### for management of sialorrhea specifically.
Head Drop Axial muscle involvement, particularly neck extensor can lead to disabling head
drop and kyphosis. A soft collar may be helpful early in the course of disease, but as the disease
progresses, a semi-rigid collar is often needed to stabilize the neck and restrict motion.
Individualized collars and adjustable head rests on wheelchairs may be needed considering the
significant variability in neck anatomy (1,2,3).
Dysphagia Dysphagia is a common bulbar manifestation of ALS and should be assessed each
visit (4). Poor nutritional status at diagnosis or disease progression has been associated with
higher mortality (5).
• Early referrals to a dietitian and speech pathologist are recommended. Use of thickened
fluids, high-protein/high-calorie supplements, and modified swallowing techniques can
mitigate the malnutrition associated with dysphagia (4,6).
• Gastrostomy tubes do not prevent aspiration, but they have been shown to improve
nutritional status and may prolong survival. It is highly recommended that if patients are
agreeable to getting a gastronomy tube, it be done before vital capacity falls below 50% of
predicted (4,7).
• Nasogastric tubes have been used as a short-term alternative, but they are uncomfortable
and may worsen sialorrhea (4,8).
Ventilatory Compromise The most common cause of death in ALS is ventilatory failure (9).
Symptoms of ventilatory compromise, such as poor nighttime sleep, daytime somnolence,
anorexia, morning headache, and weak cough, often precede dyspnea.
• Noninvasive ventilation (NIV) with bilevel positive airway pressure has been shown to prolong
survival and improve quality of life in patients with ALS who can maintain their airway (10).
Nasal masks/pillows and sip/puff devices may improve tolerability.
• Mechanical in-exufflators alternate positive and negative pressures to improve airflow and
clearance of secretions. These devices may reduce pulmonary morbidity and associated
hospitalizations in muscular dystrophy (11), but there are no similar studies specific to ALS.
• Diaphragmatic pacemakers can be surgically implanted to stimulate more forceful muscle
contractions in patients with some degree of residual diaphragm function. Their effectiveness
has yet to be confirmed in randomized controlled trials.
• When NIV is no longer adequate or tolerated (i.e. inability to clear one’s own secretions), a
small percentage of patients pursue long-term mechanical ventilation. See Fast Fact #73.
Impairment of Mobility Physical therapy and use of equipment such as canes, walkers, and
ankle-foot orthoses can minimize foot-drop, improve gait, and help prevent falls (12-14).
Occupational therapy with assistive devices such as modified cutlery, Velcro fasteners for
dressing, and bathroom modifications such as grab bars and higher toilet seats help maintain
function (12-14). In patients with prominent distal weakness, wrist braces at 30 to 35 degrees can
improve grip efficiency while a universal cuff can assist with eating and typing (14). Early
intermittent use of a wheelchair is recommended for energy conservation (14). Modifiable
controls, such as a joystick that requires minimal arm/hand strength (12), make power
wheelchairs a better long-term option than power scooters for maintaining mobility. Modified
remote controls and security systems may allow patients to maintain employment (12).
Impairment of Communication Communication boards can be useful even after hand motor
function is lost. Computer, tablet, or smartphone applications can be used to generate electronic
speech from typed language. Patients can preemptively record their speech using voice banking
!25
systems to preserve the personalization, inflection, and accent of the electronic speech (15). Eye-
tracking software can be used to generate typewritten language and electronic speech.
References
1. Gordon PH. Amyotrophic Lateral Sclerosis: An update for 2013 Clinical Features,
Pathophysiology, Management and Therapeutic Trials. Aging Dis. 2013;4(5):295-310.
2. Jenkins TM, Hollinger H, McDermott CJ. The evidence for symptomatic treatments in
amyotrophic lateral sclerosis. Curr Opin Neurol. Oct 2014;27(5):524-531.
3. Dal Bello-Haas V, Kloos AD, Mitsumoto H. Physical therapy for a patient through six
stages of amyotrophic lateral sclerosis. Phys Ther. Dec 1998;78(12):1312-1324.
4. Andersen PM, Abrahams S, Borasio GD, et al. EFNS guidelines on the clinical
management of amyotrophic lateral sclerosis (MALS)--revised report of an EFNS task
force. Eur J Neurol. Mar 2012;19(3):360-375.
5. Marin B, Desport JC, Kajeu P, et al. Alteration of nutritional status at diagnosis is a
prognostic factor for survival of amyotrophic lateral sclerosis patients. J Neurol Neurosurg
Psychiatry. Jun 2011;82(6):628-634.
6. Desport JC, Preux PM, Truong CT, Courat L, Vallat JM, Couratier P. Nutritional
assessment and survival in ALS patients. Amyotroph Lateral Scler Other Motor Neuron
Disord. Mar 2000;1(2):91-96.
7. Heffernan C, Jenkinson C, Holmes T, et al. Nutritional management in MND/ALS patients:
an evidence based review. Amyotroph Lateral Scler Other Motor Neuron Disord. Jun
2004;5(2):72-83.
8. Scott AG, Austin HE. Nasogastric feeding in the management of severe dysphagia in
motor neurone disease. Palliat Med. 1994;8(1):45-49.
9. Mitchell JD, Borasio GD. Amyotrophic lateral scerosis. Lancet. June 2007;369(9578):
2031-2041.
10. Bourke SC, Tomlinson M, Williams TL, Bullock RE, Shaw PJ, Gibson GJ. Effects of non-
invasive ventilation on survival and quality of life in patients with amyotrophic lateral
sclerosis: a randomised controlled trial. Lancet Neurol. Feb 2006;5(2):140-147.
11. Bach JR, Ishikawa Y, Kim H. Prevention of pulmonary morbidity for patients with
Duchenne muscular dystrophy. Chest. 1997;112(4):1024-1028.
12. Ng L, Khan F. Multidisciplinary Rehabilitation in Amyotrophic Lateral Sclerosis. In: Mauer
MH, ed. Amyotrophic Lateral Sclerosis. Rijeka, Croatia: InTech; 2012:557-578.
13. Blatzheim K. Interdisciplinary palliative care, including massage, in treatment of
amyotrophic lateral sclerosis. J Bodyw Mov Ther. Oct 2009;13(4):328-335.
14. Francis K, Bach JR, DeLisa JA. Evaluation and rehabilitation of patients with adult motor
neuron disease. Arch Phys Med Rehabil. Aug 1999;80(8):951-963.
15. Yamagishi J, Veaux C, King S, Renals S. Speech synthesis technologies for individuals
with vocal disabilities: Voice banking and reconstruction. Acoust Sci Technol. 2012;33(1):
1-5.
Author’s Affiliations: Mayo Clinic, Jacksonville, FL
!26
!
PHARMACOLOGIC MANAGEMENT STRATEGIES IN ALS
Kristin Scott MD, Robert Shannon MD FAAHPM, Alva Roche-Green MD, Randi Searcy BS,
Gerard Woolyhand AA, Gavin Meeks AA, Michael Schuh Pharm.D, R.Ph
Background Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disorder

which can affect the muscles involved in swallowing, speaking, breathing, and ambulation (1).
This Fast Facts discusses pharmacologic management strategies for patients with ALS; see Fast
!27
Fact #300 for non-pharmacologic management strategies and Fast Fact #299 for management of
sialorrhea specifically.
Pseudobulbar Affect (PBA) This term refers to disordered emotional expressions caused by
disruption of cortico-pontine-cerebellar tracts. It typically manifests as inappropriate and
uncontrollable laughing or crying inconsistent with the patient’s mood and can be socially
debilitating.
• The combination drug dextromethorphan/quinidine is the only FDA approved treatment of
PBA. Its mechanism of action for pseudobulbar affect seems to be related to its anti-
glutamatergic and anti-NMDA actions (2). The recommended dose is 20 mg
dextromethorphan/10 mg quinidine twice daily. The rationale for combination therapy is
that dextromethorphan is rapidly metabolized by an enzyme that is inhibited by quinidine.
• Tricyclic and SSRI anti-depressants have shown benefit, but clinical trial data is limited by
small numbers of patients and poor standardization of PBA diagnostic and severity criteria
(3).
Depression Major depressive disorder is a common in ALS. Selective serotonin reuptake

inhibitors are often used; however, there are no randomized controlled trials specific to ALS (4).
Although the American Academy of Neurology advocates treatment of depression in ALS, there
are insufficient data to recommend any specific treatment with regard to particular SSRIs, SNRIs,
etc. (5).
Spasticity Damage to the upper motor neurons in ALS leads to spasticity, which can be
associated with cramps and incoordination of movement. There are no high-quality, controlled
trials evaluating pharmacologic treatments for spasticity (6) and clinicians should be aware that
some degree of spasticity can be useful for maintenance of posture. Although baclofen and
tizanidine are both commonly used, experts tend to reserve tizanidine for more severe cases (4).
• Baclofen: initial dosing is 5-10 mg BID-TID; doses up to 120 mg per day may be needed
(7).
• The starting dose for tizanidine is 2-4 mg BID with 24 mg as the maximum daily dose (7).
• Intrathecal baclofen pumps are considered only for patients with medically refractory
spasticity.
Pain Spasticity, muscle spasms, joint stiffness and skin breakdown related to immobility are all
potential sources of pain in ALS, which occurs in the later stages in up to 80% of patients (8).
There is insufficient evidence on which to base specific recommendations for the treatment of
pain in ALS. However, as in other conditions, non-opioid analgesics and anti-inflammatory
medications are generally considered first-line. When these medications fail, opioids are used
commonly.
Dyspnea Air hunger due to ventilatory failure is common in the later stages of ALS, occurring in
up to 85% of patients (9). According to the American Academy of Neurology, there are insufficient
data to support specific treatments for dyspnea in ALS (5). In addition to non-invasive ventilation,
opioids are used commonly to relieve air hunger. One small, non-randomized prospective study
demonstrated that morphine appears to be both safe and effective in this patient population (10).
Furthermore, studies evaluating the safety of opioids for dyspnea in general have not
demonstrated any excess mortality (11).
Riluzole It is the only proven disease-modifying pharmacologic agent in ALS, providing a

modest survival benefit of 2-3 months and likely works via inhibition of glutamate release (12).
Unfortunately, its cost can often be prohibitive and it does not palliate any ALS-associated
symptoms or improve quality of life. In fact, side effects such as fatigue can be significant enough
to warrant discontinuation (5). Given these factors, it is reasonable to discontinue the medication
at the time of hospice enrollment (or when a patient becomes ventilator-dependent), although
there are no published guidelines regarding these considerations.
References
!28
1. Gordon, PH. Amyotrophic lateral sclerosis: an update for 2013 clinical features,
pathophysiology, management and therapeutic trials. Aging Dis. Oct 2013; 4(5):295-310.
2. Brooks BR, Thisted RA, Appel SH, et al. Treatment of pseudobulbar affect in ALS with
dextromethorphan/quinidine: a randomized trial. Neurology. 2004;63(8):1364-1370.
3. Miller A, Pratt H, Schiffer RB. Pseudobulbar affect: the spectrum of clinical presentations,
etiologies and treatments. Expert Rev Neurother. Jul 2011;11(7):1077-1088.
4. Jenkins TM, Hollinger H, McDermott CJ. The evidence for symptomatic treatments in
amyotrophic lateral sclerosis. Curr Opin Neurol. Oct 2014;27(5):524-531.
5. American Academy of Neurology. AAN Summary of Evidence-based Guideline for
Clinicians. The Care of the Patient with Amyotrophic Lateral Sclerosis: Multidisciplinary
Care, Symptom Management, and Cognitive/Behavioral Impairment. https://
www.aan.com/Guidelines/Home/GetGuidelineContent/377. Updated October 2009.
Accessed May 1, 2015
6. Ashworth NL, Satkunam LE, Deforge D. Treatment for spasticity in amyotrophic lateral
sclerosis/motor neuron disease. Cochrane Database Syst Rev. 2012;2:CD004156.
7. Borasio GD, Voltz R, Miller RG. Palliative care in amyotrophic lateral sclerosis. Neurol
Clin. Nov 2001;19(4):829-847.
8. Brettschneider J, Kurent J, Ludolph A. Drug therapy for pain in amyotrophic lateral
sclerosis or motor neuron disease. Cochrane Database Syst Rev. 2013;6:CD005226.
9. Oliver D. The quality of care and symptom control – the effects on the terminal phase of
ALS/MND. J Neurol Sci. 1996;139(Suppl.):134-136.
10. Clemens KE, Klaschik E. Morphine in the management of dyspnoea in ALS. A pilot study.
Eur J Neurol. 2008;15:445-450.
11. Hallenbeck J. Pathophysiologies of dyspnea explained: why might opioids relieve
dyspnea and not hasten death? J Palliat Med. 2012;15(8):848-853.
12. Miller RG, Mitchell JD, Moore DH. Riluzole for amyotrophic lateral sclerosis (ALS)/motor
neuron disease (MND). Cochrane Database Syst Rev. 2012;3:CD001447.
Author’s Affiliations: Mayo Clinic, Jacksonville, FL; University of Florida

!29
!

LOCKED-IN SYNDROME
Samuel Maiser MD, Asish Kabir MD, David Sabsevitz PhD, & Wendy Peltier MD
Background: Locked-in Syndrome (LIS) is a rare neurologic condition characterized by

quadriparesis and an inability to articulate speech, but with preserved self-awareness (1,2). It is
easily misdiagnosed and once identified, a constellation of medical, psychological, social, and
ethical issues may ensue (3,7).
Pathophysiology and Prognosis: LIS is caused by the disruption of motor tracts in the ventral
brainstem. At least 60% of cases are caused by an acute stroke (4). LIS patients have a high risk
of dying within the first several months; however, those that survive that period are likely to live 10
years or more (3, 5-7). They often have limited motor recovery of their extremities, but with long-
!30
term survival, many patients eventually have their tracheostomy and gastrostomy tubes safely
removed (7). The severe neurologic disability results in a low health-related quality of life, yet, the
global quality of life and rate of depression may be no different than healthy controls (7-9). There
are no particular symptoms associated with LIS other than those expected from immobility. The
prevalence of bodily pain is felt to be similar to healthy controls, although inadequate pain relief is
associated with suicidal thoughts (9). Because the etiology is often restricted to the brainstem,
LIS typically does not affect cognition (10-12).
Diagnosis: Diagnosis is dependent upon the physical examination, but unless the examiner is
familiar with LIS, LIS may be mistaken for coma (eyes closed, does not follow commands) or a
vegetative state (eyes may open and move, but not to command) (7). Therefore, physical exam
is best performed by a neurologist. If LIS is suspected, clinicians should assess for abnormal
brainstem respiratory patterns such as central neurogenic hyperventilation (rapid and deep
breaths 20-40/min), apneustic breaths (prolonged inspiratory pause) or ataxic respirations
(irregularly irregular). A complete coma exam including cranial nerves and volitional eye/eyelid
movements should be performed. Cranial imaging is typically performed to elucidate the
diagnosis with magnetic resonance imaging as the preferred modality.
Care Decisions: The common care decisions in LIS are related to the consequences of the
severe impairment of muscles that control eating and breathing. Thus, decisions about the use of
mechanical ventilation, artificial nutrition and hydration, and 24 hour nursing care will be
paramount. Considering the communication challenges clinicians may encounter, consultation
with neuropsychology to assess decision-making capacity should be done early in the patient’s
course, especially since delirium can be a confounding variable. Though prior wishes expressed
in advance care planning documents may be useful, misunderstandings regarding LIS patient’s
cognition and care preferences are common.
Communication Strategies: As portrayed in the 1997 book The Diving Bell and the Butterfly,
written by a locked-in patient, communication is possible but it requires patience (13) and for the
patient, it may be limited to vertical/lateral eye movements or blinking of the upper eyelid (2).
Hence, consultation with speech language pathology is advised. The following communication
strategies are recommended:
• Establish a reliable and consistent communication method, such as a vertical eye
movement up means “yes,” and vertical eye movement down means “no.”
• Phrase questions so that the answers must be “yes” or “no.”
• Present a list of words (i.e. symptoms), and allow the patient time to respond.
• To improve reliability of the decisionality assessment, present questions in both an
affirmative and negative manner: “Do you want a PEG tube?” and “Do you want to refuse
PEG tube placement?” An orientation question might be, “Is the year 1999? 2019?
2015?” Comprehension can be tested with questions such as “Can a shark fly? Can a
hammer pound a nail?”
• Apply the basic principles of determining decisionality as in any other patient (see Fast
Fact #55)
• Utilize augmentative communication tools such as alphabet boards or eye-tracking
devices when available.
• Permit extra time for fluctuating arousal and fatigue.
• Family members and/or primary caregivers may have insights into communication and
subtle signals of distress on the part of the patient. These can be elicited and posted at
the bedside.
Cautions:
• LIS patients are at risk for being talked about at the bedside as if they are dead or in a
coma by hospital staff (1). Always assume the patient can hear you.
• Assess decisionality and the patient’s care preferences as soon as possible. If an
advance directive is available, review for care preferences that may guide decision
making if the patient is deemed non-decisional.
• Be aware that surrogates and clinicians may wrongly assume that quality of life is poor
and not worth living and thereby advocate for the early withdrawal of life sustaining
!31
therapies (7, 14-16).
• Clinicians should be aware of their own values and personal responses to a LIS patient,
and be careful not to assume they are shared by the patient. Efforts should be made to
insure alignment of goals of care between the patient and surrogate throughout the
disease trajectory.
• Clinicians should be transparent with patients/surrogates about what the future may look
like and discuss a full range of care options such as life prolongation (PEG tube,
tracheostomy, nursing home placement) vs a comfort plan of care.
References:
1. Plum F, Posner JB. The diagnosis of stupor and coma. 1st ed. Philadelphia, PA: F A
Davis; 1966.
2. American Congress of Rehabilitation Medicine. Recommendations for use of uniform
nomenclature pertinent to patients with severe alterations in consciousness. Archives of
Physical Medicine and Rehabilitation 1995; 76:205-209.
3. Leon-Carrion J, Van Eckhout P, Dominguez-Morales Mdel R, et al. The locked-in
syndrome: A syndrome looking for a therapy. Brain Injury 2002; 16:571-582.
4. Schnakers C, Majerus S, Goldman S, et al. Cognitive function in the locked-in

syndrome. J Neurology 2008; 255:323-330.
5. Patterson JR GM. Locked-in syndrome: A review of 139 cases. Stroke 1986; 17:758-764.
6. Doble JE, Haig AJ, Anderson C, et al. Impairment, activity, participation, life satisfaction,
and survival in persons with locked-in syndrome for over a decade: Follow-up on a
previously reported cohort. Journal of Head Trauma Rehabilitation 2003; 18:435-444.
7. Laureys S, Pellas F, Van Eeckhout P, et al. The locked-in syndrome: What is it like to be
conscious but paralyzed and voiceless? Progress in Brain Research 2005; 150:495-511.
8. Rousseau C, Pietra S, Nadja M, et al. Evaluation of quality of life in complete locked-in
syndrome patients. J Pall Medicine 2013; 16(11):1455-1458.
9. Lule D, Zickler C, Hacker S, et al. Life can be worth living in locked-in syndrome.
Progress in Brain Research 2009; 177:339-351.
10. Allain P, Jospeh PA, Isambert JL, et al. Cognitive functions in chronic locked-in
syndrome: A report of two cases. Cortex; A Journal Devoted to the Study of the Nervous
System and Behavior 1998; 34:629-634.
11. Cappa SF VL. Locked-in syndrome for 12 years with preserved intelligence. Annals of
Neurology 1982; 11:545.
12. Cappa SF, Pirovano C, Vignolo LA. Chronic 'locked-in' syndrome: Psychological study of
a case. European Neurology 1985; 24:107-111.
13. Bauby JD. The Diving Bell and the Butterfly. New York: Vintage International, 1997.
14. Doble JE, Haig AJ, Anderson C, et al. Impairment, activity, participation, life satisfaction,
and survival in persons with locked-in syndrome for over a decade: Follow-up on a
previously reported cohort. Journal of Head Trauma Rehabilitation 2003; 18:435-444.
15. Bruno, MA, Pellas F, Schnackers C, et al. Blink and you live: The locked-in syndrome.
Review Neurology (Paris) 2008b; 164:322-335.
16. Thiel A, Schmidt H, Prange H, et al. Treatment of patients with thromboses of the basilar
artery and locked-in syndrome: An ethical dilemma. Nervenartz 1997;68(8):653-658.
Author Affiliations: Hennepin County Medical Center; Medical College of Wisconsin

Version History: First electronically published August 2015.
!32
!
PALLIATIVE CARE ISSUES IN GLIOBLASTOMA
Roshni Abee Patel MD, Elizabeth Neil MD, Sam Maiser MD
Background Glioblastoma (previously known as glioblastoma multiforme or GBM) is the most

common incurable primary brain malignancy in adults. This Fast Fact addresses symptom
management, prognosis, and medical decision-making in glioblastoma patients.
Prognosis Median age at diagnosis is 64; median survival from diagnosis is 15 months.
Extended survival may be seen with favorable genetic mutations (e.g. MGMT and IDH), age < 50
years, and a fully independent postoperative functional status (1,2). Two-year survival after
diagnosis is 27%; 5-year survival is 10% (3). Its illness trajectory is associated with a rapid rate of
cognitive decline preceding the steep functional decline indicative of the usual dying phase of
cancer.
!33
Symptom Presentation and Management Tumor size, tumor location, and cancer treatment
side effects are the most common determinants of how symptoms manifest.
• Focal deficits. Hemiparesis, aphasia, paresthesias, dysarthria, dysphagia, visual changes,
and neglect are common. Management includes physical, occupational and speech therapy,
psychosocial support, and corticosteroids (e.g. dexamethasone 2-4 mg daily or twice a day)
(2,4).
• Cognitive changes. Depression and anxiety are common; hence many glioblastoma patients
are initiated on antidepressants. Memory loss, personality changes, fatigue, agitation, and
delirium are also common. Management options include psychotropics, assessment of
decision-making capacity, and off-label use of psychostimulants for depression, apathy, or
drowsiness (see Fast Fact #173) (5,6). While corticosteroids can help with vasogenic-related
symptoms such as headaches or nausea, they can exacerbate behavioral changes via
psychiatric side effects (see Fast Fact # 323).
• Seizures. Even though seizures are a common presenting sign of glioblastoma,
prophylactic antiepileptic drugs (AEDs) are not recommended. Instead, active seizures are
treated with benzodiazepines, and AEDs are initiated thereafter. Consultation with a clinical
pharmacist or a neurologist is advised to minimize drug interactions and identify appropriate
routes of administration for AEDs. At the end-of-life, oral administration may not be feasible.
See Fast Fact #229 for more information on rectal, sublingual, subcutaneous, or intravenous
routes (2,11,2).
• Headache, nausea, and fatigue. These symptoms can result from the effects of
chemotherapy or radiation therapy or from a disease-related increase in the intracranial
pressure (ICP). Beyond conventional treatments, corticosteroids may help if vasogenic
edema is present; radiation therapy and ventriculoperitoneal shunts can help manage
increased-ICP-related symptoms (2,4,7).
Cancer-Directed Therapy For newly diagnosed patients with a preserved performance status,
standard treatment involves maximal safe surgical resection followed by concomitant
temozolomide (TMZ) chemotherapy and 6 weeks of radiotherapy (2,3). Essentially all patients will
experience disease recurrence for which no standard treatment exists (1,2). Instead, various
strategies are individualized.
• Any combination of repeat surgical resection, re-irradiation, and chemotherapy (TMZ or
other) (8).
• Bevacizumab: A monoclonal antibody that can yield radiographic improvement of the tumor
and thereby reduce functional deficits and the need for corticosteroids. Although it may
improve quality of life, current data shows it does not prolong survival and can precipitate
strokes and cardiovascular events via side effects including bleeding and clotting (9,10).
• Tumor Treating Fields (TTF): A headpiece that is worn 24 hours per day and applies low-
intensity alternating electric fields to disrupt cell division of cancer cells. TTF is a new
treatment with relatively limited evidence to suggest it can prolong survival when combined
with TMZ for newly diagnosed and recurrent glioblastoma (12). The cosmetic appearance
and burden of wearing a device all day, is a considerable trade-off that may impact quality of
life.
• Hospice is an appropriate care plan for any patient with recurrent glioblastoma, particularly
those with comfort-based goals of care and/or a poor performance status.
Medical-Decision Making Deciding when to stop life prolonging treatment can be challenging
in glioblastoma. As with any other type of cancer or life-limiting illness, this should be a shared-
decision between patients and clinicians based on performance status, treatment expectations,
and quality of life preferences. Below are additional medical-decision-making elements worth
highlighting for glioblastoma:
• In most cases, patients will not be able to enroll in hospice if they are continuing anti-cancer
treatments like radiation or chemotherapy. There is some controversy around abruptly
stopping bevacizumab for fear of rebound vasogenic edema contributing to a faster decline.
Despite these concerns, bevacizumab is associated with its own side effects (loss of
appetite, nausea, constipation, bleeding, clotting) and burdens. Hence, most experts
recommend its discontinuation in the event of tumor progression so that patients can
maximize their access to hospice support (11).
!34
• Close collaboration with treating oncologists is crucial when interpreting tumor status on
radiologic imaging, as microscopic progression may make radiologic interpretation
challenging (11).
• Given the high risk for early cognitive changes, early advance care planning (ACP),
including identification of a surrogate decision-maker, is critical with glioblastoma. ACP
discussions should begin at diagnosis, and be revisited at oncologic touch points such as
completion of first-line treatment, disease recurrence, hospitalizations, and any decline in
functional status (6,13,14).
• Disease-related behavioral and/or cognitive changes can lead to caregiver burden and make
home hospice dispositions challenging. This can create caregiver guilt, especially for
patients who expressed a wish to die at home. Clinicians may need to support surrogates by
highlighting the patient care needs and the safety benefits of a more supervised care setting.
References
1. Louis DN, Suva ML, Burger PC et al. Chapter 1: Diffuse astrocytoma and
oligoendendroglial tumors – Glioblastoma, IDH wildtype. In: Louis DN, Ohgaki H, Wiestler
OD, et al. WHO Classification of Tumours of the Central Nervous System. 4th ed. Lyon:
International Agency for Research on Cancer; 2016: 28-45.
2. Preusser M, de Ribaupierre S, Wohrer A, et al. Current concepts and management of
glioblastoma. Ann Neurol. 2011; 70(1): 9-21.
3. Strupp R, Hegi ME, Mason WP, et al. Effects of radiotherapy with concomitant and
adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a
randomised phase III study: 5-year analysis of EORTC-NCIC trial. Lancet Oncol. 2009;
10(5): 459-66.
4. Omuro A, DeAngelis LM. Glioblastoma and other malignant gliomas: a clinical review.
JAMA. 2013; 310(17): 1842-50.
5. Boele FW, Rooney AG, Grant R, Klein M. Psychiatric symptoms in glioma patients: from
diagnosis to management. Neuropsychiatr Dis Treat. 2015; 11: 1413-20.
6. Fritz L, Dirven L, Reijneveld JC, et al. Advance care planning in glioblastoma patients.
Cancers (Basel). 2016; 8(11): E 102.
7. Cetin OE, Isler C, Uzan M, Ozkara C. Epilepsy-related brain tumors. Seizure. 2017; 44:
93-97.
8. Franceschi E, Minichillo S, Brandes AA. Pharmacotherapy of glioblastoma: established
treatments and emerging concepts. CNS Drugs. 2017; 31(8): 675-684.
9. Gilbert MR, Dignam JJ, Armstrong TS, et al. A randomized trial of bevecizumab for newly
diagnosed glioblastoma. N Engl J Med. 2014; 370(8): 699-708.
10. Chinot OL, Wick W, Mason W, et al. Bevacizumab plus radiotherapy-temozolomide for
newly diagnosed glioblastoma. N Engl J Med. 2014; 370(8): 709-22.
11. Kesselheim JC, Norden AD, Wen PY, Joffe S. Discontinuing bevacizumab in patients with
glioblastoma: an ethical analysis. Oncologist. 2011; 16(10): 1435-9.
12. Mehta M, Wen P, Nishikawa R, Reardon D, Peters K. Critical review of the addition of
tumor treating fields (TTFields) to the existing standard of care for newly diagnosed
glioblastoma patients. Crit Review Oncol Hematol. 2017; 111: 60-65.
13. Kuchinad KE, Strowd R, Evans A, Riley WA, Smith TJ. End of life care for glioblastoma
patients at a large academic care center. J Neurooncol. 2017; 134(1): 75-81.
14. Thier K, Calabek B, Tinchon A, et al. The last 10 days of patients with glioblastoma:
assessment of clinical signs and symptoms as well as treatment. Am J Hosp Palliat Care.
2016; 33(10): 985-988.
15. Valko PO, Siddique A, Linsenmeier C, et al. Prevalence and predictors of fatigue in
glioblastoma: a prospective study. Neuro Oncol 2015;17(2):274-281.

Author Affiliations: University of Minnesota Medical School, Minneapolis, MN (RP, EN, SM),
Hennepin County Medical Center, Minneapolis, MN (SM).
Version History: Originally edited by Sean Marks MD; first electronically published in February
2018
!35
Facts.

PARKINSON’S DISEASE: PART 1 DISEASE TRAJECTORY
Danny Estupinan MD1; Alva Roche’-Green MD2; Maisha Robinson MD2; Robert P. Shannon
MD2
This Fast Fact will address the natural history and illness trajectory of Parkinson’s Disease (PD).
See Fast Fact #362 for information on palliation strategies of non-motor symptoms associated
with PD.
Illness Background PD is a degenerative central nervous system disorder which

disproportionately affects the motor system leading to asymmetric muscle rigidity, bradykinesia,
and a resting “pill-rolling” tremor (1). It involves a section of the midbrain called the substantia
nigra which leads to a depletion of the neurotransmitter dopamine. Dopamine derivatives (levo-
dopa) and agonists are pharmacologic mainstays for the motor symptoms. The illness trajectory
varies by Parkinsonian syndrome. Typically PD has a longer prognosis and progresses slower
with less nonmotor symptoms and cognitive impairment early in the disease course compared
with atypical Parkinsonism which includes a variety of disorders such as Multisystems Atrophy,
Corticobasal Degeneration, and Lewy Body Dementia (2).
Impact of Illness While the progression of functional impairment and disability is quite variable,
typically PD progresses over many years, not months. In general, patients begin to have levo-
dopa related treatment complications such as dyskinesia (irregular, jerky movements), psychosis,
!36
and dystonia, within 5 years of diagnosis (3-5). Within 12 years of disease onset, most PD
patients have issues with falls, gait disturbance, and balance; within 15-20 years of disease
onset, issues with either hallucinations or dementia are common (6). The symptom burden from
the motor and non-motor symptoms of PD has been shown to be comparable to metastatic
cancer (3,4). The slow erosion of functional capacity and the increased dependence on
caregivers leads many PD patients to suffer from a diminished sense of personhood and identity
(1). This can lead to significant caregiver distress, financial hardship, and consequently a high
utilization of nursing home placement in the last years of life (7). These factors plus a variable
and long prognosis can lead many PD patients to make requests for a hastened death to their
clinicians and caregivers. See Fast Facts 156 and 159. Involvement of an interdisciplinary team
is often necessary to address the unmet spiritual, psychological, and social needs of PD patients
(3,4).
Prognosis With the improvement in disease-modifying therapies such as deep brain

stimulators, life expectancy is only modestly decreased compared to aged-matched controls and
is roughly 6 to 22 years at disease onset (8,9). The long illness prodrome should allow for early
advance care planning and appropriate palliative care interventions prior to late complications.
Late-term PD complications are listed below. When encountered, they should prompt clinicians
to help patients and families prepare for a peaceful death and should also prompt clinicians to
consider hospice care (10)
• Dementia: approximately 40% of PD patients develop dementia (11). It is a significant risk
factor for nursing home placement and one-year mortality (7,9).
• Delirium: Visual hallucinations and delirium are common in the last years of life. They are
also a predictor of nursing home admission (7).
• Extrapyramidal symptoms: the presence of muscle rigidity and dyskinesia despite best
medical management is associated with an elevated one-year mortality (9).
• Dysphagia: this may occur from progression of motor symptoms or dementia. Recurrent
hospitalizations and/or aspiration events are common. There is no evidence that feeding
tubes improve survival at this stage nor quality of life. Honey-thickened liquids and
encouraging a “chin-down” feeding posture are more effective strategies for managing
dysphagia in advanced PD (12).
Hospice Considerations There are no specific hospice criteria for PD nor are there reliable
indicators to help clinicians predict a < 6 month survival. Medicare claims data suggest that only
54% of PD patients utilize hospice prior to death; although, nursing home residents and patients
seen by an outpatient neurologist may be more likely to utilize hospice care (13). To better
identify hospice-eligible PD patients, clinicians should look for a pattern of recurring
hospitalizations, dysphagia, and/or progressive dementia. See Fast Facts #125 and #150 for
hospice admission guidelines for general neurologic illnesses.
End of Life Pharmacologic Considerations There are no current PD specific guidelines

regarding end-of-life care medication management, however, many experts recommend
continuing levo-dopa derivatives and agonists as long as the patient is able to swallow pills.
Abrupt discontinuation of these medications can be associated with intense and uncomfortable
muscle rigidity. Although levo-dopa associated symptoms like dyskinesia may fluctuate
dramatically throughout the day and be difficult to observe, patients often prefer these symptoms
to the underlying muscle rigidity associated with PD.
References
1. Poewe W. The natural history of Parkinson's disease. J. Neurol. 2006 Dec;253(7): VII2–
6.
2. Miyasaki JM. Palliative care in Parkinson's disease. Curr Neurol Neurosci Rep. Aug
2013;13(8):367.
3. Saleem TZ, Higginson IJ, Chaudhuri KR, Martin A, Burman R, Leigh PN. Symptom
prevalence, severity and palliative care needs assessment using the Palliative Outcome
!37
Scale: a cross-sectional study of patients with Parkinson's disease and related
neurological conditions. Palliat Med. Sep 2013;27(8):722-731.
4. Miyasaki JM, Kluger B. Palliative care for Parkinson's disease: has the time come? Curr
Neurol Neurosci Rep. May 2015;15(5):26.
5. Giugni JC, Okun MS. Treatment of advanced Parkinson's disease. Curr Opin Neurol. Aug
2014;27(4):450-460.
6. Poewe W. Clinical measures of progression in Parkinson's disease. Mov Disord. 2009;24
Suppl 2:S671-6.
7. Aarsland D, Larsen JP, Tandberg E, Laake K. Predictors of nursing home placement in
Parkinson's disease: a population-based, prospective study. J Am Geriatr Soc. 2000 Aug;
48(8):938-42.
8. Wu GF, Hurtig HI, et al. Palliative care in amyotrophic lateral sclerosis, Parkinson’s
disease, and multiple sclerosis. J Palliat Med 2007; 10(2):433-57.
9. Louis ED, Marder K, Cote L, Tang M, Mayeux R. Mortality from Parkinson disease. Arch
Neurol. 1997 Mar;54(3):260-4.
10. Morrison RS, Meier DE. Clinical practice: palliative care. NEJM 2004; 350(25):2582-90)
11. Aarsland D., Kvaloy J. T., Anderson K., Larsen J. P., Tang M. X., Lolk A., Kragh-Sørensen
P., Marder K. (2007). The effect of age of onset of PD on risk of dementia. J. Neurol. 254,
38–4510.
12. Logemann JA, Gensler G, Robbins J, et al. A randomized study of three interventions for
aspiration of thin liquids in patients with dementia or Parkinson’s disease. J Speech Lang
Hear Res 2008; 51(1):173-83.
13. Safarpour D, Thibault DP, DeSanto CL, Boyd CM, Dorsey ER, Racette BA, Willis AW.
Nursing home and end-of-life care in Parkinson disease. Neurology. 2015 Aug 4;85(5):
413-9.
Authors’ Affiliations: 1Cleveland Clinic, Cleveland OH; 2 Mayo Clinic College of Medicine,
Rochester, MN.
Version History: First electronically published in August 2018; originally edited by Sean Marks
MD
Facts.
!38
!

PARKINSON’S DISEASE: PART 2 PALLIATION FOR COMMON NON-MOTOR SYMPTOMS
Danny Estupinan MD1; Alva Roche-Green MD2; Maisha Robinson MD2; Robert P. Shannon
MD2
Background Nonmotor symptoms likely affect overall quality of life in Parkinson Disease (PD)
as much as motor symptoms (1). Fast Fact #361 discussed the natural trajectory of PD. This
Fast Fact will focus on management strategies of common non-motor symptoms in PD patients.
Pain Nearly 85% of PD patients report pain (2). Musculoskeletal pain from limitations in mobility
is the most commonly reported pain type. While there are no comparative analgesic studies for
PD, NSAIDs, acetaminophen, physical rehabilitation, and low dose opioids are commonly utilized
analgesic strategies. Dystonia is a prolonged involuntary muscle contraction which often leads to
foot cramping, muscle spasms, and a sensation of muscles twisting. In addition to the analgesic
strategies listed above, skeletal muscle relaxants and botulinum toxin injections may be
warranted (see Fast Facts #340 & 324). Neuropathic pain, which is often described as a shooting
pain or a sensitivity to light touch within a dermatome, is a less common pain reported in PD.
Gabapentin, pregabalin, duloxetine, venlafaxine, and/or interventional strategies (e.g. spinal cord
stimulator or a nerve block) are preferred over tricyclic antidepressants (TCAs) due to the risk for
delirium and falls in PD patients.
Neuropsychiatric Symptoms As many as 40% of patients with advanced PD experience

neuro-psychiatric symptoms, most commonly visual hallucinations (3). The assessment and
treatment is similar to delirium in general (see Fast Fact #1) with a few special considerations
(3-10):
!39
• Several PD medications are associated with psychosis: amantadine; monoamine oxidase
type B (MAOB) inhibitors, catechol-O-methyl transferase inhibitors (e.g. entacapone); and
dopamine agonists (e.g. pramipexole). Before initiating new pharmacotherapies, reduce or
discontinue offending medications as appropriate. Pharmacy and neurology input may be
necessary.
• Common neuroleptics used to treat delirium such as haloperidol, risperidone, and
olanzapine should be avoided as they may worsen motor symptoms by blocking dopamine
and raise mortality risk.
• Quetiapine is the preferred pharmacologic treatment in PD because it seems to have the
least effect on motor symptoms. Because PD patients may be more prone to somnolence,
many experts recommend initiating at a low dose such as 12.5 mg to 25 mg at bedtime or
BID.
• Clozapine has the most compelling evidence of all anti-psychotics for treating PD-related
psychosis; however, its use is reserved to psychiatrists due to its association with
agranulocytosis.
• Pimavanserin is a FDA approved oral medication for PD-related hallucinations at a usual
dose of 34 mg a day. Although randomized, placebo controlled trials show efficacy with little
worsening of motor symptoms or other adverse effects (12-14), its use is limited by its cost
which is >$80/day.
Daytime Sleepiness Excessive daytime somnolence is common in PD. Beyond best nocturnal
sleep hygiene practices (see Fast Facts 101, 104 & 105), expert considerations include (15-17):
• AM intake of caffeine or a prescribed psychostimulant such as methylphenidate 5-10 mg
twice a day or modafinil 100-200 mg per day.
• Screen for comorbid sleep disorders such as rapid eye movement behavior sleep disorder,
restless leg syndrome, and obstructive sleep apnea as roughly 85% of PD patients have a
sleep disorder. Refer to a sleep specialist when appropriate.
• Screen for sudden bouts of excessive daytime drowsiness or sleep (often referred as a
“sleep attacks”) which can be common and hazardous in PD. If present, patients should
avoid driving.
Depression There is no clear consensus regarding the best antidepressant in PD. Duloxetine,
venlafaxine, buproprion, sertraline, and escitalopram are preferred by many experts over
mirtazapine and TCAs which have higher anticholinergic activity. Clinicians should be cautious
when combining any antidepressants with MAOB inhibitors to avoid serotonin syndrome
(10,18,19).
Dementia The only FDA-approved treatment for PD-related dementia is rivastigmine. It has
been associated with moderate improvements in cognition and anxiety in mild to moderate
dementia. Its cholinergic properties can lead to significant rates of nausea, vomiting, and
worsening tremor (10,20).
Orthostatic Hypotension Nonpharmacologic interventions like increased fluid/salt intake and

compression stockings are first-line treatments as are a reduction of antihypertensive medications
if medically appropriate. Fludrocortisone or midodrine can be added in refractory cases (5).
Sialorrhea Sialorrhea and drooling are common in PD because of the reduced oromotor control
and autonomic dysfunction. Chewing gum or hard candy may encourage swallowing and reduce
drooling in mild cases (21). For moderate to severe symptoms, the use of glycopyrrolate 1-2 mg
by mouth three times a day; sublingual atropine 1% ophthalmic solution 1-2 drops once to twice a
day; ipratroprium spray, or botulinum toxin injections into salivary glands has been described
(20-22)
References
1. Giugni JC, Okun MS. Treatment of advanced Parkinson's disease. Curr Opin Neurol. Aug
2014;27(4):450-460.
2. Geroin C, Gandolfi M, Bruno V, Smania N, Tinazzi M. Integrated Approach for Pain
Management in Parkinson Disease. Curr Neurol Neurosci Rep. Apr 2016;16(4):28.
!40
3. Forsaa EB, Larsen JP, Wentzel-Larsen T, et al. A 12-year population-based study of
psychosis in Parkinson disease. Arch Neurol. Aug 2010;67(8):996-1001..
4. Fenelon G, Mahieux F, Huon R, Ziegler M. Hallucinations in Parkinson's disease:
prevalence, phenomenology and risk factors. Brain. Apr 2000;123 ( Pt 4):733-745
5. Zesiewicz TA, Sullivan KL, Arnulf I, et al. Practice Parameter: treatment of nonmotor
symptoms of Parkinson disease: report of the Quality Standards Subcommittee of the
American Academy of Neurology. Neurology. Mar 16 2010;74(11):924-931.
6. Fernandez HH, Friedman JH, Jacques C, Rosenfeld M. Quetiapine for the treatment of
drug-induced psychosis in Parkinson's disease. Mov Disord. May 1999;14(3):484-487.
7. Morgante L, Epifanio A, Spina E, et al. Quetiapine versus clozapine: a preliminary report
of comparative effects on dopaminergic psychosis in patients with Parkinson's disease.
Neurol Sci. Sep 2002;23 Suppl 2:S89-90.
8. Juncos JL, Roberts VJ, Evatt ML, et al. Quetiapine improves psychotic symptoms and
cognition in Parkinson's disease. Mov Disord. Jan 2004;19(1):29-35.
9. Pollak P, Tison F, Rascol O, et al. Clozapine in drug induced psychosis in Parkinson's
disease: a randomised, placebo controlled study with open follow up. J Neurol Neurosurg
Psychiatry. May 2004;75(5):689-695.
10. Miyasaki JM, Shannon K, Voon V, et al. Practice Parameter: evaluation and treatment of
depression, psychosis, and dementia in Parkinson disease (an evidence-based review):
report of the Quality Standards Subcommittee of the American Academy of Neurology.
Neurology. Apr 11 2006;66(7):996-1002.
11. Weintraub D, Chiang C, Kim HM, et al. Association of Antipsychotic Use With Mortality
Risk in Patients With Parkinson Disease. JAMA Neurol. May 1 2016;73(5):535-541.
12. Cummings J, Isaacson S, Mills R, et al. Pimavanserin for patients with Parkinson's
disease psychosis: a randomised, placebo-controlled phase 3 trial. Lancet. Feb 8
2014;383(9916):533-540.
13. Seppi K, Weintraub D, Coelho M, et al. The Movement Disorder Society Evidence-Based
Medicine Review Update: Treatments for the non-motor symptoms of Parkinson's
disease. Mov Disord. Oct 2011;26 Suppl 3:S42-80.
14. Connolly BS, Lang AE. Pharmacological treatment of Parkinson disease: a review. JAMA
2014; 311(16):1670-1683.
15. Adler CH, Caviness JN, Hentz JG, Lind M, Tiede J. Randomized trial of modafinil for
treating subjective daytime sleepiness in patients with Parkinson's disease. Mov Disord.
Mar 2003;18(3):287-293.
16. Gjerstad MD, Alves G, Wentzel-Larsen T, Aarsland D, Larsen JP. Excessive daytime
sleepiness in Parkinson disease: is it the drugs or the disease? Neurology. Sep 12
2006;67(5):853-858.
17. Hobson DE, Lang AE, Martin WR, Razmy A, Rivest J, Fleming J. Excessive daytime
sleepiness and sudden-onset sleep in Parkinson disease: a survey by the Canadian
Movement Disorders Group. JAMA; 2002: 287(4):455-463.
18. Menza M, Dobkin RD, Marin H, et al. A controlled trial of antidepressants in patients with
Parkinson disease and depression. Neurology. Mar 10 2009;72(10):886-892.
19. Hauser RA, Zesiewicz TA. Sertraline for the treatment of depression in Parkinson's
disease. Mov Disord. Sep 1997;12(5):756-759.
20. Lee AH, Weintraub D. Psychosis in Parkinson's disease without dementia: common and
comorbid with other non-motor symptoms. Mov Disord. Jun 2012;27(7):858-863.
21. Srivanitchapoom P, Pandey S, Hallett M. Drooling in Parkinson's disease: a review.
Parkinsonism Relat Disord. Nov 2014;20(11):1109-1118.
22. Chou KL, Koeppe RA, Bohnen NI. Rhinorrhea: a common nondopaminergic feature of
Parkinson's disease. Mov Disord. Feb 1 2011;26(2):320-323.
23. Thomsen TR, Galpern WR, Asante A, Arenovich T, Fox SH. Ipratropium bromide spray as
treatment for sialorrhea in Parkinson's disease. Mov Disord. Nov 15 2007;22(15):
2268-2273.
24. Hyson HC, Johnson AM, Jog MS. Sublingual atropine for sialorrhea secondary to
parkinsonism: a pilot study. Mov Disord. Nov 2002;17(6):1318-1320.
!41
Authors’ Affiliations: 1Cleveland Clinic, Cleveland OH; 2 Mayo Clinic College of Medicine,
Rochester, MN.
Version History: First electronically published in August 2018; originally edited by Sean Marks
MD
Facts.
!42
!
Oncology

Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2-3
#14 Palliative
Chemotherapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4-5
#62 Early Diagnosis of Epidural

Metastases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6-7
#65 Radiation for Palliation – Part I . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . 8-9
#91 Interventional Options for Malignant Upper GI Obstruction. . . . . . . . . . . . . . . . .

. . . 10-11
#99 Chemotherapy: Response and Survival Data. . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . 12-13
#129 Steroids in the Treatment of Bone Pain . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . 14-15
#135 Neoplastics Meningitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . 16-17
#151 Hypercalcemia of
Malignancy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .18-19
#157 Malignant Pleural Effusions: Interventional

Management . . . . . . . . . . . . . . . . . . . . . .20-21
#173 Cancer-Related
Fatigue . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
22-24
#176 Evaluation of Malignant Ascites . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . .25-26
#177 Palliative Treatment of Malignant

Ascites . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27-28
!1
#190 Parenteral Nutrition in Advanced Cancer Patients . . . . . . . . . . . . . . . . . . . . . .
. . . . . . .29-30
#209 Malignant Pericardial

Effusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31-33
#236 Pharmacologic Treatment of Acute Venous Thromboembolism in Patients

with Advanced Cancer 3rd Edition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . 34-36
#359 Palliative Care Issues for Transfusion-Dependent Patients . . . . . . . . . . . . . . . . .

. . . . . 37-39

David E Weissman MD
patients, especially when informed that there are no further effective anti-neoplastic treatment
options. Although prognostication is not an exact science, there are data to help clinicians
provide useful information to patients and families – information critical to making realistic end-of-
life decisions and referrals for home hospice service (see Fast Fact #30).
Performance Status The single most important predictive factor in cancer is Performance
Status (‘functional ability,’ ‘functional status’): a measure of how much a patient can do for
themselves, their activity and energy level. Patients with solid tumors typically lose ~ 70% of their
functional ability in the last 3 months of life. The most common scales used to measure
functional ability are the Karnofsky Index (100 = normal; 0 = dead) and the ECOG scale (Eastern
Cooperative Oncology Group), (0 = normal; 5 = dead). A median survival of 3 months roughly
correlates with a Karnofsky score <40 or ECOG > 3. Newer prognostic scales have been
developed to help provide prognostic information (See Fast Facts #124, 125).
The simplest method to assess functional ability is to ask patients: How do you spend your time?
How much time do you spend in a chair or lying down? If the response is >50% of the time, and
is increasing, you can roughly estimate the prognosis at 3 months or less. Survival time tends to
decrease further with increasing numbers of physical symptoms, especially dyspnea, if secondary
to the cancer.
Other Factors Several common cancer syndromes have well-documented short median
survival times:
• Malignant hypercalcemia: 8 weeks, except newly diagnosed breast cancer or myeloma
(see Fast Fact #151)
• Malignant ascites (see Fast Fact #176), malignant pleural effusion (#209), or malignant
bowel obstruction: < 6 months.
• Modified Glasgow Prognostic Score (mGPS): multiple studies have shown that an
increased mGPS -- meaning an elevated serum c-reactive protein and a reduced serum
albumin – is associated with a reduced cancer specific survival curve irrespective of
cancer type.
!2
Other Comments In general, a patient with metastatic solid cancer, acute leukemia or high-
grade lymphoma, who will not be receiving systemic chemotherapy (for whatever reason), has a
prognosis of less than 6 months. Notable exceptions to this are patients with metastatic breast or
prostate cancer with good performance status, as these cancers may have an indolent course. In
these patients additional features suggesting short prognosis are needed (declining functional
status, dyspnea, weight loss).
Discussing Prognosis When discussing prognosis with patients/families, the following four
step approach is recommended: Preparation; Content; Patient’s Response; Close. Remember
to:
References
1. Lamont EB, Christakis NA.. Complexities in prognostication in advanced cancer. JAMA.
2003; 290:98-104.
2. den Daas, N. Estimating length of survival in end-stage cancer: a review of the literature.
J Pain Symp Manage. 1995; 10:548-555.
3. Lassauniere JM, Vinant P. Prognostic factors, survival and advanced cancer. J Pall Care.
1992; 8:52-54.
5. Reuben DB, Mor V. Clinical symptoms and length of survival in patients with terminal
6. McMillan DC, Crozier JE, et al. Evaluation of an inflammation-based prognostic score
(GPS) in patients undergoing resection for colon and rectal cancer. Int J Colorectal Dis
2007; 22: 881-6.
7. Proctor MJ, Morrison DS, et al. An inflammation based prognostic score (mGPS)
predicts cancer survival independent of tumour site: a Glasgow inflammation outcome
study. British Journal of Cancer 2011; 104: 726-734.
!3
!

PALLIATIVE CHEMOTHERAPY
David E Weissman MD
Introduction One often hears the term palliative chemotherapy, but what exactly does it mean
and how can a non-oncologist decide if it has potential value?
Why is chemotherapy used? From the perspective of the patient with locally advanced or
metastatic cancer, chemotherapy is used with one of two intents: Hope for cure or hope for life-
prolongation. Oncologists use the term palliative chemotherapy as a euphemism for
chemotherapy that is not expected to be curative. What about chemotherapy used solely for
symptom control—is that a realistic goal? Oncologists will occasionally recommend
chemotherapy for symptom control, as there are some clinical trial data that in selected cancers
chemotherapy may improve quality of life and/or symptom control, without impacting survival.
However, as a general rule, physical symptoms related to the cancer highly correlate with tumor
burden; chemotherapy that does not effect tumor growth will generally not improve physical
symptoms caused by the tumor.
What information do you need from the consulting oncologist to help a patient decide on
the value of chemotherapy in advanced cancer?
1. What is the Response Rate of the proposed chemotherapy? Response Rate = (# of

complete responses + # of partial responses)/total # of treated patients; as studied in clinical
trials. To qualify as a Response, the reduction in tumor must last for at least one month:
• Complete Response = complete eradication of measurable tumor

• Partial Response = > 50% reduction in measurable tumor
• Progressive Disease = > 25% growth in measurable tumor
• Stable Disease = anything between partial response and progressive disease
Note: response rate data that are generally quoted to patients comes from clinical trials involving
closely monitored patients with good performance statuses. The response rates for patients
outside of clinical trials can be expected to be lower – See Fast Fact # 99.
2. What is the Median Duration of Response of the proposed chemotherapy regimen? This
number is vital for patients to make an informed decision and roughly correlates to months of
added life to be expected if the chemotherapy is effective. The MDR, also known as Time to
Progression (TTP), can be explained to the patient as: if the chemotherapy is effective at
shrinking or stabilizing your cancer (if you are a chemotherapy responder), you can expect it will
work for X-X months.
3. What is the potential treatment burden? Including acute and delayed toxicities, direct and
indirect costs (lost work for family members), need for clinic visits or inpatient stays, need for
treatment monitoring (e.g. blood tests, x-rays). See Fast Facts # 276 and 277 for a discussion of
the role of targeted cancer therapies in limiting the potential treatment burden.
4. How long must treatment be continued? Standard practice is to wait for two full cycles of
treatment before assessing response. However, if a patient is progressing during the first cycle,
they will almost always continue to progress through a second cycle. For responding patients,
chemotherapy is generally continued until there is disease progression or intolerable toxicities.
Reference
!4
Ellison N, Chevlin EM. Palliative Chemotherapy. In: Principles and Practice of Palliative Care
and Supportive Oncology. 2nd Edition. Berger A, Portenoy R, Weissman DE, eds. New York,
NY: Lippincott-Raven; 2002.
!5
!

EARLY DIAGNOSIS OF EPIDURAL METASTASES
David E Weissman MD
Background Epidural metastases are very common in patients with advanced cancer.
Cancers most often associated with epidural spread include lung, prostate, breast, kidney,
myeloma and melanoma. They are also common in testicular cancer, lymphomas, and Hodgkin’s
disease. Ovarian and pancreatic cancer rarely lead to epidural metastases. Tumor reaches the
epidural space via contiguous spread from adjacent vertebral body metastases or, less
commonly, from direct extension of tumor through the intervertebral foramina from adjacent tissue
(e.g. retroperitoneal lymphoma or posterior lung cancer).
The importance of early diagnosis Back pain is the herald symptom of epidural metastases;
occurring, on average, many weeks to months prior to any neurological damage. That is, pain
occurs long before there is any direct compression of the spinal cord, at a time when early
diagnosis can be established and treatment started. Neurological deficits from spinal cord
compression are a late finding of epidural metastases; serious damage is usually preventable by
early diagnosis.
Characteristics of pain from epidural metastases Pain from epidural metastases occurs
due to vertebral body fracture, structural spine instability, periosteal or nerve root irritation. The
various descriptions of pain from epidural metastases are protean. Most commonly, patients say
it is ‘dull’ or ‘aching,’ often with a sensation of ‘muscle spasm.’ Pain typically worsens gradually,
so that over a period of weeks patients require increasing analgesics and have a corresponding
decrease in function. This is in contrast to benign compression fractures, where severe pain
occurs suddenly, followed by slow improvement over weeks. If there is nerve root irritation,
patients will describe neuropathic symptoms in a radicular pattern (e.g. burning or shock-like pain,
and/or dysesthesias). The pain is usually located in the central back or paravertebral region and/
or in a radicular distribution. Commonly missed radicular symptoms are tip of shoulder pain from
C7-T1 metastases; lateral or anterior rib pain from thoracic metastases; anterior abdominal, flank
or hip pain from T12-L2 metastases. Pain is often made worse by increasing the spinal cord load
that occurs with standing, coughing or valsalva. Pain in the thoracic region is particularly
worrisome due to the narrow spinal canal and minimal epidural space; patients with thoracic
metastases often complain of increasing pain when recumbant.
Diagnostic strategies The key to early diagnosis is a high index of suspicion. A good rule to
use is that the cancer patient with progressive back or radicular pain, for more than 1-2 weeks,
has epidural metastases unless proven otherwise; this is especially true in the high risk cancers
(breast, prostate, lung, myeloma). Various protocols describing diagnostic approaches have
been developed to aid clinicians (see references); all agree that in the setting of a normal
neurological examination, early radiological imaging is essential for diagnosis and treatment
planning. Rodichok et al demonstrated in 1981 that plain spine x-rays, in the region of back pain,
can be an excellent first screening tool; MRI is the definitive diagnostic study and is necessary for
planning radiation or surgical intervention. If neurological signs have become evident, emergent
MRI is the diagnostic test of choice.
Summary/Key Teaching Points:
• Epidural metastases (tumor in the epidural space), occurs prior to actual spinal cord
compression and neurological damage.
• Pain will precede neurologic deficits by weeks to months.
• Early diagnosis will preserve neurological function.
• Progressive back or radicular pain is an indication for radiographic investigation to rule out
epidural metastases, especially in high risk cancers.
References
1. Schmidt MH, Klimo P Jr, Vrionis FD. Metastatic spinal cord compression. J Natl Comp
Cancer Network. 2005; 3(5):711-9.
!6
2. Byrne TN. Spinal cord compression from epidural metastases. NEJM. 1992;
3217:614-619.
3. Rodichok LD, Harper GR, Ruckdeschel JC. Early diagnosis of spinal epidural
metastases. Am J Med. 1981; 70:1181-1188.
4. Posner JB. Neurologic complications of cancer. Contemporary Neurology Series, Vol 45.
Philadelphia, PA: FA Davis; 1995.
May 2015.
!7
!

RADIATION FOR PALLIATION—PART 1
Carolyn Rutter MD, Candice Johnstone MD and David E Weissman MD
Background Radiation therapy (XRT) is used with palliative intent to improve quality of life by
improving function and/or diminishing symptoms – most commonly pain, bleeding, or pressure on
vital structures. This Fast Fact describes the physiology and methods of delivering radiation
therapy; Fast Fact #66 discusses common indications for and outcomes of palliative XRT.
How it works XRT is the use of ionizing radiation to damage a cell’s DNA. This can happen
to a DNA molecule itself via a direct effect of the radiation (this is less common), or indirectly via
an oxygen compound (OH, HOOH) which reacts with a DNA molecule (this pathway is more
common). Damage only occurs in cells within the radiation field—the area through which the
radiation beam passes. Both malignant and normal cells within the field are affected. Malignant
cells are less efficient at repairing DNA damage and are, therefore, more likely to die. The goal is
to design a radiation field that includes all of the tumor cells while excluding as much normal
tissue as possible.
Types of radiation therapy XRT can be delivered 1) from outside the body as external beam
radiation (EBRT), 2) from within the body by placement of a radiation source near the cancer
(brachytherapy), or 3) as a radio-pharmaceutical given by mouth (e.g. iodine-131) or by
intravenous injection (e.g. Strontium89).
Fractionation In EBRT patients typically receive one fraction per day, but other schedules are
sometimes used (e.g. hyperfractionation, or at least 2 doses per day). Fractionation takes
advantage of the different rates at which malignant and non-malignant cells repair damage
caused by XRT; it gives normal tissues an opportunity to recover while continually reducing the
tumor cell population.
Dosing Radiation doses are described in units called Gray (Gy) or centiGray (cGy): 1 Gy =
100 cGy. Note: in the older literature, the term rad was used: 1 rad = 1 cGy. A radiation
prescription includes the site being treated, beam orientation and number (e.g. two beams, AP
and PA), beam type (photons or electrons) and energy (in Volts), dose per fraction (typical daily
doses for palliative EBR range from 150-400 cGy), number of fractions per day, and total dose. A
radiation boost is an extra dose of radiation, given during the last treatments, to a smaller field
within the original field. The total administered dose is based on a balance between giving
enough radiation to control the tumor while respecting normal tissue tolerance to minimize the
risk of late side effects. Different tissues have different radiation tolerances; liver and kidney can
only tolerate a small total radiation dose (< 2400 cGy), whereas bone and peripheral nerves can
tolerate much larger total doses (>5000 cGy).
Simulation Prior to the first treatment, patients undergo simulation, where the exact location of
the field is mapped. Permanent or temporary marks are placed on the skin to help ensure that
the treatment field can be reproduced in the same location at every treatment. Various types of
immobilization ranging from standard pads, head cups to customizable devices are utilized
depending on the clinical situation.
Delivering EBRT If the radiation prescription calls for daily fractions, patients come to the
radiation therapy department once a day, five days a week. While most XRT regimens for
curative intent often last 5-7 weeks, most palliative XRT regimens can be condensed to a shorter
range of one day (e.g. to relieve pain from bone metastases) to three weeks. Treatments are
delivered inside a shielded, enclosed room. A radiation therapist operates the radiation machine
(typically a linear accelerator) from outside the room while watching the patient on a camera.
Each daily treatment takes only a few minutes and is painless.
Toxicity At least once a week patients see the radiation oncologist to evaluate response and
assess/treat toxicity. Toxicity depends upon the area being treated and, except for fatigue, is
!8
limited to tissues within that field. Early/acute toxicities occur during or shortly after treatment and
resolve within one to two months (e.g. oral mucositis during oral radiation). Late toxicities occur
months to years after treatment (e.g. coronary artery disease following chest radiation). Early
toxicity is related to inflammation and death of rapidly dividing cells (such as in the skin or
gastrointestinal tract), while late effects result from vascular changes and cell death of slowly
dividing cells. Radiation oncologists have a host of medications, salves, and mouth rinses to help
alleviate acute toxicities (see Fast Facts #121, 130, 185).
References
1. Ciezki JP. Palliative Radiotherapy. Seminars in Oncology. 2000; 27(1):90-3.
2. Kirkbride P. The role of radiation therapy in palliative care. J Palliat Care. 1995; 11(1):
19-26.
3. Perez C, Brady L, Chao KSC. (Eds). Radiation Oncology: Management Decisions. 3rd
Ed. Philadelphia, PA: Lippincott-Raven; 1999.
4. Tisdale BA. When to consider radiation therapy for your patient. Am Fam Phys. 1999;
59(5):1177-84.
5. Johnstone C, Lutz ST. External beam radiotherapy and bone metastases. Annals of
Palliative Medicine 2014; 3:114-122.
published July 2006; 3rd Edition April 2016 after editing by Candice Johnstone MD.
!9
!

INTERVENTIONAL OPTIONS FOR MALIGNANT UPPER GI OBSTRUCTION
James Ouellette DO, Lisa Patterson MD, and Paula Termuhlen MD
Background Patients with unresectable cancers of the upper gastrointestinal tract often suffer
severe symptoms due to pain, nausea and vomiting, weight loss, cachexia, and poor food
tolerance. This can be related to gastric and duodenal cancers causing intrinsic obstruction of the
intestinal lumen or pancreatic and biliary cancers causing extrinsic biliary compression.
Management options vary depending on the site of obstruction, the patient’s functional status, the
patient-defined goals of care, and estimated prognosis. Fast Fact #45 discussed medical
management options. This Fact Fact reviews interventional approaches for upper GI
obstructions, especially when further radiation, chemotherapy, medical management, or curative
surgical options are longer helpful. Listed below are treatment options for managing different
sites of obstruction (listed from least invasive to most invasive). Management decisions for these
problems are complex, requiring a multi-disciplinary approach (involving surgery,
gastroenterology, medical and radiation oncology, radiology, and palliative care) to achieve the
best possible outcome with minimum morbidity.
Esophageal obstruction
1) External beam radiation therapy (successful in 40% of patients).
2) Endoscopic laser therapy (can be repeated every 4-6 weeks).
3) Endoscopic/fluoroscopic stenting (different stent materials are available for different
situations).
Gastric or Duodenal obstruction
1) Nasogastric tube decompression (poor long-term solution due to patient discomfort).
2) Venting gastrostomy tube, which allows for drainage of intestinal contents (can be placed
endoscopically, laparoscopically, or with open surgery).
3) Janeway gastrostomy (surgically created gastrocutaneous fistula).
4) Endoscopically/fluoroscopically placed stent across the site of obstruction (e.g. pylorus).
5) Laparoscopic gastrojejunostomy.
6) Open gastrojejunostomy.
If unable to restore continuity of the gastrointestinal tract with a surgical procedure to bypass the
obstruction, a combination of a gastrostomy tube with a separate jejunostomy tube can be used.
This can provide enteral nutrition to the small intestine while venting the stomach. Patients can
enjoy the pleasure of eating, even if the food is drained through the G-tube.
Pancreaticobiliary obstructions
1) Stent placement (plastic or metal) across obstruction through an endoscopic procedure
(ERCP).
2) Stent/drain placement across obstruction by a radiologic procedure (transhepatic).
3) Laparoscopic cholecystojejunostomy (after gallstone absence is confirmed).
4) Open choledochojejunostomy, cholecystojejunostomy or hepaticojejunostomy.
Adjuvant medications may augment the efficacy of these interventions.
• Proton pump inhibitor to reduce gastric secretions.
• Sucralfate (Carafate) slurry, 1 gram q6 hours, for patients with ulcerated esophageal or
gastric lesions.
• Metoclopramide (Reglan) 10 mg tid to qid, as a prokinetic drug.
• Octreotide (Sandostatin) 50-100 micrograms q6-8 h for high volume output conditions.
• Dexamethasone 4-8 mg per day.
References
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1. Harris G, Senagore A, et al. The management of neoplastic colorectal obstruction with
colonic endoluminal stenting devices. Am J Surg. 2001; 181:499-506.
2. Acunas B, Poyanli A, Rozanes I. Intervention in gastrointestinal tract: the treatment of
esophageal, gastroduodenal and colorectal obstructions with metallic stents. Eur J Rad.
2002; 42:240-248.
3. Choi Y. Laparoscopic gastrojejunostomy for palliation of gastric outlet obstruction in
unresectable gastric cancer. Surg Endoscop. 2002; 16:1620-1626.
4. Tang CN, Siu WT, et al. Laparoscopic biliary bypass – a single centre experience.
Hepatogastroenterology. 2007; 54:503-7.
5. Jeurnink SM, Steyerberg EW, et al. Gastrojejunostomy versus stent placement in patients
with malignant gastric outlet obstruction: a comparison in 95 patients. J Surg Oncol. 2007;
96:389-96.
6. Frech EJ, Douglas AG. Endoscopic therapy for malignant bowel obstruction. J Supp Oncol.
2007; 5:303-310,319.
7. Laval G, Arvieux C, et al. Protocol for the treatment of malignant inoperable bowel
obstruction: a prospective study of 80 cases at Grenoble University Hospital Center. J
edited by Drew A Rosielle and published December 2007; 3rd Edition June 2015. Current version
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!

CHEMOTHERAPY: RESPONSE AND SURVIVAL DATA
Narendranath Epperla MD and David E Weissman MD
Background Key data in the decision process regarding chemotherapy include the response
rate, median duration of response, and median survival, along with toxicity and quality of life
information (see Fast Fact #14). The table below synthesizes data for several common cancers.
The data were derived by reviewing standard oncology textbooks, along with a Medline search of
recent relevant articles.
Comments on the Response and Survival Data

• All data is for patients receiving first-line, commercially available, oral or IV chemotherapy
and/or biological therapy (e.g. monoclonal antibodies).
• ‘Response Rate’ is defined as the percentage of complete and partial responders in a given
trial, where ‘Partial Response’ = > 50% reduction in measurable tumor for one month.
• Response is typically determined after 2 cycles of treatment (usually one cycle every 21-28
days). Note: patients who progress after 1 cycle will generally continue progressing after
two.
• The data reflect mid-point ranges derived from the available clinical trials; most of the data
represent combination chemotherapy trials. Note: for certain cancers, the benefit of
combination vs. single agent therapy is not proven (e.g. pancreas, biliary, liver).
• This information is not representative of all cancer patients. The data represent the ‘best
case’ outcome, from a population of patients who were in good enough health to participate
in a clinical trial (e.g. ambulatory, good functional status). Actual responses and response
durations for a non-clinical trial population will likely be poorer.
• Second-line chemotherapy, following disease progression from first-line treatment, can be
expected to have a lower response rate and shorter duration of response.
• Median survival data includes both responders and non-responders. Note: patients who
respond to chemotherapy typically live longer than those who do not.
Response Median Duration of Median Survival

Rate Response
Breast 25-55% 8-12 months 24-36 months
Lung (Non-Small Cell)

NSCLC, squamous 20-36% 4-6 months 6-11 months
NSCLC, non-squamous 20-35% 4-6 months 10-12 months
Esophagus 30-50% 4-6 months 6-9 months
GEJ 40-60% 6-8 months 9-12 months
Gastric
HER2 negative 20-40% 4-7 months 6-11 months
HER2 positive ~50% 6-7 months 12-14 months
Pancreas 20-32% 4-6 months 8-11 months
Liver (Hepatocellular-HCC) 25-40% 2-5 months
Non Hepatitis C related HCC 6-10 months
Hepatitis C related HCC 14 months
Biliary (Cholangiocarcinoma) 20-35% 4-8 months 9-14 months
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Colon 30-45% 8-10 months 16-21 months
Melanoma 15-40% 4-14 months 6-15 months
References
1. DeVita, Hellman, and Rosenberg. Cancer: Principles and Practice of Oncology. 10th
Edition. Philadelphia, PA: Lippincott Williams & Wilkins; 2014.
2. Waun Ki Hong, et al, eds. Holland-Frei Cancer Medicine. 8th Edition. Hamilton, Ontario:
BC Decker; 2010.
edited by Drew A Rosielle and published November 2007. 3rd edition edited with data updates in
August 2015.
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!
STEROIDS IN THE TREATMENT OF BONE PAIN
Elizabeth Weinstein and Robert Arnold MD
Background Corticosteroids are recommended as an adjuvant analgesic for cancer-related

bone pain. The mechanism of action is likely related to decreasing tumor-related edema or
inhibition of prostaglandin and leukotriene synthesis. This Fast Fact discusses the use of
corticosteroids for painful bone metastases; see also Fast Facts #66, 67, and116 about palliative
radiotherapy. Steroids have been shown to prevent pain flare associated with palliative radiation
of bone metastases.
Dosing The ideal corticosteroid, dose, and duration of therapy for bone pain is unknown;
current practice is derived from expert opinion and anecdotal case series. Dexamethasone is
commonly used due to its lower mineralocorticoid effect and long half-life, which allows once-daily
dosing. One randomized controlled trial demonstrated a decrease in pain scores in patients with
cancer-related pain using oral methylprednisolone 16 mg PO twice a day. Other starting dosages
reported in the literature include dexamethasone 4-8 mg PO daily, methylprednisolone 16-32mg
PO 2-3 times per day or prednisone 20-30 mg PO 2-3 times per day.
Duration of Therapy The optimal duration of steroid therapy is unknown. If no benefit is seen
within 5-7 days the drug should be discontinued. If beneficial, the drug should be tapered to the
lowest effective dose or, if possible, discontinued to avoid long-term adverse effects.
Side Effects Side effects account for discontinuation of steroids in 5% of patients. Acute side
effects include thrush (~30%), edema (20%), dyspepsia and peptic ulcer diseases, psychiatric
symptoms (insomnia, delirium and anxiety), and glucose intolerance. Delayed side effects from
long term use include adrenal suppression, moon facies/fat redistribution, increased susceptibility
to infection, osteoporosis, skin fragility and impaired wound healing. A prospective review of 373
inpatients with advanced malignant disease demonstrated that the side effect profile of
dexamethasone and prednisone are similar, although at equipotent doses dexamethasone
causes slightly more thrush and psychiatric symptoms and less edema, weight gain and
dyspepsia. The relationship between peptic ulcer disease and steroids is controversial; in one
nested case-control study it appeared correlated with concurrent NSAID use and a cumulative
dose greater than 1000 mg of prednisolone or 140 mg of dexamethasone. Case reports and
prospective series suggest that psychiatric symptoms are most commonly seen in middle-aged
women, are directly related to dosage, and usually resolve with dose reduction.
Summary Steroids are recommended for use in bone pain, but the choice of dose, duration
and specific drug is largely empiric. Steroid toxicities are a concern; the duration of treatment
should be minimized to reduce the risk of adverse events.
Resources
1. Berger AM, Koprowski C. Bone pain: assessment and management. In: Berger AM,
Portenoy RK, Weissman DE, eds. Principles and Practice of Palliative Care and
Supportive Oncology. 2nd edition. Philadelphia, PA: Lippincott, Williams and Wilkins;
2002.
2. Pereira J. Management of bone pain. In: Portenoy RK, Bruera E, eds. Topics in Palliative
Care Volume 3. New York, NY: Oxford University Press; 1998.
3. Bruera E, Roca E, Cedaro L, et al. Action of oral methyl-prednisolone in terminal cancer
patients: a prospective randomized double-blind study. Cancer Treat Rev. 1985;
69:751-754.
4. Twycoss R. The risks and benefits of corticosteroids in advanced cancer. Drug Safety.
1994; 11(3):163-178.
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5. Hanks GW, Trueman T, Twycoss RG. Costicosteroids in terminal cancer-a prospective
analysis of current practice. Postgraduate Med J. 1983; 59(697):702-706.
6. Klein JF. Adverse psychiatric effects of systemic glucocorticoid therapy. Am Fam Phys.
1992; 46(5):1469-1474.
7. Piper JM, Ray WA, Daugherty JR, Griffin MR. Corticosteroid use and peptic ulcer
disease: role of nonsteroidal anti-inflammatory drugs. Annals Intern Med. 1991;
114:735-740.
8. Yousef AA, El-Mashad NM. Pre-emptive value of methylprednisolone intravenous infusion
in patients with vertebral metastases. A double-blond randomized study. J Pain Symptom
Manage. 2014; 48(5):762-769.
9. Leppert W, Buss T. The role of corticosteroids in the treatment of pain in cancer
patients.Curr Pain Headache Reo. 2012; 16:307-313.
in January 2005. Version copy-edited in April 2009; revised again October 2015 by Mary Rhodes
MD.
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!
Background Neoplastic meningitis (NM) – also known as leptomeningeal metastases,

meningeal carcinomatosis, or leukemic meningitis, is a common oncologic complication
representing spread of tumor cells to the subarachnoid space (SAS). It is a complication which
often portends a very short prognosis.
Epidemiology NM is found in 20% of cancer patients at autopsy. Among solid tumors, NM is
common in breast cancer, small cell lung cancer, and melanoma while rare in gastrointestinal and
gynecologic cancers. 90% of solid tumor patients with NM have widespread metastatic disease.
NM is found in 40-50% of patients with hematological malignancies, mostly commonly the acute
leukemias and high-grade lymphomas (such as large cell and Burkitt lymphomas).
Signs/Symptoms Tumor reaches the SAS by hematogenous spread via arachnoid vessels or
direct invasion along nerve roots. Cancer cells in the subarachnoid space have the potential to:
a) settle in dependent portions of the neuraxis (base of brain/cranial nerves or lower spinal canal),
b) grow into the surface of the brain and fill the sulci, and c) block normal paths of cerebral spinal
fluid (CSF) flow. Thus, the hallmark of diagnosis is neurological signs/symptoms at more than
one level of the neuraxis:
• Spinal – radicular pain, weakness (usually legs), parenthesis, bladder and bowel
dysfunction.
Diagnosis Lumbar puncture typically reveals a CSF profile of high opening pressure, low
glucose, high protein, and lymphocytic pleocytosis. Sensitivity for finding malignant cells is 50-
70% for one sample, increasing to 80-90% with three samples. MRI can identify nodular/bulky
areas of disease, hydrocephalus, and/or enhancement of the cortex/tentorium if tumor growth
along the sulci leads to neovascularization. NM commonly causes abnormal CSF flow; this can
be demonstrated by a radionucleotide cisternogram.
Prognosis and Treatment Patients with breast cancer or hematological malignancies that
have not been extensively treated with chemotherapy, have a reasonable chance at remission of
their CNS disease if their systemic cancer can also be controlled. In contrast, patients with other
cancers (e.g. lung, melanoma) typically have a dismal prognosis (1-4 months) with or without
treatment. In fact, the median survival of patients who underwent placement of an implanted
intraventricular reservoir (Ommaya reservoir) for intrathecal chemotherapy administration was
only 72 days in a multicenter retrospective analysis. Unlike spinal cord compression or brain
metastases, there is no accepted role for corticosteroids except in lymphoid malignances.
Treatment options include chemotherapy and/or radiation.
• Radiation: Either cranio-spinal irradiation (entire spinal column) or focused radiation
therapy to sites of bulky or symptomatic areas (e.g. cauda equina for radicular leg pain).
• Chemotherapy: Options include systemic high-dose chemotherapy (Ara-C or
Methotrexate) intrathecal chemotherapy (1-2 times per week) administered either by
repeated lumbar puncture or via repeated puncture of an Ommaya reservoir. Commonly
used intrathecal drugs include methotrexate or Ara-C.
Summary For many patients, NM represents a pre-terminal diagnosis and no anti-neoplastic
therapy is warranted. Establishing the diagnosis in such patients may be important to help
prognosticate and to anticipate future neurological problems (e.g. seizures, headache, radicular
pain). The decision whether or not to begin anti-neoplastic treatment should be made in
consultation with a medical, radiation, or neuro-oncologist.
References
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1. Wasserstrom WR, Glass JP, Posner JB. Diagnosis and treatment of leptomeningeal
metastases from solid tumors. Cancer. 1982; 49:759-772.
3. Kaplan JG, DeSouza TG, Farkash A, et al. Leptomeningeal metastases: comparison of
clinical features and laboratory data of solid tumors, lymphomas and leukemias. J
Neurooncol. 1990; 9:225-9.
4. Demopoulos A, et al. Leptomeningeal metastases: a review. Curr Neurol Neurosci Rep.
2004; 4(3):196-204.
5. Roguski M, Rughani A, et al. Survival following Ommaya reservoir placement for
neoplastic meningitis. Journal of clinical neuroscience. 2015; article in press.
in April 2005. Version re-copy-edited in April 2009; edited again by Sean Marks MD July 2015
!17
!

HYPERCALCEMIA OF MALIGNANCY
Fareeha Siddiqui MD and David E Weissman MD
Background Up to 30 percent of patients with cancer develop hypercalcemia. Approximately
50% of these patients will die within 30 days of a hypercalcemia diagnosis, even if the
hypercalcemia is corrected, which suggests that hypercalcemia is a sign of hormonally advanced
cancer. It is most commonly associated with squamous cell cancers of lung, head and neck, and
esophagus, breast cancer, renal cell carcinoma, lymphomas and multiple myeloma.
Pathophysiology
• Local osteolytic hypercalcemia due to direct effect of bone metastases.
• Humoral Hypercalcemia of Malignancy – secretion of parathyroid hormone related protein
(PTHrP) by malignant tumors.
• 1,25(OH)2D (vitamin D) secreting lymphomas.
• Ectopic secretion of authentic PTH (very rare).
Symptoms/Signs Symptoms roughly correlate with the degree of hypercalcemia (corrected)
and the rapidity of rise: Mild (10.5-11.9 mg/dl); Moderate (12-13.9 mg/dl) Severe(>14 mg/dl).
• Cognitive: sedation, delirium, coma.
• Gastrointestinal: anorexia, nausea, vomiting.
• Renal: dehydration, polyuria, thirst/polydipsia.
Diagnostics
• Total serum calcium, corrected for albumin (Formula: [(4 - albumin) x 0.8] + Ca++]).
• Ionized calcium.
• Renal function, phosphate, magnesium and potassium—monitor during treatment.
Anti-Tumor Therapy Treatment of the underlying malignancy with systemic therapy (e.g.
chemotherapy) is essential for long-term management. In cases where further anti-neoplastic
therapy is not feasible, the decision to treat or not treat hypercalcemia should be made by careful
exploration of the patient’s goals of care. In advanced untreatable cancer, the decision to not treat
hypercalcemia may be very appropriate.
Supportive measures
• Saline hydration and loop diuretics: Normal saline 200-500 ml/hr increases GFR,
increases filtered load of calcium, and is calciuretic. Loop diuretics (e.g. furosemide)
blocks calcium resorption in the loop of Henle. Note: only use diuretics once dehydration
has been corrected.
• Discontinue medications that can increase serum calcium (e.g. lithium, Vitamin D,
supplements containing calcitriol, thiazides, calcium antacids); remove calcium from TPN.
• Increase mobility if possible.
• Bisphosphonates are the drug class of choice for most patients. They work via blocking
osteoclastic bone resorption. Pamidronate and zoledronic acid are used in the US with
full efficacy noted 2-4 days after administration; responses last 1-3 weeks. May lead to
hypocalcemia or azotemia; use with caution in renal dysfunction. Pamidronate = 60-90
mg. Repeat only after 7 days have elapsed after 1st dose. Repeat infusions every 2-3
weeks or longer according to the degree and of severity of hypercalcemia. Zoledronic
acid = 4 mg (maximum). Wait at least 7 days before considering retreatment.
• Denosumab is a human monoclonal antibody that is a potent inhibitor osteoclast
mediated bone resorption. In repeated studies, it has led to durable responses in over
60% of patients with hypercalcemia refractory to bisphosphonates. Its cost may be
prohibitive in hospice settings.
• Other Agents: Glucocorticoids are useful in lymphoid malignancies that secrete
1,25(OH)2 Vitamin D. Calcitonin may lead to transient and reductions in serum calcium
(12-24 hours). It is administered intramuscularly or subcutaneously; initially 4 units/kg
every 12 hours; may increase up to 8 units/kg every 12 hours to a maximum of every 6
hours. Mithramycin was the standard agent prior to bisphosphonates; now it is used only
!18
rarely due to a higher side effect profile. Gallium nitrate is usually impractical due to the
need for a 5 day IV infusion. Renal Dialysis can be used in cases of acute/chronic renal
failure.
Summary Hypercalcemia is a common oncologic complication that often portends a very short
prognosis. The decision to attempt reversal should be made after first exploring the goals of care
and assessing the feasibility of future systemic anti-cancer treatments. Vigorous hydration and
bisphosphonates are the cornerstones of short-term hypercalcemia therapy.
Reference
1. Stewart AF, et al. Malignancy-Associated Hypercalcemia. In: DeGroot L, et al, eds.
Endocrinology. 5th Edition. Philadelphia, PA: Saunders; 2005
2. Roodman GD, et al. Mechanisms of bone metastasis. NEJM. 2004; 350:1655-64.
3. Ralston SH, et al. Cancer associated hypercalcemia: morbidity and mortality: Clinical
experience in 126 treated patients. Ann Intern Med. 1990; 112:499-504.
4. Hu MI, Glezerman IG, et al. Denosumab for treatment of hypercalcemia of malignancy.
J Clin Endocrinol Metab 2014;99:3144-3152.
5. Gucalp R, Insogna K, et al. Denosumab For The Treatment Of Hypercalcemia Of
Malignancy Refractory To IV Bisphosphonates In Patients With Hematologic
Malignancies. Blood 2013;122: 2536-2536.
in February 2006. Version re-copy-edited in April 2009; revised again by Sean Marks MD July
2015 with references #4 and #5 added and incorporated into the text.
!19
!

MALIGNANT PLEURAL EFFUSIONS: INTERVENTIONAL MANAGEMENT
Vincent Thai MD and Ron Damant MD
Background Malignant pleural effusions can cause dyspnea, cough, and reduced exercise
tolerance. Over three quarters of malignant pleural effusions are due to lymphomas or cancers of
the breast, lung, and ovary. The average survival of patients with refractory cancer and pleural
effusions is 4-6 months (1). Survival is considerably worse for patients with poor functional status
due to progressive cancer. This Fast Fact reviews key facts regarding effusion management.
Symptom Causality and Goals of Care The cause of dyspnea, even in the presence of a
known malignant effusion, is not always evident. Common confounding problems include
congestive heart failure, chronic obstructive pulmonary disease, pulmonary emboli, pericardial
effusions, parenchymal lung metastases, ascites, and radiation lung injury. A ‘diagnostic’
therapeutic thoracentensis may be indicated to determine if removal of fluid leads to an
improvement in the patient’s dyspnea. The decision to proceed with thoracentensis should be
made after considering the overall goals of care, functional status, prognosis, and presence of co-
morbid conditions. Guidelines suggest that no more than 1.5 L of fluid can be safely removed at
any one time to prevent reexpansion edema, but some authors suggest that as much as 20ml/kg
of fluid can be safely removed (2).
Management Options:
• Repeated thoracentesis is appropriate for patients with a short prognosis (weeks). The
re-accumulation rate is approximately 98% by 30 days (3). Problems associated with this
approach include the need for repeated procedures, pneumothorax, infection, and the
development of loculation.
• Chest tube drainage alone involves the use of a large-bore tube to drain the pleural cavity
followed by the tube’s removal, without sclerosis. This prevents re-accumulation in 11-40%
of patients at 30 days follow-up (4).
• Systemic chemotherapy or hormonal therapy is the best long-term management option
for treatment sensitive tumors (see Fast Facts #14, 99).
• Chemosclerosis requires chest tube insertion followed by instillation of a sclerosing agent.
It has a success rate of 70-95% with no fluid re-accumulation at 1 month (if the pleural and
parietal surfaces are apposed after drainage and pleural fluid drainage is less than 100 ml/
day at the time of instillation) (5). Heavy tumor burden, reflected by low pleural pH (<7.2) or
glucose concentration (< 3.3 mmol/L), is associated with a lower success rate and shorter
survival (6). Talc is inexpensive and has the lowest re-accumulation rates (3-8% after 30
days), compared to doxycycline and bleomycin (1). Talc is rarely associated with ARDS and
systemic embolization; more common side effects are pain and fever. Sclerosis requires a
large-bore chest tube which often remains in place for 5-7 days – a major consideration in
patients with a short prognosis. Thorascopic installation of talc is the most effective
technique in highly selected patients, but it is more costly (7,8). Providing adequate pain
management is crucial for chest tube insertion and any sclerosis technique.
• Small-bore catheters can be inserted radiologically in the ambulatory setting and
connected to a drainage bag for intermittent drainage by nurses or family members at
home. Chemosclerosis can be accomplished through the small catheter. When done in the
inpatient setting, sclerosis via a small catheter has a success rate of 62 to 95%; outpatient
chemosclerosis may be less efficacious but there has been no head-to-head comparison.
• Tunneled pleural catheters are similar to small-bore catheters but involve a cuff which is
tunneled under the skin to prevent infections. In a 2012 cost analysis, tunneled pleural
catheters were found to be the most cost effective management approach when prognosis
was 3 months or less (9). A retrospective study showed symptom improvement in 96% of
patients at 2 weeks post insertion; spontaneous pleurodesis was noted in 44% of all
patients (10).
• Pleuroperitoneal shunts are occasionally indicated in patients with intractable effusions
and trapped lungs. The shunt drains pleural fluid into the abdomen via a subcutaneous
!20
reservoir that the patient must pump ~ 400 times/day. Cost, limited efficacy and frequent
malfunctioning all limit usefulness of this procedure. In addition, the development of
malignant ascites can occur if the patient lives long enough.
• Pleurectomy is only indicated in patients who are expected to have a prolonged survival.
There is significant associated morbidity (20%) and mortality (10%) (11).
References
1. Belani CP, Pajeau TS, Bennett CL. Treating malignant pleural effusions cost consciously.
Chest. 1998; 113:78S-85S.
2. Putnam JB,Jr. Malignant pleural effusions. Surg Clin North Am. 2002; 82:867-883.
3. Anderson CB, Philpott GW, Ferguson TB. The treatment of malignant pleural effusions.
Cancer. 1974; 33:916-922.
4. Grodzin CJ, Balk RA. Indwelling small pleural catheter needle thoracentesis in the
management of large pleural effusions. Chest. 1997; 111:981-988.
5. DeCamp MM,Jr, Mentzer SJ, Swanson SJ, Sugarbaker DJ. Malignant effusive disease of
the pleura and pericardium. Chest. 1997; 112:291S-295S.
6. Heffner JE, Nietert PJ, Barbieri C. Pleural fluid pH as a predictor of pleurodesis failure:
Analysis of primary data. Chest. 2000; 117:87-95.
7. Shaw P, Agarwal R. Pleurodesis for malignant pleural effusions. Cochrane Database of
10.1002/14651858.CD002916.pub2.
8. Belani C, Einarson TR, Arikian SR, Doyle J. Cost-effectiveness analysis of pleurodesis in
the management of malignant pleural effusion. J Oncology Management. 1995; Jan/Feb:
24-34.
9. Puri V, Pyrdeck TL, et al. Treatment of malignant pleural effusion: a cost-effectiveness
analysis. The Annals of Thoracic Surgery 2012; 94:374-380.
10. Tremblay A, Michaud G. Single-center experience with 250 tunnelled pleural catheter
insertions for malignant pleural effusion. Chest. 2006; 129:362-368.
11. Rusch VW. Pleurectomy/decortication and adjuvant therapy for malignant mesothelioma.
Chest. 1993; 103:382S-384S.
in June 2006. Version copy-edited in April 2009; revised again July 2015 with reference #9 added
and incorporated into the text.

CANCER-RELATED FATIGUE
!21
Background While several studies have found fatigue to be the single most prevalent, severe,
and disabling symptom in cancer patients – exceeding even pain – it remains both
underrecognized and poorly treated by physicians (1). This Fast Fact reviews diagnostic and
treatment approaches in the palliative care setting.
Characteristics of Cancer Related Fatigue (CRF) CRF is a persistent sense of tiredness/
diminished energy related to cancer and/or its treatment, which is not relieved by rest, and which
causes diminution in functional capacity and quality of life. Additional proposed ICD-10 features
include: diminished concentration; diminished motivation; insomnia or hypersomnia;
nonrestorative sleep; short-term memory deficits, and marked emotional reactivity to fatigue that
are not primarily consequences of depression.
Causes CRF is often multifactorial, with biochemical, physiological, psychological, and
behavioral dimensions that remain poorly defined. Assessment is aimed at identifying correctable
causes and determining the impact of CRF on both patients and caregivers. Common causes of
CRF include:
• Direct effect from cancer and/or treatments
• Sedating medications
• Deconditioning
• Psychiatric co-morbidities (e.g. depression, anxiety)
• Hypoxemia, or severe anemia (Hb ≤8 g/dL) and possibly moderate anemia (Hb ≤11g/dL)
• Systemic infection and/or or significant organ dysfunction (e.g. heart, liver, kidney, lung)
• Electrolyte abnormalities (e.g. ↓Na+, ↓K+, ↓Mg++ , ↑Ca++)
• Nutritional imbalance/impairment
• Sleep disturbance
• Uncontrolled pain (2)
Specific Treatments should be directed toward correcting identifiable causes, e.g. elimination of
sedating drugs, correction of anemia or electrolyte imbalance.
Non-Specific Treatments may help in reduce fatigue, optimize function, and promote adaptation.
• Education: Educate patient/family about CRF in order to normalize the symptom and promote
adaptation/adjustment through setting realistic goals; modifying and prioritizing activities; and
planning activities around diurnal variations in energy levels.
• Exercise: A meta-analysis suggested that aerobic exercise can improve cancer-related fatigue
symptoms (3). Aerobic exercise (low to moderate intensity; progressive) is ideal, but benefits
may also be realized with resistance training (4). A reasonable goal is 20-30 minutes of
(cumulative) exercise per day, at least 3 days per week.
• Drug Therapy: There is little good data for non-specific drug therapy in CRF. The following
drugs have been used with variable success:
o Psychostimulants: While there is a growing literature on the use of psychostimulants for
CRF, there is a lack of good controlled trails. Methylphenidate: a meta-analysis indicated
superiority of methylphenidate over placebo for treatment of CRF (6). Start with 2.5-5 mg
and titrate as necessary to 15-30 mg po at 08:00 and noon. Modafanil: pilot studies
indicated efficacy in the treatment of fatigue associated with depression, multiple sclerosis,
ALS, and HIV with potentially fewer side effects than other psychostimulants. However, a
more recent meta-analysis showed no benefit over placebo (5). Suggested initial dosing is
50 mg po qam and titrate as necessary to 200-400 mg po qam. See Fast Facts #61 and
259.
o Corticosteroids: These may provide a modest duration of benefit (2-4 weeks) offset by the
potential for significant toxicity (6). Reported regimens have included prednisone 7.5-10
mg po qday; dexamethasone 1-4 mg po qday; methylprednisolone 32 mg po qday.
o Megestrol acetate: Two double-blind, crossover studies showed reduction in CRF with
doses of 160 mg by mouth three times a day (7,8).
• Dietary Supplements: Ginseng: A randomized trial of 2000 mg of daily oral ginseng vs
placebo showed significant improvement in cancer-related fatigue at 8 weeks with no adverse
effects (9). L-carinitine has been investigated for CRF in a non-controlled fashion, but the
quality of these studies have been suboptimal.
!22
• Complementary Therapies: Acupuncture: a systemic review indicated potential benefit in
CRF, but also cited a need for more rigorously designed trials before conclusions may be
drawn (10).
References
1. Morrow GR, Shelke AR, Roscoe JA. Management of cancer-related fatigue. Cancer
Investigation. 2005; 23:229-239.
2. Fatigue PDQ. National Cancer Institute. Available at: http://www.cancer.gov/about-
cancer/treatment/side-effects/fatigue/fatigue-pdq.
3. Tian L, Hui JL, Lin L, Hu Y. Effects of aerobic exercise on cancer-related fatigue: a meta-
analysis of randomized controlled trials. Support Care Cancer. 2015. Epub ahead of print.
4. Mock V. Evidence-based treatment of cancer-related fatigue. J Natl Cancer Inst Monogr.
2004; 32:112-118.
5. Qu D, Zhang Zm Yu X, et al. Psychotropic drugs for the management of cancer-related
fatigue: a systematic review and meta-analysis. Eur J Cancer Care. 2015. Epub ahead of
print.
6. Yennurajalingam S, Frisbee-Hume S, Palmer JL, et al. Reduction of cancer-related
fatigue with dexamethasone: a double-blind, randomized, placebo-controlled trial in
patients with advanced cancer. J Clin Oncol. 2013; 31(25):3076-3082.
7. Bruera E, Macmillan K, Hanson J, et al. A controlled trial of megestrol acetate on
appetite, caloric intake, nutritional status, and other symptoms in patients with advanced
cancer. Cancer. 1990; 66:1279-1282.
8. Bruera E, Ernst S, Hagen N, et al. Effectiveness of megestrol acetate in patients with
advanced cancer: a randomized, double-blind, crossover study. Cancer Prev Control
1998; 2:74-78.
9. Barton DL, Liu H, Dakhil SR, et al. Wisconsin gineng (Panax quinquefolius) to improve
cancer-related fatigue: a randomized, double-blind trial, N07C2. J Natl Cancer Inst. 2013;
105(16):1230-1238.
10. Posadzki P, Moon TW, Choi TY, et al. Acupuncture for cancer-related fatigue: a
systematic review of randomized clinical trials. Support Care Cancer. 2013; 21(7):
2067-2073.
in January 2007. Copy-edited in April 2009. Re-copy edited in November 2015 by Mary G
Rhodes, MD.
!23
!

Background Malignant ascites is the accumulation of abdominal fluid due to the direct effects
of cancer. This Fast Fact reviews the causes and diagnosis of malignant ascites. Fast Fact #177
will review its treatment.
Pathophysiology The pathophysiology of malignant ascites is incompletely understood.
Contributing mechanisms include tumor-related obstruction of lymphatic drainage, increased
vascular permeability, over-activation of the renin-angiotensin-aldosterone system, neoplastic
fluid production, and production of metalloproteinases that degrade the extracellular matrix.
Portal venous compression can also occur from metastatic invasion of the liver, leading to
peritoneal fluid accumulation.
Natural History The most common cancers associated with ascites are adenocarcinomas of
the ovary, breast, colon, stomach and pancreas. Median survival after diagnosis of malignant
ascites is in the range of 1-4 months; survival is apt to be longer for ovarian and breast cancers if
systemic anti-cancer treatments are available.
Presentation and Diagnostics Symptoms include abdominal distension, nausea, vomiting,
early satiety, dyspnea, lower extremity edema, weight gain, and reduced mobility. Physical exam
findings may include abdominal distention, bulging flanks, shifting dullness, and a fluid wave.
Plain abdominal x-rays are not specific, but may show a hazy or a “ground glass” appearance.
Ultrasound or CT scanning can confirm the presence of ascites and also demonstrate if the fluid
is loculated in discrete areas of the peritoneal cavity.
There are many potential causes of ascites in the cancer patient: peritoneal carcinomatosis,
malignant obstruction of draining lymphatics, portal vein thrombosis, elevated portal venous
pressure from cirrhosis, congestive heart failure, constrictive pericarditis, nephrotic syndrome,
and peritoneal infections.
Depending on the clinical presentation and expected survival, a diagnostic evaluation is usually
indicated as it will impact both prognosis and treatment approach. Key tests include the serum
albumin and protein level and a simultaneous diagnostic paracentesis, checking ascitic fluid white
blood cell count, albumin, protein, and cytology.
A SAAG > 1.1 g/dl indicates ascites due to, at least in part, increased portal pressures, with an
accuracy of 97%. This is most commonly seen in patients with cirrhosis, hepatic congestion,
CHF, or portal vein thrombosis.
A SAAG < 1.1 g/dl indicates no portal hypertension, with an accuracy of 97%; most commonly
seen in peritoneal carcinomatosis, an infectious process of the peritoneum, nephrotic syndrome,
or malnutrition/hypoalbuminemia.
Cytological evaluation is approximately 97% sensitive in cases of peritoneal carcinomatosis, but
is not helpful in the detection of other types of malignant ascites due to massive hepatic
metastasis or malignant obstruction of lymph vessels.
References
Roenn J, Schuster J, eds. Principles and Practice of Palliative Care and Supportive
Oncology. 3rd edition. Philadelphia, PA: Lippincott, Williams & Wilkins; 2006.
!24
198:999-1011.
4. Becker G. Galandi D. Blum HE. Malignant ascites: systematic review and guideline for
!25
!

Background The natural history, presenting signs/symptoms, and diagnostic approach to the
patient with malignant ascites are discussed in Fast Fact #176; readers are encouraged to read
this Fast Fact to review the important role of determining the Serum Ascites-Albumin Gradient as
a diagnostic and treatment aid. This Fast Fact will review treatment approaches.
although no randomized trials have been completed. Patients with evidence of portal
hypertension (SAAG > 1.1) are more likely to respond to diuretics.
2. Paracentesis: Paracentesis can provide immediate relief of symptoms in up to 90% of

patients. Drainage of uncomplicated large-volume ascites (4-6 L/session) can be done
safely and quickly in the outpatient setting—including the home—or at the hospital bedside;
ultrasound guidance is necessary only when there is loculated fluid.
3. Drainage catheters: For patients who require frequent paracentesis, external drainage
catheters placed through the abdominal wall allow frequent or continuous drainage of ascites
fluid without repetitive needle insertions. Patients or caretakers may perform the drainage,
reducing visits to medical clinics. Several types of catheters are available:
a. Pigtail Catheter: A simple, temporary all-purpose catheter; they are prone to
complications when used over an extended duration (peritonitis, accidental removal,
leakage, occlusion), hence are rarely used now.
b. Tunneled Catheter: A catheter that prevents infection by promoting scarring around an
antibiotic-impregnated Dacron cuff in subcutaneous tissue. Used conventionally for
peritoneal dialysis, it is placed with ultrasound or fluoroscopic guidance and has lower
risks of infection and leakage than the pigtail catheter. Complications are reduced by
daily drainage for the first two weeks of cuff healing. The PleurX catheter is FDA
approved for malignant ascites and features a one-way rubber valve to prevent leaks
between draining sessions. Tunneled catheters are used in patients with life expectancy
of at least one month.
4. Vascular Shunts:
a. Peritovenous shunt (PVS) systems are designed to channel peritoneal fluid and proteins
in benign ascites back into the circulation via the superior vena cava. PVS has not been
shown to have clinically significant risk of disseminating tumor cells in malignant ascites.
A PVS is placed by interventional radiology under conscious sedation, and patients
typically require 24 hours of monitoring with a central venous line after the procedure.
The best response to PVS (only about 50%) is in ovarian and breast cancers. PVS is
recommended only in patients with a life expectancy of one to four months, considering
that eventual occlusion rate is up to 24%.
b. Transjugular Intrahepatic Portosystemic Shunt (TIPS) is a shunt between the portal vein
and hepatic vein, designed to reduce portal hypertension and improve sodium balance.
Most patients with malignant ascites do not have portal hypertension although TIPS
might be helpful in the occasional cancer with evidence of increased portal pressures
(SAAG > 1.1).
5. Hyperthermic Intraperitoneal Chemotherapy (HIPEC): This procedure is performed by

surgical oncology specialists and entails warmed chemotherapy being infused into the
peritoneal cavity for a short period of time. Most commonly this procedure is done along
with tumor debulking or cyto-reductive surgery (CRS). However, considering that recovery
from HIPEC with CRS can take 3 to 6 months, CRS-HIPEC is typically reserved for low-
!26
grade appendiceal primary cancers seeing that these cancers are associated with a longer
survival. For patients with anticipated shorter survivals, HIPEC without CRS can be done
laparoscopically (and is therefore associated with less morbidity) with high rates of ascites
control.
References
Roenn J, Schuster J. Principles and Practice of Palliative Care and Supportive Oncology.
3rd edition. Philadelphia, PA: Lippincott, Williams & Wilkins; 2006.
2. Adam RA, Adam YG. Malignant ascites: past, present, and future. J Am Coll Surg.
2004; 198:999-1011.
4. Becker G, Galandi D, Blum HE. Malignant ascites: systematic review and guideline for
5. Aslam N, Marino CR. Malignant ascites: new concepts in pathophysiology, diagnosis,
and management. Arch Int Med 2001;161:2733-7.
6. Smith EM, Jayson GC. The current and future management of malignant ascites.
Clinical Oncology. 2003; 15:59-72.
7. Pockros PJ, Esrason KT, Nguyen C, Duque J, Woods S. Mobilization of malignant
ascites with diuretics is dependent on ascitic fluid characteristics. Gastroenterology.
1992; 103:1302-1306.
8. Abeloff M, Armitage J, Niederhuber J, Kastan M, McKenna WG, eds. Clinical Oncology.
3rd edition. New York, NY: Churchill Livingstone; 2004: 1199-1205.
9. Covey AM. Management of malignant pleural effusions and ascites. J Support Oncol..
2005; 3:169-73.
10. White MA, Agle SC, et al. Denver peritoneovenous shunts for the management of
malignant ascites: a review of the literature in the post-LeVeen era. The American
Surgeon 2011;77: 1070-1075.
11. Randle RW, Swett KR, et al. Efficacy of cytoreductive surgery with hyperthermic
intraperitoneal chemotherapy in the management of malignant ascites. Ann of Surg Onc
2014;21: 1474-1479.
Version History: Current version copy-edited in May 2009; then again July 2015 by Sean Marks
MD: references #10 and #11 were added and incorporated into the text.
!27
PARENTERAL NUTRITION IN ADVANCED CANCER PATIENTS
Mehrnoush Mirhosseini MD and Robin Fainsinger MD
Background Concerns about anorexia and weight loss are commonly expressed by advanced
cancer patients and their families. Parenteral nutrition is a controversial and expensive treatment
that is sometimes considered to assist with nutrition in advanced cancer patients. PN involves
the intravenous delivery of a mixture of lipids, carbohydrates, amino acids, vitamins, and
minerals. This Fast Fact reviews the role of PN in advanced cancer patients.
The Problem Weight loss in advanced cancer is frequently due to insufficient caloric intake as
well as cancer-mediated hypermetabolism and hypercatabolism. These latter problems are
caused by catabolic proinflammatory cytokines and eicosanoids and are responsible for much of
the accelerated muscle wasting (cachexia) seen in advanced cancer. Patients and families
frequently worry about malnutrition and starvation and request help from physicians to ameliorate
these.
The Role of PN PN is usually considered outside the standard of care for most patients with
advanced cancer. This is based on clinical research findings and other observations:
1. With a few specific exceptions (such as head and neck cancer patients undergoing
radiation therapy), caloric supplementation of any kind has not been shown to benefit
advanced cancer patients, and – if indicated – can almost always be achieved enterally.
2. There is no physiologic basis to assume that PN would affect the inflammatory and
catabolic aspects of cachexia.
3. PN brings potential risks and burdens: laboratory testing, indwelling intravenous lines,
infections, metabolic derangements, liver and pancreatic dysfunction.
Patients with progressive weight loss should have careful clinical assessments for potentially
reversible causes (such as inadequate caloric intake or depression). Education and emotional
and family support are the cornerstones of treatment otherwise. Drug interventions are an active
focus of research although their efficacy remains controversial (see Fast Facts #93, 100).
PN guidelines There does remain however a small subset of advanced cancer patients for
whom PN may be an appropriate therapy to improve quality and/or length of life. The following
guidelines have been suggested to identify patients appropriate for PN:
• Enteral nutrition (including tube feeding) is not an option or there is a specific benefit
expected from parenteral nutrition (e.g. inoperable malignant bowel obstruction, short
bowel syndrome, and malabsorption). These are patients for whom a non-functional GI
tract, and not cachexia itself, is the major problem.
• Death is probable from starvation or malnutrition earlier than anticipated from disease
progression alone.
• The patient has a life expectancy of at least several months to allow a proper trial of PN
(Karnofsky Performance Scale Score >50 or ECOG performance status ≤2).
• The patient has a good self-assessed quality of life; life-prolongation is consistent with their
goals of care and the potential risks of PN are acceptable to the patient.
• The patient or caregiver can safely accommodate PN if at home: the home environment is
safe and clean; someone is able to set-up and administer the PN; and the patient can be
clinically monitored, including laboratory investigation.
• Typically close monitoring of electrolytes, liver and renal function, and triglycerides is
required. In addition, careful assessments of the patient’s response to treatment and global
clinical course are needed to ensure PN remains an appropriate intervention.
Summary
PN can be an important palliative treatment, but for only a small group of cancer patients. Careful
patient selection and monitoring is important to ensure that PN is meeting patient-defined goals of
care.
!28
References
1. Moynihan T, Kelly DG, Fisch MJ. To feed or not to feed: Is that the right question? J Clinical
Oncol. 2005; 23(25):6526-6529.
2. Bondly C, Jotoi A. Overview of the management of the anorexia/weight loss syndrome. In:
Bruera E, Higginson I, Ripamonti C, Von Gunten CF, eds. Textbook of Palliative Medicine.
New York, NY: Oxford University Press; 2006:538-545.
3. Strasser F, Bruera E. Update on anorexia and cachexia. Hematol Oncol Clin North Am.
2002; 16:589-617.
4. Nitenberg G, Raynard B. Nutritional support of the cancer patient: Issues and dilemmas. Crit
Rev Oncol Hematol. 2000; 34:137-168.
5. MacDonald N, Easson AM, Mazurak VC, Dunn GP, Baracos VE. Understanding and
managing cancer cachexia. J Am Coll Surg. 2003; 197:143-161.
6. Mirhosseni N, Fainsinger RL, Baracos V. Parenteral nutrition in advanced cancer:
Indications in clinical practice guidelines. J Palliat Med. 2005; 8(5):914-918.
7. Turelli GF, Campos AC, Meguid MM. Use of TPN in terminally ill cancer patients. Nutrition.
1999; 15(9):665-667.
8. Dy SM. Enteral and parenteral nutrition in terminally ill cancer patients: A review of the
literature. Am J Hosp Palliat Care. 2006; 23(5):369-377.
9. CH Regional Palliative Care Program. Clinical Practice Guidelines: Home parenteral nutrition
and cancer selection criteria for patients with advanced cancer. Available at: http://
palliative.org/NewPC/_pdfs/management/
3A10%20Home%20Parenteral%20Nutrition%20and%20Cancer%20Selection%20Criteria%2
0Guideline.pdf. Accessed July 28, 2015.
again July 2015 – reference #9 updated.
!29
!

Vincent Thai MD
Introduction Malignant pericardial effusions (MPEs) are a rare complication of advanced
cancer, but are associated with high morbidity and mortality. This Fast Fact discusses the
diagnosis and management of MPEs.
metastases, with ~75% of these affecting the epicardium (1, 2). Only a third of these, however,
will develop clinically significant MPEs (1). Lung and breast cancers are the most common
causes. MPEs are associated with a poor prognosis. Studies suggest a median survival of 2-3
months after a MPE is diagnosed, with a mean survival of 5 months for solid tumors and 20
months for hematologic malignancies (3, 4).
Physiology and Symptoms The pericardial space is normally filled with <50 ml of serous fluid.
As this volume increases due to epicardial or pericardial metastases or lymphatic obstruction,
both right and left ventricular failure can occur due to inadequate filling. Signs and symptoms
include peripheral and pulmonary edema, chest discomfort, cough, shortness of breath, and
orthopnea. Severity of symptoms depends on the volume of the MPE as well as the rapidity of its
accumulation; severe cases can present with cardiac tamponade and shock. An echocardiogram
is indicated whenever a MPE is suspected. Not only does it confirm the presence of an effusion,
but its findings can dictate whether or not urgent treatment is indicated (e.g. if signs of tamponade
are evident). A diagnostic pericardiocentesis or pericardial biopsy is sometimes needed to
confirm the cause of the effusion.
Treatment Options
• Systemic chemotherapy or radiotherapy are effective for chemo- or radio-sensitive tumors
such as previously untreated breast cancer and many lymphomas. Reaccumulation rates for
both modalities are about 1/3 overall, depending on the patient’s overall course and response
to therapy (5).
• Pericardiocentesis results in immediate symptom relief in most patients, however the effusion
may re-accumulate, requiring repeat pericardiocentesis (within 1-2 weeks in some series) (6).
• Pericardial sclerosis involves instilling a sclerosing agent with the intention of scarring the
pericardium to the epicardium, preventing reaccumulation of the MPE (similar to pleural
effusions – see Fast Fact #157). Multiple agents have been studied including doxyclycline,
minocycline, and bleomycin. Success rates (no reaccumulation at 30 days) are about
70-90% (7, 8). Longer term success rates are undefined due to the poor survival of study
patients. The major side effect is chest pain (50-70%), cardiac arrhythmias, and fever (8, 9,
10). In head to head comparisons with doxycycline, bleomycin has been shown to have
fewer side effects and to lead to shorter hospitalizations (10, 11, 12).
• Surgical decompression therapies range from less invasive (balloon pericardiotomy,
subxiphoid or thorascopic pericardiostomy) to more extensive (open thoracotomy with
pericardial stripping). A pericardial ‘window’ (which allows ongoing drainage of fluid externally
or internally such as into the pleural cavity) is often created. Case series have suggested
reaccumulation rates with surgical therapies are low (less than 15% up to 10 months out) (13,
14, 15).
Decision-Making The treatment of MPEs depends on how urgently treatment is needed, the
likelihood of the tumor responding to anti-neoplastic treatments, and the anticipated survival of
the patient. A multidisciplinary approach to decision-making, involving input from medical and
radiation oncology, cardiology, and thoracic surgery is recommended. Simple pericardiocentesis
may be appropriate for patients with short prognoses (<1 month), particularly if their MPE is not
expected to re-accumulate in their remaining life-span. A symptomatic patient with no signs of
tamponade and a chemotherapy-sensitive tumor such as untreated breast cancer may receive a
!30
durable response from a pericardiocentesis for symptom relief, followed by chemotherapy.
Patients with longer prognoses (>1 month) who are expected to re-accumulate their MPEs will
likely benefit most from sclerosis or surgical decompression; there is no clear evidence currently
suggesting one strategy is superior to the other. Symptom directed care without specific
intervention for the MPE is an appropriate option for patients with very short prognoses and for
those who decline more invasive treatments.
References
2. Abraham KP, Reddy V, Gattuso P. Neoplasms metastatic to the heart: review of 3314
consecutive autopsies. Am.J.Cardiovasc.Pathol. 1990; 3:195-198.
3. Moores, D.W, Allen K.B, Faber L.P, Dziuban S.W, Gillman D.J, Warren W.H., Ilves R,
Lininger L, Subxiphoid pericardial drainage for pericardial tamponade, J Thoracic
Cardiovascular Surg. 1995; 109:546-552.
4. Dosios T, Theaskos,N, Angouras D, et al. Risk factors affecting the survival of patients
with pericardial effusion submitted to subxiphoid pericardiostomy. Chest. 2003; 124:242
5. Lamont E, Hoffman PC. Oncologic emergencies. In: Hall JB, et al, eds. Principles of
Critical Care. 3rd Edition. New York, NY: McGraw Hill; 2005.
6. Laham RJ, Cohen DJ, Kuntz RE et al. Pericardial effusion in patients with cancer:
outcome with contemporary management strategies. HEART. 1996; 75(1):67-71.
7. Lashevsky I, Ben Yosef R, Rinkevich D, Reisner S, Markiewicz W. Intrapericardial
minocycline sclerosis for malignant pericardial effusion. Chest. 1996; 109(6):1452-54.
8. Maher EA, Shepherd FA, Todd TJR. Pericardial sclerosis as the primary management of
malignant pericardial effusion and cardiac tamponade. J Thoracic Cardiovascular Surg.
1996; 112(3):637-643.
9. Ben Yosef,R, Phefer,R, Ge,A, Catane,R. Management of malignant pericardial effusion
Harefuah, 1988; 115:138-141.
10. Liu G, Crump M, Goss PE, Dancey J, Shepherd FA. Prospective comparison of the
sclerosing agents doxycycline and bleomycin for the primary management of malignant
pericardial effusion and cardiac tamponade. J Clin.Oncol. 1996; 14(12):3141-47.
11. Yano T, Yokoyama H, Inoue T, et al. A simple technique to manage malignant pericardial
effusion with a local instillation of bleomycin in non-small cell carcinoma of the lung.
Oncology. 1994; 51:507-509.
12. van Belle SJ, Volckaert A, Taeymans Y, Spapen H, Block P. Treatment of malignant
pericardial tamponade with sclerosis induced by instillation of bleomycin. Int.J.Cardiol.
1987; 16(2):155-160.
13. Galli M, Politi A, Pedretti F, Castiglioni B, Zerboni S. Percutaneous balloon pericardiotomy
for malignant pericardial tamponade. Chest. 1995; 108(6):1499-1501.
14. Palacios IF, Tuzcu EM, Ziskind AA, Younger J, Block PC. Percutaneous balloon
pericardial window for patients with malignant pericardial effusion and tamponade.
Cathet.Cardiovasc.Diagn. 1999; 22(4):244-49.
15. Ziskind AA, Pearce AC, Lemmon CC, et al. Percutaneous balloon pericardiotomy for the
treatment of cardiac tamponade and large pericardial effusions: description of technique
and report of the first 50 cases. J.Am.Coll.Cardiol. 1993; 21(1):1-5.
!31
!32
!

PHARMACOLOGIC TREATMENT OF ACUTE VENOUS THROMBOEMBOLISM IN PATIENTS
WITH ADVANCED CANCER 3RD EDITION
René Claxton MD and Robert Arnold MD
Background Venous thromboembolism (VTE) is a common complication of malignancy which
carries a poor prognosis (1). This Fast Fact discusses the approach to VTE in patients with
advanced cancer.
Does anticoagulation for VTE improve outcomes? There is little randomized, placebo
controlled data on anticoagulation for the treatment of VTE (2). The only study comparing heparin
and warfarin for acute pulmonary embolism (PE) versus no treatment found a decrease in
mortality with a number needed to treat (NNT) of four (3). Data from non-placebo controlled trials
shows anticoagulation for acute VTE decreases recurrence (4) and clot propagation (5). Based
on this evidence and clinical consensus, anticoagulation is recommended to decrease mortality
and VTE recurrence in patients with a new VTE.
What is the best treatment for VTE for cancer patients? Current evidence-based guidelines
recommend LMWH instead of oral vitamin K antagonists (e.g. warfarin) for at least 6 months in
the treatment of acute VTE for advanced cancer patients, even if the patient has a primary CNS
malignancy (6). The CLOT trial (7) demonstrated a decreased risk for recurrent VTE in patients
maintained on LMWH versus oral anticoagulation with a number needed to treat (NNT) of 13.
The major risk of anticoagulation is bleeding. In the CLOT trial major bleeding occurred in ~5% of
patients regardless of the type of anticoagulation. A Cochrane review of LMWH versus oral
anticoagulants for VTE in patients with cancer showed a statistically significant decrease in
recurrent VTE in favor of LMWH (8). There is emerging evidence that novel anticoagulants like
dabigatran (a direct thrombin inhibitor) and rivaroxaban (a direct factor Xa inhibitor) may be
equally effective at treating acute VTE in cancer but with less overall associated bleeding (though
perhaps more GI bleeding) and less need for serum monitoring (9). Although the use of these
agents has greatly increased in the last several years, the role of these novel oral anticoagulants
vs more established agents such as LMWH is not yet clearly established (6).
Does the evidence supporting the use of anti-coagulation for treatment of VTE apply to
cancer patients with short prognoses? Unfortunately, most studies exclude patients with
increased creatinine, those in bed greater than 50% of the day, and those with less than a three-
month prognosis (see Fast Fact #13). Thus, there are no research data to guide clinicians on the
efficacy (does it prolong life or reduce symptoms?), safety (what is the bleeding risk?), and
tolerability of treating acute VTE in cancer patients with prognoses of weeks to a few months.
What other considerations should be made in the decision to treat acute VTE in cancer
patients with short prognoses?
1. Decide whether to anticoagulate or treat symptomatically. This decision is largely empiric
and should be based on clinical judgment about prognosis, symptom burden, and patient
preference. For instance, for a patient with a prior history of VTE who remains ambulatory
and who develops symptomatic VTE (e.g. a painful, swollen leg), providing anti-coagulation
may be appropriate to prevent additional symptomatic events. If this same patient was
already bedbound with a prognosis of weeks, it is doubtful anti-coagulation would provide
substantial benefit. Though current evidence-based guidelines recommend anticoagulation
for incidental VTE in advanced cancer (6), there is no strong rationale for this
recommendation when a patient has a prognosis of weeks and the patient’s primary goal of
treatment is comfort.
2. If anticoagulation is chosen, then determine whether to use an oral vitamin K antagonists
like warfarin, LMWH, or a novel oral anticoagulant such as dabigatran or rivaroxaban.
LWMH and the newer oral anticoagulants do not require routine laboratory testing, have
fewer drug-drug interactions, and are less diet dependent for safe administration than
!33
warfarin. In addition, a patient’s INR is highly diet dependent and can rise dangerously in
patients with diminishing oral intake, which is common for advanced cancer patients. Hence
warfarin may require frequent laboratory monitoring of the INR. However, LMWH and new
oral anticoagulants are far more expensive than warfarin; furthermore, unlike warfarin, there
is no effective antidote for these agents if the anticoagulant effect as needs to be reversed.
Warfarin costs approximately $0.11/day compared to $100/day for enoxaparin. However,
this comparison does not take into account the cost of laboratory tests to monitor a patient’s
INR or the administration costs for patients unable to self-administer LMWH. Given its high
cost LMWH may not be available for many patients receiving hospice care.
Bottom Line The patient’s prognosis and preferences should be considered prior to starting
anticoagulation therapy. Clinicians should work with hospice agencies to determine an affordable
plan to safely administer and monitor anticoagulation for acute VTE in hospice patients.
Clinicians should prepare patients who decide to initiate anticoagulation for discontinuing it once
expected survival is short or worsening risks such as uncontrolled INR become apparent.
*Major bleeding includes any bleeding associated with death, located at a critical site (intracranial,
intraspinal, intraocular, retroperitoneal or pericardial area), resulting in the need for a transfusion
of at least two units of blood or leading to a drop in hemoglobin of at least 2.0 g per deciliter.
References
1. Sorensen HT, Mellemkjoer L, Olsen JH and Baron JA. Prognosis of cancers associated
with venous thromboembolism. N Eng J Med. 2000; 343(25):1846-1850.
2. McManus RJ, Fitzmaurice D, Murray ET and Taylor C. Thromboembolism. Clinical
Evidence. 2009; 3(208). Retrieved Oct 8, 2009 from http://clinicalevidence.bmj.com/
ceweb/conditions/cvd/0208/0208.jsp
3. Barritt DW and Jordan SC. Anticoagulant drugs in the treatment of pulmonary embolism:
a controlled trial. Lancet. 1960; 1:1309-1312.
4. Brandjes DP, Heijboer H, Büller HR, de Rijk M, Jagt H, ten Cate JW. Acenocoumarol and
heparin compared with acenocoumarol alone in the initial treatment of proximal vein
thrombosis. N Engl J Med. 1992; 327(21):1485-1489.
5. Belcaro G, Laurora G, Cesarone MR et al. Prevention of the extension of distal deep
venous thrombosis: A randomized controlled trial with a 6 month follow up. Minerva
Med. 1997; 88(12):507-514.
6. Lyman GH, Khorana AA, et al. Venous thromboembolism prophylaxis and treatment in
patients with cancer: American Society of Clinical Oncology clinical practice guideline
update J Clin Onc 2013;31:2189-2204.
7. Lee AY, Levine MN, Baker RI et al. Low-molecular-weight heparin versus a coumadin for
the prevention of recurrent venous thromboembolism in patients with cancer. N Engl J
Med. 2003; 349(2): 146-153.
8. Akl EA, Barba M, Rohilla S et al. Anticoagulation for the long term treatment of venous
thromboembolism in patients with cancer. Cochrane Database Syst Rev. 2008;
16(2):CD006650.
9. Prins MH, Lensing AWA, et al. Oral rivaroxaban versus enoxaparin with vitamin K
antagonist for the treatment of symptomatic venous thromboembolism in patients with
cancer (EINSTEIN-DVT and EINSTEIN-PE): a pooled subgroup analysis of two
randomised controlled trials." Lancet Haematology 2014;1.1:e37-e46.
10. Noble SI, Shelley MD, Coles B, Willams SM, Wilcock AW, Johnson MJ. Management of
venous thromboembolism in patients with advanced cancer: A systematic review and
meta-analysis. Lancet Oncol. 2008; 9(6):577-584.
Version History: Originally published December 2010; Copy-re-edited August 2015 by Sean
Marks MD in which references # 6 and #9 were added and incorporated into the text to reflect the
advances in novel oral anticoagulants.
!34

PALLIATIVE CARE ISSUES FOR TRANSFUSION-DEPENDENT PATIENTS
!35
Mansour Gergi MD and Maria Aileen Soriano-Pisaturo MD
Introduction Although no standardized definition exists, transfusion dependence (TD) usually

describes patients receiving regular platelet and/or red blood cell (RBC) transfusions more
frequently than every 8 weeks due to persistently low counts (1). Myelodysplastic syndrome,
myeloproliferative neoplasms, and leukemias are most commonly associated (2). Transfusion
thresholds have been subjects of debate, vary by population, and should answer the goals of
therapy. Still, many with life-prolonging goals of care become accustomed to basing the need for
transfusion on a diagnostic threshold (e.g. hemoglobin < 7), rather than a specific symptom. As
TD patients near the end-of-life, they often face emotionally-wrought decisions about the
continued role of transfusions.
Potential Benefits of Continuing Transfusions

• Patients may receive significant improvement in fatigue and dyspnea within hours from RBC
transfusions when hemoglobin levels are < 7. These benefits likely dissipate after 13 days
(3).
• Platelets transfusions can stop or prevent bleeding caused by severe thrombocytopenia
within hours but usually have a life span of only 4-8 days (4). Although the usual threshold at
which prophylactic platelet transfusions is considered is 10,000 (5), that threshold and the
role of prophylactic platelet transfusions in seriously ill TD patients remains controversial and
unstudied.
• A retrospective analysis of dying cancer patients suggested that RBC transfusions were
associated with a longer survival (15 days) than anemic patients who were not transfused (7
days), and platelet transfusions increased the interval between hospitalizations from 10 to 16
days (6).
• Regular transfusions based on threshold lab values often become a familiar component of
the care plan recommended by the cancer team. Transitioning to a care plan in which
transfusions are based on how they feel, not lab values, can therefore be unsettling to
patients.
Potential Harms of Continuing Transfusions

• Not only is TD a marker of disease severity, organ damage from iron overload can result from
multiple transfusions. Thus, there is a 2.2-fold increase in 1-year mortality risk and a 4-year
survival of only 47% among TD patients (7-10).
• Although transfusions often can be coordinated for hospice patients with a specific symptom
need, logistical complexities do not allow transfusions to be done in a patient’s home.
• For patients who desire to continue regular lab draws and blood transfusions, frequent visits
to infusion clinics ensue and are associated with a diminished quality-of-life (8,11).
Furthermore, hospice involvement is often delayed, thereby increasing the chances of death
in a hospital (11,12).
Counseling Patients and Families A hospitalization due to a major medical crisis often
prompts a discussion about discontinuing transfusions in the context of a larger discussion about
transitioning to comfort-focused care. This can be a challenging time to discuss transfusion
discontinuation, as patients can be overwhelmed by their overall medical situation. The following
pearls may assist clinicians:
• Once TD is realized and eventual clinical deterioration is anticipated, discuss the
expectations of transfusions along with clinical signs which would suggest an appropriate
timing to discontinue them. This would pre-empt initiating such discussions during a time of
medical crisis.
• Patient and families may worry about inciting imminent death or demise from discontinuing
transfusions. For example, they may have been told that discontinuation of platelet
transfusions can trigger massive bleeding. Fortunately, most dying patients who stop platelet
transfusions do not suffer significant bleeding and most TD patients live > a week after
transfusions are discontinued (6). Transparent disclosure of these prognostic implications
may alleviate, not exacerbate, concerns.
!36
• Inquire about ethical, legal, cultural, and/or religious concerns which may lead patients to
associate transfusion discontinuation with “giving up” or euthanasia. Involve a chaplain or
spiritual leader if concerns are identified.
• If a time-limited trial of continued transfusions is pursued, be specific about signs which would
signify an appropriate time to discontinue transfusions. Examples of reasonable “end-points”
include: a) an anticipated prognosis of weeks or less; b) platelet values which no longer
respond to transfusions; c) a terminally-ill, home-bound patient who develops a moribund
functional status, as the burden of transport to an infusion clinic will likely supersede any
clinical benefit.
• Involve the patient’s oncologist or hematologist. Patients may need to hear from a trusted
clinician that it is ok to stop transfusions.
Novel Programs Open access or concurrent care, is offered by select hospice agencies in
coordination with some insurers. Through models such as these, patients who are willing to come
into clinics for ongoing blood product transfusions may be able to also have access to an
interdisciplinary hospice team. Coordination with clinical social workers can help patients and
families explore these possibilities.
References
1. Malcovati L, Germing U, Kuendgen A, et al. Time-dependent prognostic scoring system
for predicting survival and leukemic evolution in myelodysplastic syndromes. J Clin
Oncol. 2007;25(23):3503-3510.
2. Gale RP, Barosi G, Barbui T, et al. What are RBC-transfusion-dependence and -
independence? Leuk Res. 2011;35(1):8-11.
3. Preston NJ, Hurlow A, Brine J, Bennett MI (2012). Blood tranfusions for anemia in
patients with advanced cancer. Cochrane Database Syst Rev, 2, CD 009007.
4. Knut A, Gardner FH. Survival of blood platelets labeled with chromium. The J of Clin
Investigation 1958; 37:1257-68
5. Kaufman RM, Djulbegovic B, et al. Platelet transfusion: a clinical practice guideline from
the AABB. Annals of Int Med 2015; 162(3):205-13.
6. Goksu SS, Gunduz S, Unal D, et al. Use of blood transfusion at the end of life: does it
have any effects on survival of cancer patients? Asian Pac J Cancer Prev. 2014;15(10):
4251-4254.
7. Platzbecker U, Hofbauer LC, Ehninger G, Holig K. The clinical, quality of life, and
economic consequences of chronic anemia and transfusion support in patients with
myelodysplastic syndromes. Leuk Res. 2012;36(5):525-536.
8. Goldberg SL, Chen E, Corral M, et al. Incidence and clinical complications of
myelodysplastic syndromes among United States Medicare beneficiaries. J Clin Oncol.
2010;28(17):2847-2852.
9. Bartoszko J, Panzarella T, Lau A, et al. Effect of Red Blood Cell Transfusion Dependence
on the Natural History of Myeloproliferative Neoplasm-Associated Myelofibrosis. Clin
Lymphoma Myeloma Leuk. 2015;15(11):e151-156.
10. Szende A, Schaefer C, Goss TF, et al. Valuation of transfusion-free living in MDS: results
of health utility interviews with patients. Health Qual Life Outcomes. 2009;7:81.
11. Olszewski A PCE, LeBlanc T. Transfusion dependance and use of Hospice among
Medicare beneficiaries with Leukemia. American Society of Hematology. 2017;59 th
Annual Meeting & Exposition:277.
12. Fletcher SA, Cronin AM, Zeidan AM, et al. Intensity of end-of-life care for patients with
myelodysplastic syndromes: Findings from a large national database. Cancer.
2016;122(8):1209-1215.

Authors’ Affiliations: Roger Williams Medical Center, Providence, Rhode Island; Kent Hospital –
Care New England Health System, Warwick, Rhode Island
Version History: Originally edited by Sean Marks MD; first electronically published in July 2018.
!37
Palliative Care Network of Wisconsin (PCNOW); the authors of each individual Fast Fact
are solely responsible for that Fast Fact’s content. The full set of Fast Facts are available at
Facts.
NonCommercial 4.0 International Copyright (http://creativecommons.org/licenses/by-nc/
4.0/). Fast Facts can only be copied and distributed for non-commercial, educational purposes.
If you adapt or distribute a Fast Fact, let us know!
!38
Palliative Care Teams
#22 Writing a Condolence Letter . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . .2-3
#42 Broaching the Topic of a Palliative Care Consultation with Patients and Families . . .
. . .4-5
#167 Health Professional Burnout – Part I . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . 6-7
#168 Health Professional Burnout – Part

II . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8-9
#169 Health Professional Burnout – Part III . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . 10-11
#170 Health Professional Burnout – Part IV . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . 12-13
#172 Professional-Patient Boundaries in Palliative Care . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . 14-15
#253 Palliative Care Consultation in the ICU . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . 16-18
#266 Consultation Etiquette in Palliative Care . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . .19-20
#267 Writing the Consultation Note . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . .21-22
#298 Palliative Care consultation in the Emergency Department . . . . . . . . . . . . . . . . . . .

. . . . 23-24
#310 The Oncology-ICU-Palliative Care

Interface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25-26
1
#334 The Role of Clinical Pharmacists on the Interdisciplinary Team . . . . . . . . . . . .. . . .
. . . . 27-29
#347 Chaplaincy: Participate as a Member of

IDT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .30-31
#360 The Surprise Questions as a Prognostic Tool . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . 32-34
#368 The Pre-Meeting Family Huddle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . 35-36

WRITING A CONDOLENCE LETTER
Ron Wolfson PhD and Elizabeth Menkin MD
Introduction One of the most meaningful acts of kindness you can do for a mourner is to write a letter
of condolence. The words of sympathy and memory are comforting to the bereaved. More importantly,
mourners are very appreciative that you took the time to sit and compose a personal message to them or
share a memory of the deceased. For professionals who work with dying patients, writing a condolence
letter is an opportunity to reflect on both the pain and the rewards of our work. When we can appreciate
the privilege it is to bear witness to the courage, kindness, caring and dignity that our patients and their
families exhibit under duress, it gives us strength to continue this work.
A good condolence letter has two goals: to offer tribute to the deceased and to be a source of comfort to
the survivors. The best letters are like conversations, as if you were talking during a visit. Most often, they
are written to the bereaved person to whom you feel closest, although it could be a general letter to the
family. It should be written and sent promptly, generally within two weeks after the death. Use any
standard stationery and write it by hand. Here are some specific guidelines for writing a good condolence
letter:
• Acknowledge the loss and name the deceased. This sets the purpose and tone of the letter.
Let the bereaved know how you learned of the death and how you felt upon hearing the news.
Using the name of the deceased is a tribute that comforts most mourners.
• Express your sympathy. Use words of sympathy that remind the bereaved that they are not
alone in their feelings of sadness and loss.
• Note special qualities of the deceased. Acknowledge those characteristics that you cherished
most about the person who has died. These might be qualities of personality (courage,
sensitivity), or attributes (funny, affable), or ways the person related to the world (religious,
devoted to community welfare).
• Recall a memory about the deceased. Talk about how the deceased touched your life. Try to
capture what it was about the person in the story that you admired, appreciated or respected. You
may use humor – the funny stories are often the most appreciated by the bereaved.
• Remind the bereaved of their personal strengths. Bereavement often brings with it self-doubt
and anxiety about one's own personal worth. By reminding the bereaved of the qualities they
possess that will help them through this period, you reinforce their ability to cope. Qualities to
mention might be patience, optimism, religious belief, resilience, and competence. If you can
2
recall something the deceased used to say about the mourner in this regard, you will really be
giving the bereaved a gift. An example: “I was (impressed, inspired, awed, strengthened) by the
devotion you and your family evidenced during the period of Mort's illness. Your presence
(concern, care, attentiveness) was only one indication of your love for him.”
• Offer help, but be specific. “If there is anything I can do, please call” actually puts a burden on
those in grief who may be totally at a loss about what needs to be done. A definite offer of help is
more appreciated. Whatever you offer, do it – don't make an offer you cannot fulfill.
• End with a word or phrase of sympathy. Somehow, “sincerely,” “love,” or “fondly,” don't quite
make it. Try one of these: “You are in my thoughts and prayers.” Or, “My fond respects to you
and yours.”
If you don't have enough to say for a formal condolence letter, you may prefer to send a sympathy note.
These are shorter communications that can be written on personal stationery or added to a commercially
available card. As with a condolence letter, the major goal is to offer a tribute to the deceased and to offer
comfort to the bereaved.
Reference
Wolfson, R. A Time to Mourn, A Time to Comfort. Woodstock, VT: Jewish Lights Publishing; 1993: pp
223-226.
3
BROACHING THE TOPIC OF A PALLIATIVE CARE CONSULTATION
WITH PATIENTS AND FAMILIES
Robert Arnold MD and David E Weissman MD
Introduction Palliative care consultative services are becoming commonplace in academic and
community hospitals and clinics. Patients and families may have negative perceptions of palliative care
and hospice – viewing such a discussion as signaling that the physician is “giving up on the patient” and
that the reality of impending death must be faced. For the attending physician, the decision to convey to
a patient and family that a consultation is needed can provoke anxiety. Physicians may fear such a
discussion will provoke anxiety, anger or a sense of hopelessness. This Fast Fact provides tips for
beginning a discussion leading to a visit by a palliative care consultation team.
First, decide why you want assistance from the palliative care team. Typically, physicians seek assistance
in four domains: 1) pain and non-pain symptom assessment and management; 2) assistance in making
difficult decisions, usually about continued use or withdrawal of potentially life-prolonging treatments such
as feeding tubes, antibiotics, dialysis, or ventilators; 3) assistance in planning for the most appropriate
care setting to meet patient/family goals for end-of-life care; and 4) providing psychological support to
patients, families and the health care team.
Second, contact the palliative care team. Discuss your reason(s) for consultation along with pertinent
details of the patient’s history and family support structure. Describe both what your goals are for the
consultation, as well as what the family’s/patient’s goals may be. This is a good time to discuss any
concerns you have about using the term palliative care with the patient or family.
Third, engage the patient/family in a discussion of the current medical condition and goals of care.
Introduce the topic of a consultation by saying: To best meet some of the goals we’ve been discussing (fill
in with the goals mentioned by the family/patient) I’d like to have some consultants from the Palliative
Care Team visit with you. You can follow this by saying, They are experts in treating the symptoms you
are experiencing (fill in symptom). They are also good at helping your family deal with all the changes
brought on by your illness; they can answer your questions about (fill in previously discussed patient
questions).
You should not say that the reason you are asking Palliative care to be involved is “that there is nothing
more to do” or because “I have nothing more to offer.” Talk about the positive goals Palliative Care can
help you and the patient achieve.
Finally, emphasize your continued involvement: You and I will talk about the recommendations of the
palliative care experts. I'll make sure all your questions are answered. This can help relieve fears of
abandonment. If a patient or family reacts negatively to the suggestion for a consultation, explore their
concerns. Someone may have mentioned palliative care and this may have negative connotations to
them. Ask, What experience do you have with hospice/palliative care? What are your concerns? It may
be important to discuss that palliative care is compatible with aggressively treating the underlying
disease. Emphasize the positive aspects of what palliative care can do, rather than focusing on how the
palliative care team will help them accept death and dying. After all, the goal of palliative care is to
achieve the best possible quality of life through relief of suffering, control of symptoms and restoration of
functional capacity, while remaining sensitive to the patient and family’s values. Palliative Care guides the
patient and family as they face disease progression and changing goals of care, and helps those who
wish to address issues of life completion and life closure.
References
1. Weissman DE. Consultation in Palliative Medicine. Arch Int Med. 1997; 157:733-737.
2. Last Acts Campaign Task Force on Palliative Care. Precepts of Palliative Care. J Pall Med. 1998;
1:109-115.
4
5
HEALTH PROFESSIONAL BURNOUT – PART I
Linda Blust MD
Background Compared with other American workers, health care professionals suffer more burnout
(1). Amongst US physicians burnout rates range from 30% to 65% across specialties, with the highest
rates of burnout incurred by physicians at the front line of care (e.g. emergency medicine and primary
care) and those who are frequently exposed to distressing emotional situations and profound suffering
(e.g. palliative medicine) (2,3). Lack of attention to health providers’ stress responses to the witnessed
suffering contributes to the high prevalence of burnout in US health professionals. This has
consequences for the provider and his/her interpersonal relationships. This Fast Fact will describe
burnout and its risk factors, and review essential research regarding health professionals and burnout.
Fast Facts #168-170 will address symptoms, consequences, avoidance and assessment of burnout.
• Definitions: Burnout is a . . .
o “Psychological syndrome in response to chronic interpersonal stressors on the job” (7).
o “State of mental and/or physical exhaustion caused by excessive and prolonged stress” (4).
• Common features (adapted from Maslach 1982)

o A predominance of mental or emotional exhaustion, fatigue, and depression.
o The symptoms are more mental and behavioral than physical.
o The symptoms are work-related.
o Burnout manifests in persons with no previous history of psychopathology.
o Decreased effectiveness and work performance result from negative attitudes and behaviors.
• Situational Risk Factors

o Physician Worklife Study: 2326 US physicians identified via AMA masterfile responded to a
38-item mailed questionnaire developed and validated for this study. Predictors of stress
were:
▪ Demands of solo practice, long work hours, time pressure, and complex patients.
▪ Lack of control over schedules, pace of work, and interruptions.
▪ Lack of support for work/life balance from colleagues and/or spouse.
▪ Isolation due to gender or cultural differences.
o Hospital consultants in the UK: 882 gastroenterologists, radiologists, surgeons, and
oncologists responded to 12-item General Health Questionnaire and Maslach Burnout
Inventory. Sources of stress were:
▪ Work overload and its effect on home life.
▪ Feeling poorly managed and resourced.
▪ Managerial responsibility.
▪ Dealing with patients’ suffering.
• Individual Risk Factors

o At risk earlier in career
o Lack of life-partner
o Attribution of achievement to chance or others rather than one’s own abilities
o Passive, defensive approach to stress
o Lack of involvement in daily activities
o Lack of sense of control over events
o Not open to change
References
1. Shanafelt TD, Boone S, Tan L, et al. Burnout and satisfaction with work-life balance among US
physicians relative to the general US population. Arch Intern Med. 2012;172:1377-1385.
6
2. Linzer M, Levine R, Meltzer D, Poplau S, Warde C, West CP. 10 bold steps to prevent burnout in
general internal medicine. J Gen Intern Med. 2014;29:18-20
3. Kamal A, Bull J, et al. Burnout among palliative care clinicians in the United States: Results of a
national survey.J Clin Oncol 2014; 32: suppl; abstr e20530.
4. Girdin DA, Everly GS, Dusek DE. Controlling Stress and Tension. Needham Heights, MA: Allyn &
Bacon; 1996.
5. Linzer M, et al. Physician stress: results from the physician worklife study. Stress and Health.
2002; 18: 37-42.
6. Linzer M, et al. Predicting and preventing physician burnout: results from the United States and
the Netherlands. Am J Med. 2001; 111:170-175.
7. Maslach C. Burnout: The Cost of Caring. Englewood Cliffs, NJ; Prentice-Hall; 1982.
8. Maslach C, Schaufeli WB, Leiter MP. Job burnout. Annual Review of Psychology. 2001;
52:397-422.
9. Ramirez AJ, et al. Mental health of hospital consultants: the effects of stress and satisfaction at
work. Lancet. 1996;347: 724-728.
10. Ramirez AJ, et al. Changes in mental health of UK hospital consultants since the mid-1990s.
Lancet. 2005; 366:742-744.
11. Schaufeli WB, Maslach C, Marek T, eds. Professional Burnout: Recent Developments in Theory
and Research. Washington, DC: Taylor & Francis; 1993.
November 2006. Version copy-edited in April 2009; revised again by Sean Marks MD July 2015 with
7
HEALTH PROFESSIONAL BURNOUT – PART II
Linda Blust MD
Background As described in Fast Fact #167, burnout is a “psychological syndrome in response to

chronic interpersonal stressors on the job” (Maslach 1982). This Fast Fact will explore symptoms of
burnout and its personal and professional consequences. Fast Facts #169 and 170 will describe
avoidance and assessment of burnout.
Symptoms of each sequential stage of burnout

• Stress Arousal: anxiety, irritability, hypertension, bruxism, insomnia, palpitations, forgetfulness,
and headaches.
• Energy Conservation: Work tardiness, procrastination, resentment, morning fatigue, social
withdrawal, increased alcohol or caffeine consumption, and apathy.
• Exhaustion: Chronic sadness, depression, chronic heartburn, diarrhea, constipation, chronic
mental and physical fatigue, the desire to “drop out” of society.
Consequences
• Personal
▪ Depletion of emotional and physical resources.
▪ Negative self-image: feelings of incompetence and lack of achievement.
▪ Self-neglect: 35% of Johns Hopkins’ medical graduates had no a regular source of
health care.
▪ Questioning of previously held spiritual beliefs.
▪ Neglect of family and social obligations.
▪ Mental Illness: anxiety, depression, substance abuse, suicide.
→ Substance Abuse: MD lifetime risk is 10-14%.
→ MD suicide rates similar to general population for both genders
→ Relative Risk of MD suicide versus other professionals
• Male MDs: 1.1-3.4
• Female MDs: 2.5-5.7
• Female MDs complete suicide as often as male MDs
• Professional
▪ Longer Work hours: If I work harder, it will get better.
▪ Withdrawal, absenteeism, and reduced productivity.
▪ Depersonalization: attempt to create distance between self and patients/trainees by
ignoring the qualities that make them unique individuals.
• Loss of professional boundaries leading to inappropriate relationships with patients/
trainees.
▪ Compromised patient care. Burnout has been linked to
• More medical errors
• Diminished sense of empathy for patients
• Impaired decision-making
• 45% of University of Washington residents who self-report burnout also
report providing “suboptimal care.”
References:
8
1. Booth JV, Grossman D, Moore J, et al. Substance abuse among physicians: a survey of
academic anesthesiology programs. Anesthesia Analg. 2002; 95: 1024-1030.
2. Center C, et al. Confronting depression and suicide in physicians: a consensus statement.
JAMA. 2003; 289:3161-3166.
3. Gross CP, et al. Physician heal thyself? Regular source of care and use of preventive health
services among physicians. Arch Int Med. 2000; 160:3209-3214.
4. Linzer M, et al. Predicting and preventing physician burnout: results from the United States and
the Netherlands. Am J Med. 2001; 111:170-175.
5. Maslach C. Burnout: The Cost of Caring. Englewood Cliffs, NJ: Prentice-Hall; 1982.
6. Maslach C, Schaufeli WB, Leiter MP. Job burnout. Ann Rev Psychology. 2001; 52:397-422.
7. Shanafelt TD, Bradley KA, Wipf JE, Back AL. Burnout and self-reported patient care in an internal
medicine residency program. Ann Int Med. 2002; 136:358-367.
8. Pereira SM, Fonseca AM, et al. Burnout in palliative care: a systematic review. Nurs Ethics 2011;
18:317-326.
9. Dunwoodie DA, Auret K. Psychological morbidity and burnout in palliative care doctors in Western
Australia. Intern Med J 2007;37:693-698.
November 2006. Version copy-edited in April 2009; revised again July 2015 with references #8 & #9
9
HEALTH PROFESSIONAL BURNOUT – PART III
Linda Blust MD
Background Fast Facts #167 and 168 described burnout, its risk factors, symptoms, and
consequences. This Fast Fact will address strategies to avoid burnout while sustaining personal and
professional health, integrity, and growth. Fast Fact #170 will describe assessment tools validated for
burnout.
I. Individual Strategies
• Reflection upon work: journaling, discussion with colleagues.
o Am I burned-out/healthy?
o Why do I do this/continue to do this?
o What inspired/moved/surprised me today?
• Attend to health: diet, exercise, rest, regular health care.
• Plan activities that rejuvenate: Play!
• Professional supervision: Regular interaction with a mental health professional with the express
purpose of exploring dynamics of the provider/patient relationship.
• Make time for yourself
o Plan vacations at regular intervals.
o Allow for “time-out” when stressors increase.
II. Interpersonal Strategies

• Give important relationships priority – strengthen existing relationships with family and friends.
• Expand your community beyond existing relationships through activism or spiritual engagement.
III. Professional Strategies

• Debrief emotional events:
o Reach out to colleagues.
o Seek out or strengthen a mentor relationship.
o Write about your work for a larger audience.
o Utilize your institution’s Critical Incident Response Team if available.
o Psychosocial rounds with colleagues to explore these issues.
o Schwartz Center Rounds: interdisciplinary hospital rounds to explore emotions
surrounding provider/patient interactions.
• Advocate for change in your job, organization, or profession.
Triggers for Professional Counseling

• Persistent feelings of sadness, exhaustion, anger, worthlessness, hopelessness, suicidal
ideation, or anxiety interfering with work or interpersonal relationships.
• Self-prescribing sedative/hypnotic medication.
• Substance abuse: alcohol, prescription, or non-prescription drugs.
• Other ‘addictions’ interfering with work/relationships: gambling, exercise.
• Persistent sleep disturbance: nightmares, difficulty initiating or staying asleep, early morning
awakening.
• Loss of professional boundaries:
o Inappropriate relationships with patients, families, or trainees.
o Lack of attention to patients’ rights, safety, or autonomy.
If, after careful attention to the variables within your control, you still feel burned-out and at risk for serious
consequences, it may be necessary to temporarily or permanently leave your current job to regain your
health.
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References
1. Gundersen L. Physician burnout. Ann Int Med. 2001; 135:145-148.
2. Kuehn Kelly C. Strategies to Balance Training, Your Personal Life. ACP-ASIM Observer. 2001.
3. Meier DE, Back AL, Morrison RS. The inner life of physicians and care of the seriously ill. JAMA.
2001; 286:3007-3014.
4. Remen RN. The doctor’s dilemma: returning service, grace, and meaning to the art of healing.
Whole Earth. Summer 2000: 4-10.
5. The Kenneth B Schwartz Center. Available at: http://www.theschwartzcenter.org/.
November 2006. Version copy-edited in April 2009; then again July 2015.
11
HEALTH PROFESSIONAL BURNOUT – PART IV
Linda Blust MD
Background Fast Facts #167-169 described burnout, its risk factors and consequences, and coping
strategies. This Fast Fact will briefly describe assessment tools used in health professional research.
Additionally, it provides a validated screening tool utilized widely in education.
1. Maslach Burnout Inventory (CPP, Inc.)
a. Designed for use in health care and other service industries.
b. Evaluates emotional exhaustion, depersonalization, and reduced personal
accomplishment.
c. Well-validated; readily available; utilized by Physician Worklife Study.
d. 10-15 minutes to complete.
e. Cost: approximately $1.25 per test, with additional fee for scoring key.
2. General Health Questionnaire (Bank 1980)

a. 12-item screen for symptoms of psychiatric morbidity
b. Reliable in community and occupational settings
c. Utilized in conjunction with Maslach Burnout Inventory in ongoing, longitudinal UK study
of burnout and psychiatric morbidity in hospital consultants
3. Self Assessment Exercise (Girdin 1996)

How often do you . . .
a) almost always; b) often; c) seldom; d) almost never
1. Find yourself with insufficient time to do things you really enjoy?
2. Wish you had more support/assistance?
3. Lacksufficient time to complete your work most effectively?
4. Have difficulty falling asleep because you have too much on your mind?
5. Feel people simply expect too much of you?
6. Feel overwhelmed?
7. Find yourself becoming forgetful or indecisive because you have too much on your
mind?
8. Consider yourself in a high pressure situation?
9. Feel you have too much responsibility for one person?
10. Feel exhausted at the end of the day?
Calculate your total score: a) = 4, b) = 3, c) = 2, d) = 1. Your total? _____

A total of 25-40 indicates a high stress level that could be psychologically or physically
debilitating.
References
1. Bank M, et al. The use of the general health questionnaire as an indicator of mental health in
occupational settings. Journal of Occupational Psychology. 1980; 53:187-194.
2. Maslach Burnout Survey. CPP, Inc. Available at: https://www.cpp.com/en/detailprod.aspx?pc=35.
3. Girdin DA, Everly, GS, Dusek DE. Controlling Stress and Tension. Needham Heights, MA: Allyn
& Bacon; 1996.
4. Maslach C. Burnout: The Cost of Caring. Englewood Cliffs, NJ: Prentice-Hall; 1982.
5. Ramirez AJ, et al. Mental health of hospital consultants: the effects of stress and satisfaction at
work. Lancet. 1996; 347:724-728.
6. Ramirez AJ, et al. Changes in mental health of UK hospital consultants since the mid-1990s.
Lancet. 2005; 366:742-744.
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November 2006. Version re-copy-edited in April 2009; then again July 2015.
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PROFESSIONAL-PATIENT BOUNDARIES IN PALLIATIVE CARE
Lise Taylor Barbour MD
Background Boundaries in patient care are “mutually understood, unspoken, physical and emotional
limits of the relationship between the trusting patient and the caring physician or provider” (Farber 1997).
Health professional boundaries represent a set of culturally and professionally derived rules for how
health professionals and their patients interact. Boundaries serve to establish and maintain a trusting
provider-patient relationship and help clinicians maintain “justice and equity in dealing with all of their
patients”, not only a special few (Spence 2005). This Fast Fact reviews issues in health professional-
patient boundaries in palliative care.
Causes of Boundary Problems In caring for seriously ill or dying patients it is common for strong
emotional bonds to develop. However, when the limits of the provider-patient/family relationship are not
clear or where normal professional boundaries are not respected, problems are likely to arise. Common
reasons for boundary problems include:
• Personality styles or psychiatric disorders in which normal boundaries are not recognized or
respected.
• Health professional stress/burnout (see Fast Facts #167-170).
• Cultural misunderstandings.
Examples Warning signs and examples of potential boundary blurring include:

• Gift giving from/to patient/family.
• Patients having or wanting access to provider’s home phone number, or other personal
information.
• Patient/family expectations that the provider will provide care or socialize outside of clinical care
settings.
• Patient/family requests that the provider participate in prayer (See Fast Facts #120).
• The health care provider revealing excessive personal information with patient/family.
Self-Monitoring Not all ‘boundary issues’ are detrimental to the provider-patient relationship – some
clearly enhance compassionate care and serve to reinforce a trusting therapeutic relationship. However,
it is important for the provider to self-reflect when boundaries are approached.
• Am I treating this patient or family differently than I do my other patients?
• What emotions of my own does this patient/family trigger and are the emotions impacting my
clinical decision-making?
• Are my actions truly therapeutic for the patient, or am I acting in a manner to meet my personal
needs?
• Would I be comfortable if this gift/action was known to the public or my colleagues?
• Could this boundary issue represent a sign that I am experiencing professional burnout?
Managing boundary concerns

• Set clear expectations with patients and families as to your role in the context of their care, your
availability and best ways to communicate with you.
• Use professional colleagues or a mental health professional as a sounding board when you are
uncertain about your own or your patient/family behaviors.
• Address issues as they arise with the patient/family. Acknowledge importance of feelings,
emphasize the provider-patient relationship and the importance of maintaining objectivity;
emphasize that the rejection of a requested behavior does not imply a lack of caring.
• Seek professional counseling for yourself or the patient/family when boundary issues impact your
ability to provide objective, compassionate care.
References
14
1. Gabbard GO, Nadelson C. Professional boundaries in the physician-patient relationship. JAMA.
1995; 273:1445-1449.
2. Farber N, Novak D, O’Brien M. Love, boundaries, and the physician-patient relationship. Arch Int
Med. 1997;157:2291-2294.
3. Elder W. Erotic undercurrents and boundary violations in medical care. Clin Fam Prac. 2004;
6:975-82.
4. Spence S. Patients bearing gifts: are there strings attached? BMJ. 2005; 331:1527-1529.
5. Post S, Puchalski C, Larson D. Physicians and patient spirituality: professional boundaries,
competency, and ethics. Ann Internal Med. 2000; 132:578-583.
January 2007. Version copy-edited in April 2009; then again in July 2015.
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PALLIATIVE CARE CONSULTATION IN THE ICU
Margaret L Campbell PhD, RN, David E Weissman MD, and Judy E Nelson MD, JD
Background The Intensive Care Unit (ICU) is the setting for high-intensity health care designed to
resolve life-threatening illnesses and extend life. However, risks of mortality and severe morbidity remain
high and virtually all ICU patients have palliative care needs. Integration of palliative care services into
ICU care is increasingly seen as a method to improve clinical care (1,10). This Fast Fact reviews the role
of palliative care consultations in the ICU along with options for more generalist palliative care services
provided by ICU clinicians.
What occurs in an ICU Palliative Care Consultation

• Assess/treat distressing physical, psychological, and spiritual symptoms/problems.
• Communicate information about prognosis and treatment options to patient/family in concert with ICU,
primary care and subspecialty colleagues.
• Establish/clarify goals of care that are realistic and appropriate in relation to the patient’s condition,
values and preferences, and help match treatments to these goals.
• Formulate a transition care plan that accounts for prognosis, goals of care and patient/family needs.
• Provide support for the families.
• Support the ICU medical team in making clinically, ethically, and emotionally challenging decisions.
Research Data on Benefits of Palliative Care ICU Consultation

• Early identification of a dying trajectory leading to decreased time to institution of patient- and family-
centered, comfort-focused treatment goals (2-3).
• Movement of appropriate patients to lower intensity care sites (ward, palliative care unit, home
hospice) (5-6).
• Reduction in ICU length of stay for adult patients (2-4, 7).
• Reduction in the cost of care, without an increase in mortality, due to early establishment of realistic
treatment goals leading to reduction in use of high-cost ICU resources/interventions (2-4, 7-8).
• Support for staff in challenging and emotionally draining/morally distressing patient/family care
situations.
• Palliative Care consultation for hospitalized patients can reduce the need for ICU admission through
establishment of treatment goals that preclude future ICU admission (7-8).
• Continuity of care when the patient transitions from the ICU to ward or palliative care unit as the
Palliative Care team follows the patient.
ICU/Palliative Care Collaboration A range of options exist for integrating palliative care services into
the ICU. At one extreme, ICU staff consult a palliative care specialist team for problems the ICU staff
deems appropriate for consultative advice on an ad hoc basis. At the other extreme, the ICU embeds
systems in place to provide ICU-led generalist palliative care services to all ICU patients, utilizing
palliative care specialists for complex problems. Embedding systems that ensure the needs of all
patients are met includes screening all patients on admission and daily for unmet palliative care needs,
early identification of a surrogate, timely symptom management, and routinely-scheduled family meetings
to discuss goals of care (1,9,10). Quality outcomes related to patient and family experience and to health
care utilization should be tracked within the framework of available resources (1,11).
When to use Specialist Palliative Care Services Consultations can either be initiated on a case-by-
case basis by ICU or other primary clinicians, or triggered proactively using a system to identify patients
at high-risk for unmet needs (2-4). Key indications for consultation include:
• Difficult-to-control physical symptoms despite usual treatment approaches.

• Patients/surrogates wish to explore non-ICU supportive care options such as hospice services.
• Staff have questions about the appropriateness of life-sustaining therapies in the setting of advanced
complex illnesses.
• There are complex family dynamics impacting decisions about use of life-sustaining treatments.
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• There are disagreements among staff or between staff and patients/surrogates about prognosis and/
or use of life-sustaining treatments.
• Patients are being readmitted to the ICU more frequently within a given time frame.
Summary Specialist palliative care consultations, together with integration of palliative care principles
into the care of all ICU patients, can improve the patient/family experience, reduce length of stay and
improve ICU throughput without increasing mortality, and lower health care costs.
Additional resources: Fast Facts # 122-123.
References
1. Nelson JE, Mulkerin CM, Adams LL, Pronovost PJ. Improving comfort and communication in the
ICU: a practical new tool for palliative care performance measurement and feedback. Qual Saf
Health Care. 2006; 15(4):264-271.
2. Campbell ML, Guzman JA. Impact of a proactive approach to improve end-of-life care in a medical
ICU. Chest. 2003; 123(1):266-271.
3. Campbell ML, Guzman JA. A proactive approach to improve end-of-life care in a medical intensive
care unit for patients with terminal dementia. Crit Care Med. 2004; 32(9):1839-1843.
4. Norton SA, Hogan LA, Holloway RG, Temkin-Greener H, Buckley MJ, Quill TE. Proactive palliative
care in the medical intensive care unit: effects on length of stay for selected high-risk patients. Crit
Care Med. 2007; 35(6):1530-1535.
5. Carlson RW, Devich L, Frank RR. Development of a comprehensive supportive care team for the
hopelessly ill on a university medical service. JAMA. 1988; 259(3):378-383.
6. Smith TJ, Coyne P, Cassel B, Penberthy L, Hopson A, Hager MA. A high-volume specialist palliative
care unit and team may reduce in-hospital end-of-life care costs. J Palliat Med. 2003; 6(5):699-705.
7. Morrison RS, Dietrich J, Ladwig S, et al. Palliative care consultation teams cut hospital costs for
Medicaid beneficiaries. Health Aff (Millwood). 2011; 30(3):454-463.
8. Penrod JD, Deb P, Luhrs C, et al. Cost and utilization outcomes of patients receiving hospital-based
palliative care consultation. J Palliat Med. 2006; 9(4):855-860.
9. Weissman DE, Meier DE. Identifying patients in need of palliative care assessment in the hospital
setting: consensus recommendations. J Palliat Med. 2011; 14(1):1-7.
10. Nelson JE, Bassett R, Boss RD, et al. Models for structuring a clinical initiative to enhance palliative
care in the intensive care unit: a report from the IPAL-ICU Project (Improving Palliative Care in the
ICU). Crit Care Med. 2010; 38(9):1765-1772.
11. Nelson JE, Brasel KJ, Campbell ML, et al. Evaluation of ICU Palliative Care Quality: A technical
assistance monograph from the IPAL-ICU Project.
Authors’ Affiliations: College of Nursing, Wayne State University, Detroit, MI (MLC); Medical College of
Wisconsin, Milwaukee, WI (DEW); Mount Sinai School of Medicine, New York, NY (JEN).
Version History: Originally published April 2012; Copy-re-edited August 2015

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CONSULTATION ETIQUETTE IN PALLIATIVE CARE
Background There are generally agreed upon rules for consultation (just as there are in social life)
that can have profound consequences if they are breached. For those just starting to provide consultation
services, it is wise to follow the rules until you develop enough familiarity to know when they can be
breached. This Fast Fact reviews the rules of consultation etiquette for palliative care (PC) clinicians.
See Fast Fact #298 for more specific guidance on PC consultation in the Emergency Department.
1) Remember your stakeholders. Although the focus of the consultation is a patient/family issue, your
primary stakeholder is the attending physician that requested the consultation. Unhappy referring
physicians mean fewer palliative care consultations!
2) Make contact/clarify request. Before you see the patient, contact the referring service to
acknowledge that you received the request and to clarify the nature of the request. Determine what
questions the managing service wants answered. The phrasing of this is important. ‘Please tell me a little
about Patient X so we can be most helpful to you’ is an excellent open-ended query. Determine if there
are areas that are "off-limits" and find out who the consulting team should talk with following your
assessment – the referring clinicians or someone else on the care team. Remember, no matter what is
written in the chart, the real story exceeds what is written, and the referring clinicians often have
concerns/needs that are not evident from the chart. Particularly for palliative care consultations, this has
an important secondary importance; in telling you about the patient, the service will receive emotional
support in the telling the story. Be quiet and actively listen; acknowledge the underlying distress.
Cultural corollary: in some institutions the rank of the person calling should match or exceed the rank of
the person called. Strictly applied, for instance, an attending speaks to an attending. This is not true of
all institutions or physicians, but it is wise to know your local culture. When in doubt, or conflict occurs,
following the cultural corollary of your institution connotes respect.
3) Negotiate roles. Many referring clinicians will want the palliative care service to play an ongoing role
in the management of the patient and family. This may range from providing information and counseling,
to actively managing symptoms including writing medication orders, to assuming principal care for the
patient and family. Others will want the palliative care service to maintain a strictly consulting role while
the primary service implements recommendations.
4) See the patient & gather your own data. This includes reviewing the medical record, pertinent
laboratory and diagnostic tests, interviewing the patient and family, examining the patient, and offering
information and counseling if that was part of the nature of the request.
5) Call the referring service. Before you write in the chart, call the referring service with details of your
findings and recommendations. With experience and familiarity with frequent referrers, this step may not
be necessary. If appropriate, contact other consultants and clinicians involved with the patient
(housestaff, nurses, discharge planners, etc.).
Additional Tips
• Brevity (in general, try to limit your recommendations to < 5) and specificity (e.g., exact morphine
dose/route/schedule) are important to both communicate your key messages and increase the
likelihood that your recommendations will be acted upon.
• Plan ahead – you are often in the best position to recognize likely future needs beyond the
hospitalization; plan ahead to meet expected symptom control and other patient/family needs. Helping
to expedite and simplify patient discharge is an easy and high-yield way of demonstrating your
service’s value to referring clinicians.
• Honor turf – you may be one of many consultants; when in doubt about the expectations and plans of
the referring clinician, clarify by personal contact.
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• Be accessible – a referring physician or service needs to know how to reach you easily. He or she will
be put off if they can't reach your service. Indicate how you can be reached in your consult note.
• Be responsive – acknowledge receipt of the request as immediately as possible and plan to see the
patient the same day or within 24 hours. If unable to do this, contact the referring clinician directly to
discuss.
References
1. Cohn SL. The role of the medical consultant. Med Clin N Am. 2003;.87:1–6.
2. Goldman L, Lee T, Rudd P. Ten commandments for effective consultations. Arch Intern Med.
1983; 143(9):1753–5.
3. Morrison RS, Meier DE. Clinical practice. Palliative care. N Engl J Med. 2004; 350(25):2582–90.
4. Weissman DE. Consultation in palliative medicine. Arch Intern Med. 1997; 157(7):733–7.
5. Salerno SM, et al. Principles of effective consultation: an update for the 21st century consultant.
Arch Int Med. 2007; 167:271-275.
6. Consultation Etiquette E-Learning Course. CAPC Campus On-Line. Center to Advance Palliative
Care. Available at: http://campus.capc.org/.
Authors’ Affiliations: VP for Medical Affairs, Hospice & Palliative Care, Kobacker House, OhioHealth,
Columbus, OH (CvG); Medical College of Wisconsin, Milwaukee, WI (DEW).
Version History: First published July 2013. Re-copy-edited in September 2015.
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WRITING THE CONSULATION NOTE
Background Documentation the consultation serves to: a) communicate your findings, b) document
the service you provided and c) support your coding and billing activity. In Fast Fact # 266, the basic
principles of consultation ettiquete were reviewed as they apply to palliative care clinicians. This Fast Fact
reviews key elements of the palliative care consutation note.
1) Reason for Consultation I was asked to see this 87 year old man for problems related to
shortness of breath and setting goals-of-care by Dr. Bligh. An older etiquette form that is appreciated is to
begin the consultation note with the phrase: Thank you for asking me to see this….
2) Summarize the Case, including your activities

• I have reviewed the medical record and the chest radiographs, interviewed the patient and family,
and examined the patient. The following aspects are pertinent:
• Pertinent Current and Past History
• Pertinent Social/Family/Spiritual History
• Pertinent Medications and their effects
• Pertinent Review of Systems
• Pertinent Examination Findings
• Pertinent lab/x-ray/pathology
• Prognosis/Advance care planning/Goal setting information
3) Your Assessment Clearly and prominently indicate your assessment. This is where those who
want to know "the bottom line" will look first. It is common practice in some institutions to put your
assessment and recommendations at the very top of the note for readability. Encapsulate the case from
your point of view. This should be as concise as possible, however it should contain adequate accounting
of your medical decision making, particularly if your discussion could be surprising or unfamiliar to other
clinicians (e.g., hospice eligibility in ‘borderline’ cases, opioid hyperalgesia).
• This 87 year old man has dyspnea due to a combination of COPD and metastatic
adenocarcinoma of the lung. He understands his diagnosis and prognosis. He and his wife made
it quite clear that they do not want to suffer and would like to be cared for at home. They would
like no heroic or extraordinary measures used to keep him alive. They agree to a hospice plan of
care.
4) Recommendations Number, bullet, and/or bold your recommendations; don't bury them in a dense
paragraph. Be as specific as possible with recommendations and avoid vague statements like “start
morphine for dyspnea.”
1. Initiate oral morphine 5 mg po q 1h to relieve dyspnea
2. Initiate dexamethasone 8 mg orally q am to diminish inflammation and add to relief of dyspnea
3. Enter a DNR order in the chart and give the patient documentation to take with him at discharge.
4. Refer the patient to Pershing Hospice which serves the area where he lives. Their telephone
number is 111-222-2222. We would be happy to arrange this if you would like.
5) Closure Indicate with whom you have discussed the recommendations and your plan for following-
up the patient; conclude with the conventional etiquette.
• I have discussed these recommendations with Dr. Bligh who concurs. Further, I have discussed
my findings with the housestaff, nursing and social work staff caring for this gentleman.
• Dr. Bligh has asked us to continue to follow this patient during his hospitalization to supervise
titration of morphine and to continue to provide counseling and information. If you need us, it is
best to contact our nurse, Betty Blythe, RN at 444-4444,
• Thank you for permitting us to participate in the care of this patient.
6) Signature Clearly indicate your name and a way that the service can contact you.
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• Charles Feelbetter, MD; Office 333-3333; Pager 111-1111
7) Coding and Billing For coding and billing purposes, if you are using time to justify the level of
coding, you should include start/stop times of your face to face patient contact (see Fast Fact #48).
• I spent a total of 90 minutes on this consultation. 50 minutes of this time was spent in counseling
and information giving to the patient and his wife, starting at 1530 and ending at 1620.
References
1. Campbell M, Dahlin C. Advanced practice palliative nursing: a guide to practice and business
issues. Hospice and Palliative Nurses Association; Pittsburgh, PA: 2008. Available from:
http://www.hpna.org/Item_Details.aspx?ItemNo=978-1-934654-05-7.
2. Buppert C. Billing for Nurse Practitioner Service -- Update 2007: Guidelines for NPs, Physicians,
Employers, and Insurers. Medscape Nurses. Available at: http://www.medscape.org/
viewprogram/7767. Accessed August 3, 2012.
3. von Gunten CF, Ferris FD, Kirschner C, Emanuel LL. Coding and reimbursement mechanisms for
physician services in hospice and palliative care. J Palliat Med. 2000; 3:157-64.
4. Billing and Coding E-Learning Course. CAPC Campus On-Line. Center to Advance Palliative
Care. http://campus.capc.org /.
Authors’ Affiliations: VP for Medical Affairs, Hospice & Palliative Care, Kobacker House, OhioHealth,
Columbus, OH (CvG); Medical College of Wisconsin, Milwaukee, WI (DEW).
Version History: First published July 2013. Re-copy-edited in September 2015.
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PALLIATIVE CARE CONSULTATION IN THE EMERGENCY DEPARTMENT
Sangeeta Lamba MD, MS HPEd, Tammie E Quest, MD, David E Weissman, MD
Background Adults with chronic illnesses visit the emergency department (ED) several times in their
last months of life, with over half of older Americans presenting in their last month and many dying in the
ED. Hence, the ED serves many patients with unmet palliative care needs. Initial care decisions made in
the ED also set the future hospital trajectory of care. Early palliative care (PC) engagement in the ED has
the potential to impact these decisions. In this Fast Fact we discuss the opportunities and challenges of
the PC consultations in the ED.
Indications for Palliative Care consultation in the Emergency Department
• Difficult-to-manage pain or other symptoms
• Symptom management for an actively dying patient
• Rapid consensus for goals of care (e.g. intubation decision) or complex decision making
• Clarify provisions in an advance directive
• Withdrawal of non-beneficial treatments (e.g. help with terminal extubation)
• Bereavement support (e.g. after sudden deaths in victims of trauma or death of a child)
• Challenging dispositions requiring care coordination (e.g. home hospice)
Consultation Etiquette ED clinicians are charged to provide excellent and efficient patient care, with a
mandate to keep patient encounters as expedient as possible. ED providers often expect in-person
consultation time within 30-60 minutes. Palliative programs should proactively discuss the consultation
processes with the ED leadership to clarify when and how palliative care team members will be available
for an ED consult, by phone or person. To best serve the ED staff, palliative care clinicians are
encouraged to follow these principles of consultation etiquette:
1. Determine the question: What is needed from the ED team? Orders for symptom control, dialogue
with family, guidance with disposition planning? Certain issues, such as symptom control, may be initiated
or handled over the phone whereas more complex issues such as urgent goals of care discussions may
need in-person support.
2. Establish urgency: Be explicit in asking the ED team for the timeline of expectations.
• Emergent (e.g. clinical status unstable; decision to intubate, decision to withdraw ventilator)
• Urgent (e.g. patient relatively stable; help needed for disposition planning)
• Routine (e.g. patient is being admitted, has non-urgent needs, can be seen as inpatient).
3. Who is needed and when? Clarify care issues to determine which IDT member is best suited to
address the ED query. Be honest about timelines for in-person support and initiate telephone support as
soon as feasible.
4. Personal contact: discuss your findings and/or recommendations with the appropriate member of the
ED staff before initiating any definitive patient/family communication or intervention. Recognize that this
ED clinician may not be the one who initiated the palliative team consult due to shift schedules.
5. Gather additional data: To offer high quality care, the consultant will need to gather data
independently.
6. Brevity: A verbal 2-4 minute summary of recommendations is useful immediately after the consult.
7. Specificity: Be explicit in disposition and treatment directions (e.g., “begin with Morphine 5 mg IV and
repeat every 15 minutes until pain is less than 5”). Make sure your recommendations are feasible to
implement and fit the ED policies and protocols. Clarify who will be contacting other stakeholders (home
care, caregivers, etc) and what messages will be communicated.
8. Teach with tact: e.g. provide a Fast Fact, a protocol for pain, or an opioid equivalency table.
9. Provide continuity: Communicate the established plan of care to the patient, family, ED clinician and
the provider for the patient’s next place of disposition (e.g. the hospitalist for a patient being admitted).
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10. Honor the ED environment: Appreciate the patient load and competing emergency care demands of
the ED staff. Expect and anticipate shift changes and the need to orient new staff to your role and plans.
Summary Often a consult initiated in the ED does not have ample time to fully address patient needs or
change immediate outcomes. PC collaboration still serves a vital role in the ED as initial discussions
begun in the ED (clinician discussions about poor prognosis and introducing palliative team as part of the
next steps of care) can help prepare the patient and family for future care discussions with the palliative
team. PC clinicians are encouraged to learn about the ED culture and develop positive relationships by
joining in ED care rounds, serving as educational resources, and working collaboratively on institutional
protocols.
References:
1. Meier DE, Beresford L: Fast response is key to partnering with the emergency department.
Journal of Palliat Med 2007; 10(3):641-5.
2. Lamba S, Nagurka R, Walther S, Murphy P Emergency-Department-Initiated Palliative Care
Consults: A Descriptive Analysis. Journal of Palliative Medicine 2012; 5(6):633-636.
3. Kessler C, Kutka BM, Badillo C. Consultation in the Emergency Department; A Qualitative
Analysis and Review. J Emerg Med. 2012; 42(6):704-711
4. Hexter DA. Working with consultants. ACEP: Foresight 2002; 53.
5. Lee RS, Woods R, Bullard M, Holroyd BR, Rowe BH. Consultations in the emergency
department: a systematic review of the literature. Emerg Med J. 2008; 25(1):4–9.
6. Salerno SM, Hurst FP, Halvorson S, Mercado DL. Principles of effective consultation: an update
for the 21st-century consultant. Arch Intern Med. 2007;167(3):271–75.
7. Weissman DE. Consultation in palliative medicine. Arch Intern Med. 1997;157(7):733–37.
8. Choosing Wisely Campaign- American College of Emergency Physicians. Available at https://
www.acep.org/Clinical---Practice-Management/ACEP-Announces-List-of-Tests-As-Part-of-
Choosing-Wisely-Campaign.
Authors’ Affiliations: Rutgers New Jersey School of Medicine; Emory University School of Medicine;
Medical College of Wisconsin
24
!

THE ONCOLOGY-ICU-PALLIATIVE CARE INTERFACE
Mamta Bhatnagar, MD, Robert Arnold, MD
Background: Cancer patients may be admitted to an intensive care unit (ICU) at any point in the disease
trajectory (1). When these patients have an advanced malignancy, and/or when their disease has
progressed despite standard anti-cancer treatments, it is common for conflicts to arise between
oncologists and the critical care team regarding appropriate management. This Fast Fact discusses an
approach to conflict management for cancer patients in the ICU.
Same Patient-Different Opinions: Every specialty has a unique culture based on the type of diseases it
treats and the attitudes learned from peers and teachers during training years. Having a general
awareness of these cultural tendencies among various specialty groups could better enable Palliative
Care (PC) clinicians to manage inter-specialty conflicts.
Oncologists …
• See a wide range of patients, some who are cured and others who die.
• Are trained to examine all potential anti-cancer treatments to extend life.
• May view ICU care as nothing more than a “bump in the road,” noting that the prognosis of cancer
patients in the ICU is similar to non-cancer patients. This point of view may be especially apparent in
patients who have recently undergone a bone marrow transplant, but have not yet shown signs of
bone marrow recovery – reengraftment (1,5).
• Often have long-term outpatient relationships with patients creating strong emotional connections.
Intensivists …
• Are likely to see many cancer patients near the time of death when ICU care may represents a ‘last-
ditch’ effort to sustain life.
• Often have brief relationships with patients/families during a time of crisis.
• Like many non-oncology specialties, they may have a more negative view of the potential benefits of
anti-cancer treatments than oncologists.
• May worry about prolonging suffering through ICU interventions when death appears imminent (1).
How can palliative care help? By performing careful independent evaluations of the medical situation
and exploring the points of view of the various specialty teams, the PC team members can serve as
mediators who assist in creating a shared message for the family (2).
• Neutral Caring: An important trait of a PC consultant is the mindset of neutral caring. Neutral in that
he or she should avoid taking sides between the different clinical teams but instead work to find a
common story that they can agree on. PC consultants should be aware of their own potential biases
or conflicts of interest, which could influence the direction of the patient’s care. For example, PC
teams may be more likely to assume that a focus on comfort with a shortened hospital stay is
preferred (3). Caring because the PC consultant needs to remember that all the clinicians are doing
their best to care for the patient. Thus even if the PC clinician is sure that their view is “right”, they
need to respectfully negotiate with other clinicians who also may be sure their view is correct.
• Pre-meeting of clinicians: Regardless of who initiates the consult, PC teams should reach out to both
the oncologist and the intensivist to understand their points of view regarding disease, treatment
options and prognosis. In many such circumstances, attending-to-attending level conversations are
necessary. Given that prognosis is often uncertain, it may help to reach agreement on the best, worst,
and most likely prognosis (4). This may identify areas of agreement among the specialist teams
involved and clarify what medical data are needed to better forecast prognosis.
Managing Conflict: Multi-disciplinary goals of care meetings are often the most effective and efficient
way to bring all specialty care teams together along with the patient and/or family and negotiate the best
way forward (see Fast Facts #16, 65, 183-184, 222-227). If there is disagreement between specialty
teams, it is critical that such attending clinicians talk directly before meeting with the family. Often reports
of what one clinician said is from the family or another indirect source. Consequently, these descriptions
25
may be incomplete or filtered by the family’s hopes. In cases in which medical agreement cannot be
reached, the PC team can assist by presenting the differing opinions to the family as part of a cohesive
medical reality on which the family can base their decisions or pursue a time-limited trial.
Summary: The goal of the PC consultant is to perform an independent evaluation in order to help the
medical care team develop a unified medical narrative that is agreeable with all clinicians involved. As
such, PC teams can be vital in conveying an accurate and understandable medical narrative to the
families of critically ill cancer patients. By fostering an environment that allows regular clinician meetings
to occur throughout a patient’s hospital stay, PC teams can better ensure that medical teams talk directly
to each other about the patient’s prognosis and present a unified approach to the family and patient.
References:
1. Youngner SJ, Allen M, Montenegro H, Hreha J, Lazarus H. Resolving problems at the intensive
care unit/oncology unit interface. Perspect Biol Med. 1988;31(2):299-308. doi:10.1353/pbm.
1988.0060.
2. Meier DE, Beresford L. Consultation etiquette challenges palliative care to be on its best
behavior. J Palliat Med. 2007;10:7-11.
3. Barnard D, Towers A, Boston P, Lambrinidou Y. Crossing Over: Narratives of Palliative Care.
Oxford University Press; 2000.
4. Campbell T, Elise C, Jackson V a, et al. Discussing Prognosis: Balancing Hope and Realism.
Cancer J. 2010;16(5):461-466.
5. Staudinger T, Stoiser B, Müllner M, et al. Outcome and prognostic factors in critically ill cancer
patients admitted to the intensive care unit. Crit Care Med. 2000;28(5):1322-1328.
Authors Affiliation: University of Pittsburgh Medical Center


THE ROLE OF CLINICAL PHARMACISTS ON THE INTERDISCLIPINARY TEAM
26
Jennifer Pruskowski, PharmD
As experts in the rational, therapeutic use of medications (1), clinical pharmacists are uniquely suited to
enhance palliative care services for adults and children through patient-specific medication considerations
such as goals of care, care location, available routes of administration, pharmacokinetic and
pharmacodynamic properties, and cost. This Fast Fact will review the role of clinical pharmacists within
an interdisciplinary teams (IDT) with specific attention to hospice and palliative care teams.
Training and Certification: The Doctor of Pharmacy (PharmD) degree is awarded upon graduation from
US Schools of Pharmacy. The program requires at least 2 years of specific pre-professional
(undergraduate) coursework, followed by 4-academic years of professional study (2) in which much of the
pre-clinical content mirrors that of US medical schools. Pharmacists may then choose to complete a 1-2
year post-graduate residency (3,4) and/or fellowship (5). Specific pain and palliative care traineeships
and online masters programs are also available for pharmacists in the US (6-9) and Canada (10).
Scope of Practice Clinical pharmacists are the “translators” between the pharmacology of medications
and the clinical care of patients. Their skill set originates from their ability to identify and manage potential
drug therapy issues (11). Examples include: assistance with renal and hepatic dosing, drug-interactions,
opioid conversions, brainstorming alternative therapies or routes for refractory symptoms, and selecting
rational, cost-effective therapies. They can provide direct and indirect patient care services:
Direct patient care services:

• Medication Management: clinical pharmacists can perform regulated symptom assessments either
independently or alongside IDT members to write orders or make treatment recommendations (12).
Many states permit ‘advanced practice pharmacists’ (akin to advance practice nurses). Based on the
individual state laws and health system’s collaborative practice agreements, this can include the
prescribing of opioids and other controlled substances.
• Patient education: provision of medication counseling to improve patient adherence.
• Deprescribing (see Fast Fact #321): clinical pharmacists can incorporate the goals of care
conversations performed by the IDT as well as the estimation of the patient’s prognosis and functional
status to conduct medication-specific optimization conversations and minimize the number of
medications prescribed (13,14).
Indirect patient care services:
• Administrative and formulary management
• Education to other IDT members regarding pharmacotherapy issues
Roles of a Palliative Care Clinical Pharmacists in Various Health-care Settings (15)

• Inpatient (Hospital): Performing a comprehensive or targeted medication review at admission,
discharge, and as needed. This includes a chart review and face-to-face interaction with the patient
to detect adverse drug events and medication misuse as well as reconciling the appropriateness of all
inpatient medications with their outpatient regimen (16).
• Outpatient (Clinic) (17-19): Clinical pharmacists can identify patients on long acting opioids and
ensure an appropriate bowel regimen is co-prescribed to prevent opioid induced constipation or
review state-wide drug monitoring databases. If transitions in goals of care occur, clinical pharmacists
can utilize this information to deprescribe medications or identify new medications or routes of
administration in the palliation of new or anticipated symptoms.
• Senior Communities (Skilled Nursing Facilities): In this setting, deprescribing is especially relevant in
minimizing iatrogenic harm and ensuring a smooth transition to hospice when appropriate. In this
regard, clinical pharmacists can direct medication-specific optimization conversations with the patient
and their families and/or caregivers. They can also focus on the pharmacokinetic changes that occur
with aging, and research non-traditional routes of administration for medications.
• System-Level Positions: Clinical pharmacists can be instrumental in optimizing direct patient-care
services, procedural guidelines, electronic medical order entry systems, medication formularies, and/
or policies to improve medication usage across entire health-care systems (20). This can include
improve the availability of medications necessary for the management of refractory or end of life
symptoms such as: ketamine, lidocaine, methadone, glycopyrrolate, etc.
27
• Hospice: Beyond identifying drug-related problems and recommending appropriate drug therapy at
hospice IDT meetings (21), they must be familiar with medication reimbursement requirements. The
Centers for Medicare and Medicaid Services (CMS) stipulates that hospices are responsible for the
costs associated with medications if related to the terminal diagnosis and related conditions. (22)
Therefore, clinical pharmacists should be involved from the point of hospice admission to review
medications for appropriateness. They can also provide efficient mechanisms for extemporaneous
compounding of nonstandard dosage forms (23). 
Efficacy in Improving Patient Care: Retrospective evidence suggests clinical pharmacists may be
associated with a reduction of hospital admissions, length of hospital or ICU stay, 30-day readmissions,
drug-induced adverse reactions, and cost (22).
References:
1. Clinical Pharmacy Defined: American College of Clinical Pharmacy. Accessed 2 August 2016.
Available at: https://www.accp.com/about/clinicalPharmacyDefined.aspx.
2. Accreditation Council for Pharmacy Education. Accreditation standards and key elements for the
professional program in pharmacy leading to the doctor of pharmacy degree (“Standards 2016”).
February 2, 2015. Available at: https://www.acpe-accredit.org/pdf/Standards2016FINAL.pdf.
Accessed 12 August 2016.
3. Juba KM. Pharmacist credentialing in pain management and palliative care. J Pharm Pract. 2012
Oct;25(5):517-20.
4. American Society of Health-Systems Pharmacy Online Residency Directory: Search: (PGY2)
Palliative Care/Pain Management Pharmacy. Accessed 2 August 2016. Available at: https://
accred.ashp.org/aps/pages/directory/residencyProgramDirectory.aspx?pageno=1.
5. James J. Peters Veterans Affairs Medical Center VISN 3 GRECC Interprofessional Palliative Care
Fellowship Program. Accessed 2 August 2016. Available at: http://www.nynj.va.gov/docs/
greccpallfellapp.pdf.
6. ASHP Foundation Advanced Pain Management Traineeship. Accessed 2 August 2016. Available
at: http://www.ashpfoundation.org/MainMenuCategories/Traineeships/PainMgmtTraineeship.
7. ASCP Foundation Pharmacotherapy Pain Management Traineeship. Accessed 2 August 2016.
Available at: http://www.ascpfoundation.org/traineeships/train_painmanagement.cfm.
8. Harvard Interprofessional Palliative Care Fellowship Program. Accessed 1 December 2016.
Available at: https://www.hms.harvard.edu/pallcare/Fellowships/Fellowships.htm.
9. University of Maryland Graduate School Online Master of Science and Graduate Certificates in
Palliative Care. Accessed 1 December 2016. Available at: https://graduate.umaryland.edu/
palliative/.
10. Victoria Hospice Palliative Care: Medical Intensive Course. Accessed 1 December 2016.
Available at: http://www.victoriahospice.org/courses/palliative-care-medical-intensive-course.
11. Walker KA, Scarpaci L, McPherson ML. Fifty reasons to love your palliative care pharmacist. Am
J Hosp Palliat Care. 2010 Dec;27(8):511-3.
12. Dispennette R, Hall LA, Elliott DP. Activities of palliative care and pain management clinical
pharmacists. Am J Health Syst Pharm. 2015 Jun 15;72(12):999-1000.
13. Pruskowski J. Deprescribing #321. J Palliat Med. 2016 Nov 2. [Epub ahead of print] .
14. Lindsay J, Dooley M, Martin J, Fay M, Kearney A, Khatun M, Barras M. The development and
evaluation of an oncological palliative care deprescribing guideline: the 'OncPal deprescribing
guideline'. Support Care Cancer. 2015 Jan;23(1):71-8.
15. Herndon CM, Nee D, Atayee RS, Craig DS, et al. ASHP Guidelines on the Pharmacist's Role in
Palliative and Hospice Care. Am J Health Syst Pharm. 2016 Sep 1;73(17):1351-67.
28
16. Lucas C, Glare PA, Sykes JV. Contribution of a liaison clinical pharmacist to an inpatient palliative
care unit. Palliat Med. 1997 May;11(3):209-16.
17. DiScala SL, Onofrio S, Miller M, Nazario M, Silverman M. Integration of a Clinical Pharmacist into
an Interdisciplinary Palliative Care Outpatient Clinic. Am J Hosp Palliat Care. 2016 Jul 14. pii:
1049909116657324. [Epub ahead of print]
18. Ma JD, Tran V, Chan C, Mitchell WM, Atayee RS. Retrospective analysis
of pharmacist interventions in an ambulatory palliative care practice. J Oncol Pharm Pract. 2015
Oct 1. pii: 1078155215607089.
19. Atayee RS, Best BM, Daniels CE. Development of an ambulatory palliative care pharmacist
practice. J Palliat Med. 2008 Oct;11(8):1077-82.
20. Pruskowski J, Arnold R, Skledar SJ. Development of a health-system palliative care clinical
pharmacist. Am J Health Syst Pharm. 2017 Jan 1;74(1):e6-e8.
21. Lee J, McPherson ML. Outcomes of recommendations by hospice pharmacists. Am J Health Syst
Pharm. 2006 Nov 15;63(22):2235-9.
22. Centers for M, Medicaid Services HHS. Medicare and Medicaid programs: hospice conditions of
participation. Final rule. Fed Regist. Jun 5 2008;73(109):32087-32220.
23. American Society of Health-System Pharmacists. ASHP statement on the pharmacist’s role in
hospice and palliative care. Am J Health-Syst Pharm. 2002; 59:1770–3.
24. Walker KA. Role of the pharmacist in palliative care. Prog Palliat Care 2010;18(3):132-139.
Authors Affiliations: University of Pittsburgh Medical Center
Version History: Initially edited by Sean Marks MD; first electronically published in May 2017.
29
THE ROLE OF CHAPLAINCY IN CARING FOR THE SERIOUSLY ILL
Rebekah Schmidt, BCC
Background: Spirituality refers to the way individuals seek and express meaning, purpose, and
connectedness with the sacred or significant (1). Patients and families dealing with serious illness often
experience spiritual distress or desire spiritual support. Chaplains’ roles are often misunderstood as being
religious faith leaders for patients, but a more accurate description would be that of spiritual care
specialists who identify and support patients with spiritual distress or unmet spiritual needs (1,2). This
Fast Fact addresses the scope of clinical chaplaincy practice within an inter-disciplinary team (IDT).
Why is Spirituality a Key Component to Quality Care? Studies have shown that many patients want
their clinicians to ask them about spirituality, as many utilize spirituality to cope with health threats to their
mortality (1,3). Inattention to spiritual distress by clinicians has been associated with higher end-of-life
costs, including more ICU deaths and less hospice utilization (4). By addressing spiritual needs,
chaplains provide a safe forum for patients and families to acknowledge their sources of spiritual distress,
as well as identify ways to improve their spiritual health. A qualitative study identified the following
common spiritual needs and sources of spiritual distress in patients nearing the end-of-life (5):
Spiritual Needs Sources of Spiritual Distress

• To finish business: such as forgiveness, • Fear: of death, the afterlife, separation
reconciliation, or to review their lives for meaning. from loved ones, pain and suffering, and
• To have involvement and control: in their care not leaving a legacy.
plan, medical decisions, hospital or home • Losses or grief: such as a loss of
environment. independence, mobility, life, control.
• To maintain a positive outlook: by utilizing spiritual • Other negative emotions: despair,
strengths and personal resources to keep an open anger, frustration, helplessness
mind and live in the present.
Who are Chaplains? Board Certified Chaplains (BCC) complete graduate-level theological training and
at least 1600 hours of supervised clinical training called “clinical pastoral education.” Subsequently, they
appear before a national committee for approval, and participate in continuing education to maintain
certification. No matter what their own faith tradition may be, BCCs are interfaith, meaning they are
trained to assist patients and families of any faith as well as those of no faith or those unsure of their faith.
How Can Unmet Spiritual Needs Be Identified? As spiritual care generalists, nurses, social workers,
physicians, and other IDT clinicians have the responsibility to screen for spiritual distress and spiritual
needs as part of the consultation or history and physical process (see Fast Facts #19 and 274) (7). This
includes listening for phrases which may indicate a need for spiritual support such as: “Why is this
happening to me?”, “What God would allow this?”, “I still have things to do in my life!” or “I’ve lost touch
with my faith leader since I’ve been in the hospital.” Alternatively, when pain or other physical symptoms
are refractory, clinicians should consider whether spiritual or existential distress may be present.
Clinicians should refer to a chaplain if unmet spiritual needs and/or spiritual distress are suspected.
What Do Chaplains Do? Chaplains serve as the spiritual care specialists on an IDT. They perform an
independent assessment of the patient and family’s spiritual needs, as well as cultural and religious
factors which may be influencing medical decision-making. They utilize their training to design an
individualized spiritual care plan. Interventions may include reflective listening, prayer, empathetic
support, contacting the faith community, performing a life review, and assisting patients in integrating their
spiritual beliefs with their new medical reality (6).
30
How Can Chaplains be Effectively Utilized? There is no “one-size-fits-all” approach to utilizing
chaplaincy. Ideally, a hospice or palliative care program would have a chaplain integrated into their IDT,
but many must rely upon unit-based chaplains. Examples of potential approaches include:
• Routinely informing patients and families of the availability of chaplains.
• Involving chaplains in the discussion of patients during IDT meetings. Chaplains add a spiritual
lens which helps IDTs with identifying patients with spiritual or existential sources of suffering.
• Incorporating chaplains into usual IDT care practices by performing bedside rounds with the
chaplain. By doing so, the IDT can address spiritual issues in real time and demonstrate spiritual
care priorities to patients and families. Chaplains can also role-model and educate best spiritual
care practices to IDT members or trainees.
• Involving chaplains when cultural or religious beliefs are cited as reasons for disagreement with
medical recommendations, as chaplains may be able to function as cultural/religious translators.
• Including chaplains in goals-of-care discussions. Often, non-medical factors influence patient or
surrogate decision-making. Chaplains listen for spiritual or religious coping influences during goals-
of-care meetings and offer a unique, real-time perspective.
References
1. Puchalski C, Ferrell B, Virani R, et al. Improving the Quality of Spiritual Care as a Dimension of
Palliative Care: The Report of the Consensus Conference. Journal of Palliative Care.
2009;12(10):885-904
2. Handzo G, Koenig H. Spiritual Care: Whose Job Is It Anyway? Southern Medical Journal.
2004;97(12):1242-1244.
3. Otis-Green S, Ferrell B, Borneman T, Puchalski C, Uman G, Garcia A. Integrating Spiritual Care
within Palliative Care: An Overview of Nine Demonstration Projects. Journal of Palliative
Medicine. 2012; 15(2):154-162
4. Baloboni T, Balboni M, Paulk ME, et al. Support of cancer patient's spiritual needs and
associations with medical care costs at the end of life. Cancer. 2011;117(23):5383-5391.
5. Edwards A, Pang N, Shiu V, Chan C. The understanding of spirituality and the potential role of
spiritual care in the end-of-life and palliative care: a meta-study of qualitative research. Palliative
Medicine. 2010; 24(8):753-770.
6. Jeuland J, Fitchett G, Schulman-Green D, Kapo J. Chaplains working in palliative care: who they
are and what they do. J Palliat Med. 2017 May;20(5):502-508
7. Balboni TA, Fitchett G, Handzo G, Johnson KS, Koenig H, Pargament K, Puchalski C, Sinclair S,
Taylor EJ, Steinhauser KE. State of the science of spirituality and palliative care research PART
II: screening, assessment, and anterventions. J Pain Symptom Manage. 2017 Jul 19.

Author Affiliations: Medical College of Wisconsin
Version History: Originally edited by Sean Marks MD; first electronically published in December 2017.
31

Background: Clinicians have been encouraged to utilize the surprise question (SQ) -- “Would I be
surprised if this patient died within 12 months?” – to identify patients at high 1-year mortality risk. When
clinicians answer “No – I would NOT be surprised if this patient died within 12 months,” the SQ may help
clinicians identify patients with unmet palliative care needs who could benefit from advance care planning
discussions and/or a palliative care referral (1). This Fast Fact reviews the clinical utility of the SQ.
Rationale of the SQ: As difficult as it is for clinicians to prognosticate accurately, multiple studies have
shown that patients with incurable disease desire more prognostic information the sicker they get and
prognosis is a major factor in preferences for rehospitalizations, life support, and CPR (2-4). Although,
patients and surrogates often want temporal prognostic predictions (the clinician’s estimated length of
time he or she predicts the patient will live), clinicians are more accurate and willing to offer probabilistic
predictions (the clinician’s estimate, often in a percentage, of the chance of death in a set time frame,
such as 1 year) (4-6). The SQ was designed as a clinical tool that generalist clinicians would utilize
willingly and routinely to identify patients at risk of death in a year and thereby lead to more appropriate
advance care planning, goals of care discussions, symptom management, and hospice referrals.
Effectiveness of the SQ: Although variations on the SQ have been described in the published literature
including “Would I be surprised if this patient died this hospitalization?” or “Would I be surprised if this
patient died in 3 months?”, the SQ most commonly referred is “Would I be surprised if this patient died
within 12 months?” This SQ has been studied in diverse populations, including a general inpatient setting
(7), high-risk primary care clinic (8), pediatric patients (9), advanced kidney disease (10-12), cancer
(13,14), acute surgical patients (15), emergency department settings (1,16), and nursing home settings
(17). In general, the SQ has performed modestly well in identifying patients with a prognosis of < 1 year
across these various patient populations (18,19). Notable findings from these studies include:
• A meta-analysis of the SQ among 26 studies across these patient populations found that it had a
pooled accuracy of 75%, a sensitivity of 67% and specificity of 80% (18).
• “Yes” answers appear to be much more accurate than “No” answers. The predictive value of a “Yes”
answer was 93%, while only 37% for a “No” answer (18). This means that the SQ is likely better
designed to identify patients who will live more than a year vs the patients who live less a year. It also
suggests that there is “false positives” are relatively common when clinicians answer “No” to the SQ.
• The SQ may be slightly more accurate for cancer patients (pooled accuracy 79%) and renal patients
(76%) vs other disease groups (72%) (18). This may reflect a more predictable illness trajectory in
cancer and renal disease. See Fast Fact #326 for more information on illness trajectories.
• In most studies, the SQ was utilized as one aspect of a broad prognostic assessment which included
clinician gestalt and/or other prognostic tools. Hence, used in isolation, its accuracy is unclear (18).
Implementing the SQ Into Clinical Practice: The SQ can be helpful in identifying patients at risk of
medical decline and death in a certain time frame when used as part of a larger prognostic assessment
(19). Yet, considering the relatively high false positive rate of a “No” answer, it is not established if the SQ
is a cost-effective tool nor an effective way to trigger a palliative care consultation on its own. A consensus
panel of experts suggested that a “No” answer trigger generalist clinicians to perform a primary palliative
care assessment or screening for unmet palliative care needs (20). Sentinel medical events like
hospitalization, decline in performance status, or disease progression are reasonable triggers to
implement the SQ into clinical practice. Note templates, medical rounding tools, and electric medical
record prompts are potential system-based approaches to accomplish this. Reasonable components of
the primary palliative care assessment triggered by a “No” include (20):
32
• Identification of whether the patient completed an advance directive such as a health care power of
attorney that is available in the medical records.
• Assessment of patient, family, and/or surrogate’s understanding of the underlying illness, treatment
options, and prognostic trajectory.
References:
1. Haydar SA, Almeder L, Michalakes L, Han PKJ, Strout TD. Using the surprise question to identify
those with unmet palliative care needs in emergency and inpatient settings: what do clinicians
think J Palliat Med. 2017 doi:10.1089/jpm2016.0403
2. Weeks JC, Cook EF, et al. Relationship between cancer patients’ predictions of prognosis and
their treatment preferences. JAMA 1998;279(21):1709-1714.
3. Murphy DJ, Burrows D, et al. The influence of the probability of survival on patients' preferences
regarding cardiopulmonary resuscitation. NEJM 1994; 330:545-549.
4. Gaston CM, Mitchell G. Information giving and decision-making in patients with advanced
cancer: a systematic review. Soc Sci and Med 2005;61(10):2252-64.
5. Christakis NA, Lamont EB. Extent and determinants of error in doctors’ prognoses in terminally ill
patients: prospective cohort study. BMJ 2000; 320;469-472.
6. Hagerty RG, Butow PN, et al. Communicating prognosis in cancer care: a systematic review of
the literature. Ann of Onc 2005; 16(7):1005-53.
2017;189(13):484-93.
8. Larkin JR, Robinson MG, Bernacki RE, et al. Estimating 1-year mortality for high-risk primary care
patients using the “surprise” question. JAMA Intern Med. 2016;176(12):1863-1865.
9. Burke K, Coombes LH, Menezes A, Anderson AK. The ‘surprise question’ in paediatric palliative
care: a prospective cohort study. Palliative Medicine 2018; 32(2):535-42.
10. Moss AH, Ganjoo J, Sharma S, et al. Utility of the “surprise” question to identify dialysis patients
with high mortality. Clin J Am Soc Nephrol. 2008;3(5):1379-84.
11. Pang WF, Kwan BC, Chow KM, Leung CB, Li PK, Szeto CC. Predicting 12-month mortality for
peritoneal dialysis patients using the “surprise” question. Perit Dial Int. 2013;33(1):60-6.
12. Javier AD, Figueroa R, Siew ED, et al. Reliability and utility of the surprise question in CKD
stages 4 to 5. Am J Kidney Dis. 2017 doi: 10.1053/j.ajkd.2016.11.025.
13. Moss AH, Lunney JR, Culp S, et al. Prognostic significance of the “surprise” question in cancer
patients. J Palliat Med. 2010;13(7):837-40.
14. Moroni M, Zocchi D, Bolognesi D, et al. The ‘surprise’ question in advanced cancer patients: a
prospective study among general practitioners. Palliat Med. 2014;28(7):959-964.
15. Lilley EJ, Gemunden SA, Kristo G, et al. Utility of the “surprise” question in predicting survival
among older patients with acute surgical conditions. J Palliat Med. 2017;20(4):420-23.
16. Ouchi K, Jambaulikar, et al. The “surprise question” asked of emergency physicians may predict
12-month mortality among older emergency department patients. J Pall Med 2018; 21(2): 236-40.
17. Rice J, Hunter L, Hsu AT, Donskov M, Luciani T, Toal-Sullivan D, Welch V, Tanuseputro P. Using
the ‘Surprise Question’ in Nursing Homes: A Prospective Mixed-Methods Study. J Palliat Care.
2018; 33(1):9-18.
18. White N, Kupeli N, Vickerstaff V, Stone P. How accurate is the ‘Surprise Question’ at identifying
patients at the end of life? A Systematic review and meta-analysis. BMC Med. 2017; 15(1):139.
19. Romo RD and Lynn J. The utility and value of the “surprise question” for patients with serious
illness. Canadian Medical Association Journal 2017; 189(33):E1072-1073.
20. Weissman DE, Meier DE. Identifying patients in need of a palliative care assessment in the
hospital setting: a consensus report from the Center to Advance Palliative Care. J Palliat Med.
14(1):1-6.
33
Author Affiliations: 1University of Colorado School of Medicine, Aurora, CO, USA; 2Medical College of
Wisconsin, Milwaukee, WI; 3Veterans Affairs Eastern Colorado Geriatric Research Education and Clinical
Center, Denver, CO, USA
34
THE PRE-FAMILY MEETING HUDDLE
Mamta Bhatnagar MD, MS and Robert Arnold MD
Background Family meetings are important events in the care of hospitalized patients to ensure that
patients & families understand what is happening medically, to support the patient and family emotionally,
and to promote shared decision-making (1). Common topics include delivering bad news, discussing care
goals, and clarifying the plan of care and patient disposition (see also Fast Facts #222 & 223). Pre-
meetings among relevant clinicians are helpful for family meetings to run smoothly (1). This Fast Fact
provides practical guidance to holding a successful pre-family meeting ‘huddle.’
Basics of the ‘Huddle’ The huddle typically occurs just prior to family meeting, ideally in a private
setting (and not right in front of the patient’s room). Along with the primary medical team, the huddle may
include key specialists/consulting team members including members of the palliative interdisciplinary
team, the bedside nurse and/or unit charge nurse, the unit care coordinator and/or social worker, spiritual
care, and other professionals as relevant such as speech language pathology, physical therapy, etc.
Huddles often take between 5-15 minutes. Goals of the huddle include: (1) achieving a common
understanding of the medical situation and possible options and outcomes, (2) agreeing on the family
meeting’s purpose, (3) sharing what is known about the family and their concerns, and (4) determining
professionals’ roles during the family meeting.
Data There are no specific data on the effectiveness of huddles prior to family meetings. However,
huddles have been used for improving care in different settings, ranging from facility safety huddles to
perioperative settings. Evidence suggests huddles identify safety challenges (2), decrease laboratory and
pharmacy costs (3), and improve family and provider satisfaction (4).
Facilitating a common understanding of the clinical situation The first task of the huddle is to
ensure that everyone is on the same page about what is happening medically, what range of
interventions/options are appropriate to offer the patient/family, and what range of likely outcomes should
be outlined. The clinician leading the huddle might say, “I want to make sure we all have the same view
about what is going on with the patient and what we think her future might be.” In cases where health
care providers have divergent thoughts, it is helpful to discuss the best- and worst-case scenarios and the
milestones that will help determine how the patient is doing (5). The goal is to generate a consensus and
allow the meeting leader to present this information to the patient/family in a cohesive fashion.
Agreeing on the goals of the meeting Second, the huddle participants should come to an agreement
regarding the meeting’s purpose, incorporating what is known about the patient’s/family’s hopes for the
meeting. The patient or family is likely to be confused if some health care providers are asking about the
patient’s values while others are viewing the meeting merely an opportunity to update the family or
discuss disposition. It is always a goal to make sure the patient/family leave the meeting better informed
about the situation/options, and feel heard and valued. Clarifying the meeting’s purpose further than that
“What’s the fundamental message we want to convey during this meeting?” and “What, from our point of
view, are acceptable outcomes?”, helps avoid mixed messages. It is also very important to clarify in
advance if decisions about the plan of care need to be made urgently.
Sharing information & concerns Third, the huddle is the time for health care providers to share
information about the family structure, who the legal decision-maker is (if not the patient), how the patient/
family make decisions, and places where the meeting might go “off track.” Given not all huddle members
have met all family members, the huddle can update everyone on family dynamics (e.g., “The children
always defer to their mom,” or “The cousin is a nurse and asks of biomedical questions”). Bedside nurses,
social workers, and chaplains are particularly important as they may have spent much time with the
35
patient/family and may have a different view and experience of the patient/family than other providers.
Helpful questions include “What do we know about how this family makes decisions?” or “What are some
specific concerns folks have about what might happen in the meeting?”
How to facilitate the family meeting Finally, it is important to decide who will lead the family meeting,
taking into account who the patient/family may have the strongest therapeutic relationship with, and to
name key roles in the meeting as relevant (e.g., the surgical consultant will be sharing the news that the
patient is no longer a surgical candidate, or the oncologist will be reviewing chemotherapy options and
outcomes). Often the leader is a physician or an advanced practice nurse, especially if biomedical facts
are being shared, but this depends on institutional culture and the purpose of the family meeting.
References
1. Singer AE, Ash T, Ochotorena C, et al, A Systematic Review of Family Meeting Tools in Palliative
and Intensive Care Settings. Am J Hosp Palliat Med. 2016; 33:797-806.
2. Setaro J, Connolly M. Safety Huddles in the PACU: When a Patient Self-Medicates. J.
Perianesthesia Nurs. 2011; 26:96-102.
3. Chan AY, Vadera S. Implementation of interdisciplinary neurosurgery morning huddle: cost-
effectiveness and increased patient satisfaction. J. Neurosurg. 2018; 128:258-261.
4. Awdish RL, Buick D, Kokas M, et al, H. A Communications Bundle to Improve Satisfaction for
Critically Ill Patients and Their Families: A Prospective, Cohort Pilot Study. J Pain Symptom
Manage. 2017; 53:644-9.
5. Schwarze ML, Taylor LJ. "Managing Uncertainty — Harnessing the Power of Scenario Planning.
NEJM. 2017; 377: 206-8.
Authors Affiliations: University of Pittsburgh Medical Center, Pittsburgh, PA.

Version History: Originally edited by Drew A Rosielle MD; first electronically published in December
2018.
36
Psychiatry
#1 Diagnosis and Treatment of Terminal Delirium . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . 2-3
#7 Assessing Depression in Advanced Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . 4-5
#32 Grief and

Bereavement. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . .6-7
#43 Is it Grief or
Depression? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . 8-9
#59 Dealing with the Angry Dying Patient . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . .10-11
#60 Pharmacologic Management of Delirium: Update on Newer

Agents . . . . . . . . . . . . . . . . . . . . . . . . . . . 12-14
#88 Nightmares . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . 15-16
#101 Insomnia: Patient

Assessment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
17-19
#104 Insomnia: Non-Pharmacologic Treatments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . 20-21
#105 Insomnia: Drug

Therapies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. .22-24
#145 Panic Disorder at the End-Of-

Life . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25-26
#146 Screening for Depression in Palliative

Care . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27-28
#156 Evaluating Requests for Hastened

Death. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29-30
!1
#159 Responding to a Request for Hastening Death. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . .31-32
#186 Anxiety in Palliative Care- Causes and Diagnosis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . . .33-34
#210 Suicide Attempts in the Terminally Ill . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . .35-37
#254 Complicated Grief. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . 38-40
#309 Pharmacologic Management of Depression in Advanced

Illness . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .41-43
#332 End of Life Care for Patients with

Schizophrenia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44-46
#371 Transference and Countertransference in Palliative

Care . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . .47-49

DIAGNOSIS AND TREATMENT OF TERMINAL DELIRIUM
Background Some degree of loss of cognitive function occurs in most patients in the week or two
before death. The typical scenario presented to housestaff is a late-night call from a ward nurse saying,
“Mr. Jones is confused, what should we do?” This Fast Fact reviews assessment and management issues
in terminal delirium. See Fast Fact #60 for a discussion of newer pharmacological treatments.
Key teaching points:

1. The term “confusion” is not an accurate descriptive term—it can mean anything from delirium,
dementia, psychosis, obtundation, etc. Patients need a focused assessment, including a brief mini-
mental examination. Clinicians should use one of several validated delirium assessment tools to help
quantify and document cognitive function.
2. “Terminal delirium” is not a distinct diagnosis, although it is a commonly used phrase. It implies
delirium in a patient in the final days/weeks of life, where treatment of the underlying cause is
impossible, impractical, or not consistent with the goals of care.
3. Delirium can be either a hyperactive /agitated delirium or a hypoactive delirium. The hallmark of
delirium is an acute change in the level of arousal; supporting features include altered sleep/wake
cycle, mumbling speech, disturbance of memory and attention, and perceptual disturbances with
delusions and hallucinations.
4. The most common identifiable cause of delirium in the hospital setting is drugs: anti-cholinergics (e.g.
anti-secretion drugs, anti-emetics, anti-histamines, tricyclic anti-depressants, etc.), sedative-hypnotics
(e.g. benzodiazepines), and opioids. Other common causes include metabolic derangements
(elevated sodium or calcium, low glucose or oxygen); infections; CNS pathology; or drug/alcohol
withdrawal.
5. The degree of work-up to seek the cause of delirium is determined by understanding the disease
trajectory and overall goals of care (see Fast Fact #65).
6. The drug of choice for most patients is a neuroleptic. There is one controlled clinical trial of
haloperidol versus lorazepam in HIV patients; haloperidol was the superior agent. Haloperidol is
administered in a dose escalation process similar to treating pain. Start haloperidol 0.5-2 mg PO or
!2
IV q1hour PRN. Atypical antipsychotics have also been studied for delirium are probably as
efficacious as haloperidol. There are insufficient data to make a strong recommendation about the
best drug or dosing of antipsychotics for delirium.
7. It is best to think of benzodiazepines as sedatives and anxiolytics but not as therapy for underlying
delirium. On the rare occasion one wants to actually sedate a delirious patient a benzodiazepine may
be indicated. If anxiety is a prominent part of a patient’s delirium, a benzodiazepine may help.
Generally, however, benzodiazepines should be avoided as they can cause paradoxical worsening of
the delirium and agitation.
8. Non-pharmacological treatments should always be used in delirium management: reduce or increase
the sensory stimulation in the environment as needed; ask relatives/friends to stay by the patient;
frequent reminders of time/place.
References
1. Yennaurjalingam S et al. Pain and terminal delirium research in the elderly. Clin Geriatr Med.
2005;21(1):93-119.
2. Lawlor PG, et al. Occurrence, causes and outcome of delirium in patients with advanced cancer.
Arch Int Med. 2000;160:786-794.
3. Brietbart W, Marotta R, Platt M, et al. A double blind trial of Haloperidol, Chlorpromazine and
Lorazepam in the treatment of delirium. Am J Psych. 1996; 153:231-237.
4. Breitbart W, Alici Y. Agitation and delirium at the end of life. “We couldn’t manage him.” JAMA.
2008; 300(24):2898-2910.
5. Maneeton B, Maneeton N, Srisurapanont M, Chittawatanarat K. Quetiapine versus haloperidol in
the treatment of delirium: a double-blind, randomized, controlled trial. Drug Des Devel Ther. 2013;
7:657-67. doi: 10.2147/DDDT.S45575.
July 2005. Current version re-copy-edited, with additional reference added, March 2009. 3rd Edition edited
by Drew A Rosielle MD with additional material added November 2014.
!3
ASSESSING DEPRESSION IN ADVANCED CANCER
Eric Warm MD and David E Weissman MD
Background Diagnosing and providing treatment for a major depressive episode in patients with
advanced cancer can improve quality of life. However, diagnosing major depression in an advanced
cancer can be complicated by the fact that many cancer symptoms overlap with the somatic symptoms of
depression. Furthermore, although depressive thoughts and symptoms may be present in up to 15-50%
of cancer patients, only 5% to 20% will meet diagnostic criteria for major depressive disorder. This may
create a clinical dilemma in determining when it is appropriate to add pharmacotherapies for depressive
symptoms or whether reflective listening and exploration of the patient’s concerns may be the only
needed intervention.
Assessment Clinicians often rely more on the psychological or cognitive symptoms of depression
(worthlessness, hopelessness, excessive guilt, and suicidal ideation) than the physical/somatic signs
(weight loss, sleep disturbance) when making a diagnosis of major depressive disorder in advanced
cancer patients. Endicott has proposed substituting somatic criteria with affective criteria when evaluating
depression in advanced cancer patients: 
 
Physical/somatic symptoms…
1. Change in appetite/weight
2. Sleep disturbance
3. Fatigue, loss of energy
4. Diminished ability to think or concentrate
…are replaced by psychological symptoms

1. Tearfulness, depressed appearance
2. Social withdrawal, decreased talkativeness
3. Brooding, self-pity, pessimism
4. Lack of reactivity, blunting
Screening Tools The Association of Palliative Medicine Science Committee performed a thorough
assessment of available screening tools and rating scales for depression in palliative care. While they
found that commonly used tools such as the Edinburgh Depression Scale and the Hospital Anxiety and
Depression Scale have validated cut-off thresholds for palliative care patients, the depression screening
!4
tool with the highest sensitivity, specificity and positive predictive value was the single question: “Are you
feeling down, depressed, or hopeless most of the time over the last two weeks?”
Other Etiologies Medication side effects from commonly used therapeutics in this patient population,
like chemotherapeutic agents, opioids, benzodiazepines or glucocorticorticoids, can mimic the symptoms
and signs of depression. Clinicians should be especially aware of hypoactive delirium in the differential
diagnosis of depressive symptoms in cancer patients. Delirium is a particularly important consideration in
the final days of life as its prevalence may reach up to 90% during this critical time.
 
Teaching Point: The key indicators of depression in the terminally ill are persistent feelings of
hopelessness and worthless and/or suicidal ideation. Symptoms of depression can overlap with those of
anticipatory grief, a normal aspect of the dying process. See Fast Fact # 43 for a complete description of
anticipatory grief and how to differentiate from major depression. See Fast Fact #146 on screening for
depression in palliative care. 
References
1. Endicott J. Measurement of depression patients with cancer. Cancer. 1983; 53:2243-8.
2. Block SD. Assessing and managing depression in the terminally ill. Ann Inter Med. 2000;
132:209-217.
3. Chochinov H, et al. Prevalence of depression in the terminally ill: effects of diagnostic criteria and
symptom threshold judgments. Am J Psychiatry 1994;151:537-40.
4. Massie MJ. Prevalence of depression in patients with cancer. JNCI Monographs 2004;57-71.
5. Spiller JA, Keen JC. Hypoactive delirium: assessing the extent of the problem for inpatient
specialist palliative care. Palliative Med 2006;20:17-23.
6. Williams ML, Spiller J. Which depression screening tools should be used in palliative care. Pall
Med 2003;17:40-43.
7. Chochinov HM, et al. “Are you depressed?” Screening for depression in the terminally ill. Am J
Psychiatry 1997;154:674-6.
!5
GRIEF AND BEREAVEMENT
James Hallenbeck MD
Introduction Grief is a normal response to loss, any loss: a job, a limb, a life. Clinicians have an
important role in facilitating healthy grieving, and observing for signs of complicated grief. Grief
experienced by dying patients and loved-ones prior to and in anticipation of death is called anticipatory
grief (or mourning); grief of loved-ones following a death is termed bereavement. This Fast Fact provides
an overview of grief and bereavement.
What is Grief? Grief is a normal response to loss that involves processes and tasks at emotional,
cognitive and behavioral levels. The initial shock of learning of impending or actual loss evolves into a
process of creating a new relationship between the grieving person and the person (or object) of loss.
Grief tends to be experienced in waves, triggered predictably by new losses (such as a loss of functional
status) or unpredictably, by seemingly trivial events. Over time the intensity of these waves tends to
decrease. Grief does not have a set schedule; individuals progress through the grief process at different
speeds. However, no progress, getting stuck in one phase of grief, can be cause for concern.
What is Anticipatory Grief? Anticipatory grief for patients involves reviewing one's life; for families/
friends it means looking to a future without the dying person. Byock has suggested that patients and
families may wish to say to each other, in some way, "Forgive me, I forgive you, thank you, I love you and
good-bye." People from different cultural backgrounds may differ in terms of how and what they want to
say or do in preparation for death. Not knowing or acknowledging that a person is dying will likely delay
or interfere with normal anticipatory grief. Grief reactions in dying patients may be confused with pain,
depression, and even imminent death (e.g. social withdrawal may imply pain, depression, or anticipatory
grief).
Distinguishing Grief from Depression Neither pain nor depression are normal aspects of the dying
experience, they should be carefully evaluated as both are treatable (See Fast Fact #43). Grief tends to
be experienced as sadness, whereas depression is associated with lack of self-worth. The question, "Are
you sad or are you feeling depressed?" may help begin a dialog to help you distinguish between grief and
clinical depression.
What is Complicated Grief? About 10-20% of the bereaved can experience a persistent or prolonged
period of intense loss. There is debate regarding the precise diagnostic criteria for complicated grief and
duration of symptoms (see Fast Fact # 254 for further information). However, insecure attachment styles,
weak parental bonding in childhood, childhood abuse and neglect, female gender, low perceived social
support, supportive marital relationships, and low preparation for the loss are all felt to be risk factors.
What can the physician do to facilitate normal grieving?
!6
Be honest when discussing prognosis, goals and treatment options; nothing inhibits normal anticipatory
grief more than ambiguity from the physician. Listen; open the door to meaningful discussion. Ask, "How
are you doing with this recent news?" “Are you scared?" "Tell me what is going through your mind?” Ask
for help – you are not the only health professional available to help with grief. Contact a nurse, social
worker, chaplain or psychologist/psychiatrist if you need assistance. Assess for and aggressively treat
pain and depression.
References
1. Byock I. The Four Things that Matter Most. New York, NY: Simon & Schuster; 2004.
2. Markowitz AJ, Rabow MW. Caring for bereaved patients: "All the doctors just suddenly go.”
JAMA. 2002; 287(7):882.
3. Rando TA. Clinical Dimensions of Anticipatory Mourning. Champaign, IL: Research Press; 2000.
August 2005; 3rd Edition May 2015. Current version re-copy-edited March 2009; then again May 2015.
!7
IS IT GRIEF OR DEPRESSION?
VJ Periyakoil MD
Background Distinguishing between a dying patient’s normal grief and a major depression is a part of
routine care for patients near the end-of-life. This Fast Fact will review the definitions and clinical features
that distinguish these conditions. See Fast Facts #7, #32, and #254 for further discussions of depression,
grief, and complicated grief.
Definitions
• Preparatory (or anticipatory) grief. This is the grief, "that the terminally ill patient has to undergo in
order to prepare himself for his final separation from this world" (1). Features include rumination about
the past, withdrawal from family/friends, and periods of sadness, crying or anxiety. Preparatory Grief
is a normal, not pathological, life cycle event.
• Depression. Clinically significant depression in a population of dying patients is likely somewhat
more common (25-77%) than in the general population (2). However, depression is not an inevitable
part of the dying experience and is treatable. Somatic symptoms (anorexia, weight changes,
constipation, etc.) are often present as a part of the normal dying process and may not help to
distinguish between preparatory grief and depression. Feelings of guilt, hopelessness,
worthlessness, and suicidal ideation are the key factors that differentiate grief from depression.
When in doubt, treat for depression. Utilize mental health professionals when available. The
following additional points are offered to help the clinician distinguish between preparatory grief and
depression.
!8
Distinguishing preparatory grief from depression
• Temporal Variation. A temporal variation of mood is normal in preparatory grief—a mixture of “good
and bad days.” In contrast, persistent flat affect or dysphoria is characteristic of depression.
Depression is a pathological state; patients can 'get stuck' in this state without treatment. Self-Image.
A disturbed self-esteem is not typically seen in grief; however, it is a common feature of depression.
Overwhelming and persistent feelings of worthlessness to others and of being a burden are common
in depression. Distressing guilt is usually generalized to all facets of life in depression, while in grief,
the guilt is focused around specific issues (e.g. not being able to attend a child’s wedding).
• Hope. A grieving patient's hope shifts, but is not lost. (Hope may shift from a hope for cure to hope
for life prolongation to hope for dying well). In contrast, the depressed patient will comment on
feelings of hopelessness and helplessness.
• Anhedonia. The ability to feel pleasure is not lost in preparatory grief. Note: grieving patients often
need social interaction to help them through the grief process. Anhedonia is an important clue to
underlying depression.
• Response to Support. Social support helps provide the acceptance and assistance necessary for
completion of grief work (3). While social interaction may be helpful in some depressed patients, it will
typically not provide the assistance necessary to resolve depression.
• Active Desire for an Early Death. An active desire for an early death is not typical of preparatory
grief. A persistent, active desire for an early death in a patient, whose symptomatic and social needs
have been reasonably met, is suggestive of clinical depression (4).
• Self-Image. A disturbed self-esteem is not typically seen in grief; however, it is a common feature of
depression. Overwhelming and persistent feelings of worthlessness to others and of being a burden
are common in depression. Distressing guilt is usually generalized to all facets of life in depression,
while in grief, the guilt is focused around specific issues (e.g. not being able to attend a child’s
wedding).
References
1. Kubler-Ross E. On Death and Dying. New York, NY: Simon and Schuster; 1997: pp123-124.
2. EPEC Project Module 6: Anxiety, Delirium, Depression. In: Emanuel LL, von Gunten CF, Ferris FF,
eds. The EPEC Curriculum: Education for Physicians on End-of-life Care. Chicago, IL: The EPEC
Project; 1999. http://www.EPEC.net.
3. Education on Palliative and End-of-Life Care. http://www.epec.net. 1999.
4. Rando TA. Grief, Dying, and Death. Clinical Interventions for the Caregiver. Champaign, IL: Research
Press Company; 1984.
5. Chochinov HM, et al. Desire for death in the terminally ill. Am J of Psychiatry. 1995; 152:1185-91.
6. Billings JA, Block SD. Depression. J Pall Care. 1995; 11:48-54.
7. Block SD, for the ACP-ASIM End-of-Life Care Consensus Panel. Assessing and managing
depression in the terminally ill patient. Annals Intern Med. 2000; 132:209-218.
8. Block SD. Psychological considerations, growth, and transcendence at the end of life: the art of the
possible. JAMA. 2001; 285:2898-905.
August 2005; 3rd Edition May 2015. Current version re-copy-edited April 2009; then again May 2015.
!9

DEALING WITH THE ANGRY DYING PATIENT
Rebekah Wang-Cheng MD, FACP
Background Anger is a common emotion expressed by seriously ill patients and their families. A
typical reaction by the health professional, confronted by the angry patient or family, is to either get angry
back or to physically and psychologically withdraw; neither are particularly helpful coping strategies. A
guide to managing these situations is presented below.
Look for the underlying source of anger. Fear is probably the most common source of anger,
especially in the dying and their families – fear of the unknown, being in pain or suffering, the future well-
being of family members, abandonment, leaving unfinished business, losing control of bodily functions or
cognition, being a burden to the family, and dying alone.
Other sources of anger include: 1) a genuine insult – so called “rational anger” (e.g. waiting six hours to
see the doctor); 2) organic pathology: frontal lobe mass, dementia or delirium; and 3) personality style/
disorder – the person whose approach to much of life is via anger or mistrust.
Recognize the direction of anger. Recognizing the difference between internal and external anger is
critical to effective management, because internal anger may lead to potentially harmful patient
consequences. When the patient directs anger internally because of fear and guilt (e.g. I didn’t take care
of myself; I’m abandoning my family.), this can lead to withdrawal, self-neglect, anxiety, depression, or a
combination of these. Others direct their anger outward at physicians, hospitals, family members or a
deity. Particularly in the case of an angry parent of a dying child, he or she may feel helpless and guilty
about many things – not bringing the child for medical care soon enough, not being a loving enough or
“great” parent (1). This internal guilt and blame can then be displaced towards health care professionals.
Engage rather than withdraw from the patient. The natural tendency for clinicians is to cut short the
office or hospital visit, find ways to avoid contact with the angry patient or family member, or to try to mask
his/her own anger in order to continue to interact with the patient. Robert Houston MD has written a very
helpful article listing 10 rules for engaging the dying patient which will have a beneficial impact on the
physician/patient relationship and the quality of the patient’s end-of-life experience (2). One of his most
important tips is to refrain from personalizing the anger when the patient accuses you of “missing the
diagnosis” or under treating the pain. Some of his rules which are pertinent to this discussion are:
• Engage the patient, but do not enmesh with and do the emotional work for the patient.
• Maintain adult-adult communication rather than fostering the patient’s dependency.
!10
• Do not personalize the patient’s anger.
• Adopt a patient-centered worldview by ascertaining his/her values, priorities, hopes.
• Normalize anger so that the patient can move through this stage.
Use the "BATHE" approach to create an empathic milieu (3). As with any difficult patient situation,
communication techniques are especially important so that both the patient and physician do not become
further embittered and frustrated.
• Background: Use active listening to understand the story, the context, the patient's situation.
• Affect: Name the emotion; for instance, You seem very angry…. It is crucial to validate feelings
so the angry person feels that you are listening. Attempting to defuse it, counter it with your own
anger or ignore it, will be counter-productive. Acknowledging their right to be angry will help start
the healing process and solidify the therapeutic relationship.
• Troubles: Explore what scares or troubles them the most about their present and future. Just
asking the question Tell me what frightens you? will help them to focus on circumstances they
may not have considered.
• Handling: Knowledge and positive action can help mitigate fears and reduce anger. How are
they handling the dying – are they making concrete plans about their finances, their things, their
family? Have they thought about formal counseling to help deal with the depression, the anger?
• Empathy: By displaying empathy and concern you can help the person feel understood, less
abandoned and alone. Avoid trite statements such as I know what you're going through.
Paraphrasing the patient’s comments is an effective way to convey that you heard and are
seeking to understand: You feel like it's so unfair that the cancer appeared out of nowhere after
all these years.
Summary The journey from life to death almost always is accompanied by some degree of anger. A
caring, patient clinician can assist the patient and the family in recognizing, mobilizing, and modifying the
anger into positive emotional energy. Established communication approaches are available such as
BATHE which have shown improvements in self-efficacy for communicating with angry patients.
References
1. Grossman L. Understanding anger in parents of dying children. Am Fam Physician. 1998; 58(5):
1211-2.
2. Houston RE. The angry dying patient. Prim Care Companion J Clin Psychiatry. 1999; 1:5-8.
3. Stewart MR, Lieberman J, III. The Fifteen Minute Hour: Applied Psychotherapy for the Primary
Care Physician. 2nd Edition. Westport, CT: Praeger Publishing; 1993.
4. Rueth TW, Hall SE. Dealing with the anger and hostility of those who grieve. A J Hos Pall Care.
1999; 16:743-746.
5. Bialer PA, Kissane D, et al. Responding to patient anger: Development and evaluation of an
oncology communication skills training module. 2011; 9: 359-65.
!11

PHARMACOLOGIC MANAGEMENT OF DELIRIUM: UPDATE ON NEWER AGENTS
Earl Quijada MD and J Andrew Billings MD
Background Delirium is common in those with serious medical illness (See Fast Fact #1). Delirium is
an acute change in mental status that fluctuates and has underlying physiologic causes and can be
categorized as hyperactive, hypoactive, or mixed. Common reversible etiologies include constipation,
urinary retention, medications (benzodiazepines, opioids, steroids, and anticholinergic drugs), electrolyte
abnormalities, and sleep deprivation. Initial management strategies include identifying and treating the
underlying cause, as well as non-pharmacological treatment. However, when these strategies are not
effective pharmacological interventions may be necessary. The below pharmacological interventions are
for potentially reversible, hyperactive delirium.
1st Generation Antipsychotics
Haloperidol Although no medication has been approved by the FDA for the treatment of delirium, the
best studied antipsychotic, and the agent of choice for most patients, is haloperidol (Haldol), which can be
administered safely through oral and parenteral routes. Starting doses are 0.5 – 1 mg PO or IV. Titration
can occur by 2 – 5 mg every 1 hour until a total daily requirement is established, which is then
administered in daily or twice daily doses. Recommended maximum dose is 100 mg/day. Intravenous
haloperidol may cause less extrapyramidal symptoms than oral haloperidol.
Chlorpromazine Chlorpromazine (Thorazine) has more sedative effects than haloperidol for patients in
whom sedation is desired. The starting dose is 25 - 50 mg PO. Titration can occur by 25 - 50 mg every 1
hour until a total daily requirement is established, which is then administered in daily or twice daily doses.
Recommended maximum dose is 2000 mg/day.
2nd Generation Antipsychotics
Also known as atypical antipsychotics, no evidence currently exists for improved efficacy with 2nd
generation antipsychotics, so they are not considered to be first-line treatment. These agents are
associated with fewer extrapyramidal side effects than 1st generation antipsychotics, hence, in
Parkinson’s disease and related neuromuscular disorders and in patients with a history of extrapyramidal
reactions from 1st generation antipsychotics this class of agents may be preferred. For acutely agitated
patients requiring onset of action within minutes, providers should know that these agents do not work as
fast as conventional antipsychotics.
Olanzapine The starting dose for olanazapine (Zyprexa) is 5 mg PO every day; after one week, the
dose can be raised to 10 mg a day; then to 20 mg a day. It is available as an orally disintegrating tablet.
Quetiapine Quetiapine (Seroquel) is initially given 25 mg PO twice a day which can be raised by 25 –
50 mg per dose every 2 – 3 days up to a target of 300 – 400 mg a day, divided into 2 – 3 doses.
Compared to the atypical neuroleptics, it is the most sedating and causes the least extrapyramidal side
effects. It has more orthostasis than olanzapine and risperidone.
Risperidone Resperidone (Resperidal) is given 1 – 2 mg PO at night and is gradually raised 1 mg every
2 – 3 days until an effective dose (usually 4 – 6 mg PO hs) is reached. It has minimal anticholinergic
effects and does not cause orthostasis. It is the least sedating of this class of antipsychotics
!12
Newer antipsychotics include ziprasidone (Geodon) and aripiprazole (Abilify); their role in the
management of delirium is not firmly established.
Risks The FDA has issued a black-box warning about the increased risk of death when first- or second-
generation antipsychotics are used to treat dementia-related psychosis in elderly patients. This warning is
based on a number of limited studies which have not been replicated and do not address the short-term
use of antipsychotics to manage delirium. Delirium is a poor prognostic marker. Goals of care and values
must be discussed in the management of delirium.
Benzodiazepines With the exception of treating delirium due to drug withdrawal or anticholinergic
excess, benzodiazepines should be avoided for potentially reversible, hyperactive delirium unless the
agitation is severe and uncontrolled by the neuroleptic. Benzodiazepines can make delirium worse and
precipitate withdrawal syndromes.
Melatonin This hormone is produced naturally in the pineal gland and can help regulate the sleep-wake
rhythm cycle. Randomized placebo-controlled trials have validated the use of both melatonin and a
melatonin analog (ramelteon) in the prevention of delirium in at-risk, hospitalized patients.
References
1. Breitbart W, Bruera E, Chochinov H, Lynch M. Neuropsychiatric syndromes and psychological
symptoms in patients with advanced cancer. J Pain Symptom Manage. 1995; 10:131-41.
2. Breitbart W, Marotta R, Platt MM, et al. A double-blind trial of haloperidol, chlorpromazine, and
lorazepam in the treatment of delirium in hospitalized AIDS patients. Am J Psych. 1996;
153:231-7.
3. Jackson KC, Lipman AG. Drug therapy for delirium in terminally ill patients. Cochrane Database
2004; Syst Rev 2: CD004770.
4. Inouye SK, Bogardus ST Jr, Charpentier PA, et al. A multicomponent intervention to prevent
delirium in hospitalized older patients. N Engl J Med. 1999; 4:340:669-76.
5. Lawlor PG, Gagnon B, Mancini IL, et al. Occurrence, causes, and outcome of delirium in
patients with advanced cancer: a prospective study. Arch Intern Med. 2000; 160:786-94.
6. McIver B, Walsh D, Nelson K. The use of chlorpromazine for symptom control in dying cancer
patients. J Pain Symptom Manage. 1994; 9:341-5.
7. Menza MA, Murray GB, Holmes VF, Rafuls WA. Decreased extrapyramidal symptoms with
intravenous haloperidol. J Clin Psych. 1987; 48:278-280.
8. Sadock B, Sadock V. Kaplan and Sadock’s Pocket Handbook of Psychiatric Drug Treatment. 3rd
Edition. Philadelphia, PA: Lippincott Williams and Williams; 2001.
9. Stahl S. Essential Psychopharmacology: Neuroscientific Basis and Practical Applications. 2nd
Edition. New York, NY: Cambridge University Press; 2000.
10. Schneider LS, Dagerman KS, Insel P. Risk of death with atypical antipsychotic drug treatment
for dementia. Meta-analysis of randomized placebo controlled trials. JAMA 2005;
294:1934-1943.
11. Breitbart W, Alici Y. Evidence-based treatemtn of delirium in patients with cancer. Journal of
Clinical Oncology 2012; 30: 1206-1214.
12. Navari RM, Einhorn LH, et al. A phase II trial for the prevention of chemotherapy induced
nausea and vomiting: a Hoosier Oncology Group Study. Support Care Cancer 2005; 13:
529-34.
13. Hatta K, Kishi Y, et al. Preventive Effects of Ramelteon on DeliriumA Randomized Placebo-
Controlled Trial. JAMA Psychiatry. 2014;71(4):397-403.
14. Al-Aama T, Brymer C, Gutmanis I, Woolmore-Goodwin SM, Esbaugh J, Dasgupta M.
Melatonin decreases delirium in elderly patients: a randomized, placebo-controlled trial. Int J
Geriatr Psychiatry. 2011;26(7):687-694.
15. Irwin SA, Pirrelo RD, et al. Clarifying delirium management: practical, evidence-based expert
recommendations for clinical practice. Journal of Pall Med 2013; 16: 423-435.
September 2006; 3rd Edition May 2015. Current version re-copy-edited April 2009; olanzapine orally
disintegrating tablet information added. It was re-edited in May 2015.
!13
!14
NIGHTMARES
Seema Malhotra MD, Robert Arnold MD, and Kevin Patterson MD
Background Good, restful sleep is essential to quality of life – providing renewed energy for the next
day. Nightmares are vivid, frightening dreams that typically lead to full awakening with detailed
recollection of the dream sequence and content. Following a nightmare, heart rate and blood pressure
are elevated, and residual anxiety may interfere with the ability to return to sleep. Nightmares occur
almost exclusively during REM (Rapid Eye Movement) sleep.
Causes
Psychiatric. Anxiety is a common symptom during a life-threatening illness. Specifically, anxieties related
to the illness course and prognosis, procedures and treatments, family issues, and death, can be
significant. Nightmares may arise as a complication of anxiety or other psychiatric disturbances (such as
post-traumatic stress disorder, delirium, mood disorders, schizophrenia, and adjustment disorders).
Medications/Drugs/Alcohol. Medications causally linked to nightmares include: beta-blockers, sedative/

hypnotics, amphetamines and other stimulants, dopamine agonists, and antidepressants. Withdrawal
from REM-suppressing drugs, including antidepressants, benzodiazepines, and alcohol, predisposes to
the development of nightmares.
Brain disorders. CNS infections, brain tumors and other structural problems of the brain may lead to
nightmares.
Metabolic: hypoglycemia.
Psychotherapeutic Interventions can be particularly helpful for people whose nightmares are related to
stress/anxiety or an underlying psychiatric condition.
Supportive Psychotherapy. Brief, supportive psychotherapy can address a patient’s anxieties and
concerns; the therapist helps the patient with problem solving, seeking information and support, and
accepting aspects of their situation which cannot be changed.
Behavioral techniques. Relaxation training, desensitization, and dream imagery rehearsal therapy may
help reduce nightmares. In imagery rehearsal therapy, the patient writes down the disturbing dream,
changes the content, and practices the new, positive scenario mentally during the day; this new imagery
during the day reduces nightmares at night.
Pharmacologic Management The pharmacologic treatment of nightmares has not been studied in
controlled clinical trials. Case studies and anecdotal reports suggest the following drugs or drug classes
may be effective:
• Atypical Antipsychotics: risperidone (0.5-2 mg qhs) and olanzapine (5 mg) have both been
shown to reduce nightmares in small pilot studies of patients with acute stress and PTSD,
including reduction in flashbacks, hyperarousal, and disturbed sleep.
• Alpha-1 Antagonists: prazosin (2-15 mg qhs) has been shown to reduce nightmares and other
sleep-related symptoms in PTSD patients in multiple small studies and a single randomized
controlled trial involving 13 patients.
• Benzodiazepines and Tricyclic Antidepressants may be of benefit in suppressing REM activity.
Note: trazadone does not suppress REM activity.
• Other: Both cyproheptadine and topiramate have been reported to suppress nightmares in small
case series.
!15
References
1. Berlant J. Open-Label Topiramate as Primary or Adjunctive Therapy in Chronic Civilian
Posttraumatic Stress Disorder: A Preliminary Report. J Clin Psychiatry. 2002; 63(1):15-20.
2. Buysse DJ et al. In: Gabbard G, ed. Treatments of Psychiatric Disorders, 2nd Edition. Washington,
DD: American Psychiatric Press; 1995: pp2395-2453.
3. Sateia MJ et al. In: Doyle D, et al, eds. Oxford Textbook of Palliative Medicine, 2nd Edition. New
York, NY: Oxford University Press; 1998: pp751-767.
4. Krakow B et al. Imagery Rehearsal Therapy for Chronic Nightmares in Sexual Assault Survivors
with Posttraumatic Stress Disorder: A Randomized Controlled Trial. JAMA. 2001; 286(5):537-545.
5. Labbate LA. Olanzapine for Nightmares and Sleep Disturbance in Posttraumatic Stress Disorder
[comment]. Can J Psych. 2000; 45(7):667-668.
6. Stanovic JK et al. The Effectiveness of Risperidone on Acute Stress Symptoms in Adult Burn
Patients: A Preliminary Retrospective Pilot Study. J Burn Care Rehabilitation. 2001; 22(3):
210-213.
7. Taylor, FB et al. Prazosin Effects on Objective Sleep Measures and Clinical Symptoms in Civilian
Trauma Posttraumatic Stress Disorder: A Placebo-Controlled Study. Biol Psychiatry. 2008;
15:629-32.
8. Thompson DF et al. Drug-Induced Nightmares. Ann Pharmacother. 1999; 33(1):93-98.
by Drew A Rosielle and published October 2007; 3rd Edition June 2015. Current version re-copy-edited
April 2009; then again June 2015.
!16
INSOMNIA: PATIENT ASSESSMENT
Robert Arnold MD, Michael Miller, and Rohtesh Mehta MD MPH
Background Sleep disorders are common in the general population, the elderly, and the terminally ill.
Sleep deprivation causes reduced tolerance to pain and increased fatigue that prevents patients from
participating in meaningful daytime activities and decreasing their quality of life. This Fast Fact focuses on
the assessment of insomnia; it is the first of a series of three Fast Facts about insomnia (see #104, 105).
Definitions
• Primary Insomnia: difficulty initiating or maintaining sleep, or non-restorative sleep, for at least 1
month; does not occur exclusively during another mental disorder; is not due to the direct
physiological effects of a substance/medication or a general medical condition; and significantly
impairs functional/social quality of life. [DSM-IV-TR Diagnostic Criteria 307.42]. The International
Classification of Sleep Disorders (ICSD-2) classifies insomnias into various categories:
i. Acute/Adjustment Insomnia: Usually related to an acute physical/psycho-social stressor,
change in environment; is short-term, expected to resolve when stressor disappears, usually lasts
less than 3 months.
ii. Idiopathic Insomnia/Life-Long Insomnia: Begins during infancy or childhood, etiology is
unknown; patients may have learning disabilities.
iii. Psychological Insomnia/Conditioned/Learned Insomnia: Caused by an acute event such as a
significant life stress, pain, or illness; the individual no longer associates the bed with sleeping.
iv. Paradoxical Insomnia/Pseudo-insomnia/Sleep Hypochondriasis: Subjective feeling of
insomnia, with no polysomnographic evidence of a sleep disorder.
v. Inadequate Sleep Hygiene: Related to irregular sleep schedule, consumption of caffeinated
beverages, nicotine or alcohol, or exercise before bed-time.
vi. Circadian Rhythm Sleep Disorders: Jet lag and shift-work.
• Parasomnia: a disruptive physical act that occurs during sleep or during sleep–wake transitions
which may cause awakening or other disturbance in sleep. It includes nightmare disorder, sleep terror
disorder, sleepwalking disorder and other parasomnias.
• Sleep Apnea: short periods of breathing cessation during sleep; can be obstructive or central in
origin.
• Restless Legs Syndrome (RLS): paresthesias and dysesthesias of the legs that typically occur in
the evening or at night and may be relieved by movement (see Fast Fact #217).
• Periodic Limb Movement Syndrome (PLMS): involuntary, rhythmic twitches, typically ankle
dorsiflexion, occurring every 20–40 seconds, leading to brief arousals and accidental kicking of
bedmates. In contrast to RLS, PLMS occurs during sleep and patients often are not aware of it.
• Narcolepsy: a disorder of excessive daytime fatigue associated with abnormalities in rapid-eye-
movement sleep.
Sleep History Obtain a focused sleep history from the patient and bed partner. If needed, the patient
should be asked to record their daily sleep patterns in a sleep log for one week; see http://
www.webmd.com/sleep-disorders/guide/how-to-use-a-sleep-diary.
• Sleep hygiene. Has the patient altered their bedtime routine (e.g. change in bedtime, use of sleep
aids, lying in bed watching TV prior to sleep)?
• Sleep chronology. Evaluate the onset, pattern and duration of sleep and whether the insomnia is
transient, intermittent or persistent. A persistent problem usually is a consequence of a medical,
neurologic or psychiatric disorder. Ask if the patient has difficulty initiating sleep, staying asleep, or
both. Sleep apnea rarely causes disorders in initiating sleep. Nightmares (see Fast Fact #88) cause
difficulty staying asleep and may reflect spiritual suffering. Ask about multiple nocturnal or early
!17
morning awakenings. Frequent awakening is often due to medicine and early awakening is classically
due to depression.
• Sleep environment. Are any environmental factors (e.g. noise, light, odors) preventing sleep? This
may be particularly important in the hospital or a situation where a patient has moved into an
unfamiliar setting (e.g. children’s house).
• Physical symptoms. Are there physical symptoms interfering with sleep (e.g. cough, pain, dyspnea)?
Symptoms occurring just prior to sleep may reflect primary sleep disorders.
• Medical conditions. Are there co-morbid medical conditions that are associated with insomnia?
I. Worsening of chronic medical conditions (e.g. CHF, COPD).
II. New onset or worsening depression and/or anxiety.
III. Drugs (e.g. steroids, beta blockers, psychostimulants); use of alcohol and caffeine,
especially in the evening.
IV. Restless leg syndrome or periodic limb movements in sleep (see above).
• Spiritual concerns. Fears about dying may cause a patient to be afraid of falling asleep or to not want
to turn off the lights; this is especially common in patients with dyspnea. This is in contradistinction to
more typical insomnia where the patient is bothered by the lack of sleep.
References
1. Ohayon MM, Reynolds CF 3rd. Epidemiological and clinical relevance of insomnia diagnosis
algorithms according to the DSM-IV and the International Classification of Sleep Disorders (ICSD).
Sleep Med. 2009; 10(9):952-60.
2. International Classification of Sleep Disorders: Diagnostic and Coding Manual. 2nd ed, American
Academy of Sleep Medicine, Westchester, IL; 2005.
3. Bonnet MH, Arand DL. Diagnostic evaluation of insomnia. UpToDate; 2009.
4. Schenck C, Mahowald M, Salk R. Assessment and management of insomnia. JAMA. 2003; 289(19):
2475-2463.
5. Bloom HG, Ahmed I, Alessi CA, et al. Evidence-based recommendations for the assessment and
management of sleep disorders in older persons. J Am Geriatr Soc. 2009; 57(5):761-89.
Version History: This Fast Fact was originally written by Michael Miller and Robert Arnold, edited by
David E Weissman MD, and published in November 2003. Re-copy-edited in April 2009; sleep log
website updated. 2nd Edition was updated by Robert Arnold and Rohtesh Mehta and published in
September 2011; 3rd Edition published in June 2015.
!18
INSOMNIA: NON-PHARMACOLOGIC TREATMENTS
Robert Arnold MD, Michael Miller, and Rohtesh Mehta, MD MPH
!19
Introduction This Fast Fact addresses non-pharmacologic therapies for insomnia; Fast Fact #101
discusses patient assessment and #105 discusses pharmacologic treatment of insomnia.
Non-Specific Treatments
Improving Sleep Hygiene Sleep hygiene education should be provided to anyone with insomnia. First,
there is no arbitrary rule for how much someone should sleep. Generally, older patients need less sleep.
Second, patients should be advised to keep a regular sleep schedule; this means going to bed and
getting up at the same time. Third, patients should avoid long daytime naps, alcohol, and caffeine. These
principles may be difficult for seriously ill patients, particularly maintaining a regular routine for
hospitalized patients and avoiding naps for fatigued, seriously ill patients.
Behavioral Treatments
a. Relaxation therapies: The patient can be taught to use various relaxation techniques just
prior to bedtime such as progressive muscle relaxation, guided imagery, meditation,
diaphragmatic breathing or hypnosis (see Fast Fact #211).
b. Stimulus control therapy: This focuses on establishing a connection between the bed
and sleep. It emphasizes not watching TV, reading in bed, or using bedroom for any other
activity (except sexual activity).
c. Sleep restriction therapy: This therapy requires patient motivation as it involves restricting
the time allowed in bed depending upon the actual time spent in bed over the past 2
weeks and then going to bed 15 minutes earlier every night (increased weekly) until the
target bedtime is achieved. Sleep compression therapy is a variant of sleep restriction but
the reduction is sleep is made gradually.
d. Cognitive behavioral therapy: This is a multi-component psychotherapy, and includes
sleep restriction, stimulus control and cognitive therapy which focuses on identifying
unwanted feelings or thoughts and replacing them with more positive thoughts. It is
effective in treating chronic insomnia in the general population, in patients with chronic
pain, and in women with metastatic breast cancer.
The last two therapies are the only evidence-based psychological treatments for insomnia in older adults.
Physical Exercises: Although the data is limited, studies in elderly patients suggest significantly
improved sleep duration and onset latency and minimal enhancement in sleep efficiency with community-
based endurance training programs such as low impact aerobics, brisk walking, and Tai Chi Chih.
Choosing which therapy to use first depends mainly on provider experience and patient motivation. It is
difficult to know how long non-pharmacologic therapy should be tried before attempting other measures.
This depends on the patient, the severity of the insomnia, or the severity of the illness. Many studies
which showed cognitive behavioral therapy to be effective used a treatment regimen of 7-8 weeks.
Specific Treatments Obstructive sleep apnea is treated with positive airway pressure (e.g., ‘CPAP’)
ventilation at night. Although some patients report difficulty becoming accustomed to sleeping with the
CPAP mask on, this therapy can dramatically improve symptoms. Surgery is sometimes indicated for
obstructive sleep apnea. Symptoms from an underlying medical disorder can also contribute to insomnia.
Adequately treating a patient’s pain, nausea and vomiting (See Fast Fact #5), or dyspnea (See Fast Fact
#27) should improve sleep.
Spiritual and existential concerns can be an important cause of insomnia in palliative care patients.
Patients may be able to avoid these concerns during the day through the distraction of daily activities but
have difficulty ignoring them at night. Thus, it is important to directly address a patient’s spiritual
concerns, worries, and fears about dying during the day. Brief psychotherapy may be helpful.
References
1. Montgomery P, Dennis JA. Cognitive behavioural interventions for sleep problems in adults aged
60+. Cochrane Database of Systematic Reviews 2003, Issue 1. Art. No.: CD003161. DOI:
10.1002/14651858.CD003161.
2. Montgomery P, Dennis JA. Physical exercise for sleep problems in adults aged 60+. Cochrane
10.1002/14651858.CD003404.
3. McCurry SM, Logsdon RG, Teri L, Vitiello MV. Evidence-based psychological treatments for
insomnia in older adults. Psychol Aging. 2007;22(1):18-27
!20
4. Quesnel C, et al. Efficacy of cognitive-behavioral therapy for insomnia in women treated for
nonmetastatic breast cancer. J Consulting Clinical Psych. 2003; 71(1):189-200.
5. Jungquist CR, O'Brien C, Matteson-Rusby S, et al. The efficacy of cognitive-behavioral therapy
for insomnia in patients with chronic pain. Sleep Med. 2010 Feb 2
6. Irwin MR, Olmstead R, Motivala SJ. Improving sleep quality in older adults with moderate sleep
complaints: A randomized controlled trial of Tai Chi Chih. Sleep. 2008;31(7):1001-8.
David E Weissman MD, and published in November 2003. Re-copy-edited in April 2009. 2nd Edition was
updated by Robert Arnold and Rohtesh Mehta and published in September 2011. Revised in July 2013 to
correct an error (that CPAP is the primary positive airway pressure treatment for OSA, not bilevel
ventilation).

INSOMNIA: DRUG THERAPIES
Robert Arnold MD, Michael Miller, and Rohtesh Mehta MD MPH
Introduction Fast Facts #101 and #104 reviewed assessment of insomnia and its non-pharmacological
therapy. This Fast Fact focuses on the pharmacological treatment of insomnia. Prior to pharmacological
treatment, it is important to improve sleep hygiene and treat any contributing underlying medical
conditions (e.g. depression, pain, worsening CHF or COPD).
Non-Specific Drug Treatment:
1. Benzodiazepines have been successfully used for short term insomnia as they improve sleep
quality, total sleep time and reduce night-time awakenings, although there are no systematic
studies on long-term use and rare studies in palliative care. All drugs are dosed orally, at bedtime.
Most commonly used (and FDA approved) are temazepam (start 7.5 mg), estazolam (0.5 mg),
triazolam (0.125 mg), quazepam (7.5 mg) and flurazepam (15 mg). The first two are medium half-
life benzodiazepines (10-24 hours); triazolam has a shorter half-life (< 6 hours), quazepam and
flurazepam are longer lasting (half-life up to 3-7 days in elderly). All of these undergo hepatic
metabolism via cytochrome P450 system (except temazepam which is cleared renally) and thus
!21
have numerous drug-drug interactions. Flurazepam and triazolam have active metabolites.
Benzodiazepines have a high incidence of amnesia and rebound insomnia, particularly in anxious
patients, and may cause paradoxical agitation, increased risk of falls, hip fractures and cognitive
impairment, especially in the elderly. Other side effects include tolerance and dependence with
long-term use and additive CNS and respiratory side effects when used with other drugs.
2. Benzodiazepine receptor agonists. These are rapidly absorbed, metabolized by the liver, do
not have active metabolites, have low abuse potential and do not cause rebound insomnia upon
abrupt discontinuation. Zolpidem (5-10 mg) and Zaleplon (10-20 mg), both dosed at bedtime, are
ultra-short acting agents (half-life 1-2 hours) that restore sleep in patients with nocturnal
awakenings, while eszopiclone (1-2 mg) has a half-life of 6-9 hours. Zolpidem is available in a
controlled-release formulation.
3. Antidepressants such as trazodone (25-100 mg), doxepin (10-50 mg), amitriptyline (10 -50 mg),
imipramine (10-75 mg), and mirtazapine (5-15 mg) are commonly used for insomnia due to their
sedative properties, however the evidence for their use is less convincing.
4. Atypical antipsychotics. Most of the atypical antipsychotics (quetiapine, olanzapine and
ziprasidone), except for risperidone, improve total sleep time and/or sleep efficiency in healthy
subjects and schizophrenic patients. These may be beneficial in patients with insomnia who do
not respond to front-line treatment or insomnia in medically ill patients with delirium.
5. Miscellaneous sedative hypnotics. Choral Hydrate has moderate short term efficacy but is
more toxic than benzodiazepines. Barbiturates are effective in short term treatment, but
tolerance develops rapidly. Once commonly used for insomnia, these drugs are no longer used
except in rare circumstances.
6. Antihistamines and over-the-counter drugs. Diphenhydramine or other classical anti-
histamines have sedative properties, but they are generally not preferred in the elderly due to
anticholinergic properties and drug interactions. Diphenhydramine (25-100 mg) has been shown
to increase sleep duration but not quality (as it does not affect sleep architecture). Its half-life is
~5-10 hours, but is much longer in elderly. Most over the counter products contain
diphenhydramine or a similar sedating antihistamine, including products such as Unisom, Tylenol
PM, and Nyquil.
7. Melatonin is used for circadian rhythm sleep disorders and is less effective for chronic insomnia.
It has short half-life (45-60 min), has been used in doses ranging from 0.3 to 20 mg, is not FDA
approved, and does not have any significant effects on either sleep onset latency or sleep
efficiency.
8. Melatonin receptor agonists include ramelteon, tasimelteon and agomelatine. Ramelteon (8
mg) is FDA approved, has a half-life of 1–2.6 hours; has been shown to reduce sleep latency and
increased total sleep time in patients more than 65 years old with chronic insomnia. Side effects
are similar to that of placebo and include headache, somnolence and sore throat. Its primary
advantage is that there is no evidence of abuse and dependence, rebound insomnia, or
withdrawal effects.
9. Herbal remedies. Preliminary and conflicting evidence suggest that valerian (oral extract
400-900 mg QHS) may be as effective as mild hypnotics. The major side effects are
hepatotoxicity, cardiotoxicity and delirium. Evidence is lacking for other medications like kava
kava, L-tryptophan, chamomile, St. John’s wort and Jamaican dogwood.
Drugs for specific sleep disorders: See Fast Fact #217 for treatment of Restless leg syndrome.
Discussion of therapies for narcolepsy and nocturnal myoclonus or periodic leg movements is beyond the
scope of this Fast Fact.
References
1. Hirst A, Sloan R. Benzodiazepines and related drugs for insomnia in palliative care. Cochrane
10.1002/14651858.CD003346.
2. Schenck CH, Mahowald MW, Sack RL. Assessment and management of insomnia. JAMA.
2003; 289:2475-2479.
!22
3. Cohrs S. Sleep disturbances in patients with schizophrenia: impact and effect of antipsychotics.
CNS Drugs. 2008; 22(11):939-62.
4. Wine JN, Sanda C, Caballero J. Effects of quetiapine on sleep in nonpsychiatric and psychiatric
conditions. Ann Pharmacother. 2009; 43(4):707-13.
5. Buscemi N, Vandermeer B, Hooton N, et al. Efficacy and safety of exogenous melatonin for
secondary sleep disorders and sleep disorders accompanying sleep restriction: meta-analysis.
BMJ. 2006; 332(7538):385-93.
6. Roth T, Seiden D, Sainati S, et al. Effects of ramelteon on patient-reported sleep latency in older
adults with chronic insomnia. Sleep Med. 2006; 7(4):312-8.
7. Meolie AL, Rosen C, Kristo D. Oral nonprescription treatment for insomnia: an evaluation of
products with limited evidence. J Clin Sleep Med. 2005; 1(2):173-87.
David E Weissman MD, and published in November 2003. Re-copy-edited in April 2009. 2nd Edition was
updated by Robert Arnold and Rohtesh Mehta and published in September 2011.
!23
PANIC DISORDER AT THE END-OF-LIFE
VJ Periyakoil MD
Background Anxiety and fear occur commonly in the dying patient. However, disabling anxiety and/or
panic is not a normal aspect of the dying process. Separating “normal” death-related anxiety from
pathological panic is an important palliative care skill.
Definitions
• A panic attack is defined in the DSM-IV as “a discrete period of intense fear or discomfort, in
which four (or more) of the following symptoms develop abruptly and reach a peak within 10
minutes: palpitations, pounding heart or accelerated heart rate, sweating, trembling or shaking,
sensations of shortness of breath or smothering, feeling of choking, chest pain or discomfort,
nausea or abdominal distress, feeling dizzy, unsteady, lightheaded or faint, derealization or
depersonalization, fear of losing control or going crazy, fear of dying.
• Derealization describes a sensation of feeling estranged or detached from one’s environment.
• Depersonalization is an altered and unreal perception of self, one’s feelings and/or situation.
Described by one patient as “feeling like you are on the outside looking in”.
Diagnosis
• A combination of physical symptoms (feeling dizzy, weak, nauseous, unsteady, lightheaded,
breathless) and affective symptoms (fear of loss of control) are used to diagnose a panic disorder.
• Terminally ill patients may often have many of the physical symptoms listed above as a part of
their illness process. Thus the presence of derealization, depersonalization and fear of loss of
control are more useful in making the diagnosis of panic disorder in the terminally ill.
!24
• A contributing feature to the diagnosis of panic disorder is if a patient develops recurrent
symptoms, worries about future ‘attacks’ and alters her/his behavior in anticipation of such
attacks.
• Terminally ill patients with chronic dyspnea may often worry about “suffocating to death.”
Management
• Educate patients about the diagnosis and reassure them that their symptoms can be greatly
palliated with appropriate treatment.
• Optimize medical management of symptoms like pain, non-pain symptoms (especially dyspnea)
and depression.
• Ideal therapy is a combination of medical therapy with counseling from a trained psychologist.
• Consider complementary treatments: music therapy, massage therapy, guided imagery,
biofeedback.
• Medical management is influenced by anticipated lifespan and severity of panic symptoms.
• Selective serotonin reuptake inhibitors (SSRI) either as monotherapy or augmented with low dose
benzodiazepines for a period of 3 to 4 weeks (taper off benzodiazepines after 3 weeks) is
indicated in patients with an anticipated lifespan of several weeks or more.
• SSRIs can exacerbate anxiety in some patients during the first few days of therapy. Consider
adding benzodiazepines as needed for the first few weeks in such cases.
• Benzodiazepine monotherapy should be considered in patients with anticipated lifespan of days
to weeks. Consider low dose long acting benzodiazepine therapy on schedule (e.g. diazepam 1
mg every 12 hours) with short acting benzodiazepines (e.g. lorazepam 0.5 mg every 4 to 6 hours
as needed) for acute breakthrough symptoms.
• Many terminally ill patients need maintenance therapy for the rest of their life span, as relapse
rates are high on treatment discontinuation. In cases where treatment termination is attempted, it
is recommended that the medications be tapered gradually over a several week period to allow
early detection of a relapse.
• Abrupt termination of benzodiazepine therapy often may result in intense rebound anxiety. This
may happen when the patient is actively dying and unable to take oral medications. In such
cases, use alternate routes of drug administration (diazepam gel, diazepam rectal suppository or
diazepam or midazolam infusions).
References
1. Periyakoil VS, Skultety K, Sheikh J. Panic, anxiety, and chronic dyspnea J Pallit Med. 2005;
8:453-459
2. DSM-IV: Diagnostic and Statistical Manual of Mental Disorders. 4th ed. Washington, DC:
American Psychiatric Association; 1994.
3. Anderson A, ed. The ASAP Dictionary of Anxiety and Panic Disorders. Available at: http://
anxiety-panic.com/dictionary/en-main.htm.
November 2005. Version re-copy-edited in April 2009; revised again July 2015.
!25

SCREENING FOR DEPRESSION IN PALLIATIVE CARE
Robert Arnold MD
Background Depression is a significant symptom for approximately 1 in 4 palliative care patients and
is especially common in patients with metastatic cancer (see Fast Fact #21). Up to 80% of the
psychological symptoms that occur in cancer patients go unrecognized and untreated. One reason for
this is the difficulty in diagnosing depression in palliative care patients (see Fast Fact #7). In the primary
care literature, a number of brief screening instruments such as PRIME-MD are used to identify
depression. However, the symptoms associated with depression in primary care (weight loss, loss of
energy, fatigue, insomnia) also occur in patients without depression who have a life-threatening disease.
Thus, there has been interest in developing a brief scale that can accurately identify depression in the
palliative care population. This Fast Fact reviews that literature on depression screening tools.
Single question screening: A study of palliative care inpatients found that a single question, “Are you
feeling down, depressed or hopeless most of the time over the last 2 weeks?” correctly identified patients
with 100 percent sensitivity and specificity and a positive predictive value of 1 (Chochinov 1997). Adding
a second question about anhedonia (the absence of pleasure from the performance of acts that would
normally be pleasurable), “Have you found that little brings you pleasure or joy over the last two weeks?”,
reduced the specificity and positive predictive value. Unfortunately, follow-up studies using a single
question regarding mood in other palliative care populations have shown a sensitivity of roughly 55
percent and a specificity of 75 percent.
A four-item algorithm asks questions about energy level, anhedonism, depressed mood, and
psychomotor retardation/agitation. In a study of hospice patients in Australia this tool had a sensitivity
between 62 and 72%, specificity of 75 to 89% and positive predictive value of between 68 and 89%
(Robinson 2005).
The four question Brief Case Find for Depression asks questions about sleep, depressed mood, life
satisfaction, and ability to overcome difficulties. In a study of oncology and palliative care patients this tool
had fair agreement with longer depression screening instruments (Jefford 2004).
!26
Other studies have examined 10-20 question depression instruments that have been validated in other
patient populations. The Edinburgh Postnatal Depression Scale (Lloyd-Williams 2000), a self-assessment
scale consisting of ten items each rated on a 4-point scale, had a sensitivity of 70% and specificity of 80%
in patients with metastatic cancer receiving palliative care. The Hospital Anxiety and Depression Scale
(Lloyd-Williams 2003) is a 14 item scale with separate sub-scales for anxiety and depression. In a group
of patients with metastatic cancer, summing the two subscales gave a sensitivity of 77%, specificity was
89% and a positive predicted value of 0.48. Two more recent articles reported lower sensitivity and
specificity in patients with advanced metastatic disease.
Summary and Recommendations

• Clinicians should have a high clinical suspicion for depression—especially in patients who exhibit
feelings of hopelessness, worthlessness, guilt, anhedonia, sustained periods of feeling sad, and/
or those with suicidal ideation and/or suicidal plans.
• The literature does not suggest that any of the above scales are clearly superior for helping to
diagnose depression in a population of palliative care patients.
• Depression screening scales may be helpful in individual cases to provide the clinician with
additional data in formulating a diagnosis; if used, it is suggested that clinicians be familiar with
the sensitivity/specificity data for one scale and consistently use that scale so as to gain clinical
familiarity.
• Psychiatric consultation is indicated in cases of diagnostic uncertainty and/or when patients
present with profound depression and/or are overtly suicidal.
Definitions (Further resources available at: http://www.musc.edu/dc/icrebm/diagnostictests.html.)

• Sensitivity: The fraction of those with the disease correctly identified as positive by the test.
• Specificity: The fraction of those without the disease correctly identified as negative by the test.
• Positive predictive value: The fraction of people with positive tests who actually have the
condition.
References
1. Chochinov HM, Wilson K, Enns G, et al. "Are you depressed?" Screening for depression in the
terminally ill. Am J Psychiatry. 1997; 154(5):674-676.
2. Lloyd-Williams M, Spiller J, Ward J. Which depression screening tools should be used in
palliative care? Pall Med. 2003; 17:40-43.
3. Lloyd-Williams M, Friedman T, Rudd N. Criterion validation of the Edinburgh Postnatal depression
scale as a screening tool for depression in patients with advanced metastatic cancer. J Pain
Symp Man. 2000; 20:259-65.
4. Jefford M, Mileshkin L, Richard K, Thomson J et al. Rapid screening for depression- validation of
the Brief Case-Finding for Depression (BCD) in medical oncology and palliative care patients. Br
J Cancer. 2004; 91:900-6.
5. Robinson JA, Crawford GB. Identifying palliative care patients with symptoms of depression: an
algorithm. Pall Med. 2005; 19:278-87.
December 2005. Version re-copy-edited in April 2009; revised again July 2015.
!27

EVALUATING REQUESTS FOR HASTENED DEATH
Tim Quill MD and Robert Arnold MD
Background A patient’s request to a health care professional to help hasten death is not uncommon.
The motivation for this request is usually a combination of relentless physical symptoms, progressive
debility, in combination with a loss of sense of self, loss of control, fear of the future, and fear of being a
burden on others. Some physicians are frightened by these requests, feeling that they are being asked to
cross unacceptable professional boundaries. Others may be tempted to quickly accede, imagining that
they would want the same thing in the patient’s shoes. But requests for a hastened death may provide
awareness into a patient’s experience of suffering, and may lead to opportunities for more effective
treatment if fully evaluated. In general, the clinician should clarify, explore, evaluate, intensify treatment,
and support the patient to ensure a full understanding of the request and to ensure that all alternatives
have been considered before responding. This Fast Fact provides guidance on how to evaluate and
initially respond to a patient who raises the topic of a hastened death. Fast Fact #159 will explore how to
respond when the request for a hastened death persists after a full evaluation and search for alternatives.
1. Clarify which question is being asked before responding. Is the patient simply having thoughts about
ending his life (very common), or is he exploring the possibility of a hastened death in the future if his
condition deteriorates, or is he exploring your willingness to assist right now (1, 2)?
2. Support the patient, and reinforce your commitment to trying to find a mutually acceptable solution
for the patient’s problem and to continue to work through the process. This does not mean violating
fundamental values, but it does mean searching in earnest with the patient and family to find a way to
approach the dilemma (3). Attend to your own support by discussing the patient with trusted
colleagues and/or with your multidisciplinary team.
3. Evaluate the patient’s decision-making capacity. Is she seeing her medical condition clearly? Is the
request proportionate to the level of unrelieved suffering? Are there dominating aspects of
anhedonia, worthlessness and guilt, or is the capacity for pleasure and joy preserved in some small
ways? Is this request consistent with the patient’s past values? Get help from an experienced
psychiatrist or psychologist if you are unsure (4).
4. Explore the many potential dimensions that may contribute to the patient’s “unbearable” suffering to
be sure you (and the patient) fully understand its underlying cause(s). Sometimes in may be an
unrelenting physical symptom, other times feelings of depression, or a family or spiritual crisis, or
perhaps a combination of many factors (1, 2).
!28
5. Respond to the associated emotions, which may be strong and conflicted. Try to empathically
imagine what the patient is going through and asking for. Distinguish your own feelings and reactions
from those of the patient.
6. Intensify treatment of any potentially reversible elements of the patient’s suffering. Depending on
the patient’s circumstances, offer to increase treatment of pain or other physical symptoms, consider
biological or interpersonal treatment of depression; see if an appropriate and acceptable spiritual
counselor is available. Be creative and brainstorm potential solutions with your multidisciplinary team
(1, 2).
7. Respond directly to the request for hastened death only after this multidimensional evaluation has
been completed. If the patient has full decision-making capacity and all alternative approaches to the
patient’s unbearable suffering have been fully considered, then re-explore exactly what is being
requested, and look for mutually acceptable ways to potentially respond – see Fast Fact #159 (5).
Note that many patients may be looking for the potential of an escape they will never use, but a
smaller number will be looking for a way to hasten death in the present.
References
1. Quill TE. Doctor, I want to die. Will you help me? JAMA. 1993; 270:870-873.
2. Block SD, Billings JA. Patient requests to hasten death: Evaluation and management in terminal
care. Arch Intern Med. 1994; 154:2039-2047.
3. Quill TE, Cassel CK. Nonabandonment: A central obligation for physicians. Ann Intern Med.
1995; 122:368-374.
4. Block SD. Assessing and managing depression in the terminally ill patient. ACP-ASIM End-of-
Life Care Consensus Panel. Ann Intern Med. 2000; 132:209-218.
5. Quill TE, Lo, Brock DW. Palliative options of last resort: A comparison of voluntarily stopping
eating and drinking, terminal sedation, physician-assisted suicide, and voluntary active
euthanasia. JAMA. 1997; 278:1099-2104.
Version History: This Fast Fact was originally edited by David E Weissman MD and published in May
2006. Version re-copy-edited in April 2009; then again in July 2015.
!29
RESPONDING TO A REQUEST FOR HASTENING DEATH
Timothy Quill MD and Robert M Arnold MD
Background Requests for hastened death among terminally ill patients occur commonly (see Fast
Fact #156). With good symptom management, psychological and spiritual support, most patient requests
do not persist. This Fast Fact focuses on ways of responding to patients with persistent wishes for a
hastened death despite every effort to find appropriate alternatives. This Fast Fact does not address
such requests by surrogate decision makers of patients who have lost decision-making capacity.
1. Reflect on your personal feelings about the request and discuss with other professionals.
These cases are emotionally and ethically difficult. Brainstorm options with other members of the
care team including physician colleagues, nurses, psychologists, chaplains and others. Allow trusted
colleagues to support your emotional reactions.
2. Seek out consultation/2nd Opinion. Make sure you understand the medical, legal and ethical
issues involved in responding to a particular request for hastened death. Palliative care and/or ethics
consultations are invaluable. Independent second opinions may be helpful in clarifying the prognosis
and ensuring that all potentially effective therapeutic alternatives have been considered.
3. Learn the possibilities. Possibilities are listed below from least to most ethically controversial.
Considering these possibilities assumes that aggressive measures to control physical, psychological
and spiritual suffering have been exhausted and/or rejected by the patient:
o Withdrawal of life-sustaining treatments. While most clinicians consider stopping invasive
treatments under these circumstances (e.g. ventilators, ICDs, feeding tubes), simpler therapies
such as insulin, antibiotics, oxygen, or steroids might also be voluntarily discontinued if they are
prolonging life against the patient’s wishes. (Unlike the other possibilities, there is widespread
legal and ethical consensus about the permissibility of this response based on the right to bodily
integrity.)
o Voluntary withdrawal of oral intake. Patients may choose to stop eating and drinking to
shorten the dying process. Completely stopping oral food and liquids will typically result in death
within two weeks.
o Sedation for severe intractable physical symptoms (see Fast Facts #106,107). The intent of
sedation is to relieve intolerable suffering by a reduction in patient consciousness. If artificial
hydration and feeding are simultaneously stopped, death will come within 1-2 weeks.
o Assisted Suicide. Assisted suicide is defined as someone who provides the means for another
person to end their life (e.g. prescribing an overdose amount of medication), but the patient is the
one to decide if and when the medicine is actually used, and the patient is responsible for taking
!30
the medicine. Physician-assisted suicide is illegal in the United States except for selected states
(e.g. Oregon, Washington, Vermont, and Montana).
4. Decision making process. Have a detailed conversation regarding the risk and benefits of the
different possibilities that fit the patient’s clinical circumstances, and which the patient, family and you
find ethically acceptable. Be as specific as possible, and document your thinking process clearly.
Thus, if stopping eating and drinking is being considered, be sure everyone understands the
importance of complete cessation of drinking or else the process can take months rather than weeks.
5. Balance integrity and non-abandonment. It is not always possible to find common ground
between the patient and physician. When asked if one can support a particular act, a physician
needs to be as specific as possible about what he/she can and cannot do, and why. While the
physician should not violate personal principles to respond to a request he/she finds unacceptable,
he/she should search in earnest with the patient and family for alternative options that might be
mutually acceptable. Typically, this approach will allow the physician to maintain integrity while not
abandoning the patient, even if agreement on the particular act in question is not possible (1-4).
References
1. Quill TE, Cassel CK. Nonabandonment: A central obligation for physicians. Ann Intern Med.
1995; 122:368-374.
2. Quill TE, Lo, Brock DW. Palliative options of last resort: A comparison of voluntarily stopping
eating and drinking, terminal sedation, physician-assisted suicide, and voluntary active
euthanasia. JAMA. 1997; 278:1099-2104.
3. Quill TE, Byock I. Responding to intractable terminal suffering: the role of terminal sedation and
voluntary refusal of food and fluids. ACP-ASIM End-of-Life Care Consensus Panel. Ann Intern
Med. 2000; 132:408-414.
4. Quill TE, Coombs-Lee B, Nunn S. Palliative options of last resort: Finding the least harmful
alternative. Ann Intern Med. 2000; 132:488-93.
Version History: This Fast Fact was originally edited by David E Weissman MD and published in July
2006. Version re-copy-edited in April 2009; then again November 2016 (legality of physician assisted
suicide in US updated).
!31
Background Anxiety is a state of apprehension and fear resulting from the perception of a current or
future threat to oneself. The term is used to describe a symptom and a variety of psychiatric disorders in
which anxiety is a salient symptom. This Fast Fact will discuss the causes and evaluation of anxiety.
Prevalence Anxiety is commonly reported in those facing life-threatening illnesses. At least 25% and
cancer patients and 50% of CHF and COPD patients experience significant anxiety. At least 3% of
patients with advanced cancer and 10% of COPD inpatients meet DSM criteria for Generalized Anxiety
Disorder (see below).
Etiologies
arrhythmias.
corticosteroids.
• Existential and psychosocial concerns about dying, disability, loss, legacy, family, finances, and
religion/spirituality.
• Generalized anxiety disorder is a psychiatric disorder characterized by pervasive and excessive
anxiety and worry about a number of events or activities (such as work or school performance),
occurring more days than not for at least 6 months. The anxiety and worry are associated with at least
3 of the following 6 symptoms: restlessness, easy fatigue, difficulty concentrating, irritability, muscle
tension, and sleep disturbance.
• Panic disorder is characterized by recurrent panic attacks. See Fast Fact #145 for its evaluation and
management.
• Adjustment disorder occurs within 3 months of a major stressor, and causes marked distress and
functional impairment. Usually it is characterized by a depressed mood but anxiety can also be its
most prominent affective component.
• Acute- or post-traumatic stress disorders occur after an emotionally traumatic life-event and are
characterized by anxiousness and arousal, as well as by numbness, flashbacks, intrusive thoughts,
and avoidance of stimuli which remind the patient of the trauma.
Evaluation
!32
• Seek help from a professional familiar with the psychiatric disorders when anxiety is a prominent and
functionally impairing part of a patient’s symptoms.
akathisia, an unpleasant sense of motor restlessness from dopamine-blocking medications such as
antipsychotics and some antiemetics.
• Formal screening tools exist, but there is no consensus on the benefit of their routine use. Commonly
used tools which evaluate for anxiety as a symptom include the Edmonton Symptom Assessment
Scale, the Memorial Symptom Assessment Scale, and the Hospital Anxiety and Depression Scale.
References
2. Mikkelsen RL, et al. Anxiety and depression in patients with chronic obstructive pulmonary
disease (COPD). A review. Nordic J Psychiatry. 2004; 58:65-70.
3. Friedmann E, et al. Relationship of depression, anxiety, and social isolation to chronic heart
failure outpatient mortality. Am Heart J. 2006; 11:152.
4. Tremblay A and Breitbart W. Psychiatric dimensions of palliative care. Neurol Clin. 2001; 19(4):
949-67.
5. Bjelland I, et al. The validity of the Hospital Anxiety and Depression Scale. An updated literature
review. J Psychosom Res. 2002; 52(2):69-77.
6. Bruera E, Kuehn N, Miller MJ, Selmser P, Macmillan K. The Edmonton Symptom Assessment
System (ESAS): a simple method of the assessment of palliative care patients. J Palliat Care.
1991; 7:6-9.
7. Portenoy RK, Thaler HT, Kornblith AB, et al. The Memorial Symptom Assessment Scale: an
instrument for the evaluation of symptom prevalence, characteristics and distress. Eur J Cancer.
1994; 30A(9):1326-36.
Version History: Originally published August 2007. Version copy-edited in May 2009; then again July
2015.
!33
SUICIDE ATTEMPTS IN THE TERMINALLY ILL
Background Chronic or advanced medical illness is a significant risk factor for suicidality (1). This Fast
Fact discusses evaluating and responding to suicidality in patients with life-limiting diseases. Note: this
Fast Fact does not address cases of ‘physician assisted suicide’ which have occurred after a deliberative
process including psychiatric screening such as in Oregon in the US (2).
Ethics
• Core Principles: It is a core obligation of physicians to prevent a patient from initiating suicide and to
intervene medically to prevent a patient from dying after a suicide attempt (3). This obligation can
include detaining and restraining patients against their will and the use of invasive medical interventions
such as mechanical ventilation if needed, although such restrictions to a patient’s liberty should be kept
to the minimum necessary. Most suicidal patients are considered impaired by depression or other
mental illnesses and their actions are not considered autonomous, thus justifying detaining patients and
providing medical interventions against their will (4). Such interventions can create further opportunities
to treat the patient’s psychiatric condition, and only 20% of people who are prevented from committing
suicide subsequently complete another attempt.
• Exceptions at life’s end: The above logic is less compelling in terminally ill patients who have attempted
suicide, particularly with short prognoses (e.g. <1 month). In these patients most medical interventions
are unlikely to restore health or significantly alter the dying process in a way that would materially
benefit the patient. Clinicians may opt to forgo certain interventions (e.g. mechanical ventilation),
particularly if family/proxy decision makers consider such interventions inappropriate in their dying loved
ones. In these situations clinicians are advised to 1) verify the certainty of the very short prognosis,
utilizing consultants liberally, 2) discuss with proxy decision makers all possible treatment plans
including, when feasible, less-invasive supportive care options with treatment limitations (e.g. ICU
monitoring, gastric lavage and charcoal administration for an overdose, but establishing a do-not-
resuscitate/do-not-intubate order even if the patient deteriorates), and 3) seek ethics consultation.
• Advance Directives: Advance directives such as living wills stating a patient’s wish to not be
mechanically ventilated are not binding in the setting of a suicide attempt. However, they should be
honored in patients with short prognoses per the discussion above. Advanced directives specifying
treatment limitations should be re-evaluated if it is suspected those statements were made during a
period of undetected depression (5,6).
Epidemiology and Risk Factors There has been limited research into specifically ‘terminally ill’
populations, hence the rate of suicide in the terminally ill is unknown. What is clear is that advancing age
and psychiatric comorbidity are risk factors for suicide along with male sex, AIDS diagnosis, a family
history of suicide, and uncontrolled pain (7,8). Cancer patients have nearly twice the incidence of suicide
than the general population (rate of 31.4 vs. 16.7/100,000 patient-years) and the first year after diagnosis
carries a higher risk (6,9). Lung, prostate, pancreatic, and head and neck cancers have the highest
suicide rates among all cancer types (9). Up to 8.5% of terminally ill cancer patients express a sustained
and pervasive wish for an early death, and in one survey 10% of terminally ill patients reported “seriously
pursuing” physician assisted suicide (10,11). Rates of actual suicide attempts are presumably lower.
!34
Assessment All patients with life-limiting illnesses should be routinely assessed for depression and
mood disorders (see Fast Facts #7, 43); depressed patients should be screened for suicidal thoughts.
Patients who admit to suicidal thoughts or a desire for hastened death should be asked about specific
plans for self-harm, past history of suicide attempts, access to firearms or other lethal means to carry out
a suicidal act, and level of support/supervision available in the home (e.g. family caregivers). Although
some clinicians may be concerned that exploring suicidal thoughts may make suicide more likely, there is
no evidence that this occurs. Many ill patients who express a desire for death are simply communicating
unresolved emotional and existential concerns about dying: see Fast Facts #156 & 159.
Responding to Suicidal Intent All patients who are seriously threatening self-harm, or who have
pervasive thoughts of ending their life, should be evaluated urgently by a psychiatrist (12). Immediate
resources depend on local availability and can include prompt evaluation by an established psychiatrist,
medical or psychiatric urgent care clinics or emergency departments, or even voluntary hospital
admission. Options include voluntary psychiatric treatment, arranging 24-hour safety monitoring from the
patient’s family and friends, introducing home hospice or home nursing support, removing means to carry
out a suicidal act, and imposing emergency detention. For disabled patients close to death, removing the
means of self-harm (e.g. limit access to pain medications as long as a reliable family member can
administer them) and providing close supervision through, for instance, hospice services are often
sufficient and minimally restrictive.
References
1. Hendin H. Suicide, assisted suicide and medical illness. J of Clin Psychiatry. 1999; 60 Suppl
2:46-50.
2. Death With Dignity Act Report 2007. State of Oregon Department of Human Services. Available
at: http://www.oregon.gov/DHS/ph/pas/index.shtml. Accessed November 10, 2008.
3. Lo B. Resolving ethical dilemmas: a guide for clinicians – 3rd Edition. Lippincott Williams &
Wilkins, 2005: 256-9.
4. Miller RD. Need-for-treatment criteria for involuntary civil commitment: impact in practice. Am J
Psychiatry. 1992; 149:1380-4.
5. Ganzini L, Lee MA, Heinz RT, et al. The effect of depression treatment on elderly patients’
preferences for life sustaining medical therapy. Am J of Psychiatry. 1994; 151:1631-6.
6. Sontheimer D. Suicide by advance directive. J Med Ethics. 2008; 34:e4; doi:10.1136/jme.
2008.025619.
7. Farberow NL, Banzler S, Cutter F, Reynolds D. An eight-year survey of hospital suicides.
Suicide and Life-Threatening Behavior. 1971; 1:184-201.
8. Rabins PV. Prevention of mental disorder in the elderly: current perspectives and future
prospects. J Am Geriatric Soc. 1992; 40:727-33.
9. Anguiano L, Mayer DK, et al. A literature review of suicide in cancer patients. Cancer Nursing
2012; 35:E14-E26.
9. Chochinov HM, Wilson KG, Enns M, Mowchun N, Lander S, Levitt M, et al. Desire for death in
the terminally ill. Am J Psychiatry. 1995; 152:1185-91.
10. Emanuel EJ, Fairclough DL, Emanuel LL. Attitudes and desires related to euthanasia and
physician-assisted suicide among terminally ill patients and their caregivers. JAMA. 2000;
284:2460-2468.
11. Block SD. Chapter 6: Assessing and managing depression in the terminally ill patient.
Physician’s Guide to End of Life Care. Snyder, Lois ACP Press; 2001.
Author Affiliations: Medical College of Wisconsin, Milwaukee, WI (SM), University of Minnesota

Medical School & Fairview Health Services, Minneapolis, MN (DAR).
Version History: Published November 2008; copy-edited June 2012; re-copy-edited July 2015 with
reference #9 added and incorporated into the text.
!35
!36
COMPLICATED GRIEF
René Claxton MD and Charles F Reynolds III, MD
Background The majority of individuals experience normal grief after the death of a loved one (see
Fast Fact #32). However, about 10-20% of bereaved individuals experience a persistent, debilitating
phenomenon referred to as complicated grief (CG) (1). Complicated grief has also been referred to as
prolonged or pathologic grief (2); and in the most recent revision of the Diagnostic and Statistical Manual
of Mental Disorders (DSM V), CG was relabeled as Persistent Complex Bereavement Disorder (3).
Risk Factors CG is principally considered an attachment disorder (1). Insecure attachment styles
(excessive dependency, compulsive care-giving, defensive separation) are correlated with CG.
Additionally, supportive marital relationships (characterized as security-enhancing, confiding and
emotionally supportive) are correlated with CG after the loss of a spouse suggesting that the loss of a
spouse who provides emotional stability and security may lead to an exacerbated grief reaction (4).
Other risk factors include weak parental bonding in childhood, childhood abuse and neglect, female
gender, low perceived social support, and low preparation for the loss (1,5).
Impact on Health CG is associated with mental and physical health problems including depression,
hypertension, work and social impairment and reduced quality of life. Additionally, CG increases an
individual’s risk of suicide and suicidal behavior (7).
Diagnosis CG shares characteristics with major depressive disorder (suicidal ideation, preoccupation
with worthlessness) and post-traumatic stress disorder (re-experiencing intrusive thoughts of the
deceased, avoidance of reminders of the deceased and emotional numbness). However, these are
separate entities differentiated by precipitating events, risk factors, course of illness and response to
intervention (2). The precise diagnostic criteria for CG are currently being debated (5). Commonly agreed
upon characteristics include:
• yearning, pining, or longing for the deceased
• trouble accepting the death
• feeling uneasy about moving on with one’s life
• inability to trust others since the death
• excessive bitterness or anger about the death
• persistent feeling of being shocked, stunned, or emotionally numb since the death
• frequent intense feelings of loneliness
• feeling that life is empty or meaningless without the deceased (refraining from doing things/going
places that remind one of the loss)
• frequent preoccupying thoughts about the person that died
Symptoms must cause marked dysfunction in social, occupational or other important domains. The
duration of symptoms required to meet criteria for CG has not been defined and varies between six to
twelve months after the death (1, 5).
Screening The following Brief Grief Questionnaire is a 5-item screening tool scored on a 0-2 Likert scale
(‘not at all,’ ‘somewhat,’ ‘a lot’) which has been used to screen for CG (6).
1. How much of the time are you having trouble accepting the death of a loved one?
2. How much does your grief interfere with your life?
3. How much are you having images or thoughts of your loved one when he or she died or other
thoughts about the death that really bother you?
4. Are there things that you used to do when your loved one was alive that you don’t feel
comfortable doing more, that you avoid? How much are you avoiding these things?
5. How much are you feeling cut off or distant from other people since your loved one died, even
people you used to be close to, like family or friends?
Expert recommendation is that individuals with scores of ≥5 should undergo a diagnostic evaluation by a
mental health professional (7).
!37
Treatment A recent meta-analysis on the treatment of CG showed efficacy of interventions including
cognitive-behavioral and group therapy in alleviating symptoms with a duration of benefit from 3-6
months. Limitations of the meta-analysis include under-representation of men (average 71% female),
small number of studies included (n=5), and small number of participants (n=485, 109 lost to follow up)
(8). There have been no randomized controlled trials evaluating the pharmacologic treatment of CG and
there is currently no defined role for drug therapy. A randomized trial is currently underway to evaluate the
effect of a selective serotonin reuptake inhibitor on CG. Many hospice agencies provide bereavement
services, even if the bereaved’s loved one was not a patient of the hospice agency.
Bottom Line Most bereaved individuals experience normal grief. A minority will experience long-term,
persistent, disruptive symptoms that impair functioning and increase the risk for negative mental and
physical health states. Individuals suffering from CG benefit from referral to a trained mental health
provider who can administer therapy specific to CG.
References
1. Zhang B, et al. Update on bereavement research: evidence-based guidelines for the diagnosis
and treatment of complicated bereavement. J Pall Med. 2006; 9:1188-1203.
2. Lichtenthal WG, et al. A case for establishing complicated grief as a distinct mental disorder in
DSM-V. Clin Psych Rev. 2004; 24:637-662.
3. American Psychiatric Association (2013). Diagnostic and Statistical Manual of Mental Disorders,
ed. 5. Arlington, VA, APA Press.
4. Van Doorn C, et al. The influence of marital quality and attachment styles on traumatic grief and
depressive symptoms. J Nerv Ment Dis. 1998; 186:566-573.
5. Shear KM, et al. Complicated grief and related bereavement issues for DSM-5. Depress Anxiety.
2001; 28:103-117.
6. Shear KM, et al. Screening for complicated grief among project liberty service recipients 18
months after September 11, 2001. Psychiatric Services. 2006; 57:1291-7.
7. Reynolds C, et al. Healing Emotions After Loss (HEAL): Diagnosis and Treatment of Complicated
Grief. UPMC Synergies. Spring 2011. Available at: http://healstudy.org/wp-content/uploads/
2010/10/S270-Synergies_GR_Spring_2011.pdf. Accessed March 22, 2012.
8. Wittouck C, et al. The prevention and treatment of complicated grief: a meta-analysis. Clin Psych
Rev. 2011; 31:69-78.
Version History: First published June 2012. Updated December 2012 with the addition of Reference #6.
Updated again in August 2015 with reference # 3 added and incorporated into the text.
NonCommercial 4.0 International Copyright (http://creativecommons.org/licenses/by-nc/4.0/). Fast
Facts can only be copied and distributed for non-commercial, educational purposes. If you adapt or
!38
PHARMACOLOGIC MANAGEMENT OF DEPRESSION IN ADVANCED ILLNESS
Leah Rosenberg, MD; Jane deLima Thomas, MD
!39
Adults with serious illness have a higher incidence of major depressive disorders than healthy adults, with
an estimated incidence of 15% (1). In this Fast Fact, we will provide a clinical framework for selecting
pharmacologic agents for seriously ill patients with depression. See Fast Facts # 7, 43 and 146 for
assistance in diagnosing and screening for depression in palliative care patients.
Determine the patient’s prognosis Because most traditional antidepressants take more than 4 weeks
to become effective, they should only be considered in patients expected to live at least that long (2). Use
is also limited to patients who are able to swallow oral medications or place them in a feeding tube. For
patients with a prognosis < 4 weeks, a psychostimulant such as methylphenidate or dextroamphetamine
may act within 1-2 days and be safe in patients without significant cardiovascular disease or delirium.
Although the data on psychostimulants are somewhat mixed, controlled trials have shown benefit as both
a monotherapy or to augment the effects of another anti-depressant (3-5). See Fast Fact #61.
Consider co-morbid symptoms When choosing an antidepressant, consider the patient’s other co-
morbid symptoms such as insomnia, neuropathic pain, or poor appetite (6). Other considerations include
the patient’s past responses to specific agents and possible drug interactions. Common classes of
antidepressants include serotonin-selective reuptake inhibitors (SSRIs), serotonin-selective
norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), and others.
SSRIs Also called “second generation antidepressants”, these are the most commonly prescribed
antidepressants. SSRIs should be started at a low dose and then titrated to the minimum effective dose to
minimize adverse effects such as QTc prolongation, sexual dysfunction, headaches, nausea and diarrhea.
Fluoxetine is associated with emotional activation and may worsen anxiety. Paroxetine can be sedating
and lead to withdrawal phenomena with missed doses. Because sertraline, citalopram, and escitalopram
have lower side effect profiles and are neither activating nor sedating, they may be better choices for
palliative care patients (7). The starting dose of sertraline is 25-50 mg/day with a usual effective dose of
50-200 mg/day; it is available in a concentrated liquid formulation for patients with dysphagia related
issues. Both citalopram and escitalopram have been shown to have few drug interactions. The starting
dose of citalopram is 20 mg/day with a maximum daily dose of 40 mg. The starting dose of escitalopram
is 10 mg/day with a usual effective dose of 10-20 mg/day (8-10).
SNRIs inhibit serotonin and norepinephrine reuptake, two neurotransmitters important in endogenous
pain pathways (11). This class may be helpful for neuropathic pain, vasomotor instability, and anxiety-
predominant depression. In particular, venlafaxine has shown effectiveness for the amelioration of hot
flushes and the prevention of chemotherapy-induced polyneuropathy (CIPN); duloxetine has shown
efficacy for the treatment of CIPN (12). SNRIs may prolong bleeding times and therefore may not be safe
in patients with active bleeding or intracranial metastases. The starting dose for venlafaxine is 37.5 mg
with a usual effective dose of 75-225 mg/day. It requires close monitoring for missed-dose withdrawal and
hypertension. The starting dose for duloxetine is 30 mg with a usual effective dose of 60-120 mg/day. It
has been associated with hepatic insufficiency and a worsening of acute-angle glaucoma.
TCAs are an older class of anti-depressants that can be cost-effective when used at lower doses. They
also are proven adjuvant analgesics for neuropathic and chronic low back pain. Unfortunately, their
anticholinergic properties can induce delirium, prolong the QTc interval, and be dangerous in overdose.
Therefore, their use is limited to heart-healthy patients under the age of 65 with comorbid neuropathic
pain and insomnia. Although the preponderance of supporting data for the analgesic effects is for
amitriptyline (usual starting dose 10-25 mg/day; usual effective dose is 150 mg/day), nortriptyline is felt to
be less sedating (usual starting dose 25 mg/day; usual effective dose is 50-100 mg/day).
Other Medications Mirtazapine has histaminergic side effects that can be helpful especially for cancer
patients who often experience insomnia, poor appetite, and nausea (13). It has few drug interactions but
can be associated with orthostatic hypotension. Its usual starting dose is 7.5-15 mg/nightly; usual
effective doses are 15-30 mg/day. Buproprion is thought to be less sedating and have a lower incidence
of sexual side effects, but it may lower the seizure threshold. The usual starting dose for buproprion is
150 mg/day; the usual effective dose is 150-300 mg/day (14). Single-dose treatment with NMDA
antagonist ketamine has shown promise in early investigational studies (15). Aripiprazole may
augment the antidepressant effects of SSRIs and SNRIs as early as a week after initiation (16).
!40
Summary Recommendations:
• For patients with prognoses of weeks, consider the use of a psychostimulant like methylphenidate.
• Consider duloxetine or venlafaxine when neuropathic pain is present.
• When polypharmacy is present, consider citalopram, escitalopram or mirtazapine.
• If the patient has insomnia, nausea, or anorexia, consider the use of mirtazapine.
• Closely monitor patients initiated on an antidepressant for adverse effects and dose titration.
• Refer to a mental health clinician for pre-existing major depression, the presence of comorbid
psychiatric illness, suicidal ideation, refractory symptoms, or psychiatric polypharmacy.
• Refer to social work and/or spiritual support services if the depression appears to be escalating in
relation to social or spiritual factors.
References:
1. Hotopf M, Chidgey J, Addington-Hall J, Ly KL. Depression in advanced disease: a systematic
review Part 1. Prevalence and case finding. Palliat Med. 2002 Mar;16(2):81-97.
2. Block SD. Assessing and managing depression in the terminally ill patient. Ann Intern
Med. 2000;132(3):209-218.
3. Woods SW, Tesar GE, Murray GB, Cassem NH. Psychostimulant treatment of depressive
disorders secondary to medical illness. J Clin Psychiatry. 1986 Jan;47(1):12-5.
4. Olin J, Masand P. Psychostimulants for depression in hospitalized cancer patients.
Psychosomatics. 1996 Jan-Feb;37(1):57-62.
5. Lavretsky H, Reinlieb M, et al. Citalopram, methylphenidate, or their combination in geriatric
depression: a randomized, double-blind, placebo-controlled trial. Am J Psychiatry 2015;
172:561-69.
6. Janberidze E, Hjermstad MJ, Brunelli C, Loge JH, Lie HC, Kaasa S, Knudsen AK; EURO
IMPACT. The use of antidepressants in patients with advanced cancer--results from an
international multicentre study. Psychooncology. 2014 Oct;23(10):1096-102.
7. Lloyd Williams M, Friedman T, Rudd N. A survey of antidepressant prescribing in the terminally
ill. Palliat Med 1999;13:243–8.
8. Rayner L, Price A, Hotopf M, Higginson IJ. Expert opinion on detecting and treating depression in
palliative care: A Delphi study. BMC Palliative Care. 2011;10:10.
9. Sanchez C, Reines EH, Montgomery SA. A comparative review of escitalopram, paroxetine, and
sertraline: are they all alike? International Clinical Psychopharmacology. 2014;29(4):185-196.
10. Preskorn SH. Recent pharmacologic advances in antidepressant therapy for the elderly. Am J
Med 1993;94:2S–12S.
11. Marks DM, Shah MJ, Patkar AA, Masand PS, Park G-Y, Pae C-U. Serotonin-Norepinephrine
Reuptake Inhibitors for Pain Control: Premise and Promise.Current Neuropharmacology.
2009;7(4):331-336.
12. Piccolo J, Kolesar JM. Prevention and treatment of chemotherapy-induced peripheral neuropathy.
Am J Health Syst Pharm. 2014 Jan 1;71(1):19-25.
13. Theobald DE, Kirsh KL, Holtsclaw E, et al. An open-label, crossover trial of mirtazapine (15 and
30 mg) in cancer patients with pain and other distressing symptoms. J Pain Symptom Manage
2002;23:442–7.
14. Shopsin B. Bupropion: a new clinical profile in the psychobiology of depression. J Clin Psychiatry
1983;44:140–2.
15. Mathew SJ, Shah A, Lapidus K, et al. Ketamine for Treatment-Resistant Unipolar Depression:
Current Evidence. CNS drugs. 2012;26(3):189-204.
16. Thase ME, Trivedi MH, et al. Examining the efficacy of adjunctive aripiprazole in major depressive
disorder: A pooled analysis of 2 studies. Prim Care Companion J Clin Psychiatry 2008;10:440–
447.
Author Affiliations: Massachusetts General Hospital and Dana-Farber Cancer Institute, Boston, MA.
!41

END-OF-LIFE CARE FOR PATIENTS WITH SCHIZOPHRENIA
Daniel Shalev MD, Katharine K Brewster MD, Jon A Levenson MD
Schizophrenia is a chronic and debilitating psychotic illness affecting 1% of the population. Patients with
schizophrenia are at risk of receiving worse end-of-life care than other patients (1). This Fast Fact reviews
relevant medical evidence and offers care suggestions for seriously ill patients with schizophrenia.
Illness Background: Schizophrenia is characterized by:

• Positive psychiatric symptoms: these include paranoid delusions and auditory hallucinations which
often have a relapsing-remitting pattern and respond to anti-psychotic medications.
• Chronic negative symptoms: cognitive changes such as executive dysfunction, amotivation, blunted
affect, and social withdrawal. These symptoms are often refractory to pharmacotherapies.
!42
• 10-20 year shortened survival: Medication side-effects; a reduced access to medical care; an
increased rate of substance abuse (particularly tobacco); and an increased prevalence of comorbid
illnesses such as cardiovascular disease, cancer, and emphysema are all contributing factors (2-4).
Access to Palliative Care: In the last six months of life, patients with schizophrenia are about half as
likely to access palliative care specialists (1). Additionally, they receive less opioid analgesia, have a
higher likelihood of spending extended time in a nursing home, and are less likely to engage in advance
care planning despite evidence that many schizophrenic patients are capable of doing so (1,5).
Determining Capacity: Many patients with schizophrenia retain capacity for medical decision-making
especially when the support of trusted providers, friends, or family is sought out (6-8). Some patients who
lack capacity to make complex medical decisions, such as determining code status, may nonetheless
retain capacity to make less complex decisions such as designating a surrogate decision-maker (9).
Because symptoms of schizophrenia can make the determination of capacity challenging, psychiatric
consultation is often essential (10). Some patients with schizophrenia will have legal guardians who may
be a family member or a non-family member appointed by the legal system. Depending on state laws,
guardians may be limited in their capacity to withdraw life-extending treatment such as artificial feedings
(11,12). In such cases, involvement of social work and bioethics may be necessary.
Advance Care Planning: Even when patients with schizophrenia are medical candidates for life-
extending treatments like dialysis or chemotherapy, psychotic symptoms such as paranoia may make
them unwilling to cooperate with treatment, requiring ethically problematic interventions such as the use
of restraints or sedation to deliver treatment. This can generate conflict about the best treatment course
and necessitate the involvement of psychiatry and clinical ethics consultants.
• Outpatient discussions regarding potential conflicts with the patient and/or surrogate should occur
prior to an acute medical or psychiatric crisis (11).
• Psychiatric-specific advance directives exist which detail not only medical contingencies, but
psychiatric treatment preferences and outpatient mental health providers (e.g. case managers and
group home staff) in the event of a psychiatric decompensation (13). Although supporting data on
these tools are inchoate, they may reduce violent episodes and need for crisis management (14,15).
Pain Management: Schizophrenic patients often struggle to recognize and report pain (16,17),
especially in inpatient settings when cared for by clinicians unfamiliar to them. The Pain Assessment in
Advanced Dementia Scale (PAINAD) has been utilized even though it was not designed nor validated for
this patient population (17). Otherwise, engaging longstanding caregivers in symptom assessment may
foster trust and empower patients to share their symptoms more openly.
Psychiatric Care: Antipsychotic dosing may be much greater for schizophrenia (haloperidol doses of
20-30 mg/day are not uncommon) than for treatment of delirium, agitation, or nausea. Antipsychotics
exhibit dose-dependent QT prolongation and resultant risk of torsade de pointes, which can be worsened
when combined with other QT-prolonging medications such as anti-emetics, methadone, and antibiotics.
In patients with estimated survivals longer than a few months, recurrent ECG monitoring may be
necessary. Clinicians should be cautious about deprescribing antipsychotics, however, in patients who
are not imminently dying, as the stress of medical illness may worsen positive psychiatric symptoms. If a
medical issue arises in a schizophrenic patient who is not imminently dying preventing intake of the oral
psychopharmacologic regimen, psychiatric consultation should be considered.
Psychosocial Support: Schizophrenic patients are at risk for poverty, homelessness, hunger, and
violence (18-20). Such concerns can be primary drivers in medical decision making. Unfortunately,
finding safe and appropriate care settings can be challenging for terminally ill patients with schizophrenia.
Psychiatric group homes and inpatient psychiatric care settings may be poorly equipped to offer a
sufficient end of life care plan and environment; conversely, hospices or nursing homes may be poorly
equipped to address uncontrolled psychiatric symptoms. Thus, patients with schizophrenia may be at
heightened risk for prolonged hospitalizations at the end of life. Social workers, chaplains, psychiatrists,
and/or community case managers may be able to clarify unmet psychosocial and spiritual needs (20).
Summary of Key Points:

• Schizophrenic patients are at risk for suboptimal symptom control and unmet psychosocial needs.
!43
• Schizophrenic patients do not inherently lack capacity, but may require medical explanations and
advance care planning for medical and psychiatric contingencies “early and often”.
• Involvement of multiple disciplines including psychiatry, social work, trusted outpatient providers and
clinical ethicists may be necessary.
References:
1. Chochinov HM, Martens PJ, Prior HJ, et al. Comparative health care use patterns of people with
schizophrenia near the end of life: a population-based study in Manitoba, Canada. Schizophr Res
2012;141:241–6.
2. Piatt EE, Munetz MR, Ritter C. An examination of premature mortality among decedents with
serious mental illness and those in the general population. Psychiatr Serv Wash DC
2010;61:663–8.
3. Viron MJ, Stern TA. The impact of serious mental illness on health and healthcare.
Psychosomatics 2010;51:458–65.
4. Irwin SA, Ferris FD. The opportunity for psychiatry in palliative care. Can J Psychiatry Rev Can
Psychiatr 2008;53:713–24.
5. Cai X, Cram P, Li Y. Origination of medical advance directives among nursing home residents
with and without serious mental illness. Psychiatr Serv Wash DC 2011;62:61–6.
6. Howard LM, Barley EA, Davies E, et al. Cancer diagnosis in people with severe mental illness:
practical and ethical issues. Lancet Oncol 2010;11:797–804.
7. Grisso T, Appelbaum PS. Comparison of standards for assessing patients’ capacities to make
treatment decisions. Am J Psychiatry 1995;152:1033–7.
8. Irwin KE, Henderson DC, Knight HP, et al. Cancer care for individuals with schizophrenia. Cancer
2014;120:323–34.
9. Foti ME, Bartels SJ, Merriman MP, et al. Medical advance care planning for persons with serious
mental illness. Psychiatr Serv Wash DC 2005;56:576–84.
10. Docherty AR, Sponheim SR, Kerns JG. Further examination of ambivalence in relation to the
schizophrenia spectrum. Schizophr Res 2014;158:261–3.
11. Foti ME, Bartels SJ, Merriman MP, et al. Medical advance care planning for persons with serious
mental illness. Psychiatr Serv Wash DC 2005;56:576–84.
12. Hastings KB. Hardships of end-of-life care with court-appointed guardians. Am J Hosp Palliat
Care 2014;31:57–60.
13. National Resource Center on Psychiatric Advance Directives: State by State Information. http://
www.nrc-pad.org/state-by-state (accessed 18 Mar 2017)
14. Campbell LA, Kisely SR. Advance treatment directives for people with severe mental illness.
Cochrane Database Syst Rev 2009;:CD005963. doi:10.1002/14651858.CD005963.pub2
15. NAMI: National Alliance on Mental Illness | Learn more about mental health. http://www.nami.org/
Learn-More/Mental-Health-Public-Policy/Psychiatric-Advance-Directives-(PAD) (accessed 26 Feb
2017).
16. Dworkin RH. Pain insensitivity in schizophrenia: a neglected phenomenon and some implications.
Schizophr Bull 1994;20:235–48.
17. Lautenbacher S, Krieg JC. Pain perception in psychiatric disorders: a review of the literature. J
Psychiatr Res 1994;28:109–22.
18. Folsom DP, Hawthorne W, Lindamer L, et al. Prevalence and risk factors for homelessness and
utilization of mental health services among 10,340 patients with serious mental illness in a large
public mental health system. Am J Psychiatry 2005;162:370–6.
19. Bettigole E, Kovasznay B, Chung M, et al. Hunger and mental illness. Psychiatr Serv Wash DC
1997;48:543–4.
20. Foti ME, Bartels SJ, Van Citters AD, et al. End-of-life treatment preferences of persons with
serious mental illness. Psychiatr Serv Wash DC 2005;56:585–91.
!44
Authors’ Affiliations: Department of Psychiatry, Columbia University College of Physicians and
Surgeons, New York Presbyterian Hospital, New York State Psychiatric Institute.
Version History: Initially edited by Sean Marks MD; first electronically published in March 2017.

TRANSFERENCE AND COUNTERTRANSFERENCE IN PALLIATIVE CARE
Ashwini C. Bapat MD1, Emeric F. Bojarski MD2
Background: Transference and countertransference influence any human interaction, including the
patient-clinician relationship. Transference is the unconscious redirection of a patient’s feelings, attitudes,
desires, often regarding a close personal relationship in their earlier life, onto the clinician (1). Counter-
transference is the unconscious redirection of a clinician’s feelings, attitudes, and desires about a close
personal relationship onto the patient (1). This Fast Fact illustrates the impact of unrecognized
transference and countertransference and offers strategies to mitigate their consequences.
Importance: Transference phenomena is common in clinical care. It is not inherently pathologic, nor does
it reflect failure on the part of the clinician or patient. Yet, if unrecognized, it can potentially lead to harmful
consequences for patients and clinicians. For example, transference phenomena can contribute to implicit
biases toward certain ethnic or socio-economic groups (2,3); avoidance behaviors which may contribute
to the inappropriate use of life-sustaining medical technologies via the failure to identify patient-centered
goals; and mistrust of the health care system (4). Unlike psychiatrists, psychologists and social workers,
most clinicians lack the training to recognize and understand this phenomenon (4). Hence, transference
feelings go unrecognized by many clinicians and may contribute to professional loneliness, cynicism,
burnout, and depression (4). This topic is particularly relevant for hospice and palliative care clinicians
who often care for dying patients who may evoke intense, often unexamined emotions. The following
cases illustrate how transference phenomena can impact palliative care encounters.
!45
Case 1: A 54-year-old male with an opioid use disorder and lung cancer presents for opioid management
of cancer-related chest pain which has stabilized since his tumors have regressed in response to cancer
treatment. The clinician introduces titrating down his opioids, but the patient responds in anger.
Transference: The patient feels stigmatized within the healthcare system (5). He interprets tapering of
opioids as a sign the clinician no longer believes his pain reports (5), leading to feelings of helplessness
and clinician abandonment. The patient is unconsciously reminded of prior experiences of abandonment
within the healthcare system or from family members from whom he was hoping to obtain support. This
impacts his willingness to discuss non-opioid analgesic approaches.
Countertransference: The clinician is influenced by prior patients with substance use disorder who
diverted or misused opioids and left the clinician feeling betrayed and helpless. This reactivates childhood
experiences of feeling powerless within his family. To avoid these feelings, the clinician desires to taper
the opioids quickly. He severely enforces the terms of the taper and spends less time with the patient,
which compromises the clinician’s pain assessment and care.
Reflection: Both the patient and clinician act out transferred feelings of alienation and helplessness. A
clinician unable to recognize these reactions likely will not engage in a constructive pain assessment and
discussion of analgesic management.
Case 2: A 32-year-old female who is an internal medicine chief resident is seen in a palliative care clinic
to discuss her goals of care regarding progressive glioblastoma. After two months of treatment, she now
spends more time in bed, has a poor appetite, and is withdrawn from her family.
Transference: As a young physician, she does not want to burden her colleagues nor be perceived as a
“needy” patient (6). She minimizes her daily challenges (6) and does not share her feelings regarding her
transition from a high-achieving physician to feeling like an “invalid”.
Countertransference: The clinician feels that the patient has a high-level of health literacy and would be
forthcoming with her concerns (6). The clinician does not want to offend and therefore avoids asking
questions the patient will recognize as screening for depression or suicidal ideation.
Reflection: Failure to recognize transference phenomena contributes to substandard care by missing
opportunities to explore the patient’s feelings of helplessness and to screen for depression.
Conclusions and next steps: Whenever a clinician experiences intense emotion during a clinical
encounter, be it pleasant or unpleasant, this may signify the presence of transference and/or
countertransference (6). A methodical approach to self-reflection, self-monitoring, and coping can help
clinicians recognize these feelings more consciously and thereby prevent harmful consequences (4).
1. Name the feeling: Transference and countertransference are unconscious processes. Naming the
associated feeling(s) enables conscious awareness and thereby more control over behaviors.
2. Normalize the feeling: Anger, guilt, helplessness, and betrayal, though distressing, are common in
clinical care. Acknowledging and normalizing these feelings can prevent clinicians from over-
catastrophizing unwanted emotions triggered during the clinical encounter.
3. Name the behaviors triggered by the feeling: After bringing their feelings to conscious awareness,
clinicians should reflect on how that emotion impacted their behavior. Doing so could lead to more
adaptive responses should the unwanted feelings reemerge. For example, if a clinician notices inner
helplessness, he or she could utilize those feelings to screen the patient for emotional distress.
4. Incorporate routine consultation with trusted colleagues. Sharing an intense patient interaction with
colleagues can decrease isolation and build social support (4). Interdisciplinary teams should create
intentional venues where clinicians feel safe to discuss the lived experience of caring for seriously ill
patients. Such forums should be distinct from Morbidity and Mortality rounds since they are not
intended to act as quality-improvement-themed “fix-it” rounds (7,8). Rather, they should help clinicians
safely examine the social, emotional, and personal aspects of care, ideally in the presence of a
mental-health professional.
References:
1. Boston PH, Mount BM. The caregiver's perspective on existential and spiritual distress in
palliative care. J Pain Symptom Manage 2006;32:13-26. doi: 10.1016/j.jpainsymman.
2006.01.009.
2. Hamer FM. Racism as a transference state: episodes of racial hostility in the psychoanalytic
context. The Psychoanalytic quarterly 2006;75:197-214.
!46
3. Nelson A. Unequal treatment: confronting racial and ethnic disparities in health care. J Natl Med
Assoc 2002;94:666-8.
4. Meier DE, Back AL, Morrison RS. The inner life of physicians and care of the seriously ill. JAMA
2001;286:3007-14.
5. St Marie B. Health care experiences when pain and substance use disorder coexist: "just
because i'm an addict doesn't mean i don't have pain". Pain medicine (Malden, Mass)
2014;15:2075-86.
6. Fromme E, Billings JA. Care of the dying doctor: on the other end of the stethoscope. Jama
2003;290:2048-55.
7. https://www.mcw.edu/departments/palliative-care-program/education/fellowship-in-palliative-
medicine. Accessed 11/6/18.
8. The Schwartz Center for Compassionate Healthcare. http://www.theschwartzcenter.org/
supporting-caregivers/schwartz-center-rounds/ Accessed 11/6/18.

Authors' Affiliations: Massachusetts General Hospital, Boston, MA: 1Division of Palliative and Geriatric
Medicine; 2Child and Adolescent Psychiatry, Department of Psychiatry
Version History: Originally edited by Sean Marks MD; first electronically published in January 2019.
!47
!

Pulmonary
#33 Ventilator Withdrawal Protocol . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . 2-3
#34 Symptom Control for Ventilator Withdrawal in the Dying Patient . . . . . . . .

. . . 4-6
#35 Information for Patients and Families about Ventilator

Withdrawal . . . . . . . . . .7-8
#122 Palliative Care and ICU: Pre-Admission

Assessment . . . . . . . . . . . . . . . . . . . . . .9-10
#123 Palliative Care and ICU Care: Daily ICU Care Plan
Checklist . . . . . . . . . . . . . . . . 11-12
#141 Prognosis in End-Stage COPD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . 13-14
#160 Screening for ICU

Delirium . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15-16
#199 Opioids for Cough . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . . 17-18
#200 Non-Opioid Anti-

Tussives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19-21
#230 Using Non-Invasive Ventilation at the End of

Life . . . . . . . . . . . . . . . . . . . . . . . .22-24
#231 Practical Aspects of Using NPPV at the End of

Life . . . . . . . . . . . . . . . . . . . . . . .25-26
#235 Prognostic Models in Critically Ill Adults. . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . .27-28
!1
#250 Tracheostomy
Care . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
29-30
#253 Palliative Care Consultation in the

ICU . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31-33
#264 Prostacyclin Withdrawal in Pulmonary

Hypertension . . . . . . . . . . . . . . . . . . . . 34-35
#265 Palliative Care for Patients with Cystic

Fibrosis . . . . . . . . . . . . . . . . . . . . . . . . . 36-38
#310 The Oncology-ICU-Palliative Care

Interface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39-40
#343 Chronic Critical Illness in Adults . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . 41-43

VENTILATOR WITHDRAWAL PROTOCOL
Charles von Gunten MD, PhD and David E Weissman MD
Introduction This is the first part of a three-part series on withdrawing ventilators in patients
expected to die. Fast Fact #34 will review use of sedating medication for ventilator withdrawal and
Fast Fact #35 will review information for families.
Once it is decided that further aggressive medical care is incapable of meeting the desired goals
of care for a ventilator-dependent patient, discussing ventilator withdrawal to allow death is
appropriate (see Fast Fact #16). Such a decision is never easy for family members, doctors,
nurses, and other critical care staff. All members of the care team should be involved and
apprised of the decision-making process and have the opportunity to discuss the plan of care.
Options for Ventilator Withdrawal Two methods have been described: immediate extubation
and ‘terminal weaning.’ The clinician’s and patient’s comfort, and the family’s perceptions, should
influence the choice. In immediate extubation, the endotracheal (ET) tube is removed after
appropriate suctioning. Humidified air or oxygen is given to prevent the airway from drying;
comfort medications are administered. This is the preferred approach to relieve discomfort if the
patient is conscious, the volume of secretions is low, and the airway is unlikely to be
compromised after extubation. In terminal weaning, the ventilator rate, positive end-expiratory
pressure (PEEP), and oxygen levels are decreased while the endotracheal tube is left in place.
Terminal weaning may be carried out over a period of as little as 30 to 60 minutes (see reference
3 for a protocol). If the patient survives they can be extubated with ongoing symptomatic care. If
it is decided to leave the endotracheal tube in place (to, for instance, ensure the patency of the
upper airway) a Briggs T-piece can be placed.
Prior to Immediate Ventilator Withdrawal

1. Encourage family to make arrangements for special music or rituals or support during
and following the procedure. (See Fast Fact #35).
2. Counsel families on potential outcomes following withdrawal.
3. Document clinical findings, discussion with families/surrogates, and goals of care.
!2
4. Ensure that all monitors and alarms are turned off. Ensure that respiratory therapy or
nursing staff is assigned to override alarms that cannot be turned off.
5. Remove restraints and unnecessary medical paraphernalia.
6. Turn off blood pressure support and paralytic medications; discontinue other life-
sustaining treatments (e.g. artificial nutrition/hydration, antibiotics, dialysis).
7. Maintain intravenous access for administration of sedating medications.
8. Clear a space for family access to the bedside. Invite family into the room if they wish to
be present. If the patient is an infant or young child, offer to have the parent hold the
child.
9. Establish adequate symptom control prior to extubation (See Fast Fact #34).
10. Have a syringe of an additional sedating medication at the bedside (midazolam,
morphine, or lorazepam) to use in case distressing tachypnea or other symptoms.
At the time of ventilator withdrawal

1. Once you are sure the patient is comfortable, set the FiO2 to 21% (room air); observe for
signs of respiratory distress; adjust medication as needed to relieve distress before
proceeding further.
2. If the patient appears comfortable, prepare to remove the ET tube; try a few minutes of
“no assist” ventilation before the ET tube is removed.
3. A nurse or respiratory therapist should be stationed at the opposite side of the bed with a
washcloth and oral suction catheter.
4. When ready to proceed, deflate the ET tube cuff. If possible, someone should be
assigned to silence, turn off the ventilator, and move it out of the way. Once the cuff is
deflated, remove the ET tube under a clean towel which collects most of the secretions
and keep the ET tube covered with the towel. If oropharyngeal secretions are excessive,
suction them away.
5. The family and the nurse should have tissues for extra secretions, and for tears. The
family should be encouraged to hold the patient’s hand and provide assurances to their
loved one.
6. Be prepared to spend additional time with the family discussing questions concerns. After
death occurs, encourage the family to spend as much time at the bedside as they
require; provide acute grief support and follow-up bereavement support
References
1. Marr L, Weissman DE. Withdrawal of ventilatory support from the dying adult patient. J
Supp Onc. 2004; 2:283-288.
2. Adapted from: Emanuel LL, von Gunten CF, Ferris FF, eds. Module 11: Withholding and
Withdrawing Therapy. The EPEC Curriculum: Education for Physicians on End-of-life
Care. Chicago, IL: The EPEC Project; 1999. http://www.EPEC.net.
3. Rubenfeld GD, Crawford SW. Principles and practice of withdrawing life-sustaining
treatment in the ICU. In Managing Death in the Intensive Care Unit. Curtis JR and
Rubenfeld GD, eds. New York, NY: Oxford University Press; 2001: pp127-147.
again May 2015.
!3
!4
!

SYMPTOM CONTROL FOR VENTILATOR WITHDRAWAL IN THE DYING PATIENT
Introduction This is the second of a three-part series. Fast Fact #33 reviewed a protocol for
removing the ventilator, and Fast Fact #35 will review information for families.
The most common symptoms related to ventilator withdrawal are breathlessness and anxiety.
Opioids and benzodiazepines are the primary medications used; concerns about unintended
hastened death are exaggerated, particularly if established dosing guidelines are followed (see
Fast Fact #8). There is no medical or ethical justification for withholding sedating medication
when death following ventilator withdrawal is the expected outcome. However, increasing doses
beyond the levels needed to achieve comfort/sedation, with the intention of hastening death, is
euthanasia and is not acceptable/legal medical practice.
A 2004 study suggests that opioids and benzodiazepines do not shorten survival but do help
minimize respiratory distress in terminal extubations. Therefore, pre-bolus doses should be
strongly considered even for those who are comatose, in order to control labored breathing. The
doses needed to control symptoms depend on the neurological status of the patient and presence
of drug tolerance (these same drugs are commonly used in routine ICU care). In all cases, a
senior-level physician should remain at the bedside prior to and immediately following extubation
until adequate symptom control is assured.
Medication Protocol
1. Discontinue paralytics; do not use paralytic agents for ventilator withdrawal. Besides
ensuring a patient cannot breathe, they do not prevent or treat any discomfort in patients
off ventilators, and prevent patients from communicating or demonstrating distress. When
patients have multi-organ failure, some paralytics may not be cleared for 2-18 hours.
Therefore, if there is doubt as to whether the paralytics have worn off, utilize a peripheral
nerve stimulator. It is ok to extubate when you see muscle twitches with 4 consecutive
nerve stimulations.
2. Administer glycopyrrolate (Robinul®) 0.2 to 0.4 mg IV 20-30 minutes prior to the
extubation to minimize secretions.
3. Administer an IV bolus dose of an opioid (i.e. morphine 2-10 mg IV) and a
benzodiazepine (lorazepam 1-2 mg IV) if anxiety is anticipated. Consider an IV
continuous infusion of sedating medication (see below). Do not rely on subcutaneous or
enteral drug administration as these take longer to work. For children, obtain dosing
advice from a pharmacist or pediatric intensivist.
4. Titrate medications to control labored respirations and achieve the desired state of
sedation prior to extubation. Testing the eyelid reflex is a common method of quickly
assessing level of consciousness.
5. Have additional medication drawn up and ready to administer at the bedside if needed.
6. After ventilator withdrawal: Most respiratory distress ensues in the first few hours after the
extubation. If distress is noted, utilize additional bolus doses of opioids and
benzodiazepines (e.g. morphine 5-10 mg IV push q 10 min, and/or midazolam, 2-4 mg IV
push q 10 min, until distress is relieved). You can adjust infusion rates to maintain relief,
but remember infusion rates have a delayed effect. Therefore, avoid relying on infusion
rates to control distress seen after the extubation.
7. Specific dosages are less important than the goal of symptom relief. A goal should be to
keep the respiratory rate < 30 and eliminate grimacing, agitation, and labored
respirations.
8. Orders such as “morphine drip 1-20 mg/hr, titrate as needed” are inappropriate as they
will likely mismanage the acute symptom distress and place undue burden on the
bedside nurse to make clinical management decisions.
NOTE: The following regimens are commonly used; all require a bolus dose commonly followed
by a continuous infusion. Dose ranges are approximations and depend in part on patients’ prior
!5
exposure to opioids and benzodiazepines. Clinicians should use clinical judgment when deciding
on what specific drugs and doses to use. Many institutions have policy and clinical guidelines
about the use of opioids and sedatives in these circumstances. Clinicians unfamiliar with the use
of these agents in the setting of ventilator withdrawal are urged to consult with an
anesthesiologist, critical care specialist, or pain/palliative specialist prior to use.
Regimen A: Morphine plus Midazolam (Adult doses)

Good for comatose patients or patients with limited consciousness and/or patients with little
prior exposure to these drugs (and thus less risk of tolerance).
Bolus: Morphine 2-10 mg; Midazolam 1-2 mg
Infusion: Morphine 50% of the bolus dose in mg/hr; Midazolam 1 mg/hr
Regimen B: Pentobarbital (Adult doses)
Good for the awake patient who can be expected to have respiratory distress following
ventilator withdrawal.
Bolus: 1-2 mg/kg (at rate of 50 mg/min)
Infusion: 1-2 mg/kg/hr
Regimen C: Propofol (Adult doses)
Good for the awake patient who can be expected to have demonstrable respiratory distress
following ventilator withdrawal.
Bolus: 20-50 mg
Infusion: 10-100 mg/hr
References
1. Rousseau PC. Palliative Sedation. Am J Hosp Pall Care. 2002; 19:295-297.
2. Truog RD. Barbiturates in the care of the terminally ill. NEJM. 1992; 327:1678-1681.
3. Chan JD, et al. Narcotic and benzodiazepine use after withdrawal of life support:
Association with time to death? Chest. 2004; 126:286-293.
6. McWilliams K, et al. Propofol for terminal sedation in palliative care: a systematic review.
J Palliat Med. 2010; 13:73-6. doi:10.1089/jpm.2009.0126.
published July 2005; 3rd Edition May 2015. Re-copy-edited March 2009; then again December
2012: reference 6 on Propofol added; then again May 2015.
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!7
!

INFORMATION FOR PATIENTS AND FAMILIES ABOUT VENTILATOR WITHDRAWAL
Introduction This is Part 3 of a three-part series on ventilator withdrawal. Fast Fact #33
reviewed a protocol for removing the ventilator; Fast Fact #34 reviewed medications for symptom
control. Physician-counseling of families is a critical aspect of care for the dying patient who is to
be removed from a ventilator. Ideally the family will be involved in the decision to withdraw the
ventilator and thus apprised of the goals of care. Before withdrawal, the following issues should
be discussed.
Potential outcome of ventilator withdrawal

Assuming all other life-sustaining treatments have been stopped, including artificial hydration and
nutrition, there are several potential outcomes: rapid death within minutes (typically patients with
sepsis on maximal blood pressure support), death within hours to days, or stable
cardiopulmonary function leading to a different set of care plans, including potential hospital
discharge. If the latter possibility is realistic, future management plans should be discussed prior
to ventilator removal, since some families may desire to resume certain treatments, notably
artificial hydration/nutrition. Generally, by the nature of the underlying illness and the established
goals, it is fairly easy to predict which category will be operative, but all families should be
prepared for some degree of prognostic uncertainty (see Fast Fact #30).
The procedure of ventilator withdrawal

Never make assumptions about what the family understands; describe the procedure in clear,
simple terms and answer any questions. Families should be told before-hand the steps of
withdrawal and whether or not it is planned/desired to remove the endotracheal tube. In addition,
they should be counseled about the use of oxygen and medications for symptom control. Assure
them that the patient’s comfort is of primary concern. Explain that labored breathing and signs of
breathlessness may occur shortly after the extubation, but that they can be managed. Confirm
that you will have medication available to manage any discomfort. Ensure they know that the
patient will likely be asleep and that involuntary moving, noisy or irregular breathing, or gasping
do not reflect suffering if the patient is properly sedated or in a coma. Some families may wonder
if leaving their loved one intubated and on the ventilator may be more comfortable. Explain that
ET tubes are a source of discomfort and anxiety for most patients and therefore are not
recommended at the end of life when comfort is the primary goal.
Explain how the family, clergy and others can be at the bedside before, during and after
withdrawal. If asked, explain that they can show love and support through touch, wiping of the
patient’s forehead, holding a hand and talking to him or her.
Support the decision

Even though a family is able to make a definite decision for ventilator withdrawal, such a decision
is always emotionally charged. Families may constantly second-guess themselves, especially if
the patient appears to linger following ventilator withdrawal. Physician support, guidance and
leadership are crucial, as the family will be looking to the physician to ensure them that they are
“doing the right thing.” Furthermore, it is common for families to have concerns that their decision
constitutes euthanasia or assisted suicide—explicit counseling from a physician will be needed.
Finally, support needs to continue following death during the bereavement period (see Fast Fact
#22).
References
!8
again May 2015.
!9
!

PALLIATIVE CARE AND ICU CARE: PRE-ADMISSION ASSESSMENT
Richard A Mularski MD and Molly L Osborne MD
Background What are the indications for Intensive Care Unit (ICU) admission in the
chronically and/or terminally ill and how can one integrate palliative care into the daily
interdisciplinary agenda? A good approach is to determine the patient-centered goals of care and
then decide if ICU care will help promote or detract from these goals. The use of a pre-admission
checklist can be helpful to determine the appropriateness of ICU therapy and to initiate
communication about goals and preferences before a trial of ICU care. With use of a
complementary strategy after admission, the patient can benefit from a care plan that integrates
palliation into the daily agenda and anticipates needs. This Fast Fact will discuss the pre-ICU-
admission assessment of patients with advanced illnesses; Fast Fact #123 will discuss ongoing
ICU assessment of these patients to ensure appropriate symptom management and medical
decision-making.
Pre-Admission ICU Checklist

A. Clarify the underlying medical condition and possibilities with ICU treatment:
1. What is/are the underlying chronic fatal illness disease(s)?
2. What has been the clinical course of the chronic illness over the past few months/
year?
3. What was the patient’s functional status and quality of life in the weeks preceding
admission?
4. What are the acute illnesses and conditions that the ICU might improve?
5. What interventions do you expect will be required in the first 48 hours?
6. What do you foresee as the best possible outcome from treatment in ICU:
a. Cure the acute process with return to baseline function (e.g. pneumonia).
b. Cure or improve the acute process but the patient will likely have a reduced
functional capacity permanently (e.g. large stroke).
7. Is there prognostic information to guide you/patient/family in decision making?
B. Address and document decision-making with patient/family/surrogate:

1. Does the patient have decision-making capacity (see Fast Fact #55)?
2. Does the patient have an advance care planning document or a legally designated
agent?
3. Who are the important people that assist the patient in decision making?
4. With or without an advance care planning document, has the patient or surrogate
expressed clear goals of care with their physician in the recent past or during the
current illness?
C. Discuss and document ICU-based and patient-focused goals and preferences:
1. Review what therapeutic trials and palliative care issues can be addressed by an
interdisciplinary ICU team; consider whether needs can be met in alternative care
settings.
2. Document advance care planning and do not resuscitate orders (see Fast Facts #23,
#24, #292).
3. Agree upon specific, time-limited, ICU goals (e.g. three days trial of mechanical
ventilation).
4. Identify physical symptoms and develop a treatment plan for palliation.
D. Coordinate interdisciplinary communication & time reappraisal of therapy and

goals:
1. Meet with ICU team members to review goals of care, symptoms, family needs, etc.
!10
2. Document goals of care and details of decision making in medical record.
3. Schedule a time to assess clinical response and whether goals need to be changed.
References
1. Back AL, Arnold RM, Quill T. Hope for the best, and prepare for the worst. Ann Intern
Med. 2003; 138(5):439-43.
2. Mularski RA, Osborne ML. End-of-life care in the critically ill geriatric population. Crit
Care Clin. 2003; 19:793-810.
3. Mularski RA, Bascom P, Osborne ML. Educational agendas for interdisciplinary end-of-
life curricula. Crit Care Med. 2001; 29(2 Suppl):N16-23. (Copyright permission to
reproduce modified checklist obtained from Lippincott June 2004.)
in September 2004. Version re-copy-edited in April 2009; revised again July 2015.
!11
!
FAST FACTS AND CONCEPT #123

PALLIATIVE CARE AND ICU CARE: DAILY ICU CARE PLAN CHECKLIST
Richard A Mularski MD and Molly L Osborne MD
Background A pre-admission checklist (see Fast Fact #122) can be used before intensive
care unit (ICU) admission to initiate communication about goals and preferences for an ICU trial.
An ICU daily care plan checklist can be used to promote palliative care, simultaneously with
curative or life-prolonging therapies. The checklist can help clarify the goals of care for the ICU
team, consultants, patients, and significant others and serve as a vehicle for quality improvement.
Palliative ICU Daily Care Plan Checklist

A. Address short-term medical progress and goals:
1. Assess whether specific criteria toward progress has been met (e.g. mental status or
ventilator needs). Has there been improvement, stability, or worsening in the past 24
hours?
2. Have there been clinical changes that will impact the patient’s ability to meet desired
clinical goals (e.g. new GI bleeding)?
3. Review interventions that may be needed in the next 48 hours and set overt criteria
to measure progress (e.g. objective indicators of progress towards ventilator
weaning).
4. Use this information to review goals and determine if there are changes in prognosis
that can guide you/patient/family in decision making.
B. Address patient symptoms and psychosocial needs:
1. Review progress in managing current symptoms and psychosocial needs (patient
and family).
2. Identify existing or new physical symptoms and psychosocial needs; discuss among
team members (e.g. patient depression, family stress).
3. Develop a treatment plan for each symptom/need for the next 24 hours.
4. Identify both ICU and non-ICU resources to assist in care plan (e.g. palliative care
nurse, clinical psychologist, etc.) and clarify roles for members of the interdisciplinary
team.
C. Clarify understanding and coordinate patient/family communication:

1. Review patient/family understanding and concerns about diagnosis, prognosis,
possible outcomes, and details of above items.
a. Inquire if the patient or significant others have new information or new
perspectives that can help clarify the understanding of the patient’s goals and
preferences.
b. Decide if goals of care need refinement or change.
c. Agree on specific criteria for reassessment of clinical responses and goals.
2. Determine what new information needs to be communicated within next 24 hours.
3. Agree on who and how the team will communicate with family/patient today (e.g.
attending will meet with family at 3 PM; resident will attend then call out-of-town
relative after meeting).
D. Document care plan and coordinate follow-up and next day’s assessment:
1. Document clinical status, symptoms, daily goals of care, and details of decision
making.
2. Change orders as necessary (e.g. new do-not-resuscitate order).
3. Schedule next meeting for interdisciplinary team that includes patient (if able) and
family to update goals, medical evaluation, responses to current therapy, and future
plans.
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Suggestion for Faculty - Improving the Process of Care
Establish a written checklist containing the above elements that can be completed during
daily rounds and entered into the medical record.
References
1. Curtis JR, Rubenfeld GD, eds. Managing Death in the ICU: The Transition from Cure to
Comfort. New York, NY: Oxford University Press; 2000.
2. Lilly CM, De Meo DL, Sonna LA, et al. An intensive communication intervention for the
critically ill. Am J Med. 2000; 109(6):469-75.
3. Mularski RA. Pain management in the intensive care unit. Crit Care Clin. 2004;
20:381-401.
4. Mularski RA, Bascom P, Osborne ML. Educational agendas for interdisciplinary end-of-
life curricula. Crit Care Med. 2001; 29(2 Suppl):N16-23. (Copyright permission to
reproduce modified checklist obtained from Lippincott June 2004.)
in October 2004. Version re-copy-edited in April 2009; revised again July 2015.
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!

PROGNOSIS IN END-STAGE COPD
Julie Wilson Childers MD, Robert Arnold MD, and J Randall Curtis MD
Background Prognostic variables in COPD patients are not well described, thus decision
making regarding when to move away from aggressive life-sustaining treatments is challenging.
This Fast Fact will review prognostication in patients with advanced COPD.
Ambulatory COPD Patients The forced expiratory volume in one second (FEV1) has
traditionally been used to assess COPD severity. A FEV1 of less than 35% of the predicted value
represents severe disease; 25% of these patients will die within two years and 55% by four years.
A number of other studies have shown that age, low body mass index (BMI), serum inflammatory
biomarkers (such as C-reactive protein, IL-6, and fibrinogen) and low PaO2 were independent
predictors that correlated to reduced survival time. The BODE scale, consisting of BMI, exercise
capacity, and subjective estimates of dyspnea, has been shown to help predict survival over 1-3
years (2).
Variable Points on BODE Index

0 1 2 3
FEV1 (% predicted) ≥65 50-64 36-49 ≤35

Distance walked in 6 min >350 250-349 150-249 ≤149
(meters)
MMRC dyspnea scale* 0-1 2 3 4
Body-mass index (BMI) >21 ≤21
*MMRC dyspnea scale range from 0 (none) to 4 (4 dyspnea when dressing or undressing).
BODE Index Score One year mortality Two year mortality 52 month mortality
0-2 2% 6% 19%
3-4 2% 8% 32%
4-6 2% 14% 40%
7-10 5% 31% 80%
Note: these variables do not appear to help predict prognosis within six months of death.
Hospitalized COPD Patients Mortality statistics vary for patients admitted with COPD
exacerbations depending on age, functional status, co-morbidities, and physiological variables
such as hypoxia and hypercarbia. Roughly 10% of patients admitted with a PaCO2 >50 mmHg
will die during the index hospitalization, 33% will die within six months, and 43% die within one-
year (3). Patients with less severe COPD have lower in-hospital mortality rates (4). COPD
patients who require mechanical ventilation have an-hospital mortality of ~25% (5,6). Poor
prognostic factors include: co-morbid illnesses, severity of illness (APACHE II score), low serum
albumin, and/or low hemoglobin. Previous mechanical ventilation, failed extubation, or intubation
for greater than 72 hours all increase mortality (5). In one study, patients ventilated more than 48
hours had a 50% one year survival; functional status and severity of illness were associated with
short term mortality while age and co-morbidities were associated with one year mortality (2).
National Hospice and Palliative Care Organization Criteria NHPCO guidelines for hospice
admission in COPD include factors such as cor pulmonale and pO2 <55 mmHg while on oxygen,
!14
albumin < 2.5 gm/dl, weight loss of > 10%, progression of disease, and poor functional status.
However, a study showed when using these factors, 50% of the patients were still alive at six
months, implying that the NHPCO criteria have a limited role in predicting six month mortality and
thus should be used with caution in determining hospice eligibility under the Medicare Hospice
Benefit (7).
Summary COPD is a heterogeneous disease without a simple prognostic trajectory. For

ambulatory patients, age, degree of dyspnea, weight loss (BMI), functional status, and FEV1 are
relevant prognostic factors for predicting 1-3 year survival. For hospitalized patients, the same
factors are relevant. In addition, the need for prolonged or recurrent mechanical ventilation is
predictive of a shorter prognosis.
References
1. Celli BR, Locantore N, et al. Inflammatory biomarkers improve clinical prediction of
mortality in chronic obstructive pulmonary disease. American Journal of Respiratory and
Critical Care Medicine. 2012; 185:1065-72.
2. Celli BR, Cote CG, Marin JM, et al. The body-mass index, airflow obstruction, dyspnea,
and exercise capacity index in chronic obstructive pulmonary disease. N Eng J Med.
2004; 350(10):1005-12.
3. Connors AF Jr, Dawson NV, Thomas C, et al. Outcomes following acute exacerbation of
severe chronic obstructive lung disease. The SUPPORT investigators (Study to
Understand Prognoses and Preferences for Outcomes and Risks of Treatments). Am J
Respir Crit Care Med. 1996; 154:959-967.
4. Patil SP, Kirshnan JA, et al. In-hospital mortality following acute exacerbations of chronic
obstructive pulmonary disease. Arch Intern Med. 2003; 163:1180-1186.
5. Nevins ML, Epstein SK. Predictors of outcome for patients with COPD requiring invasive
mechanical ventilation. Chest. 2001; 119:1840-9.
6. Seneff MG, Wagner DP, Wagner RP, et al. Hospital and 1-year survival of patients
admitted to intensive care units with acute exacerbation of chronic obstructive pulmonary
disease. JAMA. 1995; 274:1852-57.
7. Fox E, Landrum-McNiff K, Zhong Z, Dawson NV, Wu AW, Lynn J. Evaluation of
prognostic criteria for determining hospice eligibility in patients with advanced lung, heart,
or liver disease. JAMA. 1999; 282(17):1638-45.
in August 2005. Version re-copy-edited in April 2009; revised again July 2015 by Sean Marks MD
!15
!

SCREENING FOR ICU DELIRIUM
Richard Altman MD, Eric Milbrandt MD, MPH, and Robert Arnold MD
Background Delirium is an acute, fluctuating change in mental status, accompanied by sleep/
wake cycle disruption, inattention, and altered perceptions (hallucinations/delusions) (see Fast
Facts #1, 60). Delirium can be hypoactive or hyperactive and is often multifactorial (1). Patients
with hypoactive delirium are calm, but inattentive and manifest decreased mobility. Patients with
hyperactive delirium are agitated and combative, and also lack the ability to maintain attention to
complete tasks. Delirium can be considered a marker of acute brain dysfunction, much like shock
is evidence for dysfunction of the cardiovascular system (2). When recognized early, it is
potentially modifiable depending on the patient’s circumstances.
ICU Delirium Delirium occurring in the ICU is associated with an increased length of
hospitalization, increased need for institutionalization, and higher short and long-term mortality
(3). In the ICU, delirium occurs in as many as 80% of patients, but is often overlooked or
misdiagnosed because of the difficulty of assessing mental states in intubated patients. Three
assessment tools have been described in the literature to aid in delirium diagnosis.
1) The Confusion Assessment Method-Intensive Care Unit (CAM-ICU) Assessment Tool is
the best documented method of diagnosing delirium in the ICU (4). This tool was specifically
designed for use in non-verbal (i.e. mechanically ventilated) patients. With the CAM-ICU, delirium
is diagnosed when patients demonstrate 1) an acute change in mental status or fluctuating
changes in mental status, 2) inattention measured using either an auditory or visual test, and
either 3) disorganized thinking, or 4) an altered level of consciousness. Importantly, the CAM-ICU
can only be administered if the patient is arousable to voice without the need for physical
stimulation. The CAM-ICU includes very specific assessment questions/tools, found online at
http://www.icudelirium.org/delirium.html.
When administered by a nurse, the CAM-ICU takes only 1 to 2 minutes to conduct (3,5). A
systematic review of nine studies evaluating the CAM-ICU showed a pooled sensitivity of 80%
and a pooled specificity of 95.9% for detecting delirium as compared to full DSM-IV assessment
by a geriatric psychiatrist (6). National guidelines recommend routine use of the CAM-ICU for
delirium assessment in all critically ill patients and treatment with haloperidol when delirium is
present (7). However, these recommendations are based on expert opinion and limited case
series. It remains unknown whether diagnosis and/or treatment of delirium will lead to better
patient outcomes. While there are some early observational cohort data suggesting that patients
treated with haloperidol have lower hospital mortality, this finding needs confirmation in a
randomized, controlled trial before being applied to routine patient care.
2) The Intensive Care Delirium Screening Checklist assesses eight features of delirium:
altered level of consciousness, inattention, disorientation, hallucinations, psychomotor agitation/
retardation, inappropriate mood/speech, sleep/wake cycle disturbance, and symptom fluctuation.
The pooled sensitivity and specificity of this tool were 74% and 81.9% respectively per a
systematic review (6).
3) The Delirium Screening Checklist is another recent tool that uses a checklist similar to the
Intensive Care Delirium Screening Checklist (8).
Recommendation It is believed that prompt recognition and treatment of ICU delirium is

important for patient safety. Use of rapid tools such as CAM-ICU can help identify ICU delirium
and are recommended when assessing mental status changes. A key to effective implementation
of ICU delirium screening includes addressing attitudinal barriers that delirium is an inevitable part
of critical illness via multi-faceted training such as lectures, case-based scenarios, one-on-one
teaching, and bedside teaching to provide real time feedback (1).
!16
References
1. Brummel NE, Vasilevskis EE, et al. Implementing delirium screening in the ICU: secrets
to success. Crit Care Med 2013; 41:2196-2208.
2. Ely EW, Siegel MD, Inouye SK. Delirium in the Intensive Care Unit: An Under-
Recognized Syndrome of Organ Dysfunction. Seminars in Respiratory & Critical Care
Medicine. 2001; 22(2):115-126.
3. Ely EW, Inouye SK, Bernard GR, Gordon S, Francis J, May L, Truman B, Speroff T,
Gautam S, Margolin R, Hart RP, Dittus R. Delirium in Mechanically Ventilated Patients:
Validity and Reliability of the Confusion Assessment Method for the Intensive Care Unit
(CAM-ICU). JAMA. 2001; 286(21):2703-2710.
4. Ely EW, Truman B. The Confusion Assessment Method for the ICU (CAM-ICU) Training
Manual. Available at: http://www.icudelirium.org/delirium.html. Accessed July 24, 2015.
5. Ely EW, Margolin R, Francis J, May L, Truman B, Dittus R, Speroff T, Gautam S, Bernard
GR, Inouye SK. Evaluation of delirium in critically ill patients: validation of the Confusion
Assessment Method for the Intensive Care Unit (CAM-ICU). Crit Care Med. 2001;
29:1370-9.
6. Gusmao-Flores D, Figueira Salluhet JI, et al. The confusion assessment method for the
intensive care unit (CAM-ICU) and intensive care delirium screening checklist (ICDSC)
for the diagnosis of delirium: a systematic review and meta-analysis of clinical studies.
Crit Care 2012; 16:R115.
7. Jacobi J, Fraser GL, Coursin DB, et al. Clinical practice guidelines for the sustained use
of sedatives and analgesics in the critically ill adult. Crit Care Med. 2002; 30:119-41.
8. Otter H, Martin J, Basell K, von Heymann C, et al. Validity and reliability of the DDS for
severity of delirium in the ICU. Neurocrit Care. 2005; 2(2):150-8.
in August 2006. Version re-copy-edited in April 2009; edited again July 2015 by Sean Marks –
references #1 and 6 were added and incorporated into the text. Reference #4 updated and
modified.
!17
!

OPIOIDS FOR COUGH
Background Cough is a common, and at times distressing, symptom. Up to 40% of advanced
cancer patients report cough, and while a smaller percentage find their cough distressing, severe
cough can lead to dyspnea, nausea/vomiting, sleep impairment, chest and throat pain, and
impaired communication. This Fast Fact will focus on the use of opioids for the symptomatic
treatment of cough. Fast Fact #200 will address other agents for cough.
Etiologies & Evaluation Common etiologies of cough include infections of the upper and lower
airway, asthma and COPD, lung cancer or lung metastases, interstitial pulmonary processes
(such as lymphangitic tumor spread or pulmonary edema), gastroesophageal reflux, aspiration,
and drugs. Common drug causes include ACE inhibitors, NSAIDs, and inhalant medications.
Evaluating for reversible causes is appropriate if consistent with the goals of care and prognosis.
If feasible, treatment should be directed at the underlying cause. Many patients however will
benefit from symptomatic therapy for a distressing cough while waiting for acute therapy to work
or have a chronic cough not amenable to treatment (e.g. cough due to advanced lung cancer).
Opioids are the only clearly effective centrally-acting anti-tussive drugs and are thought to work
by suppressing the brainstem cough center through mu and kappa opioid receptor agonism.
They are the first-line symptomatic treatment for severe, distressing cough. All opioids used to
treat cough have typical opioid side effects such as sedation, constipation, and nausea.
• Codeine: Duration of action is 4 hours; usual adult dose is 10-20 mg every 4-6 hours. It has
shown to be effective for acute and chronic cough in several placebo-controlled trials. It is
available alone or as an elixir with guaifenesin.
• Dextromethorphan: Duration of action 3-6 hours; usual adult dose is 10-20 mg every 4-6
hours. It is the most commonly used anti-tussive. Confirmed to be as effective as codeine
for cough in multiple studies. It is available alone or as an elixir with guaifenesin. Note:
dextromethorphan inhibits the cytochrome P450 system and thereby affects the metabolism
of many drugs. Dextromethorphan can also cause a serotonin syndrome if used with
serotonergic drugs such as antidepressants.
• Hydrocodone: Duration of action 4-6 hours; usual dose 5-10 mg every 4 hours. Hydrocodone
is only available as a combination product in the US: as a short-acting elixir with the
anticholinergic drug homatropine or as an extended release elixir with the antihistamine
chlorpheniramine (dosed at 10 mg every 12 hours). These other agents magnify
hydrocodone’s sedative effects, and limit the maximum dose a patient can take.
Hydrocodone has been shown to be as effective as codeine in head to head studies but with
fewer gastrointestinal side-effects. For this reason it is considered by many experts as the
anti-tussive of choice (Homsi 2001).
• All opioid analgesics have anti-tussive activity and their use has been mostly based on
convention; there is no strong evidence that any one opioid has superior efficacy for cough.
For patients already taking opioids for pain, it is unclear whether adding a second opioid such
as codeine for cough is effective. One uncontrolled, open-label study showed hydrocodone
to be helpful in this setting; it has not been repeated (Homsi 2001).
Fast Fact #200 will discuss non-opioid agents for cough, as well as address some general
treatment strategies.
References
Care Cancer. 2001; 9:565-74.
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2004; 2:523-7.
2005; 8(1): 88-94.
BMJ. 1997; 315: 931-4.
6. Homsi J, Walsh D, Nelson KA, Sarhill N, Rybicki L, LeGrand SB, Davis M. A phase II
study of hydrocodone for cough in advanced cancer. Am J Hospice Palliat Care. 2002;
19:49-56.
7. Turturro MA, Paris PM, Yealy DM, Menegazzi JJ. Hydrocodone versus codeine in acute
musculoskeletal pain. Ann Emerg Med. 1991; 20:1100-03.
10. Chung KF. Currently available cough suppressants for chronic cough. Lung 2008 [E-pub
ahead of print, available Oct 2, 2007]. DOI: 10.1007/s00408-007-9030-1.
Version History: Originally published March 2008. Copy-edited in June 2009. 2nd edition
published in July 2013; minimally revised to reflect that gabapentin is a newly appreciated
centrally acting anti-tussive; copy edited again July 2015.
!19
!

NON-OPIOID ANTI-TUSSIVES
Background Cough is a common and at times distressing symptom. Fast Fact #199 discussed
opioids for the symptomatic treatment of cough. This Fast Fact will address non-opioid anti-
tussives.
Controversies Commonly used prescription and over-the-counter anti-tussive formulations

which contain some combination of antihistamines (e.g. diphenhydramine), a mucolytic (e.g.
guaifenesin), and/or dextromethorphan are often used for acute cough due to upper respiratory
infections and acute bronchitis. Evidence for these agents in the acute setting is poor (either no
better than placebo or sweet syrup) and cannot be recommended. Due to concerns about
inadvertent overdose and lack of efficacy, these products are now being actively discouraged for
use in the pediatric setting.
Centrally-acting non-opioid anti-tussives

• Gabapentin: the pathophysiology of refractory chronic cough is thought to resemble central
sensitization as seen in neuropathic pain. A randomized, double-blind placebo controlled trial
demonstrated that gabapentin can meaningfully improve cough-specific quality of life and
reduce cough frequency and severity compared with placebo. Doses up to 1800 mg a day
were studied.
• Other neuromodulating agents: paroxetine, amitriptyline, and benzodiazepines have been
anecdotally reported to have efficacy in chronic, refractory cough but lack published
controlled evidence.
Peripherally-acting anti-tussives
• Sweet syrups are commonly used as cough suppressants, whether as bases for prescription
elixirs (such as codeine with guaifenesin) or home remedies (honey, simple syrup). The
mechanism of action is unknown; some authors hypothesize it acts as a protective barrier to
sensory receptors in the throat that heighten the cough reflex. A few controlled trials have
shown sweet syrups reduce coughing in upper respiratory infections.
• Benzonatate inhibits cough by anesthetizing stretch receptors in the respiratory tract. Its
duration of action is 3-8 hours; dosed at 100-200 mg three times a day. No published
controlled studies confirm its effectiveness but multiple uncontrolled studies support its use.
Side effects are uncommon but include sedation, headache, bronchospasm, and nausea.
Empirically many experts recommend adding it to an opioid.
• Antihistamines and anticholinergics are often part of combination anti-tussive elixirs with or
without an opioid. Anticholinergics such as hyoscyamine and scopolamine are most helpful
in the setting of copious upper respiratory secretions leading to cough. See Fast Fact #109
for dosing information.
• Expectorants thin bronchial secretions and ease expectoration. Examples include
guaifenesin (200-400 mg every 4 hours) and nebulized acetylcysteine or hypertonic saline.
Empirically they have been recommended for severe, chronic, wet coughs. Because they
may increase fluid in the respiratory tract, they are not recommended if the cough reflex is
diminished.
• Nebulized local anesthetics are thought to work by anesthetizing afferent receptors in the
respiratory tract. There have been no trials evaluating their effectiveness; anecdotally they
have been reported to be effective for refractory cough. Published regimens include lidocaine
2% solution, 5 mL nebulized every 6 hours; and bupivacaine 0.25%, 5 mL nebulized every 8
hours. Bronchospasm is a potential side effect.
• Other agents such as bronchodilators and corticosteroids have not been shown to be
effective apart from specific indications (e.g. for COPD or asthma exacerbations).
!20
Recommendations Treatment for cough should be directed at the underlying cause if feasible
and consistent with a patient’s prognosis and goals of care. When symptomatic treatment for a
distressing cough is necessary, it is reasonable to start with an opioid product, adding
benzonatate if needed. A trial of anticholinergics and expectorants for the indications described
above is reasonable, but they should be stopped after a couple days if they have no effect.
Sweet syrups appear to be helpful in upper respiratory infections; their role otherwise is uncertain.
If these strategies fail to control distressing symptoms, gabapentin should be tried for chronic
cough.
References
Care Cancer. 2001; 9:565-74.
2004; 2:523-7.
2005; 8(1):88-94.
BMJ. 1997; 315:931-4.
6. Sutton PP, Gemmell HG, Innes N, Davison J, Smith FW, Legge JS, Friend JA. Use of
nebulised saline and nebulised terbutaline as an adjunct to chest physiotherapy. Thorax.
1988; 43(1):57-60.
9. Lingerfelt BM, et al. Nebulized lidocaine for intractable cough near the end of life. J
Support Oncol. 2007; 7:301-2.
10. Chung KF. Currently available cough suppressants for chronic cough. Lung. 2008 [E-
pub ahead of print, available Oct 2, 2007]. DOI: 10.1007/s00408-007-9030-1.
11. Paul IM, Beiler J, McMonagle A, Shaffer ML, Duda L, Berlin CM. Effect of honey,
dextromethorphan, and no treatment on nocturnal cough and sleep quality for coughing
children and their parents. Arch Pediatr Adolesc Med. 2007; 161:1140-1146.
12. Schroeder K, Fahey T. Systematic review of randomized controlled trials of over the
counter cough medicines for acute cough in adults. BMJ. 2002; 324:1-6.
13. Fuller RW, Jackson DM. Physiology and treatment of cough. Thorax. 1990; 45:425-30.
14. Smith SM, SchroederK, Fahey T. Over-the-countermedications for acute cough in
children and adults in ambulatory settings. Cochrane Database of Systematic Reviews
2008, Issue 1. Art. No.: CD001831. DOI: 10.1002/14651858.CD001831.pub3.
15. Ryan NM, Birring SS, Gibson PG. Gabapentin for refractory cough: a randomized,
double-blind, placebo-controlled trial. Lancet 2012; 380(9853):1583-89. PMID: 22951084
Version History: Originally published March 2008. Copy-edited in June 2009. Revised and 2nd
Edition published July 2013; mostly to reflect new evidence about gabapentin. Copy-edited again
July 2015.
!21

USING NON-INVASIVE VENTILATION AT THE END OF LIFE
Mei-Ean Yeow MD, Rohtesh S Mehta MD MPH, Douglas B White MD, MAS, and
Eytan Szmuilowicz MD
!22
Background Non-invasive positive pressure ventilation (NPPV, often called ‘BiPAP’) is
commonly used in patients with respiratory failure from COPD, CHF, and other disorders. NPPV
decreases the work of breathing and allows respiratory muscle rest during inspiration. This Fast
Fact discusses medical decision making around its use at the end of life. Fast Fact #231
discusses practical aspects of applying NPPV in dying patients, as well as how to discontinue it
safely.
Goals of NPPV at the end of life NPPV is used in 3 general circumstances in patients close to
death, all of which are likely to be encountered by palliative specialists (1):
1. Patients who desire full, life-prolonging interventions, regardless of prognosis. If the patient’s
respiratory status deteriorates, intubation and ventilation are initiated.
2. Patients who want life-prolonging therapy but with limitations (e.g., patients with a ‘Do Not
Intubate’ order but otherwise want all attempts at life prolongation). Ideally, NPPV is used
only if the etiology for the respiratory failure is thought to be reversible and is stopped if it is
not producing the desired response or the patient is not tolerating NPPV. In practice, this
may not be the case.
3. Dying patients with respiratory failure or dyspnea for palliative purposes. This category
includes dying patients who have decided to forego life-prolonging therapies and wish to
focus on comfort measures. NPPV can be used with the intention to reduce the work of
breathing, to ease dyspnea, and to help maintain wakefulness by reducing the amount of
opioids a patient needs to be comfortable. NPPV can also be used to prolong life for a short
period to meet a patient’s goals while otherwise providing a comfortable death (e.g., to allow
time for family to visit). Unlike #2, the goal is not to bridge a patient through a reversible
illness, but to forestall death to meet a specific goal.
Research Findings
• In several trials NPPV has been shown to reduce mortality, intubation rates, and hospital
length of stay in patients with COPD, as well as reduce intubation rates in patients with
respiratory failure from heart failure and in immunocompromised patients (2-4).
• For the second category of patients, there are no high-quality trials. Some observational
studies suggest that NPPV can reverse acute respiratory failure and decrease hospital
mortality in patients with COPD or CHF who have ‘Do Not Intubate’ orders (5,6). Apart from
ALS (see Fast Fact #73, #300) there are no data to affirm its use in other patient populations.
• There is a small body of research about the use of NPPV to alleviate dyspnea in dying
patients. In a survey, a majority of pulmonologists endorsed a belief that NPPV relieves
dyspnea in dying patients in addition to anxiolytics and analgesics (7). In multiple controlled
studies of hospitalized cancer patients with acute respiratory failure and life expectancy less
than 6 months, NPPV was shown to improve dyspnea much faster and have an opioid
sparing effect in the first 48 hours compared with passive oxygen therapy (8,9). However, it
is unclear what effect NPPV had on the overall quality of dying and death, a much more
complex and subjective dimension, seeing that the use of NPPV in these studies was
restricted to intensive care settings.
• With wider availability of new interfaces and ventilators (e.g. nasal NPPV), the rate of
discontinuation due to poor tolerance is estimated to be <15% when used for acute
respiratory failure (10).
Drawbacks of NPPV NPPV is noisy and can be uncomfortable and frightening. It may interfere
with sleep and family intimacy and could confuse care goals if not discussed carefully. Initiating
NPPV outside of acute care environments (e.g. at home, nursing home, or hospice facility – see
Fast Fact #231) may be challenging if not impossible. Some experts have published concerned
that NPPV may complicate end of life decision-making for the bereaved and by consequence
increase the risk of associated anxiety (11).
Medical Decision Making and Counseling

• Patients in categories #1 & 2, as with all patients nearing the end of life, need ongoing
discussions about their realistic prognosis, goals, and options (see Fast Facts # 164, 165,
222-7).
!23
• For dying patients with distressing dyspnea and comfort-only goals of care, opioids are first
line agents (see Fast Fact #27). For patients who need sedating doses of opioids to be
comfortable, and who articulate a strong preference to be as awake as possible, it is
reasonable to offer NPPV if the patient is in an environment which can accommodate it and
the risks are acceptable to the patient, including the possibility that the dying process will be
prolonged. Reassure patients that you can alleviate their symptoms even if NPPV is
unhelpful or intolerable.
• For dying patients who wish to forestall death briefly for a specific goal, it is reasonable to
start a trial of NPPV. Before initiating NPPV, it is important to discuss withdrawal of NPPV
after the above goal has been achieved, and to caution the patient/family that NPPV might
not be able to forestall death long enough as hoped.
References
1. Curtis JR, Cook DJ, Sinuff T, et al; Society of Critical Care Medicine Palliative
Noninvasive Positive VentilationTask Force. Noninvasive positive pressure ventilation in
critical and palliative care settings: understanding the goals of therapy. Crit Care Med.
2007; 35(3):932-9.
2. Peter JV, Moran JL. Noninvasive ventilation in exacerbations of chronic obstructive
pulmonary disease: implications of different meta-analytic strategies. Ann Intern Med.
2004; 141(5):W78-9.
3. Keenan SP, Sinuff T, Cook DJ, Hill NS. Does noninvasive positive pressure ventilation
improve outcome in acute hypoxemic respiratory failure? A systematic review. Crit Care
Med. 2004; 32(12):2516-23.
4. Rusterholtz T, Kempf J, Berton C, et al. Noninvasive pressure support ventilation (NIPSV)
with face mask in patients with acute cardiogenic pulmonary edema (ACPE). Intensive
Care Med. 1999; 25(1):21-8.
5. Schettino G, Altobelli N, Kacmarek RM. Noninvasive positive pressure ventilation
reverses acute respiratory failure in select "do-not-intubate" patients. Crit Care Med.
2005; 33(9):1976-82.
6. Levy M, Tanios MA, Nelson D, et al. Outcomes of patients with do-not-intubate orders
treated with noninvasive ventilation. Crit Care Med. 2004; 32(10):2002-7.
7. Sinuff T, Cook DJ, Keenan SP, et al. Noninvasive ventilation for acute respiratory failure
near the end of life. Crit Care Med. 2008; 36(3):789-94.
8. Nava S, et al. Multicenter, randomized study of the use of non-invasive ventilation (NIV)
vs oxygen therapy (O2) in reducing respiratory distress in end-stage cancer patients
(Abstract). Am J Respir Crit Care Med. 2008; 177:A767.
9. Nava S, Ferrer M, et al. Palliative use of non-invasive ventilation in end of life patients
with solid tumours: a randomized feasibility trial. Lancet Oncol 2013; 14:219-227.
10. Nava S, Evangelisti I, et al. Human and financial costs of non-invasive mechanical
ventilation in patients affected by chronic obstructive pulmonary disease and acute
respiratory failure. Chest 1997; 111:1631-1638.
11. Azoulay E, Kouatchet A, et al. Non-invasive ventilation for end-of-life oncology patients.
The Lancet Oncology, 2013; 14:e200-e201.
Author Affiliations: Northwestern Memorial Hospital, Chicago, IL (MEY, ES); University of

Pittsburgh Medical Center, Pittsburgh, PA (RSM, DBW).
Version History: Originally published April 2010; copy-edited August 2015 by Sean Marks MD
with references #9-11 added and incorporated into the text.
!24
!25
!

PRACTICAL ASPECTS OF USING NPPV AT THE END OF LIFE
Mei-Ean Yeow MD and Eytan Szmuilowicz MD
Background Non-Invasive Positive Pressure Ventilation (NPPV) can be used to palliate
dyspnea in dying patients. Fast Fact #230 discusses medical decision making around using
NPPV. This Fast Fact discusses practical aspects of using NPPV in dying patients. Little
research has occurred on this topic; unless otherwise noted the following discussion is based on
clinician opinion and common practice.
Location The cost and experience needed to initiate NPPV limit its use to the hospital setting,
with some exceptions (see below). Most NPPV use occurs in ICUs or transitional care (‘step-
down’) units, and at some institutions continuous NPPV is not allowed outside of these settings.
While the use of NPPV for palliation can occur at home or a hospice facility, it requires adequate
nursing, respiratory therapy, and physician support to employ it safely. This can be a practical
barrier to its use, and NPPV should not be offered unless one is sure it can be provided
appropriately. Ensuring adequate respiratory therapist support is particularly crucial, as they have
unique expertise at initiating and trouble-shooting the machines. Continuing NPPV for palliation
in patients and families who are already comfortable managing home NPPV (e.g. for COPD or
ALS) can be practical in the home or hospice facility setting, as long as it is consistent with care
goals. Initiating NPPV in the home setting for dying patients is impractical and, given how
uncertain its real benefits are (see Fast Fact #230), is not advised.
Starting NPPV
• Masks: While full facemasks are commonly used in the in-patient setting, some patients
find these claustrophobic. Nasal masks tend to be better-tolerated, but they do not work as
well in patients who are mouth breathers. Patient preference and clinician familiarity should
guide this decision.
• Settings: Two parameters need to be set: the inspiratory positive airway pressure (IPAP)
and end-expiratory positive pressure (EPAP). The breaths are usually triggered by the
patient. On many devices it is possible to set a back-up rate if the patient does not trigger a
breath spontaneously– this is inappropriate in dying patients receiving NPPV for symptom
relief.
• Strategies: There are two general approaches to initiating NPPV settings: a ‘high to low’
approach and a ‘low to high’ approach, referring to the initial IPAP settings. The EPAP is
usually set at 3-5 cmH2O. In order to maximize the tolerability of NPPV for symptom relief
in dying patients, a ‘low-high’ approach is recommended. Start with a lower IPAP (8-10
cmH2O), and gradually increase as tolerated to achieve alleviation of dyspnea, decreased
respiratory rate, increased tidal volume, and patient-machine synchrony.
Monitoring Pulse oximetry and arterial blood gas monitoring are not needed for patients using
NPPV only for symptom control. Rather, its effect should be based on subjective improvement of
dyspnea and decrease in respiratory rate. It is important to reassess patients frequently (looking
specifically for respiratory rate, use of accessory muscles, signs of anxiety, and facial skin
integrity), and to inquire if they are comfortable with the NPPV and deriving any benefit from it.
Breaks from NPPV to eat, drink, communicate, and alleviate skin shearing specifically on the
nasal bridge should be encouraged. Transparent films or thin foams over the bridge of the nose
are recommended to prevent facial pressure ulcers, as well as periodic repositioning of the mask
and alternating between mask types as tolerated.
Contraindications Contra-indications are facial surgery/trauma/deformities that limit

placement of the NPPV mask and patients with active nausea and vomiting. Decreased mental
status is also considered a contraindication it increases the risk of aspiration from NPPV.
!26
Discontinuing NPPV NPPV should be discontinued if it does not provide relief from dyspnea
within an hour of the maximally tolerated setting, once a patient is no longer alert, or at any point
when it is no longer meeting a patient’s goals. If the patient does not tolerate the mask, or feels
claustrophobic, a small dose of a benzodiazepine can be administered to alleviate anxiety. If the
patient is still uncomfortable, then NPPV should be stopped as it is then not adding to patient
comfort. Opioids and benzodiazepines should be used to decrease dyspnea once NPPV is
stopped. Remember that NPPV provides ventilatory support to patients and the work of
breathing can dramatically increase without it. Be prepared to rapidly control any distressing
symptoms, just as you would with discontinuing invasive mechanical ventilation (see Fast Facts
#27, 33, 34).
References
1. Nava S, et al. Multicenter, randomized study of the use of non-invasive ventilation (NIV)
vs oxygen therapy (O2) in reducing respiratory distress in end-stage cancer patients. Am
J Respir Crit Care Med. 2008; 177:A767.
2. Yeow M, Santanilla J. Non-invasive positive pressure ventilation in the emergency room.
Emerg Med Clin N Am. 2008; 26:835-847.
3. Minnesota Hospital Association. Device-related pressure ulcer prevention: respiratory
devices recommendations and guidance. Patient Safety Call to Action. August 2010;1-8.
http://www.mnhospitals.org/Portals/0/Documents/ptsafety/skin/respiratory-
recommend.doc. Accessed August 13, 2015.
4. National Pressure Ulcer Advisory Panel. Best Practices for Prevention of Medical Device-
Related Pressure Ulcers. http://www.npuap.org/wp-content/uploads/2013/04/Medical-
Device-Poster.pdf. Accessed August 13, 2015.
Author Affiliations: Northwestern Memorial Hospital, Chicago, IL
Version History: Originally published June 2010; copy-edited August 2015 by Sean Marks MD
with references #3 and #4 added and incorporated into the text.
!27
!

PROGNOSTIC MODELS IN CRITICALLY ILL ADULTS
René Claxton MD, Derek Angus MD, and Robert Arnold MD
Background Prognostication for ICU patients is challenging. Grieving families, trying to make
informed decisions about their loved ones care, often ask What are the chances he or she will get
through this? Several prognostic models have been developed to predict survival for groups of
patients stratified by severity of illness. These are used in outcomes research to compare patient
groups, assess and compare ICU performance and help guide resource allocation. Anecdotally,
data from these models is sometimes used in discussing prognosis with family members of
critically ill patients. This Fast Fact discusses common ICU prognostic models and their role in
guiding patient care and communication.
Widely used ICU prognostic models Common models for predicting mortality in medical-
surgical ICU patients include the Acute Physiologic and Chronic Health Evaluation (APACHE)
score, the Mortality Probability Model (MPM), the Simplified Acute Physiology Score (SAPS) and
the Sequential Organ Failure Assessment (SOFA) score (1-4). The SOFA score can be
calculated at the bedside based on laboratory and physiologic data; however, this model has not
been widely used in either clinical or research practice by the critical care community to predict
mortality. The APACHE, MPM, and SAPS models are more widely used and require computer
software to calculate a score based on multiple variables including type of admission, the
patient’s underlying diseases, physiologic data, and – in the case of APACHE – laboratory data.
The APACHE score is based on the worst values available during ICU Day 1 whereas MPM and
SAPS scores are calculated based on data obtained within one hour of ICU admission. The
models require re-validation over time as ICU interventions and outcomes change. The
APACHE score is currently in its fourth version. MPM and SAPS are in their third versions.
Although APACHE IV and MPM III require proprietary software to calculate a score, the SAPS3
score can be computed using a downloadable calculator (5). Individual institutions may use a
model for all ICU admissions for purposes of quality monitoring, outcome reporting, or research,
and so some clinicians may have these scores readily available to them.
Accuracy of the prognostic models The discrimination and calibration ability of ICU
prognostic models determine their predictive accuracy (6). Discrimination is the ability of a model
to predict a mortality rate similar to the observed rate; calibration reflects a model’s ability to
predict an outcome at multiple levels (mortality rates). The most recent versions of APACHE,
MPM, AND SOFA show both high discrimination and calibration. All three models report a score
based on the above variables that correlates with a predicted in-hospital mortality rate. For
example, a SAPS3 score of 73 correlates with a hospital mortality rate of 62%. The other two
models work similarly.
Clinical use of ICU prognostic models All of these models accurately predict rates of in-
hospital mortality in a population of critically ill patients. This is different than predicting survival
for an individual patient (7), let alone using them to guide individual treatment decisions. None of
the models alone can, for instance, predict 100% mortality, a standard that some families and
clinicians may require in order to limit life-sustaining treatments. Also, as these models focus
solely on in-hospital mortality as the outcome measure, a patient’s functional status, quality of life,
and long-term prognosis are not predicted. These considerations can be equally as important as
short-term survival for families and clinicians in determining appropriate treatment goals.
Practically, then, the clinical use of the models is best limited to three uses:
1. As a single ‘data point’ among many to guide patient-centered decision-making.
Clinicians can use outcome data from the tools, along with patient co-morbidity, long-term
prognosis, baseline and anticipated functional status and quality of life, etc., to guide
discussions (see Fast Facts 222-227). Chances are your loved one is not going to
survive this illness. She might, and currently we are doing everything we can to get her
through this. However, even if she does, her emphysema is severe enough that we will
!28
not be able to improve her breathing or ability to take care of herself any more than
before she became this ill, and it is very likely another event like this will happen again in
the near future.
2. As a screening tool to identify those ICU patients uniquely ‘in need’ of palliative care
evaluation.
3. As a research tool to look at the impact of interventions on mortality, morbidity and quality
of life.
References
1. Zimmerman JE, Kramer AA, McNair DS, Malila FM. Acute physiology and chronic health
evaluation (APACHE) IV: hospital mortality assessment for today’s critically ill patients.
Crit Care Med. 2006; 34(5):1297-1310.
2. Higgins TL, Teres D, Copes WS, Nathanson BH, Stark M, Kramer AA. Assessing
contemporary intensive care unit outcome: an updated mortality probability admission
model (MPM₀-III). Crit Care Med. 2007; 35(3):827-835.
3. Moreno RP, Metnitz PG, Almeida E, et al. SAPS3—From evaluation for the patient to
evaluation of the intensive care unit. Part 2: Development of a prognostic model for
hospital mortality at ICU admission. Intensive Care Med. 2005; 31:1345-1355.
4. Ferreira FL, Bota DP, Bross A, Melot C, Vincent J. Serial evaluation of the SOFA score to
predict outcome in critically ill patients. JAMA. 2001; 286(14):1754-1758.
5. SAPS3 Software. The SAPS3 Outcome Research Group. Available at: http://saps3.org/
index2.html. Accessed April 21, 2010.
6. Teres D, Lemeshow S. Why severity models should be used with caution. Crit Care Clin.
1994; 10(1):93-110.
7. Rogers J, Fuller HD. Use of daily acute physiology and chronic health evaluation
(APACHE) II scores to predict individual patient survival rate. Crit Care Med. 1994; 22(9):
1402-1405.
Version History: Originally published November 2010; Copy-re-edited August 2015.

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!

TRACHEOSTOMY CARE
Elliott Kozin MD, Joseph Straton MD, and Jennifer Kapo MD
Background Many patients with advanced illness have tracheostomies, which require careful
observation and specialized management. Common indications for tracheostomies in patients
being seen in palliative care and hospice settings include chronic long-term ventilation, aid with
ventilation weaning, and upper airway obstruction (from, for instance, head and neck cancer). A
working knowledge of tracheostomy equipment and the basic handling procedures can avoid
complications and improve a patient’s comfort.
Tracheostomy Equipment 101 At its most basic level, a tracheostomy appliance consists of a
cannula (or tube), cuff, obturator, and ties. The cannula maintains the patency of the stoma and
airway, and it facilitates movement of air into the trachea. Tracheostomy cannulas can be cuffed
or uncuffed. The inflatable cuff, typically filled with air by a syringe, surrounds a portion of the
cannula inside the trachea. The inflated cuff occludes the trachea around the cannula, which
allows for increased protection against aspiration and also for greater degrees of positive
pressure ventilation. Cuffs require monitoring to maintain a pressure of 20-25 mmHg. Higher
pressures can produce tracheal ischemia, mucosal injury, and difficulty swallowing; lower
pressures can potentially aggravate aspiration around the cannula (1,2,3). Obturators, usually
packaged with new tracheostomy tubes, are inserted into the lumen of the cannula and provide
for increased rigidity during placement of the tracheostomy tube. Tracheostomy ties secure the
tracheostomy tube to the patient and typically wrap around the back of the patient’s neck.
Complications of Tracheostomy Placement Short-term complications include bleeding from

surgical site (~5%), wound infection, subcutaneous emphysema, pneumothorax, tracheostomy
tube obstruction, recurrent laryngeal nerve damage, and posterior tracheal wall injury (4, 5).
Long-term complications include dysphagia, airway obstruction from secretions, infection, rupture
of the innominate artery, tracheo-innominate artery fistula (<0.7%), tracheosophageal fistula,
tracheal dilation, tracheal stenosis (1-2%), granuloma formation, and tracheal ischemia and
necrosis (4, 5).
Approach to Complications and Emergencies

• Acute Dyspnea. If a patient with a tracheostomy becomes acutely dyspneic, it may be due to
partial or complete blockage by retained secretions. Ask the patient to cough and then
attempt to suction the tracheostomy in place with a flexible suction catheter. If the
tracheostomy stoma and tract is not fully matured, do not attempt to remove the cannula as it
may be difficult to re-insert. (3)
• Bleeding. Bleeding from the surgical site is among the most common early complications.
Treatments include packing around the edges of the stoma with gauze, correction of
coagulopathies, and cautery or suturing of site of bleeding (3,5). Massive pulsatile bleeding
may indicate erosion of the innominate artery, which can occur days to weeks after a
tracheostomy procedure. This can rapidly lead to airway compromise and/or exsanguination.
To minimize bleeding, place a gloved finger in the stoma, feel for a pulsatile mass, and apply
forward motion on the backside of the upper border of the sternum thereby compressing the
pulsatile artery against the posterior surface of the sternum (6). Other techniques include
overinflating the cuff. If the patient’s goals of care allow this, the patient should be transported
emergently to the operating room for management (3). See Fast Fact #251for further details
about caring for hemorrhaging patients who do not want further invasive treatments.
• Accidental Decannulation. Don’t panic. Reassure the patient. If the tube has been in place
less than 5 days, consider endotracheal intubation if a tracheostomy tract cannot be
immediately re-established (5). If the tube has been in place for 5-10 days, the tract should
be well formed and should not suddenly close (2). To reinsert the tracheostomy tube, insert
the obturator (if applicable) into the cannula. Slowly insert the cannula with obturator into the
tracheostomy, following the path of the airway. When reinserting, be mindful of any
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resistance. If met with resistance, it is possible to create a false passage, and one should
reevaluate the entry approach. After insertion, remove the obturator while keeping the
cannula in place. Listen for and feel for air movement through the tracheostomy tube and
ensure that there is no subcutaneous emphysema, which may indicate improper placement.
If you cannot insert a new cannula and the patient cannot breathe comfortably on their own
through the stoma, use a bag-valve mask to ventilate the patient through the upper airway.
Ventilate gently to prevent air from escaping through the stoma or carefully occlude the stoma
with a gloved hand to maximize oxygenation. Next steps depend on the patient’s current
indication for a tracheostomy (airway patency vs. ventilation vs. secretion management) and
goals of care. If the patient has a patent airway and is not on a ventilator there may be time
to have the patient evaluated by a specialist to replace the cannula. If the patient is ventilator
dependent or has an upper airway obstruction, endotracheal intubation and/or emergency
transport is indicated.
• Resuscitation via Tracheostomy Tube. Treat the patient like patients without tracheostomy,
with the following exceptions. Do not remove the tracheostomy. Check that the cannula is
patent. Ventilate by using a manual resuscitation bag attached directly to tracheostomy tube.
If unable to ventilate, try suctioning. If still unable to ventilate, try to change tracheostomy
tube. The last resort is oral intubation.
Conclusion Careful discussions with dying patients and their families about options and
preferences if there are tracheostomy complications can help prevent chaotic, emergency
decisions about urgent transportation, surgeries, or oral intubation.
References
1. Heffner JE, Hess D. Tracheostomy management in the chronically ventilated patient. Clin
Chest Med. 2001; 22:55-69.
2. Hess DR. Tracheostomy tubes and related appliances. Respir Care. 2005; 50:497-510.
3. St. John RE and Malen JF. Contemporary issues in adult tracheostomy management. Crit
Care Nurs Clin N Am. 2004; 16:413-430.
4. Conlan AA, Kopec, SE. Tracheostomy in the ICU. J Int Care Med. 2000; 15:1-13.
5. De Leyn P, Bedert L, Delcroix M, et al. Review. Tracheotomy: clinical review and guidelines.
Eu J Cardiothoracic Surg. 2007; 32:412-21.
Author Affiliations: University of Pennsylvania School of Medicine, Philadelphia, PA.
Version History: Originally published February 2012; Copy-re-edited August 2015.

used.

PALLIATIVE CARE CONSULTATION IN THE ICU
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Margaret L Campbell PhD, RN, David E Weissman MD, and Judy E Nelson MD, JD
Background The Intensive Care Unit (ICU) is the setting for high-intensity health care
designed to resolve life-threatening illnesses and extend life. However, risks of mortality and
severe morbidity remain high and virtually all ICU patients have palliative care needs. Integration
of palliative care services into ICU care is increasingly seen as a method to improve clinical care
(1,10). This Fast Fact reviews the role of palliative care consultations in the ICU along with
options for more generalist palliative care services provided by ICU clinicians.
What occurs in an ICU Palliative Care Consultation

• Assess/treat distressing physical, psychological, and spiritual symptoms/problems.
• Communicate information about prognosis and treatment options to patient/family in concert
with ICU, primary care and subspecialty colleagues.
• Establish/clarify goals of care that are realistic and appropriate in relation to the patient’s
condition, values and preferences, and help match treatments to these goals.
• Formulate a transition care plan that accounts for prognosis, goals of care and patient/family
needs.
• Provide support for the families.
• Support the ICU medical team in making clinically, ethically, and emotionally challenging
decisions.
Research Data on Benefits of Palliative Care ICU Consultation

• Early identification of a dying trajectory leading to decreased time to institution of patient- and
family-centered, comfort-focused treatment goals (2-3).
• Movement of appropriate patients to lower intensity care sites (ward, palliative care unit,
home hospice) (5-6).
• Reduction in ICU length of stay for adult patients (2-4, 7).
• Reduction in the cost of care, without an increase in mortality, due to early establishment of
realistic treatment goals leading to reduction in use of high-cost ICU resources/interventions
(2-4, 7-8).
• Support for staff in challenging and emotionally draining/morally distressing patient/family
care situations.
• Palliative Care consultation for hospitalized patients can reduce the need for ICU admission
through establishment of treatment goals that preclude future ICU admission (7-8).
• Continuity of care when the patient transitions from the ICU to ward or palliative care unit as
the Palliative Care team follows the patient.
ICU/Palliative Care Collaboration A range of options exist for integrating palliative care
services into the ICU. At one extreme, ICU staff consult a palliative care specialist team for
problems the ICU staff deems appropriate for consultative advice on an ad hoc basis. At the
other extreme, the ICU embeds systems in place to provide ICU-led generalist palliative care
services to all ICU patients, utilizing palliative care specialists for complex problems. Embedding
systems that ensure the needs of all patients are met includes screening all patients on
admission and daily for unmet palliative care needs, early identification of a surrogate, timely
symptom management, and routinely-scheduled family meetings to discuss goals of care
(1,9,10). Quality outcomes related to patient and family experience and to health care utilization
should be tracked within the framework of available resources (1,11).
When to use Specialist Palliative Care Services Consultations can either be initiated on a
case-by-case basis by ICU or other primary clinicians, or triggered proactively using a system to
identify patients at high-risk for unmet needs (2-4). Key indications for consultation include:
• Difficult-to-control physical symptoms despite usual treatment approaches.

• Patients/surrogates wish to explore non-ICU supportive care options such as hospice
services.
• Staff have questions about the appropriateness of life-sustaining therapies in the setting of
advanced complex illnesses.
• There are complex family dynamics impacting decisions about use of life-sustaining
treatments.
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• There are disagreements among staff or between staff and patients/surrogates about
prognosis and/or use of life-sustaining treatments.
• Patients are being readmitted to the ICU more frequently within a given time frame.
Summary Specialist palliative care consultations, together with integration of palliative care
principles into the care of all ICU patients, can improve the patient/family experience, reduce
length of stay and improve ICU throughput without increasing mortality, and lower health care
costs.
Additional resources: Fast Facts # 122-123.
References
1. Nelson JE, Mulkerin CM, Adams LL, Pronovost PJ. Improving comfort and communication
in the ICU: a practical new tool for palliative care performance measurement and feedback.
Qual Saf Health Care. 2006; 15(4):264-271.
2. Campbell ML, Guzman JA. Impact of a proactive approach to improve end-of-life care in a
medical ICU. Chest. 2003; 123(1):266-271.
3. Campbell ML, Guzman JA. A proactive approach to improve end-of-life care in a medical
intensive care unit for patients with terminal dementia. Crit Care Med. 2004; 32(9):
1839-1843.
4. Norton SA, Hogan LA, Holloway RG, Temkin-Greener H, Buckley MJ, Quill TE. Proactive
palliative care in the medical intensive care unit: effects on length of stay for selected high-
risk patients. Crit Care Med. 2007; 35(6):1530-1535.
5. Carlson RW, Devich L, Frank RR. Development of a comprehensive supportive care team
for the hopelessly ill on a university medical service. JAMA. 1988; 259(3):378-383.
6. Smith TJ, Coyne P, Cassel B, Penberthy L, Hopson A, Hager MA. A high-volume specialist
palliative care unit and team may reduce in-hospital end-of-life care costs. J Palliat Med.
2003; 6(5):699-705.
7. Morrison RS, Dietrich J, Ladwig S, et al. Palliative care consultation teams cut hospital
costs for Medicaid beneficiaries. Health Aff (Millwood). 2011; 30(3):454-463.
8. Penrod JD, Deb P, Luhrs C, et al. Cost and utilization outcomes of patients receiving
hospital-based palliative care consultation. J Palliat Med. 2006; 9(4):855-860.
9. Weissman DE, Meier DE. Identifying patients in need of palliative care assessment in the
hospital setting: consensus recommendations. J Palliat Med. 2011; 14(1):1-7.
10. Nelson JE, Bassett R, Boss RD, et al. Models for structuring a clinical initiative to enhance
palliative care in the intensive care unit: a report from the IPAL-ICU Project (Improving
Palliative Care in the ICU). Crit Care Med. 2010; 38(9):1765-1772.
11. Nelson JE, Brasel KJ, Campbell ML, et al. Evaluation of ICU Palliative Care Quality: A
technical assistance monograph from the IPAL-ICU Project.
Authors’ Affiliations: College of Nursing, Wayne State University, Detroit, MI (MLC); Medical
College of Wisconsin, Milwaukee, WI (DEW); Mount Sinai School of Medicine, New York, NY
(JEN).
Version History: Originally published April 2012; Copy-re-edited August 2015

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!34
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PROSTACYCLIN WITHDRAWAL IN PULMONARY HYPERTENSION
Christi Bartlett MD and Lindy Landzaat DO in cooperation with the COPE Collaborative*
Background Pulmonary artery hypertension (PAH) is a disease of the pulmonary vascular
system characterized by elevated pulmonary vascular resistance. Patients with advanced PAH
are often treated with prostacyclins. This Fast Fact reviews suggested guidelines for withdrawal
of prostacyclin therapy in dying patients with PAH.
Physiology/Symptoms PAH is defined as a mean pulmonary arterial pressure greater than 25

mmHg and may lead to right ventricular failure (1). Symptoms include dyspnea, cough, syncope,
fatigue, angina, and peripheral edema, often progressing to respiratory failure and cardiovascular
collapse.
Prostacyclin Treatment Prostacyclin medications, epoprostenol and treprostinil, are effective

in extending life in PAH (2). These drugs are administered via continuous parenteral infusion (IV;
treprostinil can be given subcutaneously). Epoprostenol’s half life is six minutes (3); abrupt
withdrawal can lead to significant symptom burden (dyspnea, anxiety, nausea, light-headedness,
chest and abdominal pain) and rapid death.
Discontinuation of Prostacyclin Therapy Despite the use of prostacyclins and other life-
prolonging treatments, PAH is usually progressive and fatal without lung transplantation. When
the goals of care include discontinuation of prostacyclins, this process can create anxiety among
patients and caregivers due to concerns about the rapid development of distressing symptoms.
Because of this, it is felt best to taper prostacylins in a planned, controlled manner. There are no
guidelines regarding how to taper off IV prostacyclins, let alone any research data to guide
clinicians. The following recommendations, however, have been developed by the COPE
Collaborative * and are based on clinical experience and rational pharmacology.
• A benzodiazepine and/or opioid should be given as premedication and be readily available for
rapid administration following initiation of withdrawal of prostacyclin therapy. Actual doses
however need to be closely tailored to an individual patient’s prior exposure to opioids and
benzodiazepines and acceptable level of consciousness. See Fast Fact #34 (regimen A) for
some general guidelines.
• The rate of medication taper should account for the medication’s half-life. Because
epoprostenol has a short half life, we recommend waiting 4-6 half lives (generally 25-30
minutes) and monitoring for symptoms prior to further titration. Treprostinil, with a half life of
approximately 4 hours, can be titrated downward every 4-6 hours.
• Reduce the prostacyclin in 20-25% increments, with close monitoring for symptoms as a new
steady state is achieved.
• With each dose reduction, the patient should be closely monitored for increasing symptoms.
If symptoms are minimal or otherwise well controlled with opioids or benzodiazepines, the
prostacyclin taper may continue. If the patient experiences distressing symptoms (dyspnea,
anxiety, chest pain), the taper should be held until symptoms are managed and the taper
resumed at a slower rate, with smaller interval dose reductions. Conversely, if the patient is
unresponsive and is tolerating the titration well with minimal symptom burden, the rate of
titration can be cautiously increased.
• Similar to the planned discontinuation of mechanical ventilation in a dying patient (see Fast
Facts #33-35), it is recommended that the de-escalation of IV prostacyclins occur in the
inpatient setting under close physician supervision. In the home setting, a physician should
be present at the bedside along with the support of a knowledgeable hospice team, with
ample medications readily available in-home, as symptoms can develop quickly and patients
often need rapid medication adjustments to maintain comfort.
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*Care Of Pulmonary hypertension patients at End-of-life (COPE) Collaborative members: Christi
Bartlett MD, Lindy Landzaat DO, Karin Porter-Williamson MD, Lewis Satterwhite MD, Leslie
Spikes MD, Ryan Westhoff MD, Tim Williamson MD; University of Kansas, Kansas City, KS.
References
1. The Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the
European Society of Cardiology (ESC) and the European Respiratory Society (ERS),
endorsed by the International Society of Heart and Lung Transplantation (ISHLT).
Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Heart J.
2009; 30:2493-2537.
2. Skoro-Sajer N, Lang I. The role of treprostinil in the management of pulmonary
hypertension. Am J Carciovasc Drugs. 2008; 8(4):213-7.
3. Epoprostenol Sodium [Drug Monograph]. Mississauga, Ontario: GlaxoSmithKline Inc.:
2011. Available from: http://www.gsk.ca/english/docs-pdf/Flolan_2011.pdf. Accessed:
Sept 18, 2012.
Authors’ Affiliation: University of Kansas Medical Center, Kansas City, KS.
Version History: First published February 2013. Re-copy-edited in September 2015.
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!

PALLIATIVE CARE FOR PATIENTS WITH CYSTIC FIBROSIS
Juvianee Estrada-Veras MD and Hunter Groninger MD
Background Cystic fibrosis (CF) is an autosomal recessive disorder of the cystic fibrosis
transmembrane regulator (CFTR) that affects the respiratory tract, pancreas, intestines, male
genital tract, hepatobiliary system, and exocrine sweat glands resulting in multisystem disease.
This Fast Fact discusses the natural history of CF and issues related to palliative care for patients
with CF.
Morbidity and Death in CF The life expectancy of patients with CF has improved over the last
50 years. In 1959, the median age at death was 6 months and in 2008 it increased to 27 years.
For those born in the year 2010, the median age of survival is predicted to be greater than 50
years (1). This improved survival is attributed to advances in the supportive care of patients
including early diagnosis, family support, attention to nutrition, infection control, and the use of
nebulized mucolytics and antimicrobials (3).
• Chronic progressive pulmonary disease and respiratory failure remain the major cause of
morbidity and mortality. End-stage lung disease is characterized by cysts, abscesses, and
fibrosis of lungs and airways. Patients frequently die from overwhelming lung infections.
• Factors associated with earlier death in CF include the deltaF508 mutation, pancreatic
insufficiency, low body mass index, certain infections (Pseudomonas aeruginosa,
Staphylococcus aureus, and Burkholderia cepacia), low socioeconomic status, tobacco
smoke exposure and female sex (2,3).
• For select candidates, lung transplantation improves survival and quality-of-life. The 5-year
survival post-transplant is about 50%.
• Other important causes of morbidity include CF-related diabetes mellitus, pancreatic
insufficiency (manifesting as fat malabsorption, poor growth, and hemolytic anemia),
hepatobiliary disease (including portal hypertension and varices), male infertility, and
meconium ileus in newborns.
• CF patients commonly suffer from cough, fatigue, and dyspnea; these symptoms tend to
worsen as lung disease progresses. Chest wall and back pain from cough, pleurisy, rib
fractures, and chest physiotherapy is common (4). Fears of addiction, respiratory depression,
and concern that chronic opioid use complicates lung transplant success can create barriers
to appropriate opioid administration (3,5,6).
• With multiple medications, therapies, and nutritional supplements required each day, routine
care can be physically and emotionally exhausting for CF patients and family members.
• Adolescents with CF report a high quality-of-life and they abuse substances less frequently
than their healthy counterparts (7). Nonetheless, in this age group, chronic anxiety and
depressive disorders are common and treatment adherence routinely declines (7).
Common Issues Near the End-of-Life

• Prediction of short-term mortality is difficult and largely subjective. Most predictive models
focus on clinical severity of pulmonary disease using age, FEV1%, BMI, the presence of
pancreatic insufficiency, and opportunistic infections as parameters. These models however
are designed to stratify lung transplant candidates rather than assist with end-of-life care
planning (3,9).
• The dynamic, chronic, progressive course of CF creates challenges for timing goals-of-care
discussions. Periodic planned meetings amongst patient, family, and care team are advised.
Single-center studies reinforce that, despite documented need, palliative care consultation is
rarely offered until days before death or when lung transplantation becomes contraindicated
(8).
• Do-not-resuscitate (DNR) orders are often not written until the final few days of life. Many
patients continue to receive disease-modifying therapies up until the last 24 hours of life (9).
Although many disease-specific therapies can be administered in the home setting, most CF
!37
patients die in the hospital setting (5). This likely reflects a combination of prognostication
challenges, reluctance to abandon aggressive therapies, patient/family preference, and
caregiving burdens. CF patients may be uniquely suited to Medicaid ‘concurrent care’ waiver
programs in which patients can receive hospice and routine medical care simultaneously
(10).
• Although guidelines are lacking, progressive hypoxic respiratory failure may benefit from
long-term oxygen therapy (6). Non-invasive positive pressure ventilation (NIPPV) has a role
for hypercapneic respiratory failure, dyspnea management, and, in select candidates, as a
bridge to lung transplant. Use of invasive positive pressure ventilation (IPPV) should always
involve clear discussions around therapeutic options and goals-of-care (8).
• In the past, intensive care for CF patients was generally considered futile. More recently, ICU
outcomes have improved, particularly for patients requiring NIPPV (as opposed to IPPV), and
for patients who are candidates for lung transplantation (6,8). Long-term outcomes for
respiratory failure requiring IPPV remain dismal however, and intensive care management
may commit many patients to eventual end-of-life care in the ICU setting.
• Common symptoms at the end of life include dyspnea, fatigue, anxiety, anorexia, pain, and
cough (see Fast Facts #27, 199, 200). Care providers must balance benefit vs. burden of
disease-specific treatments such as nebulized medications, NIPPV, and chest physiotherapy
(6,8).
• Patients who survive multiple episodes of acute respiratory failure may come to overestimate
their resilience, making appropriate goals-of-care discussions or end-of-life care planning
more challenging (6,7).
Key teaching points

• Pulmonary involvement in CF is the most common cause of morbidity and mortality in people
affected by this disease. Symptoms such as dyspnea, anxiety, cough, and pain commonly
interfere with CF patients’ quality-of-life. For some patients, lung transplantation offers hope
of improved survival and quality-of-life. However, most will die of their disease in the hospital
setting.
• Accurate temporal prognostication in CF is challenging. However, the natural history of CF
without transplantation is well-established and patients and families should be prepared for
the physical and emotional challenges of end-stage CF, including end-of-life decision-making,
even without a precise estimation of survival time.
References
1. MacKenzie T, Gifford AH, et al. Longevity of Patients With Cystic Fibrosis in 2000 to 2010
and Beyond: Survival Analysis of the Cystic Fibrosis Foundation Patient Registry. Ann
Intern Med. 2014;161(4):233-241.
2. Barr HL, Britton J, Smyth AR, et al. Association between socioeconomic status, sex, and
age at death from cystic fibrosis in England and Wales (1959 to 2008): cross sectional
study. BMJ. 2011; 343:d4662.
3. Buzzetti R, et al, Validation of a predictive survival model in Italian patients with cystic
fibrosis, J Cyst Fibros. 2012;11(1):24-9. doi:10.1016/j.jcf.2011.08.007
4. Ravilly S, Robinson W, Suresh S, Wohl ME, Berde CB. Chronic pain in cystic fibrosis.
Pediatrics. 1996; 98:741-747.
5. Hayes M, Yaster M, Haythornthwaite J, et al. Pain is a common problem affecting clinical
outcomes in adults with cystic fibrosis. Chest. 2011; 140(6):1598-1603. doi:10.1378/chest.
11-0132
6. Sands D, Repetto T, Dupont LJ, et al. End of life care for patients with cystic fibrosis. J Cyst
Fibros. 2011; (10)2:S37-S44.
7. Ernst MM, Johnson MC, Stark LJ. Developmental and psychosocial issues in cystic
fibrosis. Pediatr Clin N Am. 2011; 58:865–885.
8. Robinson WM. Palliative and end-of-life care in cystic fibrosis: what we know and what we
need to know. Curr Opin Pulm Med. 2009; 15(6):621-5.
9. Jackson AD, Daly L, Kelleher C, et al. The application of current lifetable methods to
compare cystic fibrosis median survival internationally is limited. J Cyst Fibros. 2011; (10):
62-65.
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10. Rau J. New law could help hospice patients continue aggressive medical treatments.
Kaiser Health News. May 10, 2010. Available at: http://www.kaiserhealthnews.org/stories/
2010/may/10/hospice.aspx. Accessed: September 24, 2015.
Authors’ Affiliations: National Human Genome Research Institute, Bethesda, MD (JEV);

Clinical Center, National Institutes of Health, Bethesda, MD (HG).
Version History: First published July 2013. Re-copy-edited by Sean Marks in September 2015,
with reference # 1 added and incorporated into the text.

THE ONCOLOGY-ICU-PALLIATIVE CARE INTERFACE
Mamta Bhatnagar, MD, Robert Arnold, MD
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Background: Cancer patients may be admitted to an intensive care unit (ICU) at any point in the
disease trajectory (1). When these patients have an advanced malignancy, and/or when their
disease has progressed despite standard anti-cancer treatments, it is common for conflicts to
arise between oncologists and the critical care team regarding appropriate management. This
Fast Fact discusses an approach to conflict management for cancer patients in the ICU.
Same Patient-Different Opinions: Every specialty has a unique culture based on the type of
diseases it treats and the attitudes learned from peers and teachers during training years. Having
a general awareness of these cultural tendencies among various specialty groups could better
enable Palliative Care (PC) clinicians to manage inter-specialty conflicts.
Oncologists …
• See a wide range of patients, some who are cured and others who die.
• Are trained to examine all potential anti-cancer treatments to extend life.
• May view ICU care as nothing more than a “bump in the road,” noting that the prognosis of
cancer patients in the ICU is similar to non-cancer patients. This point of view may be
especially apparent in patients who have recently undergone a bone marrow transplant, but
have not yet shown signs of bone marrow recovery – re-engraftment (1,5).
• Often have long-term outpatient relationships with patients creating strong emotional
connections.
Intensivists …
• Are likely to see many cancer patients near the time of death when ICU care may represents
a ‘last-ditch’ effort to sustain life.
• Often have brief relationships with patients/families during a time of crisis.
• Like many non-oncology specialties, they may have a more negative view of the potential
benefits of anti-cancer treatments than oncologists.
• May worry about prolonging suffering through ICU interventions when death appears
imminent (1).
How can palliative care help? By performing careful independent evaluations of the medical
situation and exploring the points of view of the various specialty teams, the PC team members
can serve as mediators who assist in creating a shared message for the family (2).
• Neutral Caring: An important trait of a PC consultant is the mindset of neutral caring. Neutral
in that he or she should avoid taking sides between the different clinical teams but instead
work to find a common story that they can agree on. PC consultants should be aware of their
own potential biases or conflicts of interest, which could influence the direction of the patient’s
care. For example, PC teams may be more likely to assume that a focus on comfort with a
shortened hospital stay is preferred (3). Caring because the PC consultant needs to
remember that all the clinicians are doing their best to care for the patient. Thus even if the
PC clinician is sure that their view is “right”, they need to respectfully negotiate with other
clinicians who also may be sure their view is correct.
• Pre-meeting of clinicians: Regardless of who initiates the consult, PC teams should reach
out to both the oncologist and the intensivist to understand their points of view regarding
disease, treatment options and prognosis. In many such circumstances, attending-to-
attending level conversations are necessary. Given that prognosis is often uncertain, it may
help to reach agreement on the best, worst, and most likely prognosis (4). This may identify
areas of agreement among the specialist teams involved and clarify what medical data are
needed to better forecast prognosis.
Managing Conflict: Multi-disciplinary goals of care meetings are often the most effective and
efficient way to bring all specialty care teams together along with the patient and/or family and
negotiate the best way forward (see Fast Facts #16, 65, 183-184, 222-227). If there is
disagreement between specialty teams, it is critical that such attending clinicians talk directly
before meeting with the family. Often reports of what one clinician said is from the family or
another indirect source. Consequently, these descriptions may be incomplete or filtered by the
family’s hopes. In cases in which medical agreement cannot be reached, the PC team can assist
by presenting the differing opinions to the family as part of a cohesive medical reality on which
the family can base their decisions or pursue a time-limited trial.
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Summary: The goal of the PC consultant is to perform an independent evaluation in order to
help the medical care team develop a unified medical narrative that is agreeable with all clinicians
involved. As such, PC teams can be vital in conveying an accurate and understandable medical
narrative to the families of critically ill cancer patients. By fostering an environment that allows
regular clinician meetings to occur throughout a patient’s hospital stay, PC teams can better
ensure that medical teams talk directly to each other about the patient’s prognosis and present a
unified approach to the family and patient.
References:
1. Youngner SJ, Allen M, Montenegro H, Hreha J, Lazarus H. Resolving problems at the
intensive care unit/oncology unit interface. Perspect Biol Med. 1988;31(2):299-308. doi:
10.1353/pbm.1988.0060.
2. Meier DE, Beresford L. Consultation etiquette challenges palliative care to be on its best
behavior. J Palliat Med. 2007;10:7-11.
3. Barnard D, Towers A, Boston P, Lambrinidou Y. Crossing Over: Narratives of Palliative
Care. Oxford University Press; 2000.
4. Campbell T, Elise C, Jackson V a, et al. Discussing Prognosis: Balancing Hope and
Realism. Cancer J. 2010;16(5):461-466.
5. Staudinger T, Stoiser B, Müllner M, et al. Outcome and prognostic factors in critically ill
cancer patients admitted to the intensive care unit. Crit Care Med. 2000;28(5):1322-1328.
Authors Affiliation: University of Pittsburgh Medical Center


CHRONIC CRITICAL ILLNESS IN ADULTS
Amanda Hinrichs DO and Drew A Rosielle MD
Background Chronic critical illness (CCI) was first coined in 1985 (1). Although it does not
have a single accepted definition, most authors apply CCI to patients who survived an initial
critical illness with mechanical ventilation or other intensive care therapies, but remain dependent
on these technologies beyond 14 days neither improving nor imminently declining (2). The usual
CCI patient does not have respiratory failure in isolation. Instead, many have protracted
comorbidities such as neuromuscular weakness, debility, delirium, skin breakdown, and edema.
Palliative care clinicians may be asked to help in complex medical decision-making for CCI
!41
patients in various care settings. These decision points include whether to consider a
tracheostomy for long-term ventilation or whether to withdraw long-term ventilator support in a
patient at a long-term acute care hospital (LTACH) or ventilator weaning facility. This Fast Fact
reviews the long-term outcomes and palliative care challenges for CCI patients.
Prevalence Approximately 5-10% of patients who require mechanical ventilation develop CCI
(3,4). It can emerge from a critical illness of any reason, including medical (e.g., pneumonia),
surgical (complications after an operation), a stroke, or a trauma. Risk factors for developing CCI
have not been clearly established (5). Of note: CCI does not apply to all patients on long-term
mechanical ventilation as some were never critically ill. For example, a patient with amyotrophic
lateral sclerosis who electively pursued a tracheostomy and mechanical ventilation.
Outcomes For many CCI patients, proceeding to tracheostomy and long-term ventilation
represents a fundamental decision point, often 14-21 days after critical illness presentation.
Uncertainty in identifying which CCI patients will eventually functionally recover makes this
decision challenging. When leading these discussions, clinicians should be aware of the following
outcomes data:
• Mortality in CCI is high. A meta-analysis of patients requiring mechanical ventilation for > 14
days, who were either admitted to a ventilator weaning unit or had a tracheostomy found that
the pooled mortality at 1 year was 73% in the US (7). Patients >65 years of age; patients who
continue to require dialysis or vasopressor support at 14-21 days; and patients with
thrombocytopenia and acute kidney injury are at even greater 1-year mortality risk (8).
• Long-term functional outcomes in CCI are poor. In the US, < 50% of patients ventilated for
>14 days are ever weaned from the ventilator (7). A single-institution, US-based prospective
study found that only 15% of the 203 patients studied at a respiratory care unit for ventilator
weaning were functionally independent after 6 months. At 6 months ~2/3 patients had died,
and most of the survivors had profound physical, cognitive, or communication deficits (9).
• Symptom burden in CCI is high. In a prospective cohort study of 36 participatory patients
requiring tracheostomy and admission to a respiratory care unit for ventilator weaning, 44%
experienced high intensity pain, 80% reported unsatisfied thirst, > 60% reported dyspnea,
and > 60% reported worry or sadness frequently or almost constantly (6).
Communication Most CCI patients are unable to engage in medical decision making, and
family members or friends are used as surrogates. Unfortunately, current research indicates
neither patients nor surrogates are well-informed about realistic long-term outcomes of CCI.
• In one study, a majority of patients reported receiving no information about choices other than
continuing mechanical ventilation, financial burdens for the family, and expected functional
and cognitive status after hospitalization, even though >90% or participants rated these topics
as important (10). About 93% of patients reported that they did not receive information about
1-year mortality risk, even though 74% rated this as important (10).
• In another prospective study, only 26% of CCI surrogates reported that physicians discussed
prognosis, functional limitations, quality of life, or expected caregiving needs (11). Among
these surrogates, 93% expected their loved ones to survive 1 year and 71% expected their
loved one to have no major functional limitations; the physicians expected similar outcomes
only 44% and 6% of the time, respectively (11).
Recommendations Considering the poor outcomes and the communication deficiencies

involved with CCI patients, we empirically recommend the following:
• Hospitals should implement policies and practices to improve patient and surrogate
knowledge about CCI outcomes, as well as alternatives prior to tracheostomy placement
such as the discontinuation of life-prolonging technologies and the allowance of a
comfortable death (9,10) so that these goals of care discussions are not needlessly deferred
to LTACH or ventilator weaning facilities.
• Ideally, inter-disciplinary palliative care teams should be available to support clinicians in
leading these discussions not just at hospitals and ICUs, but LTACHs and ventilator weaning
facilities as well.
!42
• Patient preferences, values, and meaning should be ascertained and utilized in CCI decision-
making.
• Despite pressure to hurry the decision-making process, palliative care consultants should
avoid acting as agents of the primary team’s agenda, especially during the initial encounter.
Rather, a pause to complete an independent clinical and prognostic assessment is essential.
• Palliative care clinicians may help certain CCI patients and surrogates by offering to make a
medical recommendation. If there is still difficulty deciding on an acceptable care plan, a time
limited trial of continued endotracheal mechanical ventilation may be reasonable, as long as
there are clearly defined targets when tracheostomy placement or comfort care would be
pursued.
References
1. Girard, K., and T. A. Raffin. "The chronically critically ill: to save or let die?." Respiratory
care 30.5 (1985): 339-347.
2. Carson, Shannon S. "Definitions and epidemiology of the chronically critically ill."
Respiratory Care 57.6 (2012): 848-858.
3. Nelson, Judith E., et al. "Chronic critical illness." American Journal of Respiratory and
critical care medicine 182.4 (2010): 446-454.
4. Kahn, J. M., et al. The epidemiology of chronic critical illness in the United
States. Critical care medicine 43(2) (2015): 282-287.
5. Loss, Sérgio H., et al. "Prediction of chronic critical illness in a general intensive care
unit." Revista da Associação Médica Brasileira (English Edition) 59.3 (2013): 241-247.
6. Nelson, Judith E., et al. "The symptom burden of chronic critical illness." Critical care
medicine 32.7 (2004): 1527-1534.
7. Damuth Emily, et al. Long-term survival of critically ill patients treated with prolonged
mechanical ventilation: a systematic review and meta-analysis. The Lancet Respiratory
Medicine 3.7 (2015): 544-553.
8. Dettmer, Matthew R., et al. Prognostic factors for long-term mortality in critically ill
patients treated with prolonged mechanical ventilation: a systematic review. Critical Care
Medicine 45.1 (2017): 69-74.
9. Nelson, Judith E., et al. "Brain dysfunction: another burden for the chronically critically ill."
Archives of internal medicine 166.18 (2006): 1993-1999.
10. Nelson, Judith E., et al. Communication about chronic critical illness. Archives of internal
medicine 167.22 (2007): 2509-2515.
11. Cox, Christopher E., et al. Expectations and outcomes of prolonged mechanical
ventilation. Critical care medicine 37.11 (2009): 2888.
Authors’ Affiliations: Park Nicollet Methodist Hospital, St. Louis Park, Minnesota; University of
Minnesota; Minneapolis, Minnesota
Version History: Originally edited by Sean Marks MD; first electronically published in October
2017
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Renal
#114
Myoclonus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . 2-3
#133 Non-Oral Hydration in Palliative

Care. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4-5
#134 Non-Oral Hydration Techniques in Palliative

Care . . . . . . . . . . . . . . . . . . . . . . . . .6-7
#161 Opioid Use in Renal Failure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . . 8-9
#163 Decision Making in Chronic Kidney Disease . . . . . . . . . . . . . . . . . . . . . .

. . . . . . 10-11
#191 Prognostication in Patients Receiving Dialysis . . . . . . . . . . . . . . . . . . . .

. . . . . . 12-14
#207 Withdrawal of Dialysis: Decision-

Making . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .15-16
#208 Clinical Care Following Withdrawal of

Dialysis . . . . . . . . . . . . . . . . . . . . . . . . . . 17-18
#220 Hypodermoclysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . 19-21
#287 Drug-Induced Acute Urinary

Retention . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22-24
#313 Thirst in Palliative Care . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . . 25-27
1
#325 Uremic Calciphylaxis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . .28-30
#337 Palliation of Bladder Spasms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . 31-33
2
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MYOCLONUS
Nicholas DeMonaco and Robert Arnold MD
Background Myoclonus is an abnormal movement described as a sudden, brief, shock-like,

involuntary movement caused by active muscle contraction (positive myoclonus) or inhibition of
ongoing muscle contraction (negative myoclonus). Myoclonus can have a distribution that is
focal, multifocal, or generalized. This Fast Fact discusses its causes, evaluation, and therapy.
Characteristics and Differential Diagnosis Hiccups are an example of normal, physiological

positive myoclonus, while asterixis is an example of negative myoclonus seen with metabolic
encephalopathy. In nocturnal myoclonus or periodic leg movement disorder, there is activity in the
flexor muscles of the legs and feet during light sleep. It can be seen in the setting of chronic
nervous system diseases or in elderly patients with no other abnormalities. The brief, shock-like
movements of myoclonus may be difficult to distinguish from other involuntary movements such
as cramps, spasms, fasciculations, and dystonia. Fasciculations are brief involuntary muscle
twitches that, unlike myoclonus, often do not result in movement across a joint. Dystonia is
characterized as slow, repetitive, patterned, sustained movements (an example is writers cramp).
An acute dystonic reaction is often caused by dopamine blocking medications including certain
antipsychotics (haloperidol), antiemetics (metoclopramide), and calcium-channel blockers.
Causes The etiologies of myoclonus are numerous. Near the end of life, metabolic
abnormalities and medication-induced myoclonus predominate. Metabolic causes include liver
failure, renal failure, hyponatremia, and hypoglycemia. The medications and toxins associated
with myoclonus include opioids, anticonvulsants (gabapentin, phenytoin, valproate, lamotrigine,
and phenobarbitol), tricyclic antidepressants and selective serotonin reuptake inhibitors, contrast
dye, anesthetics, antibiotics (penicillins, cephalosporins, imipenem, and quinolones),
cannabinoids and the chemotherapeutic agent ifosfamide. Opioid-induced myoclonus occurs
commonly and is often misdiagnosed (See Fast Facts #57, 58). When myoclonus occurs due to
toxins or medications, the jerks are usually multifocal or generalized, may be provoked by a
stimulus or voluntary movement, and are often accompanied by encephalopathy. Other causes
of myoclonus include focal CNS damage from tumors, stroke, and encephalitis, generalized CNS
dysfunction such as encephalopathies (viral, metabolic, genetic, or neurodegenerative), seizure
disorders, anoxic injury, and disorders affecting the spinal cord and peripheral nerves.
Treatment Myoclonus can disrupt sleep, make coordinated movements difficult, and be
bothersome to patients or families. Treatment consists of correction of the underlying cause and
symptomatic treatment of the myoclonus. If the offending agent is a non-essential medication, it
should be discontinued. In the case of opioid-induced myoclonus, rotation to a different opioid
may help. Benzodiazepines are the primary symptomatic treatment at end-of-life. While any
benzodiazepine will work, clonazepam and lorazepam are commonly used. A continuous infusion
of midazolam has also been suggested given the drug’s compatibility with morphine and short
half-life, allowing rapid dose titration. Sedation is likely when using benzodiazepines. If sedation
is to be avoided, anticonvulsants such as levetiracetam (1,000-3,000 mg/day) and valproic acid
(1200-2000 mg/day) may be helpful. The muscle relaxant dantrolene in doses of 50-100 mg/day
has been reported as effective.
References
1. Caviness, J. Treatment of myoclonus. Neurotherapeutics. 2014; 11:188-200.
2. Daroff R, Fenichel G., et al. Bradley’s Neurology in Clinical Practice. 6th ed. Philadelpha,
PA: Elsevier Saunders; 2012.
3. Fahn S. Overview, history, and classification of myoclonus. Adv Neurol. 2002; 89:13-17.
4. Gordon MF. Toxin and drug-induced myoclonus. Adv Neurol. 2002; 89:49-76.
3
5. Jankovic J. Hyperkinetic movement disorders. In: Basow DS. UpToDate. Waltham, MA:
UpToDate; 2003.
7. Rivest J. Myoclonus (Rev). Can J Neurol Sci. 2003; 30(Suppl 1):S53-58.
in May 2004. Re-copy-edited in April 2009; copy-edited again in June 2015 by Sam Maiser MD in
which references 1 and 2 were added and incorporated into the text.
Sarah Friebert MD.
4
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NON-ORAL HYDRATION IN PALLIATIVE CARE
Robin Fainsinger MD
Background At the center of the debate with regard to hydration in terminally ill patients is the
desire to maintain comfort and avoid unnecessary/distressing procedures. There is no
controversy that terminally ill patients should be encouraged to maintain adequate oral hydration
for as long as possible. However there is debate and controversy around the use of parenteral
hydration. This Fast Fact discusses medical decision-making about non-oral hydration in
palliative care settings; Fast Fact #134 discusses techniques of hydration.
Arguments Against Hydration

• Comatose patients do not experience symptom distress.
• Parenteral fluids may prolong dying.
• With less urine there is less need to void and use catheters.
• With less gastrointestinal fluid there can be less nausea and vomiting.
• With less respiratory tract secretions there can be less cough and pulmonary edema.
• Dehydration can help reduce distressing edema or ascites.
• Dehydration may be a “natural” anesthetic to ease the dying process.
• Parenteral hydration can be uncomfortable (e.g. needles/catheters) and limit patient
mobility.
Arguments For Hydration

• Dehydration can lead to pre-renal azotemia, which in turn can lead to accumulation of
drug metabolites (notably opioids), leading to delirium, myoclonus and seizures.
Hydration can reverse these symptoms in some patients leading to improved comfort.
• There is no evidence that fluids prolong the dying process.
• Providing hydration can maintain the appearance of “doing something,” even though
there may be no medical value, and thus ease family anxiety around the time of death.
Ethical/Legal Issues In the United States, the following ethical/legal standards exist:
• Competent patients or their surrogates can accept or refuse hydration based on relevant
information.
• Non-oral hydration is considered a medical intervention, not ordinary care. As such,
there is no legal or ethical imperative to provide it unless the benefits outweigh the
burdens.
Recommendation There is published medical literature to support both the use of, and the
withholding of, non-oral hydration in patients near death; thus, there is no consensus on the
single best approach to care. A Cochrane review of 6 relevant studies showed that sedation and
myoclonus were improved with hydration in adult palliative care patients; however, discomfort
from fluid retention was significantly higher in the hydration group and survival seemed to be the
same between the groups. Key issues to be considered when determining the role of non-oral
hydration include the following:
• Expressed wishes of the patient or surrogate decision-maker regarding use of hydration.
• Patient-defined goals; the presence of a specific goal may direct the clinician to use
hydration as a means to improve delirium and potentially delay death.
• Symptom burden: symptoms related to total body water excess may improve by
withholding hydration, while delirium may lessen with hydration.
• Burden to the patient and caregivers of maintaining the non-oral route of hydration.
• Family distress concerning withholding hydration/nutrition.
• When in doubt, a time limited hydration trial is an appropriate recommendation.
5
Clinician Self-Reflection Finally, it is important to recognize that health care providers often
have biases for or against non-oral hydration near the end-of- life. Self-reflection upon these
biases is crucial to help patients and families make decisions that are based on the best interests
and goals of the patient/family unit.
References
2. MacDonald N. Ethical considerations in feeding or hydrating advanced cancer patients.
In: Ripamonti C, Bruera E, eds. Gastrointestinal Symptoms in Advanced Cancer
Patients. New York, NY: Oxford University Press; 2002.
3. Lawlor PG. Delirium and dehydration: Some fluid for thought? Supp Care Cancer.
2002; 10:445-454.
4. Sarhill N, Walsh D, Nelson K, Davies M. Evaluation and treatment of cancer related fluid
deficits: volume depletion and dehydration. Supp Care Cancer. 2001; 9:408-419.
5. Bruera E, Sala R, Rico M, et al. Effects of parenteral hydration in terminally ill cancer
patients: a preliminary study. J Clin Oncol. 2005; 23:2366-2371.
6. Good P, Richard R, et al. Medically assisted hydration for adult palliative care patients.
Cochrane Database Syst Rev 2014; 4: 1-25.
in April 2005. Version re-copy-edited in April 2009; copy-edited again July 2015 in which
reference #6 was added and incorporated into the text.
6
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NON-ORAL HYDRATION TECHNIQUES IN PALLIATIVE CARE
Robin Fainsinger MD
Background The decision to use or withhold non-oral hydration near the end-of-life is complex
(see Fast Fact #133). This Fast Fact reviews the technical aspects of providing non-oral
hydration. Fast Fact #190 discusses the related issue of parenteral nutrition in advanced cancer
patients. 
 
Nasogastric and Gastrostomy Tubes The use of enteral feeding tubes to provide nutrition is
beyond the scope of this Fast Fact (see Fast Facts #10, 84). If already in place, enteral feeding
tubes provide easy access for supplemental hydration. Placement of enteral tubes solely for
hydration management in the last few weeks of life is generally not indicated, as other less
burdensome methods of hydration can be provided (see below).
Intravenous Hydration This method includes hydration via peripheral or central catheters. For
short-term use, especially as a time-limited trial, intravenous hydration is a reasonable step.
However, both peripheral and central catheters are plagued with problems of site selection,
placement, and maintenance; clot formation; local skin irritation; and local or systemic bacterial
infections.
Hypodermoclysis (subcutaneous infusions) Hypodermoclysis offers a number of

advantages compared to the intravenous route due to greater ease of site access, the possibility
of temporary disconnection to facilitate patient mobility, and ease and suitability for home
administration. Thrombocytopenia may be a relative contraindication. Solutions with electrolytes
should be used (e.g. 0.9% sodium chloride), as non-electrolyte solutions (e.g. 5% dextrose) can
draw fluid into the interstitial space. Continuous infusion rates up to 120 ml/hr have been
reported; patients can tolerate boluses of up to 500 ml/hr two to three times per day. Traditionally
the use of hyaluronidase to promote absorption was recommended. More recent experience has
demonstrated that most patients will achieve good absorption of subcutaneous fluids without
hyaluronidase. Winged infusion sets with 25 – 27 gauge needles are recommended.
The upper chest is the commonly used site for hypodermoclysis. Utilization of the lower
abdomen and upper thigh as sites for hypodermoclysis can be associated with scrotal edema in
males. Most experts recommend avoiding the upper arm as a site for hypodermoclysis.Check
the site frequently for redness, irritation, excessive edema, or a dislodged needle. If there is a
problem with absorption it recommended to a) slow the infusion rate and consider using an
infusion pump, or b) consider dividing the total volume into two separate subcutaneous sites.
Rectal Hydration (proctoclysis) Rectal hydration is an alternative only when other resources
are not available. A 22 French nasogastric catheter can be inserted approximately 40 cm into the
rectum. The patient can be positioned as for any rectal procedure. Tap water can be used, and
the rectal infusion increased from 100 ml to a maximum of 400 ml per hour, unless fluid leakage
occurs before the maximum volume is achieved. The majority of patients can successfully
tolerate this approach at a volume of 100 to 200 ml per hour.
Fluid Volumes For all routes, a reasonable goal is 1-1.5 L/day in fluid volume.
References
2. Steiner N, Bruera E. Methods of hydration in palliative care patients. J Palliat Care. 1998;
14(2):6-13.
3. Centeno C, Bruera E. Subcutaneous hydration with no hyaluronidase in patients with
advanced cancer. J Pain Symptom Manage. 1999; 17(5):305-306.
7
4. Bruera E, Pruvost M, Schoeller T. Proctoclysis for hydration of terminally ill cancer patients.
5. Lanuke K, Fainsinger RL, de Moissac D. Hydration management at the end-of- life. J Palliat
Med. 2004; 7(2):257-263.
6. Edmonton Regional Palliative Care Program. Hypodermoclysis (HDC) Administration
Protocol for Palliative Care Patients. Edmonton, Alberta: 2003. Available at: http://
www.palliative.org/newpc/_pdfs/management/
3A7%20Hypodermoclysis%20Admin%20Protocol%20for%20PC%20Patients.pdf .
Accessed July 2015.
7. Dalal S, Bruera E. Dehydration in cancer patients: to treat or not to treat. J Support Oncol.
2004; 2:467-487.
April 2005. Re-copy-edited in April 2009; then again in July 2015 -- web-links updated.
8
OPIOID USE IN RENAL FAILURE
Robert Arnold MD, Peg Verrico RPh, Sara N Davison MD
Background Chronic pain is common in chronic kidney disease impacting 50% of
hemodialysis patients, 82% of whom experience moderate to severe pain. The absorption,
metabolism, and renal clearance of opioids are complex in renal failure. However, with the
appropriate selection and titration of opioids, patients with renal failure can achieve analgesia with
minimal risk of adverse effects. This Fast Fact reviews recommendations for opioid use in the
setting of renal failure and in patients receiving chronic dialysis.
Not Recommended for Use:
• Meperidine is not recommended in renal failure due to accumulation of
normeperidine, which may cause seizures.
• Codeine has been reported to cause profound toxicity which can be delayed
and may occur after trivial doses. We recommend that codeine be avoided in
patients with a Glomerular Filtration Rate (GFR) <30 mL/min.
• Dextropropoxyphene is associated with central nervous system (CNS) and cardiac
toxicity and is not recommended for use in patients with renal failure.
• Morphine is not recommended for chronic use in renal insufficiency (GFR <30 mL/min)
due to the rapid accumulation of active, nondialyzable metabolites that are neurotoxic. If
morphine must be used, avoid long-acting preparations and monitor closely for toxicity
Use with Caution:
• Oxycodone is metabolized in the liver with 19% excreted unchanged in the urine. There
are reports of accumulation of both the parent compound and metabolites in renal failure
resulting in CNS toxicity and sedation.
• Hydromorphone, as the parent drug, does not substantially accumulate in hemodialysis
patients. Conversely, an active metabolite, hydromorphone-3-glucuronide, quickly
accumulates between dialysis treatments but appears to be effectively removed during
hemodialysis. With careful monitoring, hydromorphone may be used safely in dialysis
patients. However, it should be used with caution in patients with a GFR < 30mL/min who
have yet to start dialysis or who have withdrawn from dialysis.
Safest in Renal Insufficiency:
• Fentanyl is considered relatively safe in renal failure as it has no active metabolites.
However, very little pharmacokinetic data exist regarding fentanyl in end stage renal
disease. While some studies have shown decreased clearance in renal failure, most
studies do not show drug accumulation. Fentanyl is not dialyzable due to high protein
binding and a high volume of distribution.
• Methadone is considered relatively safe in renal failure. It has no active metabolites and
limited plasma accumulation in renal failure due to enhanced elimination in the feces.
However, precautions regarding the use of methadone exist (See Fast Facts # 75, 86). It
does not appear to be removed by dialysis.
Opioid Dosing Given the lack of pharmacokinetic and pharmacodynamic data of
opioids in renal failure, it is difficult to advocate for specific analgesic treatment
algorithms. However, the following guide has been proposed (Broadbent 2003) for the
initial dosing of the safer opioids in renal impairment and renal failure.
• Creatinine Clearance > 50 mL/min: normal dosing.
• Creatinine Clearance of 10-50 mL/min: 75% of normal.
• Creatinine Clearance < 10 mL/min: 50% of normal.
The “normal opioid dose” for any given patient is the dose that adequately relieves pain without
unacceptable adverse effects (see Fast Fact #20). Rarely, do opioids need to be adjusted when
GFR is > 50 mL/min. While opioids can be used when GFR is <50, they require closer monitoring
and constant reassessment to ensure that accumulation of active metabolites does not result in
toxicity. This should not preclude the effective use of opioids in these patients.
9
References:
1. Chambers EJ, Germain M, Brown E, eds. Supportive Care for the Renal
Patient. New York, NY: Oxford University Press; 2004.
2. Davison SN. Pain in hemodialysis patients: prevalence, cause, severity, and
management. Am J Kidney Diseases. 2003; 42(6):1239-1247.
3. Murphy EJ. Acute pain management pharmacology for the patient with
concurrent renal or hepatic disease. Anaes Intensive Care. 2005; 33(3):311-22.
4. Dean M. Opioids in renal failure and dialysis patients. J Pain Symptom Manage.
2004; 28(5):497-504.
5. Broadbent A, Khor K, Heaney A. Palliation and chronic renal failure: opioid and
other palliative medications – dosage guidelines. Progress in Palliative Care.
2003; 11(4):183-90.
in August 2006. Version re-copy-edited in April 2009; then again July 2015.
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DECISION MAKING IN CHRONIC KIDNEY DISEASE (CKD)
Sara N Davison, MD
Background Care of patients with CKD requires expertise in advance care planning (ACP),
including attention to ethical, psychosocial, and spiritual issues related to starting, continuing,
withholding, and stopping dialysis. This Fast Fact reviews key concepts of the ACP process for
CKD patients.
Barriers to ACP in CKD

• Being unaware of a poor prognosis. CKD patients may falsely assume they can be kept
alive indefinitely on dialysis; end-of-life issues are commonly avoided until late in the illness.
• Many health professionals believe that ACP may destroy hope and that the focus of care
should be on their “life-sustaining therapy”, i.e. dialysis.
• Cognitive dysfunction associated with advanced CKD may prevent the ability for
meaningful participation in ACP. Discussions must occur early in the illness while
comprehension and decision-making capacity are preserved.
Key Aspects of ACP in CKD (See FF #162 for general ACP recommendations)
• ACP should be initiated prior to the need for dialysis. The importance of early
discussions is underscored by the fact that only ~ 60% of nephrologists would consider
stopping dialysis for a non-decisional patient with unclear prior wishes.
• Include family in ACP discussions.
o CKD patients are often afraid to talk to their loved ones about their preferences;
some patients will choose to prolong their time on dialysis due to family pressure.
o Surrogates must be aware of patient preferences and the values upon which these
preferences were based.
o Including family is critical in achieving many of the goals of ACP such as
strengthening relationships with and relieving emotional and financial burdens on loved
ones.
• Provide detailed information as part of pre-dialysis education.
o All treatment options should be fully reviewed: 1) available dialysis modalities, 2) not
starting dialysis and continuing conservative management, 3) a time-limited trial of
dialysis, and 4) stopping dialysis with expectation of death. (See below for clinical
practice guidelines on not starting or discontinuing dialysis).
o Estimate prognosis. The annual death rate for patients initiating dialysis is 20-25%;
15% - 25% of these deaths result from decisions to withdraw dialysis. Patients with CKD
who elect dialysis generally experience progressive functional decline over months to
years, punctuated by episodes of life-threatening complications. Elderly or chronically ill
patients with co-morbid diseases, at the initiation of dialysis, can be expected to have
greater complications and a shorter survival. Poor prognostic factors include older age,
low serum albumin, poor functional status, and comorbid illnesses such as diabetes and
cardiovascular disease. Anuric patients, who elect to not initiate or discontinue dialysis,
typically survive for 7-14 days. The prognosis is longer for patients with residual renal
function who continue to make urine.
o Emphasize how you expect their illness and proposed treatments will impact their
daily function. Discuss the impact of the various dialysis options on day-to-day function.
11
Patients Selection for Withholding or the Withdrawal Dialysis (1)
1. Patients who, being fully informed and making voluntary choices, decline to begin or
request dialysis be stopped.
2. Patients who no longer posses decision-making capacity, who have previously indicated
refusal of dialysis.
3. Patients who do not possess decision-making capacity and whose surrogate declines
dialysis or determines it should be discontinued.
4. Patients with irreversible, profound neurological impairment such that they lack signs of
thought, sensation, purposeful behavior, and awareness of self and environment.
5. Patients whose medical conditions precludes the technical process of dialysis.
References
1. Shared Decision-Making in the Appropriate Initiation of and withdrawal from Dialysis.
Clinical Practice Guideline. Renal Physicians Association and American Society of
Nephrology. Washington DC, 2000
2. Chambers EJ, Germain M, and Brown E, eds. Supportive Care for the Renal Patient.
Publisher: Oxford University Press; 2004.
3. Davison SN. Facilitating Advance Care Planning for Patients with End Stage Renal
Disease: the Patient Perspective. CJASN in press 2006
4. Holley JL. Palliative Care in End Stage Renal Disease: Focus on Advance Care Planning,
Hospice Referral, and Bereavement. Seminars in Dialysis 18(2): 154-156,
5. Michel DM, Moss AH. Communicating Prognosis in the Dialysis Consent Process: A
Patient-Centered, Guideline-Supported Approach. Advances in CKD. 12 (2): 196-201,
in September 2006. Version copy-edited in April 2009; then again in November 2015.
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PROGNOSTICATION IN PATIENTS RECEIVING DIALYSIS
Matthew Hudson, Steven Weisbord MD, Robert Arnold MD
Background End stage renal disease (ESRD) is a highly prevalent and rapidly increasing
condition. While dialysis prolongs life in patients with ESRD, life expectancy remains only a third
to a sixth as long as similar patients not on dialysis. The overall one and five year mortality rates
are 25% and 60%, respectively. Approximately 20% of ESRD patient deaths occur after a
decision to stop dialysis, highlighting the importance of discussions of prognosis and goals of
care with this chronically ill population. This Fast Fact reviews the current data regarding
prognostication in patients receiving chronic hemo- and peritoneal dialysis. Note: renal
transplantation reduces mortality and the following data do not consider patients with functioning
kidney transplants.
Prognostic Factors Several patient-specific factors influence prognosis:

• Age: For 1-year increments beginning at age 18, there is a 3 to 4% increase in annual
mortality compared to the general population. 1 and 2 year mortality rates go from 10 and
12% at 25-29 years of age, to 25% and 42% at 65-69 years, to 39% and 61% at 80-84 years
of age.
• Functional status: the relative risk of dying within 3 years of starting dialysis is 1.44 for those
with Karnofsky Performance Status scores of <70 compared to a score ³70 (see Fast Fact
#13).
• Albumin: a low serum albumin level, both at baseline and during the course of dialysis
treatment, is a consistent and strong predictor of death. For example, the 1 and 2 year
survival of patients with an albumin of >3.5 g/dL is 86% and 76% respectively, compared to
50% and 17% if less than 3.5.
• Surprise question: in a multivariate analysis, the likelihood of death in 6 months was
significantly greater when nephrologists answered no to the question “would I be surprised if
this patient died within 6 months?” 
Prognostic Tools It has long been recognized that patient comorbidity is strongly correlated
with prognosis in ESRD. An age-modified Charlson Comorbidity Index (CCI), which stratifies
patients based on medical comorbidities and age, has been successfully used to predict mortality
in dialysis-dependent patients (8):
Modified Charlson Comorbidity Index: Total score is the sum of the comorbidity points
Comorbidity Points
1 point each for coronary artery disease, congestive heart failure, peripheral vascular disease,
cerebrovascular disease, dementia, chronic pulmonary disease, connective tissue disorder,
peptic ulcer disease, mild liver disease, diabetes
1 point for every decade over 40 (e.g. a 65 year old would receive 3 points).
2 points each for hemiplegia, moderate-to-severe renal disease (including being on dialysis),
diabetes with end-organ damage, cancer (including leukemia or lymphoma)
3 points for moderate-to-severe liver disease
6 points each for metastatic solid tumor or AIDS
Modified CCI Score Low score Moderate High (6-7) Very High (³8)
Totals (£3) (4-5)
Annual mortality rate 0.03 0.13 0.27 0.49
13
For example, a 66 year old male on dialysis with a history of CHF, COPD, and diabetes with
retinopathy would have a CCI score of 9 and a nearly 50% chance of dying within a year. Using
this, a provider could discuss with the patient his prognosis and use this to facilitate further
discussion regarding planning for the future, including end-of-life decisions. The Index of
Coexistent Disease (ICED), a general illness severity index, has also shown predictive power in
ESRD. The scale’s complexity and length however (it entails asking over 100 questions) limit its
clinical usefulness.
Summary The age-modified CCI, in conjunction with other prognostic factors such as serum
albumin and functional status, can be used to help facilitate discussions with dialysis-dependent
patients and their families regarding goals of care and end-of-life planning.
References:
1. United States Renal Data System. Incidence and prevalence. Annual data report, 2006.
Minneapolis, MN: USRDS Coordinating Center; 2006. Available at: http://www.usrds.org/
2006/pdf/02_incid_prev_06.pdf.
2. Cohen LM, Moss AH, Weisbord SD, Germain MJ. Renal palliative care. J Pall Med. 2006;
9:977-992.
3. Renal Physicians Association and American Society of Nephrology. Clinical Practice
Guideline on Shared Decision-Making in the Appropriate Initiation of and Withdrawal from
Dialysis. Washington, DC: Renal Physicians Association, 2000. Available at: http://
jasn.asnjournals.org/cgi/content/full/11/7/1340.
4. Ifudu O, Paul HR, Homel P, Friedman EA. Predictive value of functional status for
mortality in patients on maintenance hemodialysis. Am J Nephrol. 1998; 18:109-116.
5. Owen WF, Lew NL, Yiu Y, Lowry EG, Lazarus JM. The urea reduction ratio and serum
albumin concentration as predictors of mortality in patients undergoing hemodialysis.
NEJM. 1993; 329(14):1001-1006.
6. Owen WF, Price D. African-Americans on maintenance dialysis. Adv Ren Replace Ther.
1997; 4:3-12.
7. Lowrie EG, Lew NL. Death risk in hemodialysis patients. Am J Kidney Dis. 1990;
15:458-482.
8. Cohen LM, Ruthazer R, et al. Predicting six-month mortality for patients who are on
maintenance hemodialysis. Clin J Am Soc Nephrol 2010;5:72-79.
9. Beddhu S, Bruns FJ, Saul M, Seddon P, Zeidel ML. A simple comorbidity scale predicts
clinical outcomes and costs in dialysis patients. Am J Med. 2000; 108:609-613.
10. Miskulin DC, Martin AA, Brown R, et al. Predicting 1-year mortality in an outpatient
hemodialysis population: a comparison of comorbidity instruments. Nephrol Dial
Transplant. 2004; 19:413-420.
11. Moss AH. A new clinical practice guideline on initiation and withdrawal of dialysis that
makes Explicit the role of palliative medicine. J Palliat Med. 2000; 3:253-260.
12. Nicolucci A, Cubasso D, Labbrozzi D, et al. Effect of coexistent diseases on Survival of
patients undergoing dialysis. ASAIO J. 1992; 38:M291-M295.
again in July 2015 – references #8 and #9 were added and incorporated into the text.
14
15
!

WITHDRAWAL OF DIALYSIS: DECISION-MAKING
Sara N Davison MD and Drew A Rosielle MD
Background Historically, stopping dialysis was considered by many to be a form of suicide.
Now, it is a widely accepted practice in most countries, with broad ethical and legal consensus
that dialysis can be stopped when it is no longer achieving a meaningful goal for the patient. In
fact, ~25% of deaths of dialysis patients in North America occur after its cessation. This Fast Fact
reviews key issues pertaining to the decision to stop chronic dialysis; Fast Fact #208 will discuss
the care of patients after it is stopped.
Why dialysis is stopped The goal of dialysis is not only to prolong life by providing renal
replacement therapy, but to maintain a patient’s quality of life at an acceptable level (see Fast
Fact #163). Discussions to stop dialysis usually occur when:
• Dialysis is no longer serving to substantially prolong life or is only prolonging a patient’s death
(e.g., a patient dying from advanced cancer or sepsis with multiorgan system failure).
• The burdens of dialysis and its complications outweigh its life-prolonging benefits to a patient
(e.g., a patient with progressive frailty who is becoming bedbound; a patient with severe
cognitive failure). In these scenarios dialysis is likely to prolong life but is not helping to
restore a patient to an acceptable level of quality of life as assessed by the patient or her/his
surrogate decision maker.
Demographics The demographics of dialysis withdrawal have been studied at length. Patient
characteristics associated with withdrawal are older age, female, white race, longer duration of
dialysis, higher educational level, living alone, severe pain, and comorbidity (with chronic or
progressive diseases). Ethnic differences have been observed, with African Americans and
Hispanics being less likely to stop dialysis than European Americans. Reported prevalence levels
of patient decision-making capacity at the time of withdrawal vary considerably with estimates
ranging from 37% to 80%, suggesting cognitive failure drives many of these decisions.
Nephrologists rate cognitive and physical functional status as the most important factors for their
decision-making around stopping dialysis, and 93% of North American nephrologists report a
willingness to honor a patient’s request to stop, even if they have a personal preference to
continue. Internationally, practices vary tremendously, with much lower rates of dialysis cessation
in Japan compared to North America, for instance.
Responding to a request to stop dialysis For patients who are otherwise dying, counsel
about terminal care issues surrounding dialysis withdrawal (see Fast Fact #208). For patients not
otherwise close to death, explore reasons for withdrawal, especially for treatable factors that
might contribute to the desire to withdraw dialysis. For patients whose desire to stop dialysis is
being driven by factors that are potentially ameliorable, clinicians should make sure that the
decision to stop dialysis is fully informed, including the possibility that some concerns could be
addressed. These include:
• Inadequately treated depression, anxiety, pain, and other physical or psychological symptoms
(including spiritual and existential suffering)
• Dissatisfaction or difficulties with dialysis itself (e.g., modality, time commitment, or treatment
setting)
• Inadequate social support, or concerns with being a burden to loved ones.
Offer to evaluate and treat these concerns; consider a time-limited trial to see if a patient’s quality
of life can be improved. However, once a clinician feels a patient or surrogate is making a fully
informed choice that is consistent with a patient’s values and goals, that decision should be
honored. Proactively address any concerns patients may voice about the ethics of withdrawal.
16
Broaching dialysis withdrawal Clinicians who are concerned continuing dialysis is no longer
benefitting a patient due to the reasons described above should broach discontinuation with the
patient and family. This discussion should occur as part of a larger goals-of-care conversation
which addresses prognosis (see Fast Fact #191), patient/family assessment of quality of life, and
establishes realistic care goals. Dialysis should be discussed as part of an overall medical plan
and framed as how it can or cannot address the care goals. “Dialysis will likely make your mother
live longer. However – given everything that has been happening – it is not going to improve her
strength, memory, or ability to take care of herself. Based on what you’ve told me about your
mother and what is important for her, I would recommend stopping the dialysis as it is only
serving to maintain her in a state she would find unacceptable.”
References
1. Galla JH and the Renal Physicians Association/American Society of Nephrology
Working Group. Clinical Practice Guideline on Shared Decision-Making in the
Appropriate Initiation of and Withdrawal from Dialysis. J Am Soc Nephrol. 2000;
11:1340-1342.
2. Murtagh F, Cohen LM, Germain MJ. Dialysis Discontinuation: Quo Vadis?
Advances Chronic Kid Dis. 2007; 14(4):379-401.
3. Holley JL, Davison SN, Moss AH. Nephrologists’ Changing Practices in Reported
End-of-Life Decision-Making. Clin J Am Soc Nephrol. 2007; 2:107-111.
4. White Y, Fitzpatrick G. Dialysis: prolonging life or prolonging dying? Ethical, legal
and professional considerations for end of life decision making. EDTNA ERCA J.
2006; 32:99-103.
5. Cohen LM, Germain MJ, Poppel DM. Practical considerations in dialysis
withdrawal. “To have that option is a blessing.” JAMA. 2003; 289:2113-2119.
Author Affiliations: The University of Alberta, Edmonton, Alberta (SND), and the
Medical College of Wisconsin, Milwaukee, Wisconsin (DAR).
Version History: Published August 2008; copy-edited July 2015.

CLINICAL CARE FOLLOWING WITHDRAWAL OF DIALYSIS
Sara N Davison MD and Drew A Rosielle MD
17
Background Fast Fact #207 discussed decision-making around dialysis discontinuation; this
Fast Fact addresses care of the patient around the time of discontinuation.
Communication and care-planning at the time of dialysis cessation

• Counsel about what to expect: mean survival following dialysis withdrawal is 8-10 days
(although rarely can be many weeks). Address the likelihood of progressive encephalopathy.
• Reassure patients/families that symptoms can be adequately treated (see below), although
drugs with sedating side effects may be necessary to ensure comfort.
• Discuss diet: a liberal, pleasure-based diet is appropriate for many patients although they
should be cautioned it could worsen symptoms from edema.
• Address potential care sites for the final days of life.
• Review other medical treatments the patient is receiving and discontinue those that will not
improve their quality of life while dying; clarify treatment limitations including resuscitation
(code) status.
• Provide emotional/psychological, spiritual, social work, and bereavement support services.
Symptom Management In one cohort of hospitalized patients who stopped dialysis confusion/
agitation was reported to affect 70% of patients, followed by pain (55%), dyspnea (48%), nausea
(36%), twitching/seizures (27%), anxiety/psychological distress (27%), pruritis (24%), and
peripheral edema (21%). Because of a paucity of clinical research, the following
recommendations are largely based on clinical experience and pharmacologic common sense.
Many drugs which were previously cleared by dialysis may need to be dose-adjusted or
discontinued. Treatment plans should be frequently re-evaluated, with particular attention to the
use of scheduled medications.
• Pain management: Acetaminophen is the agent of choice for mild pain. Fast Fact #161
addresses opioid use in renal failure. Fentanyl and methadone are considered safest after
dialysis discontinuation, although methadone should only be initiated by clinicians familiar
with its use. Toxic hydromorphone metabolites, previously cleared by dialysis, can
accumulate rapidly once dialysis is stopped and it should be used with caution and close
monitoring of side effects. Gabapentin and pregabalin quickly accumulate once dialysis is
stopped and should be discontinued or severely dose-reduced (see Fast Fact #49).
• Shortness of breath: Oxygen, positioning, and opioids are the mainstays of therapy (see Fast
Fact #27). Ultrafiltration is not recommended as it can be distressing for patients/family to see
the patient back on a therapy which appears similar to hemodialysis. For the occasional
patient who has a residual urine output of >100 ml/day, high dose diuretics can be used.
• Anxiety/agitation/restlessness: Assure pain and psychosocial issues are addressed.
Haloperidol or benzodiazepines are effective. Haloperidol may lower the seizure threshold
and the metabolites are excreted in the urine and feces so it is recommended to dose at half
the typical starting dose following dialysis withdrawal. While benzodiazepines do not
accumulate in chronic kidney disease, clinical experience supports starting with low doses.
• Restless legs: Clonazepam is particularly useful for the restless legs associated with uremia
(0.5 – 2.0 mg bid). Clonidine (0.1-0.2 mg bid) can also be used.
• Muscle cramps: Dialysis patients are often treated with quinine sulphate which accumulates
rapidly once dialysis is stopped and should be discontinued. Clonazepam and other
benzodiazepines are better in this setting.
• Nausea: Reduced doses of metoclopromide (starting at 5 mg bid) are effective for
gastroparesis. Uremia-induced nausea often responds well to dopamine antagonists such as
haloperidol and prochloperazine which are often sedating in the context of uremia.
Ondansetron has some advantages as it is less sedating and does not accumulate in kidney
failure.
• Pruritus: Emollients such as hydrourea cream, ondansetron, and antihistamines may be
beneficial. Gabapentin, while effective, is too toxic in this population to initiate its use.
• Myoclonus: See Fast Facts #114. Often it emerges from uremic encephalopathy and is mild
in nature (e.g. 1-3 jerks per minute involving hands or feet). However, myoclonus can be
distressful and wake patients from sleep. Empiric use of clonazepam or other
benzodiazepines is the mainstay of treatment.
References
18
1. Germain MJ, Cohen LM, Davison SN. Withholding and Withdrawing from Dialysis: What We
Know About How Our Patients Die. Seminars in Dialysis. 2007; 20:200-204.
2. Murtagh FEM, Addington-Hall JM, Donohoe P, Higginson IJ. Symptom Management in
Patients With Established Renal Failure Managed Without Dialysis. EDTNA ERCA J. 2006;
32:93-98.
3. Chambers EJ, Germain M, Brown E (Eds.). Supportive Care for the Renal Patient (1st
Edition). New York, NY: Oxford University Press; 2004.
4. Cohen LM, Germain MJ, Poppel DM. Practical considerations in dialysis withdrawal. “To
have that option is a blessing.” JAMA. 2003; 289:2113-2119.
5. Murtagh FE, Chai MO, Donohoe P, Edmonds PM, Higginson IJ. The use of opioid analgesia
in end-stage renal disease patients managed without dialysis: recommendations for practice.
J Pain Palliat Care Pharmacother. 2007; 21:5-16.
6. Lugon JR. Uremic pruritus: a review. Hemodialysis Intl. 2005; 9:180-88.
7. Caviness JN. Myoclonus. Mayo Clin Proc. 1996; 71 679-688
Author Affiliations: University of Alberta, Edmonton, Alberta (SND), and the Medical College of
Wisconsin, Milwaukee, Wisconsin (DAR).
Version History: Published October 2008; copy-re-edited July 2015 by Sean Marks MD.
19
!

HYPODERMOCLYSIS
Arif H Kamal MD and Eduardo Bruera MD
Background This Fast Fact discusses subcutaneous fluid infusions, also known as
hypodermoclysis (HDC). The use of parenteral hydration in dying patients is controversial and is
discussed in Fast Fact #133. While this Fast Fact discusses subcutaneous fluid infusions for
purposes of hydration, similar techniques can also be used to deliver medications (see Fast Fact
#28).
Historical and Current Practice Hypodermoclysis was a widely accepted route for parenteral
hydration in the 1940s and 1950s before falling out of favor after several reports of adverse
reactions, likely related to the use of hypertonic and electrolyte-free solutions. Due to its ease of
use, and subsequent research demonstrating its safety and efficacy, HDC has become more
widely used. In the US, HDC is mostly used in geriatric and palliative care settings, although it is
used more widely elsewhere in the world.
HDC vs. Intravenous Hydration Decisions for parenteral hydration in dying patients are
complex and individual decision making is paramount. When parenteral hydration is indicated,
clinicians are generally faced with a decision to use HDC or intravenous (IV) hydration (see Fast
Fact #134).
• Advantages of HDC over IV: Starting and maintaining a subcutaneous infusion catheter
is relatively pain-free. It can be done by trained patients or family caregivers, preventing
the need for frequent skilled nursing visits or trips to medical centers to maintain a
working IV. HDC provides greater potential sites for needle placement (arm, back,
abdomen, thighs), and equipment costs are generally lower than with IVs. Subcutaneous
catheters can be easily disconnected from IV tubing and re-used later, allowing a patient
to receive intermittent fluid treatments. Portable infusion devices are not needed with
HDC. HDC infusions may also cause less agitation in patients with dementia versus IV
(1).
• Disadvantages: HDC is limited by a continuous infusion rate of 1-2 ml/min or 1.5-3 L/day
(2). This is adequate for most clinical situations, and additional catheters can be added if
needed. Bolus infusions (up to 500 ml/hour) are possible with HDC, but often require
hyaluronidase (see below). Both HDC and IV infusions have similar rates of local
adverse events (e.g. erythema, cellulitis) and lifespan of infusion site (3). HDC can be
technically difficult in patients with substantial peripheral edema, as well as in cachectic
patients with little subcutaneous tissue. Patients and families may have pre-conceived
attitudes about greater benefits with IV routes even while acknowledging increased
burden (4).
Technique
• Equipment needed: Small butterfly needle (usually 22 gauge) or angiocatheter, skin
preparation (alcohol or iodine), sterile occlusive dressing, solution bag (saline or saline-
dextrose combination), tubing with drip chamber. The use of an electrolyte free solution
like 5% dextrose is discouraged due to third-spacing risks which can cause tissue
sloughing or rarely circulatory collapse.
• Procedure: After cleaning the local site, insert the needle bevel up into the subcutaneous
tissue. Attach to fluid and tubing and cover with occlusive dressing. Select an infusion
fluid and set drip rate or fluid bolus. Normal saline (NS) is typically used although half-
normal saline or 2/3 D5W in 1/3 NS have been used in clinical practice. Drip rates can be
set to 20-125 ml/hour with gravity (no pump required) or 1-2 ml/minute. Some patients
may prefer drips set to gravity 24 hours per day at a low rate (e.g. 50 ml/hour), overnight
hydration (e.g. 100 ml/hour), or intermittent fluid boluses (e.g. 500 ml). The volume of
infusion needed to keep acceptable levels of hydration in many palliative care patients is
lower than healthy patients and postulated to be ~1 L/day (5). No evidence exists for the
20
frequency of site change. Some change only when there are symptoms or needle
displacement while others choose a fixed time (e.g. every 3 or 7 days) or fluid volume
(e.g. every 1.5 L) Teflon cannulas, although expensive, can be used for a week and are
helpful for patients who have trouble maintaining a catheter site (6). Local anesthetic
creams may be helpful during catheter placement to reduce discomfort, especially in
children.
• Recombinant human hyaluronidase: RHH is an enzyme that temporarily lyses the
subcutaneous interstitial space to promote diffusion of fluid. It can be used for site
discomfort or if a faster rate of absorption is desired. Previous preparations were of
bovine origin and were associated with local allergic reactions, anaphylaxis, and pain,
making its role controversial. RHH has shown no human allergenicity (7). Recent studies
have investigated RHH versus placebo in a randomized trial with gravity-driven infusion.
The RHH group showed higher obtainable fluid rates, decreased discomfort, and similar
local reactions. Doses of 150 U to 750 U given as steady push prior to the infusion can
yield fluid rates of 380 to 520 ml/hour (8).
Cautions Uncommon local reactions include edema, local pain, or erythema. Interventions
include slowing the rate, changing the site, or using RHH. Rare complications include cellulitis
and vascular puncture. Systemic complications such as pulmonary edema can occur with all
types of artificial hydration.
References
1. O'Keeffe ST, Lavan JN. Subcutaneous fluids in elderly hospital patients with cognitive
impairment. Gerontology. 1996; 42(1):36-39.
2. Berger EY. Nutrition by hypodermoclysis. J Am Geriatr Soc. 1984; 32(3):199-203.
3. Slesak G, Schnurle JW, Kinzel E, Jakob J, Dietz PK. Comparison of subcutaneous and
intravenous rehydration in geriatric patients: a randomized trial. J Am Geriatr Soc. 2003;
51(2):155-160.
4. Mercadante S, Ferrera P, Girelli D, Casuccio A. Patients' and relatives' perceptions about
intravenous and subcutaneous hydration. J Pain Symptom Manage. 2005; 30(4):
354-358.
5. Dalal S, Bruera E. Dehydration in cancer patients: to treat or not to treat. J Support
Oncol. 2004; 2(6):467-479, 483.
6. Macmillan K, Bruera E, Kuehn N, Selmser P, Macmillan A. A prospective comparison
study between a butterfly needle and a Teflon cannula for subcutaneous narcotic
administration. J Pain Symptom Manage. 1994; 9(2):82-84.
7. Yocum RC, Kennard D, Heiner LS. Assessment and implication of the allergic sensitivity
to a single dose of recombinant human hyaluronidase injection: a double-blind, placebo-
controlled clinical trial. J Infus Nurs. 2007; 30(5):293-299.
8. Thomas JR, Yocum RC, Haller MF, von Gunten CF. Assessing the role of human
recombinant hyaluronidase in gravity-driven subcutaneous hydration: the INFUSE-LR
study. J Palliat Med. 2007; 10(6):1312-1320.
Author Affiliations: Mayo Clinic, Rochester, MN (AK) and University of Texas M.D. Anderson
Cancer Center, Houston, TX (EB).
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22
!

DRUG-INDUCED ACUTE URINARY RETENTION
Winifred Teuteberg MD
Background Acute urinary retention (AUR) is defined as a sudden inability to urinate, which is
usually painful and requires catheterization (1). This can impair quality of life, and can cause
kidney injury (2). A variety of medications used for symptom management can contribute to
urinary retention. This Fast Fact will review medication-induced AUR and offer management
strategies.
Clinical features and evaluation Signs and symptoms of AUR include bladder/suprapubic
pain and tenderness and new onset overflow incontinence. The presence of AUR should be
assessed in older patients who develop delirium, particularly if they have underlying dementia.
Medications are a common cause of AUR. Common non-drug etiologies include benign prostatic
hypertrophy, malignancy (e.g., epidural spinal cord compression), neurogenic bladder, and fecal
impaction. There are little data on the incidence of AUR in palliative care. However, a small
observational study showed that 15% of patients admitted to a large palliative care program had
urinary retention (3). In contrast to AUR, chronic urinary retention is difficult to define as urine
volumes vary greatly between patients. Chronic urinary retention is often the result of chronic
neurologic condition or benign prostatic hypertrophy. A key difference between acute and chronic
urinary retention is that chronic urinary retention is often asymptomatic and rarely painful due to
gradual distention of the bladder over time. Common symptoms of chronic urinary retention
include frequency, hesitancy and decreased force of urine stream (4).
Medications Associated with AUR Medications with anticholinergic properties (e.g.,

antipsychotics antihistamines and many anti-emetics and antidepressants) as well as opioids and
anesthetics are commonly associated with AUR. Other drugs include alpha-agonists,
benzodiazepines, NSAIDs, detrusor relaxants (e.g., oxybutynin), and calcium channel
antagonists. Elderly patients are more at risk due to increased prevalence of benign prostatic
hypertrophy (BPH) and polypharmacy.
• Selective serotonin reuptake inhibitors (SSRI’s) are an under-recognized cause of
retention. One prospective study found that urinary retention occurred in about 10% of
patients prescribed SSRI’s and the symptom often leads to the discontinuation of the
medication (5).
• Opioids causing urinary retention has long been recognized, and is most studied in post-
operative adult patients where its incidence is approximately 25% (6). All opioids can
cause urinary retention due to mu-opioid receptor agonism.
Post Void Residual is the volume of urine left in the bladder at the end of micturition. The gold
standard for PVR measurement is a transurethral catheterization; however due to the discomfort
involved, non-invasive bladder volume estimation via a portable bladder scanner is a commonly
utilized alternative often performed by the bedside nurse. Threshold values delineating what
constitutes an abnormal PVR are poorly understood and PVR measurements utilizing portable
scanners can be inaccurate in the presence of ascites (7). In general, clinical management
decisions should be based on the patient’s symptoms and the trends in the PVR measurements
rather than a strict threshold PVR measurement. For example, an acute increase in PVR values
from 200 mL to 450 mL in the setting of acute onset suprapubic pain or discomfort is indicative of
AUR, whereas an asymptomatic patient with a PVR of 300 mL may not need any intervention at
all.
Physical Exam A distended bladder is palpable as a tender suprapubic mass once it has
reached a urine volume of 150 mL. Bladders with volumes in excess of 500 mL can manifest as a
visible suprapubic mass in thin patients. Because a normal bladder volume is less than 50 mL,
AUR can be missed on physical exam, particularly in obese patients.
23
Clinical Management AUR can be a medical emergency; hence, such patients should be
catheterized to relieve bladder distension. Depending on the age of the patient, patients should
be treated with either in-and-out catheterization followed by a trial of spontaneous voiding or be
sent home with an indwelling bladder catheter for several days to a week. Patients older than 75
years and those with PVRs greater than 1000 mL are less likely to have successful voiding after a
one-time catheterization. Medications should be reviewed and offending agents should be
stopped or dose-limited. If BPH is a contributing factor, the addition of BPH drugs, such as 5-α
reductase inhibitors and α-antagonists, can help improve urine flow (6). If a spontaneous voiding
trial fails after adjustment of medication and several days of catheterization, a referral to urology
is warranted (8).
For patients with a limited life expectancy for whom causative medications cannot be adjusted,
life-long indwelling catheterization or intermittent catheterization are reasonable options. Although
many clinicians may consider catheterization to be burdensome, a survey of patients with
neurogenic bladders using long-term indwelling or intermittent self-catheterization found that the
majority of patients felt that the use of catheterization positively impacted quality of life (9).
Novel Pharmacologic Management Strategies If the offending pharmacotherapy cannot be

stopped, targeted pharmacotherapies may be able to counteract urinary retention, although such
use is considered investigational. Opioid antagonists such as naloxone and methylnaltrexone
can block opioid receptors and allow for normal urination per a case report and a single, pre-
clinical controlled trial (10,11). One case report described the reversal of citalopram-related AUR
by the addition of mirtazapine (12).
References
1. C. Dawson, H. Whitfield. ABC of Urology. Urological emergencies in general practice.
BMJ 1996; 312 : 838–840.
2. Thomas K, Chow K, Kirby RS. Acute urinary retention: a review of the aetiology and
management. Prostate Cancer Prostatic Dis. 2004;7(1):32-7.
3. Currow DC, Agar MR, To TH. Adverse events in hospice and palliative care: a pilot study
to determine feasibility of collection and baseline rates. J Palliat Med. 2011; 14(3):309-14.
4. Negro CL, Muir GH. Chronic urinary retention in men: how we define it, and how does it
affect treatment outcome. BJU Int. 2012 Dec;110(11):1590-4.
5. Uher R, Rarmer A, Henigsberg N, et al. Adverse reactions to antidepressants. Br J
Psychiatry. 2009; 195(3):202-210.
6. Verhamme K, Miriam C, Sturkenboom M, et al. Drug-induced urinary retention:

incidence, management and prevention. Drug Safety. 2008;31(5):373.
7. Asimakopoulos AD, De Nunzio C, et al. Measurement of post-void residual urine.
Neurourology and Urodynamics 2014; DOI 10.1002/
8. Sakakirbara R, Hattori T, et al. Micturitional disturbance in acute dis
9. Choong S, Emberton M. Acute urinary retention. BJU International. 2000; 85:186-201.
10. James R, Frasure HE, Mahaja ST. Urinary catheterization may not adversely impact
quality of life in multiple sclerosis patients. ISRN Neurology. 2014. Article ID 167030.
11. Rosow CE, Gomery P, Chen TY, et al. Reversal of opioid-induced bladder dysfunction by
inravenous naloxone and methylnaltrexone. Clin Pharmacol Ther. 2007; 82(1):48-53.
12. Garten L, Buhrer C. Reversal of morphine-induced urinary retention after
methylnaltrexone. Arch Dis Cild Fetal Neonatal Ed. 2012; 97(2):F151-3.
13. Lenze EJ. Reversal of SSRI-associated urinary retention with mirtazapine augmentation.
J Clin Psychopharmacology. 2012; 32(3):434.
24
Author Affiliation: University of Pittsburgh Medical Center, Pittsburgh, PA
Conflicts of Interest: The author has disclosed no relevant conflict of interest.
Version History: Published February 2015; copy-re-edited September 2015 by Sean Marks MD.
25
!

THIRST IN PALLIATIVE CARE
April Zehm MD, Jonathan Mullin MD, Haipeng Zhang DO
Background Thirst is a common source of distress in the seriously ill. This Fast Fact reviews
thirst in patients with serious illness. See Fast Fact #182 on causes and treatment of dry mouth.
Physiology Thirst is the desire to drink fluids in response to a water deficit. Social customs,
dry mouth, accompanying food intake, fluid availability, and palatability all serve as cues to drink.
Seriously ill patients encountered by hospice and palliative care clinicians are at risk for thirst due
to dehydration, electrolyte disturbances, hypotension, xerostomia, and immobility which can
impede access to water. Patients with heart failure (HF), with end stage renal disease (ESRD), on
mechanical ventilation, and taking certain medications (e.g. anti-hypertensives, tolvaptan,
diuretics, or SSRIs) are also at increased risk. While opioids cause xerostomia, whether or not
they cause thirst is controversial (1,2).
Thirst vs. xerostomia Thirst is the desire to drink, while xerostomia is subjective or objective
dry mouth. While xerostomia can contribute to thirst, not all patients with dry mouth experience
thirst. Similarly, thirsty patients may not have xerostomia present. Research studies often use
xerostomia as a surrogate for thirst, making it difficult to evaluate the prevalence and treatment
efficacy for either symptom independently. It is important that clinicians evaluate for xerostomia
or thirst as independent symptoms and determine if reversible causative factors are involved.
Measurement In clinical and research settings, thirst is self-reported and has high individual
variability. There is no consensus on the best way to measure the frequency, intensity, quality and
distress of thirst. Unidimensional severity scales and a 6-item Thirst Distress Scale have both
been used (3).
Thirst in dying patients Around 80-90% of dying patients report significant thirst (4,5). Given
its high prevalence, providers should routinely assess for thirst among dying patients who are
able to report the symptom. The use of artificial or medically-assisted hydration to alleviate
symptoms of dehydration amongst the terminally ill remains controversial. The concern that
dehydration-related symptoms, including thirst, can cause discomfort is weighed against the
concern that iatrogenic over-hydration can lead to pain and dyspnea from fluid retention. Studies
of thirst in dying patients conclude there is little relationship between artificial hydration and thirst
(5-8). Instead, daily oral care and sips of oral fluid administered for comfort can improve thirst
(5-9) and should be routinely offered (see Fast Fact #133). Concerned family and friends may be
distressed that their loved one is experiencing thirst at the end of life, which can prompt requests
for artificial nutrition or hydration. While these requests should be considered on a case by case
basis, reassurance that artificial hydration is unlikely to alleviate thirst and comes with significant
risks should be provided.
Patients with ESRD Thirst and xerostomia are associated with higher inter-dialytic weight gain
(IWG) which in turn increases cardiovascular morbidity and mortality (10,11). Increasing the
frequency of dialysis from three times per week to daily is the only change to dialysis that has
conclusively shown to reduce thirst scores, but this has obvious practical limitations (12).
Angiotensin converting enzyme inhibitors have been associated with a reduction in thirst scores
and IWG, but this benefit does not seem to last beyond six months (13-16). Frequent gum
chewing and saliva substitutes used more than six times per day may alleviate thirst for at least
several weeks after initiation (17-18).
Patients in the ICU Significant thirst has been reported in over 70% of critically ill patients
(19). An “ICU bundle” of oral swab wipes, sterile ice-cold water sprays, and a lip moisturizer has
been shown to decrease thirst intensity, thirst distress, and dry mouth in ICU patients (20).
26
Patients with HF Liberalization of fluid restrictions has been shown to decrease thirst in
patients with chronic, stable HF and hospitalized patients with acute, decompensated HF (21-22).
Importantly, these and multiple other studies did not show any change in mortality or readmission
rates. In consultation with a patient’s cardiology team, liberalization of fluid restrictions should be
considered in patients with HF and distressing thirst, along with addressing medications that are
causing dry mouth (23).
Summary In patients reporting thirst, perform a clinical assessment to differentiate xerostomia

and thirst and identify potentially reversible causes of either symptom. Available evidence
suggests thirst is common in dying patients and is unlikely to be improved with artificial hydration
especially in non-awake patients. Education, emotional support, oral care, and sips of fluid
should be offered instead. Patients with ESRD, HF, and intubated ICU patients may have specific
interventions which can improve thirst.
References:
1. Stotts N, Arai S, et al. Predictors of thirst in intensive care unit patients. J Pain Symptom
Manage. 2015; 49(3):530-8.
2. Wiffen P, Derry S, Moore R. Impact of morphine, fentanyl, oxycodone, or codeine on patient
consciousness, appetite and thirst when used to treat cancer pain. Cochrane Database
Syst Rev. 2015; 5:CD011056.
3. Welch J. Development of the thirst distress scale. Nephrol Nurs J. 2002; 29(4):337-41.
4. Ellershaw J, Sutcliff J, Saunders C. Dehydration and the dying patient. J Pain Sympt
Manag. 1995; 10(3): 192-197.
5. Morita T, Tei Y, et al. Determinants of the sensation of thirst in terminally ill cancer patients.
Suppt Care Cancer. 2001; 9(3):177-186.
6. Burge F. Dehydration symptoms of palliative care cancer patients. J Pain Sympt Manag.
1993; 8(7): 454-464.
7. Musgrave C, Bartal N, Opstad J. The sensation of thirst in dying patients receiving IV
hydration. J Palliat Care. 1995; 11(4):17-21.
8. Cerchietti L, Navigante A, et al. Hypodermoclysis for control of dehydration in terminal-
stage cancer. Int J Palliat Nurs. 2000; 6(8):370-4.
9. McCann R, Hall W, Groth-Juncker A. Comfort care for terminally ill patients. The
appropriate use of nutrition and hydration. JAMA. 1994; 272(16):1263-6.
10. Bots C, Brand H, et al. Interdialytic weight gain in patients on hemodialysis is associated
with dry mouth and thirst. Kidney Int. 2004; 66(4):1662-8.
11. Mistian, P. Thirst, interdialytic weight gain and thirst-interventions in hemodialysis patients:
a literature review. Nephrology Nursing Journal. 2001; 28(6): 601-615.
12. Kooistra M, Vos, J, et al. Daily home haemodialysis in the Netherlands: effects on
metabolic control haemodynamics, and quality of life. Nephrol Dial Transplant. 1998; 13:
2853-2860.
13. Yamamoto T, Shimizu M, et al. Role of angiotensin II in the pathogenesis of hyperdipsia in
chronic renal failure. JAMA. 1986; 256(5): 604-608.
14. Oldenburg B, MacDonald G, Shelley S. Controlled trial of enalapril in patients with chronic
fluid overload undergoing dialysis. BMJ 1988; 296(6629): 1089-91.
15. Kuriyama S, Tomonari H, Sakai O. Effect of cilazapril on hyperdipsia in hemodialyzed
patients. Blood Purif. 1996; 14(1): 35-41.
16. Hamad A, Khosrovaneh A, et al. Lack of effect of long-term use of angiotensin-converting
enzyme inhibitors by hemodialysis patients on thirst and fluid weight gain. Ren Fail. 2002;
24(4):461-6.
17. Bots C, Brand H, et al. Chewing gum and a saliva substitute
alleviate thirst and xerostomia in patients on haemodialysis. Nephrol Dial Transplant. 2005;
20(3):578-84.
18. Jagodzińska M, Zimmer-Nowicka J, et al. Three months of regular gum chewing neither
alleviates xerostomia nor reduces overhydration in chronic hemodialysis patients. J Ren
Nutr. 2011; 21(5):410-7.
19. Puntillo K, Arai S, et al. Symptoms experienced by intensive care unit patients at high risk
of dying. Crit Care Med. 2010; 38(11):2155-60.
27
20. Puntillo K, Arai S, et al. A randomized clinical trial of an intervention to relieve thirst and dry
mouth in intensive care unit patients. Intensive Care Med. 2014; 40(9): 1295-1302.
21. Holst M, Stromberg A, et al. Liberal versus restricted fluid prescription in stabilised patients
with chronic heart failure: result of a randomised cross-over study of the effects on health-
related quality of life, physical capacity, thirst and morbidity. Scand Cardiovasc J. 2008;
42(5):316-322.
22. Aliti G, Rabelo E, et al. Aggressive fluid and sodium restriction in acute decompensated
heart failure: a randomized clinical trial. JAMA Intern Med. 2013; 173(12):1058-64.
23. Li Y., Fu B, Qian X. Liberal versus restricted fluid administration in heart failure patients: a
systematic review and meta-analysis of randomized trials. Int Heart J. 2015; 56(2):192-5.
Authors’ Affiliatons: Massachusetts General Hospital; Harvard Medical School; Dana-Farber

Cancer Institute; Boston Children’s Hospital; Brigham and Women’s Hospital, Boston, MA.
Conflicts of Interest: none
Version History: Originally edited by Drew Rosielle MD; electronically published February 2016

UREMIC CALCIPHYLAXIS
Katherine Roza MD, Jason C. George DO, Maria Bermudez MD and Zankhana Mehta MD.
28
Calciphylaxis is a poorly understood disorder in which calcification of small blood vessels causes
painful ischemic skin and visceral lesions most often in patients with end-stage renal disease
(ESRD). This Fast Fact will review its clinical presentation and offer recommendations for
advance care planning and symptom management.
Epidemiology: Calciphylaxis occurs in 4% of ESRD patients on peritoneal dialysis or

hemodialysis and can occasionally occur in pre-dialysis renal disease (1). Risk factors include:
female sex; Caucasian race; obesity; diabetes mellitus; hyperparathyroidism; albumin < 3;
hypercoagulable states; and exposure to certain medications such as warfarin, iron, vitamin D,
and corticosteroids (2-7).
Pathophysiology: Uremia, calcium products, and reactive oxygen species (ROS) associated
with ESRD are thought to increase vascular calcium deposition and fibrosis, leading to
calciphylaxis (1,3). Over time this process likely precipitates arteriolar remodeling and progressive
stenosis, causing ischemia and skin infarcts. The one-year mortality rate for calciphylaxis is
estimated to be 45-80%, which may be even higher when ulcerative skin lesions are present
(7,8). Ischemic complications and difficult to treat infections given incomplete antibiotic
penetrance and poorly perfused tissues are potential mechanisms for the increased mortality risk.
Clinical Presentation: Early signs include pain and a lace-like purplish discoloration of the skin
(livedo reticularis). This is often followed by painful subcutaneous nodules or plaques that
progress to necrotic ulcerations. Areas of greatest fat tissue -- abdomen, buttocks, and inner
thighs -- are most commonly involved, although visceral organs, skeletal muscle, and heart
muscle can also be affected (5, 9). Calciphylaxis can be challenging to distinguish from a
vasculitis. Intact pulses, bilateral upper extremity involvement, and calcification seen on X-rays or
CT scans are suggestive indicators of calciphylaxis.
Diagnosis: Calciphylaxis is a clinical diagnosis. Laboratory findings are non-specific. In certain

circumstances, a dermatology consult and/or skin biopsy may be needed. However, skin biopsy is
usually deferred due to risk of pain, a false negative result, and poor wound healing (2,10).
Imaging studies can support the diagnosis by identifying calcification, but they do not confirm a
diagnosis and may lead to unnecessary discomfort (10).
Treatment: No randomized control trials exist for the treatment of calciphylaxis. In general, most
experts recommend a multi-modal approach involving adequate wound care, pain control, and
treatment of hyperparathyroidism. This includes a low phosphate diet, use of non-calcium based
phosphate binders (i.e., sevelamer), and cessation of vitamin D supplementation. In hemodialysis
patients, calcimimetics (i.e. cinacalcet) and increasing dialysis frequency to 4 to 6 sessions per
week may help but evidence is limited to case reports (3,11). Other less established options
include sodium thiosulfate infusion during hemodialysis, oxygen therapy (10-15 liters via face
mask 2 hours/day), and hyperbaric oxygen directed to the wound (3,5,12,13). Providing these
therapies may be logistically challenging for hospice agencies.
Pain Management: The mechanism of pain is poorly understood, but is thought to be due to
ischemia and resultant nerve damage. No controlled studies have confirmed an optimal analgesic
approach. However, case series suggest that combining aggressive wound care with an
analgesia regimen consisting of opioids, ketamine, and non-opioid adjuvants (e.g., gabapentin or
tricyclic antidepressants) can be effective (14). Fentanyl, buprenorphine and methadone do not
have known renal metabolites and thus may be associated with less opioid toxicity. The use of
topical ketamine or topical opioids, such as morphine-infused gels may offer local pain control
with potentially less systemic side effects, but this has not yet been studied (see Fast Facts #
185). Amputation remains an option in cases of refractory pain.
Advance Care Planning: Considering the one-year mortality risk, the diagnosis of calciphylaxis
should prompt clinicians to engage patients and families in a larger discussion regarding advance
directives, prognosis, and goals of care. A potential decision-point is whether to withhold or
withdraw hemodialysis when calciphylaxis is diagnosed. Patients may not be aware that stopping
dialysis is a viable care option unless raised by a clinician. Clinicians, however, should be aware
29
that the decision to stop hemodialysis can be exceedingly complex and dependent upon a variety
of factors such as patient-defined quality of life, symptom burden, prognosis, and care location
preferences (see Fast Fact #163). While the Medicare Hospice Benefit (MHB) can provide
important care resources and support for patients with calciphylaxis, MHB patients are typically
unable to continue dialysis with a hospice admitting diagnosis of ESRD. Thus, even a discussion
of hospice can be challenging to navigate for many clinicians. Given their skills in managing
complex analgesic regimens and their multidisciplinary approach to clinical, psychological,
spiritual, and social care, the involvement of a specialist palliative care team can be helpful when
discussing withholding or withholding dialysis.
References
1. Angelis M, Wong LL, Myers SA, Wong LM. Calciphylaxis in patients on hemodialysis: a
prevalence study. Surgery. 1997:122(6):1083-1090.
2. Fine A, Zacharias J. Calciphylaxis is usually non-ulcerating: risk factors, outcome and
therapy. Kidney Int. 2002;61(6):2210-2217.
3. Sowers KM, Hayden MR. Calcific uremic arteriolopathy: pathophysiology, reactive
oxygen species and therapeutic approaches. Oxid Med Cell Longev. 2010;3(2):109-121.
4. Mazhar AR, Johnson RJ, Gillen D, Stivelman JC, Ryan MJ, Davis CL, Stehman-Breen
CO. Risk factors and mortality associated with calciphylaxis in end-stage renal disease.
Kidney Int. 2001;60(1):324-332.
5. Wilmer WA, Magro CM. Calciphylaxis: emerging concepts in prevention, diagnosis and
treatment. Semin Dial. 2002;15(3):172-186.
6. Farah M, Crawford RI, Levin A, Yan CC. Calciphylaxis in the current era: emerging ‘ironic’
features? Nephrol Dial Transplant. 2011;26:191-195.
7. Nigwekar SU, Kroshinsky D, Nazarian RM, Goverman J, Malhotra R, Jackson VA,
Kamdar MM, Steele DJR, Thadhani RI. Calciphylaxis: risk factors, diagnosis, and
treatment. Am J Kidney Dis. 2015;66(1):133-146.
8. Weenig RH, Sewell LD, Davis MDP, McCarthy JT, Pittelkow MR. Calciphylaxis: natural
history, risk factor analysis, and outcome. J Am Acad Dermatol. 2006;56(4):569-579.
9. Janigan DT, Hirsch DJ, Klassen GA, MacDonald AS. Calcified subcutaneous arterioles
with infarcts of the subcutis and skin ("calciphylaxis") in chronic renal failure. Am J Kidney
Dis. 2000;35(4):588-597.
10. Bleibel W, Hazar B, Herman R. A case report comparing various radiological tests in the
diagnosis of calcific uremic arteriolopathy. Am J Kidney Dis. 2006;48(4):659-661.
11. Velasco N, MacGregor MS, Innes A, MacKay IG. Successful treatment of calciphylaxis
with cinacalcet – an alternative to parathyroidectomy? Nephrol Dial Transplant.
2006;21(7):1999-2004.
12. Cicone JS, Petronis JB, Embert CD, Spector DA. Successful treatment of calciphylaxis
with intravenous sodium thiosulfate. Am J Kidney Dis. 2004;43(6):1104-1108.
13. Basile C, Montanaro A, Masi M, Pati G, De Maio P, Gismondi A. Hyperbaric oxygen
therapy for calcific uremic arteriolopathy: a case series. J Nephrol. 2002;15(6):676-680.
14. Polizzotto MN, Bryan T, Ashby MA, Martin P. Symptomatic management of calciphylaxis:
a case series and review of the literature. J Pain Symptom Manage. 2006;32(2):186-190.
Authors’ Affiliations: Geisinger Medical Center, Danville, Pennsylvania.

Version History: Originally edited by Sean Marks MD; first electronically published in November
2016.
30
31
PALLIATION OF BLADDER SPASMS
Elise De MD, Pablo Gomery MD, and Leah B. Rosenberg MD
Background: Bladder spasms induced by involuntary bladder contractions are a distressing

symptom affecting 7-27% of men and 9-43% of women (1). Seriously ill patients may develop
bladder spasms as a complication from genitourinary malignancies, indwelling catheters, or other
medical issues. For some, these contractions may be imperceptible and only appreciated on
urodynamic testing; for others, they can be incapacitating and associated with urinary
incontinence.
Differential Diagnosis: Common etiologies of bladder spasms include a urinary tract infection
(UTI), ingestion of chemical irritants like diet soda or caffeine, constipation, obstruction of the
bladder outflow tract (e.g. non-emptying catheter from blood clots), disinhibition from interruption
of upper motor neurons, or irritation of the detrusor muscle from a tumor, catheter, or intramural
stone (2). Medications can also lead to spasms either by bladder irritation (e.g. diuretics) or
disruption of the detrusor muscle or bladder outlet (e.g. opioids, anticholinergics,
32

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Fast Facts Core Curriculum

#62 Early Diagnosis of Epidural Metastases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

#151 Hypercalcemia of Malignancy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

#157 Malignant Pleural Effusions: Interventional Management . . . . . . . . . . . . . . . . .

#176 Evaluation of Malignant

#177 Palliative Treatment of Malignant Ascites . . . . . . . . . . . . . . . . . . . . . . . . . . .

#209 Malignant Pericardial Effusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

#238 Management of Spinal Cord

FAST FACTS AND CONCEPTS #62

FAST FACTS AND CONCEPTS #135

Background Neoplastic meningitis (NM) – also known as leptomeningeal metastases, meningeal

FAST FACTS AND CONCEPTS #151

FAST FACTS AND CONCEPTS #157

FAST FACTS AND CONCEPTS #176

FAST FACTS AND CONCEPTS #177

2. Paracentesis: Paracentesis can provide immediate relief of symptoms in up to 90% of patients.

5. Hyperthermic Intraperitoneal Chemotherapy (HIPEC): This procedure is performed by surgical

FAST FACTS AND CONCEPTS #209

Author Affiliation: University of Alberta, Edmonton, Alberta.

Author Affiliations: University of Pittsburgh Medical Center, Pittsburgh, PA.

Version History: Originally published December 2010; Copy-re-edited November 2015.

Fast Facts Core Curriculum

#11 Delivering Bad News – Part II . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . .

#19 Taking a Spiritual History

#21 Hope and Truth

#22 Writing a Condolence Letter . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

#23 Discussing DNR Orders – Part I . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

#24 Discussing DNR Orders – Part

#47 What Do I Tell the Children? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

#64 Informing Significant Others of a Patient’s Death . . . . . . . . . . . . . . . . . . . . . . .

#76 Telephone Notification of Death – Part

#77 Telephone Notification of Death – Part II . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

#155 Completing a Death Certificate . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

#162 Advance Care Planning in Chronic Illness . . . . . . . . . . . . . . . . . . . . . . . . . . . .

#184 Conflict Resolution II: Principled Negotiation . . . . . . . . . . . . . . . . . . . . . . . . .

#222 Preparing for the Family Meeting . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

#223 The Family Meeting: Starting the Conversation . . . . . . . . . . . . . . . . . . . . . . . .

#224 Responding to Emotion in Family

#225 The Family Meeting: Causes of Conflict . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

#226 Helping Surrogates Make Decisions Meeting . . . . . . . . . . . . . . . . . . . . . . . . . .

#274 The Fica Spiritual History Tool

FAST FACT AND CONCEPT #6

Preparing to Deliver Bad News

FAST FACTS AND CONCEPTS #11

Steps in Delivering Bad News

FAST FACTS AND CONCEPTS #19

FAST FACTS AND CONCEPTS #21

FAST FACTS AND CONCEPTS #22

FAST FACTS AND CONCEPTS #23

FAST FACTS AND CONCEPTS #24

FAST FACTS AND CONCEPTS #47

I. Screening and awareness

II. Give them some words.

III. Give adults concrete examples to guide their interactions.

FAST FACTS AND CONCEPTS #64

FAST FACTS AND CONCEPTS #76

FAST FACTS AND CONCEPTS #77

Responding to Emotions Whether in person or by telephone, you should expect an

FAST FACTS AND CONCEPTS #155

• Verify the correct spelling of names.

• Immediate (or Principle) Cause = Final complication resulting in death.

Example 1 Example 2 Example 3 Example 4

Line C Chronic Ischemic Metastatic Non- Human

FAST FACTS AND CONCEPTS #178 

FAST FACTS AND CONCEPTS #90 