ILLNESS TRAJECTORY IN

PALLIATIVE CARE
SUDIRMAN
1. Systematic Screening of Symptoms
Cancer patients experience many symptoms across
the illness trajectory
Symptom Intensity & Tumor Stage (Non-hematological cancers)
N= 240 No
Median # of evidence Local Regional Metastatic
symptoms = 8 per of disease disease disease
patient disease

No. of symptoms 9 (0-24) 7 (0-17) 6 (0-15) 10 (0-25)

Moderate to severe
4 (0-14) 3 (0-12) 3 (0-12) 6 (0-20)
symptoms

Chang VT et al. Symptom and Quality of Life Survey of Medical Oncology Patients: A Role for Symptom
Assessment. Cancer 2000;88:1175-1183
Symptoms are under-reported by patients
unless standardized questionnaire used

White C, et al. ‘‘Now that You Mention it, Doctor . . . ’’:Symptom Reporting and the
Need for Systematic Questioning in a Specialist Palliative Care Unit, J Pall Med
2009; 12(5):447-450
Symptoms: Patient reporting versus systematic
assessment

 Total symptoms
identified: 2,397
– Of these, only 14%
(322) were
volunteered

Homsi J, et al. Symptom evaluation in palliative medicine: Patient report vs

systematic assessment. Support Care Cancer 2006;14:444–453.
Edmonton Symptom Assessment Scale (ESAS)
PATIENT SELF-REPORT

• ESAS R
• Patient Self-Report
Functional Status (ECOG)
• Additional questions
• Beginning process of
tailoring kiosk to clinics &
needs
Clinicians can fail to
recognize 50-80%
of patients
concerns during
consultation
Significantly
reduced symptom
distress across a
number of
symptoms
2. Useful Clinical Tools
 The Palliative Performance Scale (PPS)
Palliative Performance Scale (PPS)
ECOG Activity & Evidence of Level of
% Ambulation Self-Care Intake
Disease Consciousness
Normal activity
0 100 Full Full Normal Full
No evidence of disease
Stable

Normal activity
90 Full Full Normal Full
Evidence of disease
1
Normal activity with effort Normal/
80 Full Full Full
Evidence of disease Reduced
Unable to do normal work Normal/
70 Reduced Full Full
Evidence of disease Reduced
2
Unable to do house work Occasional Normal/ Full or
60 Reduced
Significant disease Assistance Reduced Confusion
Transitional

Mainly Unable to do any work Considerable Normal/ Full or

50
Sit/Lie Evidence of disease Assistance Reduced Confusion
3
Mainly in Mainly Normal/ Full or Drowsy
40 As Above
Bed Assistance Reduced or Confusion
Totally Bed Full or Drowsy
30 As Above Total Care Reduced
E-of-life

Bound or Confusion

4 Minimal Full or Drowsy

20 As Above As Above Total Care
Sips or Confusion

13 10 As Above As Above Total Care Minimal/nil Drowsy or Coma

Encourage patient
to see family

Palliative Alerts
physician regularly
or find one.

Explore pt’s Advance care planning.

understanding of illness, Discuss code status Establish plans
discuss prognosis & Review treatment plan to deal with
goals of care. Ensure ESAS & emergencies
PPS/ECOG done at (e.g. pain crisis)
Initiate
each visit. home
care DNR & Advanced
directives
%

Discuss
preferred
Consult versus optimal
Palliative Care place of death
Team as based on
needed needs &
circumstances

For some patients the decline may be more gradual

while for others it may be more precipitous

Death

ILLNESS TRAJECTORY IN PROGRESSIVE CANCER

14
Prognosticating using the PPS in Cancer
Patients

Lau F, Downing M, et al. J Pain,

PainSympt Manage. 2009;38(1)
Transitioning End-of-life
3. Palliative Care Earlier Than Later
Old model of Palliative Care
Palliative Care: Earlier in illness, not only at
end-of-life
Palliative and End of Life Trajectories


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Palliative and End of Life Trajectories


21
Palliative and End of Life Trajectories


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4. Selecting an analgesic: The WHO Ladder
Pain: A Multidimensional construct

“I have
pain”
 Total Suffering/Pain
Several domains merging
Pain

Spiritual & Other

existential symptoms
Total
Suffering

Cultural Psychological

Social &
25 financial
WHO Analgesic Ladder
Selecting between different opioids

 Morphine remains first line strong opioid

 Inter-individual variability between opioids
 No large studies to demonstrate that one opioid is
superior to another
 Less constipation with fentanyl
– Clinical significance?
 Renal impairment
– May still use morphine but reduce dose/prolong dosing
intervals & monitor
– Fentanyl & buprenorphine
– Beware of methadone
 Opioid Formulations

Short-acting Long-acting
formulations formulations
for  Reserve for stable
 Opioid-naïve situations
patients  Add short-acting
 Pain crises opioids for
breakthrough pain

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Opioid Neurotoxicity

 Clinical Presentation
– Myoclonus, hallucinations, cognitive impairment, delirium,
severe somnolence, dysesthesia, allodynia
 Mechanism unclear
 Management strategies
– Switching opioid (opioid rotation)
– Decreasing opioid dose (if pain is well controlled)
– Hydration

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Adjuvants for neuropathic pain

 1st line
– TCA, gabapentin, pregabalin
– Start low & go slow
– Trial of at least 5-7 days before increasing dose
– Monitor for side effects
– NNT=3-4
 2nd line
– Pregabalin, corticosteroids
 3rd line
– Ketamine, lidocaine
Adjuvants for Bone Pain
 NSAIDs
– Limited use in severe pain
– Renal and gastro-intestinal side effects
– Limitations of Cox-2 specific NSAIDs recently noted
 Steroids
– Useful in pain crises
 Radiotherapy
– 75% to 85% response rate (decreased pain)
– Few side effects with palliative therapy
– Response within 1 to 2 weeks (maximum response up to 4
weeks later)
– Duration of analgesia is several months

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Adjuvants for Bone Pain

 Bisphosphonates
– Reduction of skeletal events (good evidence)
– Management of more acute pain with parenteral infusion
(some controversy)
 Calcitonin
– Not effective

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5. Managing Breakthrough Pain
Breakthrough Pain (BTP)

• Treatment
 Transient exacerbation of pain on a
– Use a short acting opioid
background of well controlled baseline
formulation
pain.
– Use same opioid as background
 Variable in intensity, duration,
treatment if possible
frequency & cause
– Exceptions: Fentanyl
 Types
patch
– Unpredictable
– Predictable – 10% of total daily dose
• Incident Pain – Then titrate breakthrough dose
 “End-of-Dose” failure not BTP (5% to 20%)
Breakthrough pain

 Breakthrough dose needs titration (5-20%) once

baseline pain controlled
 Role of new sublingual formulations of fentanyl very
limited
– Expensive
– Patient must be on at least 60mg of oral morphine per
day
– Limited role
6. Management of Dyspnea
Is this patient short of breath?

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38
 Management Approach to Dyspnea

Screen
Assess

Identify and treat Communicate:

underlying causes + Treatment + Explain situation
if possible and of symptom to patient and family
if appropriate and reassure

39
Pharmacological Measures
to Control Dyspnea?





40
Pharmacological Measures
to Control Dyspnea

 Oxygen
 Opioids
 Adjuvant therapies

41
Non-Pharmacological Management

 Use a fan
 Position: lean forward, head up
 Avoid exacerbating activities

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7. Management of Nausea
 Brain cortex(rare)
Transmitter: GABA, Ach
Causes: Anxiety,
anticipatory nausea
Anti-emetic: Anxiolytic
Vomiting Centre
Transmitter: Ach, Dop
Causes: co-ordinates
vomiting reflex
Anti-emetic: Same as
CTZ
Vestibular apparatus (rare)
Neuro-transmitter: Histamine
Causes: Motion sickness
Anti-emetic: Antihistamine
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Nausea & Vomiting: mechanisms
Chemoreceptor Trigger Zone
Neuro-transmitter: Dopamine, 5HT3
Causes
Drugs (chemotherapy, opioids, SSRIs)
Toxins (infections, cytokines)
Biochemical (hypercalcemia, uremia)
Anti-emetic:
1st line: Metoclopramide, domperidone
2nd line: Haloperidol (small dose)
3rd line: ondansetron
Gastro-intestinal tract
Neuro-transmitter: Dopamine, 5HT3
Causes: Tumors & tumor bulk,
Obstruction, ileus, constipation
Anti-emetic: Same as CTZ
Selecting an anti-emetic

 Depends on underlying mechanism

 1st line agents:
– Usual (one of the following)
• Metoclopramide 10mg PO QID PO/Subcut
• Domperidone 10mg TID PO (max dose 30mg/day)
– In case of bowel obstruction (one of the following)
• Haloperidol 0.5-1mg subcut BID
• Dimenhydrinate
 2nd line agents:
• Dexamethasone
• Ondansetron
• Methotrimeprazine
• Cannibinioids
 If antidopamine agent: monitor for EPS & akitisea
8. The Management of Delirium in patients
with advanced cancer
CLINICAL PRESENTATION
Clinical Subtypes

 Delirium presents in one of three forms.

Hyperactive form Mixed form Hypoactive form

Meagher D. Motor subtypes of delirium: Past, present and future. Int Rev Psychiatry
2009;21:59-73;
Lawlor P et al. Occurrence, causes and outcomes of delirium in advanced cancer patients: a
prospective study. Archives of Internal Medicine. 2000;160:786-794.
CAUSES OF DELIRIUM
Causes per episode

 Often multifactorial etiology per episode

– On average, 3 causes per episode
• E.g. opioid neurotoxicity, dehydration and hypercalcemia
 Consider several causes concurrently
 Sometimes the causes are unclear or cannot be found
 Urinary retention aggravates delirium
 Consider underlying dementias in very elderly patients

Lawlor P, et al. Occurrence, causes and outcomes of delirium in advanced cancer

patients. Archives of Internal Medicine. 2000;160:786-794.
Bruera E et al. Impact of delirium and recall on the level of distress in patients with
advanced cancer and their family caregivers. Cancer 2009;115:2004-2012 48
Common Causes of Delirium in Palliative Care
 Drugs
– Opioids
– Anticholinergic drugs such as tricyclic antidepressants
– Anticonvulsants
– Benzodiazepines
 Infections
 Dehydration
 Metabolic/Organ failure
– Renal or liver failure, hypercalcemia, hyponatremia
 Hypoxemia
 Brain disease: metastases or primary brain tumors
 BZP withdrawals (uncommon)
 Full bladder (aggravates)
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Overall management approach
Role of benzodiazepines in Palliative Care

Benzodiazepines
 Appear to worsen
delirium in palliative
patients.
 Generally avoided.

Breitbart W et al. Double-

blind trial of haloperidol vs
chlorpromzine vs
lorazepam in palliative
AIDS pts. J Am Psych
1996;153(2):231-237
DELIRIUM Management Guidelines. Cancer
Care Ontario 2010
Pharmacological management
Symptom Management- 1st line
Mild
Haloperidol 0.5mg or
1mg po or subcut OD or
BID
PLUS
Haloperidol 0.5mg or 1mg
PO /subcut q1hr PRN
Then titrate dose if initial
dose ineffective
(see “moderate” doses)
Moderate
Haloperidol 2mg or
2.5mg po or subcut BID
to TID
PLUS
Haloperidol 2mg PO
/subcut q1hr PRN
OR
Methotrimeprazine
Then titrate dose if initial
dose ineffective
Severe
Single dose of midazolam
2.5mg to 5mg subcut stat
PLUS
Haloperidol 5mg subcut
stat
OR
Methotrimeprazine
Follow with haloperidol
2.5mg or 5mg q 30min
PRN subcut
(max of 10-15mg /day)
The Role of the Atypical versus Traditional
Antipsychotic medications
 Haloperidol remains 1st line
 Methotrimeprazine 2nd line
 Newer atypical antipsychotics reserved for:
– Pts requiring longer term treatment
– Pts with EPS on haloperidol
– Olanzapine can be given SC
9. Depression at the End of Life
Diagnosing depression in palliative care context

 What is the prevalence of a major depression in

patients with advanced disease?
Diagnosing depression in palliative care context

 What is the prevalence of a major depression in

patients with advanced disease?
– 10-15%
– 25% in pancreas cancer
 Challenge
– Somatic symptoms non-specific
• Weight loss, fatigue
 Pervasice Worthlessness, guilt, hopelessness,
death wish
Management

 Supportive Counseling in all

 Pharmacological management in some (where
ability function is affected)
– Citalopram (sedating)
– Venlafaxine (stimulating)
– Mirtazapine (sedating, appetite stimulation)
– Duloxetine (if requires adjuvant analgesic)
– Methylphenidate (short onset of action)
10. Airway secretions
Airway “rattle” at end of life
 Differentiate between upper and lower airway
secretions.
 Upper airway secretions:
– If mild to moderate:
• Reposition & reassure family
– If severe
• Reposition, reassure, anticholinergic
Glycopyrrolate 0.4mg Subcut q2 hrs prn
OR Scopolamine 0.4mg Subcut q 4 hrs prn
 Lower airway secretions (Pulmonary edema)
– Furosemide 20mg-40mg subcut stat
End of Life “Comfort measures” (last hrs/days)

 Avoid blanket orders

 No need to start “morphine drip” if there was no
pain before
 No need to start midazolam drip if there is no
refractory symptom and palliative sedation is not
required
THANKS….

QUESTIONS??