Liz Thomas

AM Report
April 25, 2008
 The two most common causes are gallstones and
alcohol, accounting for 60-80 percent of cases
 Other causes include
 Hypertriglyceridemia
 Drug induced pancreatitis
 Famililial hypertriglyceridemia or hereditary chronic
pancreatitis
 ERCP, surgery or abdominal trauma
 Vascular causes
 Hypercalcemia
 Polyarteritis nodosa
 Idiopathic (biliary microlithiasis, pancreas divisum, Sphincter
of Oddi dysfunction)
 Autoimmune
 Almost all patients with acute pancreatitis have
acute upper abdominal pain at onset
 Steady, often mid-epigastric, classically band-
like radiation to the back (50% of patients)
 Pain typically accompanied by nausea and
vomiting (90% of patients)
 Alcoholic pancreatitis often occurs one to three
days after binge or cessation of drinking
 Depend upon severity of attack
 In severe attacks systemic features include fever,
tachycardia, shock or coma. Patients may have abdominal
distention with rebound or guarding
 Jaudice if there is bile duct obstruction
 Ecchymotic discoloration of the flank (Grey-Turners sign) or
periumbilical region (Cullen’s sign) reflect intraabdominal
hemorrhage and are associated with a poor prognosis
 Epigastric mass due to pseudocyst formation may become
palpable during course
 Less common are subcutaneous nodular fat necrosis (0.5-
2cm tender red nodules usually located over distal
extremities), thrombophlebitis in the legs, and polyarthritis
 Grey-Turner’s Sign  Cullen’s Sign
 Laboratory data
 Amylase: most frequently ordered test, elevated within 6-12
hrs, half-life 10 hrs, sensitivity 75-92% and specificity 20-60%
 Lipase: elevated within 4-8 hrs, peak at 24 hrs, sensitivity 86-
100%, specificity 50-99%
 Other pancreatic enzymes including trypsin, phospholipase A,
corboxylester lipase, co-lipase are elevated but have not been
shown to have significant advantage over amylase or lipase
 Urinary and serum trypsinogen-2 may be useful for early
identification of pancreatitis
 Trypsinogen activation pepetide (TAP) may be useful in
detection of early acute pancreatitis. One study showed that
urinary TAP was a predictor of severity of acute pancreatitis
 Laboratory data
 Serum markers of immune activation may be useful
in predicting severity, including IL-6, IL-8, IL-10,
TNF, PMN elastase, and CRP
 CRP levels greater than 150 at 48 hrs discriminate
severe from mild disease
 Hepatic transaminase levels may be elevated in
patients with pancreatitis caused by alcohol abuse or
cholelithiasis with obstruction
 There is no value in daily measurement of enzymes
in assessing the clinical progress or prognosis of
disease
 Abdominal plain film: findings range from
unremarkable in mild disease to localized ileus of a
segment of small intestine (“sentinel loop”) or paucity
of air in colon distal to splenic flexure (“colon cutoff
sign”)
 Chest film: 1/3 of patients with acute pancreatitis have
abnormalities on CXR such as elevation of a
hemidiaphragm, pleural effusions, basal atelectasis,
pulmonary infiltrates or ARDS
 Abdominal ultrasound: due to high frequency of
incomplete exam due to overlying bowel gas, plays
very little part in diagnosis of pancreatitis, but should
be used to evaluate gallbladder and biliary tree in case
of biliary causes of pancreatitis
• CT: most important imaging test in diagnosis of acute
pancreatitis, complications, and in assessment of severity
 Should be done with oral and IV contrast in patients who do not
improve with initial conservative therapy, with severe
symptoms, fever or leukocytosis
 It takes time for pancreatic necrosis to develop, so CT may be
normal in first 48 hours. AGA guidelines suggest CT be
performed after 72 hours of illness in patients with predicted
severe disease or evidence of organ failure
 Severity of pancreatitis can be classified into 5 grades based on
CT findings (CT severity index of Balthasar)
 Although an experimental rat model showed that iodinated
contrast medium, when given at onset of pancreatitis, increased
necrosis, this was not shown in an opossum model and there is
little evidence in humans to support that contrast media increase
necrosis
 MRI
 Increasingly used in diagnosis and management of
acute pancreatitis
 Advantages include ability to better categorize fluid
collection as acute fluid collections, necrosis, abscess,
hemorrhage and pseudocyst, and greater sensitivity
for mild acute pancreatitis compared to CT
 MRCP
 Unlike CT, delineates the pancreatic and bile ducts
better and is comparable to ERCP for detection of
choledocholithiasis
 Acute pancreatitis can be divided into 2 broad
categories: edematous and interstitial or mild acute
pancreatitis, and necrotizing or severe acute
pancreatitis
 Necrotizing pancreatitis is associated with a high rate
of complications and significant mortality, so the
ability to predict the course of pancreatitis, ideally
within the first 24 hours, could permit the institution of
targeted intervention in patients at highest risk for
complications
 Several systems have been developed based upon
clinical assessment, scoring systems, serum markers
and CT scanning. However, none has yet proven to be
consistently accurate
 Clinical predictors: Advanced age >55 or 60 years in different
studies, presence of comorbid illnesses, obesity and pleural
effusion/infiltrates have been associated with severe pancreatitis
 In many studies clinical assessment including signs of peritonitis, shock or
respiratory distress were as accurate as most scoring systems
 Scoring systems:
 Ranson, Glasgow, Banks, Agarwal and Pitchumoni are all scoring systems
which take 48 hours to complete, can be used only once, and do not have
high sensitivity or specificity
 A meta-analysis of the discriminant power and information content of
Ranson’s criteria was performed and showed a poor predictive power; the
information content did not differ from clinical judgement
 The APAPCHE II has good negative predictive value and modest positive
predictive value for predicting severe pancreatitis and can be performed
daily. Decreasing values during the first 48 hours suggest a mild attack
while increasing values suggest a severe attack
 At admission:
 age in years >55years  If the score >=3, severe pancreatitis
 white blood cell count > 16000/mcL likely.
 blood glucose > 11 mmol/L (>200  If the score < 3, severe pancreatitis is
mg/dL) unlikely
 serum AST > 250 IU/L
 serum LDH > 350 IU/L  Or
 Score 7 to 8 : 100% mortality
 After 48 hours:  Score 0 to 2 : 2% mortality
 Haematocrit fall > 10%
 increase in BUN by 1.8 or more mmol/L
 Score 3 to 4 : 15% mortality
(5 or more mg/dL) after IV fluid  Score 5 to 6 : 40% mortality
hydration
 hypocalcemia (serum calcium < 2.0
mmol/L (<8.0 mg/dL))
 hypoxemia (PO2 < 60 mmHg)
 Base deficit > 4Meq/L
 Estimated fluid sequestration > 6L
 SIRS score: A simple SIRS score of 2 or more reliably
predicted severe acute pancreatitis and can be done
easily every day
 The presence of organ failure indicates a severe attack
and outcomes are even worse in patients with organ
failure at presentation and in those with persistent
organ failure at 48 hours
 CT scan is probably the most helpful means to assess
the severity of acute pancreatitis. While necrosis on CT
predicts a severe attack, there is no uniform correlation
with extent of necrosis and organ failure and/or
mortality. The finding of necrotizing pancreatitis or
even infected necrosis does not necessarily predict the
occurrence of organ failure, but may alter the
therapeutic approach.
 A prospective study found that CRP had a 95%
detection rate for necrotizing pancreatitis
 A hematocrit >44 at admission and failure of
hematocrit to decrease at 24hrs were reported to be
good predictors of necrotizing pancreatitis and organ
failure, and correlated significantly with CT severity
index of Balthazar, ICU stay, and total hospital stay
 A recent study found a correlation between increased
intra-abdominal pressure (>25cm H2O) and organ
dysfunction in severe acute pancreatitis. However,
they did not necessarily recommend that elevated IAP
be considered the single indication for emergency
decompressive laparotomy, and in the most severe
cases they recommended conservative management
with CVVH
 Treatment is initially aimed at correcting the
underlying predisposing factors and at the
pancreatic inflammation itself, including early
ERCP in patients with gallstone pancreatitis
with obstructive jaundice or biliary sepsis,
reversal of hypercalcemia, cessation of possible
causitive drugs, and administration of insulin
to poorly controlled diabetic patients with
hypertriglyceridemia
 Treatment of mild pancreatitis includes pain control, IV
fluids, and keeping the patient NPO
 In severe pancreatitis, patients require ICU monitoring and
support
 Fluid resuscitation is extremely important as patients may
accumulate vast amounts of fluid in the injured pancreatic
bed. Fluid depletion damages pancreatic microcirculation
and results in pancreatic necrosis
 Uncontrolled pain can lead to hemodynamic instability.
Traditionally meperidine has been favored over morphine
in pancreatitis due to human studies showing an increase in
sphincter of Oddi pressure, but there is no clinical evidence
to suggest that morphine can aggravate or cause pancreatitis
or cholecystitis. Repeated doses of meperidine can lead to
accumulation of the metabolite normeperidine that causes
neuromuscular irritation and rarely, seizures.
 Pancreatic infection is a leading cause of morbidity and
mortality in acute necrotizing pancreatitis; one-third of
patients with pancreatic necrosis develop infected
necrosis
 Usually occurs late in the clinical course (after 10 days)
 Organisms are usually gut-derived, including E Coli,
Pseudomonas, Klebsiella and Enterococcus. The
majority of infections are monomicrobial
 Gram positive and fungal infection are uncommon but
occur more frequently in the setting of prophylactic
antibiotic use for severe acute pancreatitis, especially
when used for more than 10-14 days
 Enteral feeding to avoid central line related
infections, maintain gut barrier integrity, and
decrease bacterial translocations
 When possible, radiologic or endoscopic placement of a
jefjunal feeding tube past the Ligament of Treitz should
be performed
 Selective decontamination of the gut with non-
absorbable antibiotics
 One study showed decreased mortality with use of oral
norfloxacin, colistin, and amphotericin, mostly
attributable to decreased gram negative infections
 Prophylactic systemic antibiotics
 Initial studies done in 1970’s failed to show benefit of
prophylactic antibiotics, possibly because they
included patients with mild disease at low risk for
infection and used antibiotics with poor penetration
into the pancreas
 Recent studies show improved outcomes with
prophylactic antibiotics in severe necrotizing
pancreatitis
 Studies have been done with cefuroxime, with ceftazidime,
amikacin, and metronidazole, and with Imipenem
 A meta-analysis of eight controlled trials concluded that
prophylactic antibiotics reduced mortality, but the advantage
was limited to patients with severe acute pancreatitis who
received broad-spectrum antibiotics capapble of achieving
therapeutic pancreatic tissue levels
 However, a meta-analysis which included 2 large
trials not showing a benefit for prophylactic
antibiotics concluded there was no mortality
benefit or reduction in the incidence of infected
necrosis
 Additionally, prophylactic antibiotics can be
associated with selection of resistant organisms
and development of fungal infections
 Fungal infections are associated with increased mortality
 Longer duration of antibiotics was associated with
increased frequency of fungal infections
 Some authorities advocate the use of prophylactic
antifungal therapy and others recommend that antibiotics
not be used for longer than 7-10 days
 American College of Gastroenterology did not
recommend prophylactic antibiotics
 American Gastroenterological Association
(AGA) recommended them for patients with
>30 percent pancreatic necrosis
 Generally suggested to treat with
Imipenem/Meropenem in severe acute
pancreatitis with significant necrosis and/or
organ failure
 If the patient becomes unstable from pulmonary,
cardiovascular or renal complications, it is
recommended that the patient undergo minimally
invasive necrosectomy (endoscopic or percutaneous
radiologic) to remove necrotic debris and pus
 If there is no improvement with one week of
antibiotics, a percutaneous CT guided aspiration
should be performed. If there is bacterial infection,
necrosectomy should be considered and antibiotics
should be selected based on culture results
 Early, open surgical necrosectomy has fallen out of
favor due to appreciation of its high mortality and
morbidity. A small study showed the mortality was
3.4 times higher in early necrosectomy (within 48-72
hours of onset) compared to late necrosectomy
 Studies have investigated the proteinase inhibitor
gabexate mesilate and somatostatin and its
analogue octreotide
 A meta-analysis showed survival benefit for
somatostatin and octreotide and reduced
complications with gabexate mesilate. However,
the benefits occurred in a very low proportion of
patients and other studies have shown conflicting
results.
 There have been case reports of treating
hypertriglyceridemic acute necrotizing pancreatitis
with plasma exchange
 De Bernardinis M, Violi V, Roncoroni L, Boselli AS, Giunta A,
Peracchia A. Discriminant power and information content of
Ranson's prognostic signs in acute pancreatitis: a meta-analytic
study. Crit Care Med. 1999 Oct;27(10):2272-83.
 Büchler M, Malfertheiner P, Schoetensack C, Uhl W, Beger HG.
Sensitivity of antiproteases, complement factors and C-reactive
protein in detecting pancreatic necrosis. Results of a prospective
clinical study. Int J Pancreatol. 1986 Oct;1(3-4):227-35.
 Pupelis G, Plaudis H, Snippe K, Rudakovska M. Increased intra-
abdominal pressure: is it of any consequence in severe acute
pancreatitis? HPB (Oxford). 2006;8(3):227-32.
 Furuya T, Komatsu M, Takahashi K, Hashimoto N, Hashizume T,
Wajima N, Kubota M, Itoh S, Soeno T, Suzuki K, Enzan K, Matsuo
S. Plasma exchange for hypertriglyceridemic acute necrotizing
pancreatitis: report of two cases. Ther Apher. 2002 Dec;6(6):454-8.
 UpToDate 2008