Section VI.
Pancreatic Diseases
Acute Pancreatitis
Darwin L. Conwell, MD, MS
Peter A. Banks, MD
ESSENTIALS OF DIAGNOSIS
»» Gallstone disease and alcohol are the most common
causes of acute pancreatitis; other causes include hyper-
triglyceridemia, drugs, and specific disorders of the bili-
ary tree and pancreas.
»»
Diagnosis is usually made based on a history of acute
abdominal pain; a threefold elevation in serum amylase
or lipase, or both; or an abnormal abdominal com-
puted tomography (CT) scan showing changes of acute
pancreatitis.
»» Severe acute pancreatitis is characterized by persistent
(>48 hours) organ failure (systemic blood pressure <90
mm Hg, PaO2 <60 mm Hg, creatinine >2.0 mg/dL) or
pancreatic necrosis.
»» Diagnosis of necrotizing pancreatitis is confirmed by
contrast-enhanced abdominal CT scan or MRI scan.
»» General Considerations
Acute pancreatitis is an acute inflammatory disorder of
the pancreas that involves the pancreas and peripancreatic
tissues but can sometimes affect other organ systems. The
initial evaluation of patients with acute pancreatitis involves
determining the cause and assessing the severity of disease
since this guides subsequent management.
A. Incidence
Acute pancreatitis is the most common inpatient gastroin-
testinal diagnosis in the United States. There were 274,119
hospitalizations in 2012 for acute pancreatitis with a median
length of stay of 4 days and median charges amounting to
$11,402. The incidence rate of acute pancreatitis appears to
be increasing without any changes in the short-term or long-
term case fatality rates.
Greenberger_CH26_p335-342.indd 335
335
26
B. Causes and Risk Factors
The most common causes of acute pancreatitis in the
United States are gallstones and alcohol abuse, accounting
for 70–80% of cases. Table 26–1 lists other causes, includ-
ing hypertriglyceridemia, drug reactions, iatrogenic causes
(eg, postsurgical or endoscopic retrograde cholangiopan-
creatography [ERCP]), hereditary factors, and idiopathic
causes.
The first attack of alcohol-induced acute pancreatitis
typically occurs after many (eg, 8–10) years of heavy alcohol
consumption, and recurrent episodes can be anticipated
if alcohol abuse continues. Gallstone-induced pancreatitis
occurs in the setting of choledocholithiasis and is believed
to be related to transient or complete obstruction of pan-
creatic ductal flow or reflux of bile into the pancreatic duct.
Hypertriglyceridemia-associated acute pancreatitis does
not typically occur unless the triglyceride level exceeds
1000 mg/dL and is often seen in patients with type I and V
hyperlipidemia as well as in alcoholics. Because triglyceride
levels fall by one-half in patients who have been fasting for
24 hours, levels are best assessed after an episode of acute
pancreatitis with a fasting lipid profile in patients who are
consuming a normal diet.
Although many drugs have been associated with acute
pancreatitis, the strength of association between the use of
a particular drug and the development of acute pancreatitis
warrants careful scrutiny. Table 26–2 lists drugs that have a
strong association with acute pancreatitis based on a recent
review.
ERCP-induced acute pancreatitis is another cause of
pancreatic injury. Acute pancreatitis is seen in 5–7% of
ERCP cases and, despite extensive research into the medi-
cal and endoscopic prevention of post-ERCP pancreatitis,
there has been little decline in the rates of occurrence.
Recently, use of a prophylactic pancreatic duct stent placed
after retrograde pancreatography has shown promise but
requires further prospective evaluation. In addition, rectal
indomethacin has been shown to decrease post-ERCP
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 336 CHAPTER 26
Table 26–1. Causes of acute pancreatitis.
Alcohol
Autoimmune
Biliary (eg, gallstones, gallbladder microlithiasis/sludge)
Drug-induced (see Table 26–2)
Iatrogenic
Surgery (eg, common bile duct exploration, sphincterotomy,
splenectomy, distal gastrectomy)
ERCP
Idiopathic
Infectious (eg, ascariasis, clonorchiasis, mumps, toxoplasmosis,
­coxsackievirus, cytomegalovirus, tuberculosis, Mycobacterium
avium complex)
Inherited
PRSS1 (cationic trypsinogen) mutations: hereditary pancreatitis)
CFTR (cystic fibrosis transmembrane conductance regulator)
mutations
SPINK1 (serine protease inhibitor, Kazal type 1) mutations
Metabolic (eg, hypercalcemia, hypertriglyceridemia)
Neoplastic (eg, pancreatic or ampullary tumors)
Structural (eg, pancreatic divisum, annular pancreas, sphincter of
Oddi dysfunction, periampullary diverticula, duodenal ­duplication
cysts, choledochocele, anomalous pancreaticobiliary junction,
regional enteritis
Toxic (eg, organophosphates, scorpion venom)
Traumatic (especially motor vehicle accidents)
Vascular
pancreatitis in a randomized clinical trial. Risk factors for
post-ERCP pancreatitis based on a recent prospective study
include minor papilla sphincterotomy, sphincter of Oddi
dysfunction, prior history of post-ERCP pancreatitis, age
younger than 60, more than two contrast injections into the
pancreatic duct, and involvement of endoscopic trainees in
the procedure.
In recent years, molecular genetic techniques have
increased our understanding of acute pancreatitis. Heredi-
tary pancreatitis is an autosomal-dominant disease most
commonly associated with mutations in the cationic tryp-
sinogen PRSS1 gene that leads to the inability to deactivate
intracellular trypsin resulting in acinar cell autodigestion.
Hereditary pancreatitis should be suspected in patients
with early-onset (before 20 years of age) acute pancreatitis
or those with a strong family history of idiopathic acute
pancreatitis in first- or second-degree relatives. Mutations
in the cystic fibrosis transmembrane conductance regulator
(CFTR) gene are increasingly being recognized as a cause
of both acute and chronic pancreatitis. The mechanism of
injury is not completely known but is most likely related to
decreased pancreatic juice flow due to duct cell secretory
dysfunction. Patients with a family history of cystic fibrosis
or a history of recurrent pulmonary symptoms (eg, bronchi-
tis, asthma), nasal polyps, or sterility among males should be
considered for genetic testing.
Greenberger_CH26_p335-342.indd 336
Badalov N, Baradarian R, Iswara K, et al. Drug-induced acute pan-
creatitis: an evidence-based review. Clin Gastroenterol Hepatol.
2007;5:648–661. [PMID: 17395548]
Cheng CL, Sherman S, Watkins JL, et al. Risk factors for post-
ERCP pancreatitis: a prospective multicenter study. Am J
Gastroenterol. 2006;101:139–147. [PMID: 16405547]
Elmunzer BJ, Scheiman JM, Lehman GA, et al. A randomized trial
of rectal indomethacin to prevent post-ERCP pancreatitis. N
Engl J Med. 2012;366:1414–1422. [PMID: 22494121]
Fagenholz PJ, Castillo CF, Harris NS, Pelletier AJ, Carmago CA
Jr. Increasing United States hospital admissions for acute pan-
creatitis. 1998–2003. Ann Epidemiol. 2007;17:491–497. [PMID:
17448682]
Frank CD, Adler DG. Post-ERCP pancreatitis and its prevention.
Nat Clin Pract Gastroenterol Hepatol. 2006;3:680–688. [PMID:
17130878]
Keiles S, Kammesheidt A. Identification of CFTR, PRSS1, and
SPINK1 mutations in 381 patients with pancreatitis. Pancreas.
2006;33:221–227. [PMID: 17003641]
Peery AF, Dellon ES, Lund J, et al. Burden of gastrointestinal
disease in the United States: 2012 update. Gastroenterology.
2012;143:1179–1187. [PMID: 22885331]
Shelton CA, Whitcomb DC. Genetics and treatment options for
recurrent acute and chronic pancreatitis. Curr Treat Options
Gastroenterol. 2014;12:359–371. [PMID: 24954874]
Tenner S. Drug induced acute pancreatitis: does it exist? World J
Gastroenterol. 2014;20:16529–16534. [PMID: 25469020]
»» Pathogenesis
Acute pancreatitis develops in response to premature activa-
tion of intracellular trypsinogen (which causes acinar cell
injury) and the release of chemokines and cytokines (which
results in the recruitment of neutrophils and macrophages).
Recent advances in our understanding of hereditary pan-
creatitis include the discovery of trypsinogen gene muta-
tions, PRSS1 and SPINK1. Mutations in these genes lead to
an imbalance of proteases and their inhibitors within the
pancreatic parenchyma, resulting in inappropriate activation
of pancreatic zymogens with subsequent autodigestion and
inflammation. This, in turn, produces further injury to the
acinar cells and elevation of proinflammatory mediators.
The exact mechanisms leading to alcoholic and biliary
acute pancreatitis remain to be defined. Gallstone pancreati-
tis, however, is now the most common etiology. Only a small
proportion of patients who abuse alcohol develop pancreati-
tis. Alcohol metabolism is governed by both oxidative and
nonoxidative processes. The oxidative pathway lies primarily
within the liver while the nonoxidative pathway lies primar-
ily in the pancreas. The nonoxidative pathway leads to the
formation of fatty acid ethanol esters (FAEEs). It is postulated
that accumulation of FAEEs may result in alcoholic acute pan-
creatitis. Biliary pancreatitis is most commonly caused by the
passage of a stone from the gallbladder through the cystic duct
into the common bile duct; impaction at the ampulla of Vater
causes either reflux of bile into the pancreatic duct (Opie 1) or
outflow obstruction of the pancreatic duct (Opie 2).
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 Acute Pancreatitis 337

Table 26–2. Drugs implicated in acute pancreatitis based on class.

Class IAa Class IBb Class IIc

α-Methyldopa All-transretinoic acid Acetaminophen
Arabinoside Amiodarone Chlorothiazide
Azodisalicylate Azathioprine Clozapine
Bezafibrate Clomiphene Dideoxyinosine (DDI)
Cannabis Dexamethasone Erythromycin
Carbimazole Ifosfamide Estrogen
Codeine Lamivudine L-Asparaginase
Cytosine Losartan Pegasparaginase
Dapsone Lynestrenol/methoxyethinylestradiol Propofol
Enalapril 6-Mercaptopurine Tamoxifen
Furosemide Meglumine
Isoniazid Methimazole
Mesalamine Nelfinavir
Metronidazole Norethindronate/mestranol
Pentamidine Omeprazole
Pravastatin Premarin
Procainamide Sulfamethoxazole
Pyritinol Trimethoprim–sulfamethoxazole
Simvastatin
Stibogluconate
Sulfamethoxazole
Sulindac
Tetracycline
Valproic acid
a
Class IA: at least one case report with positive rechallenge, excluding all other causes of acute pancreatitis.
b
Class IB: at least one case report with positive rechallenge; however, other causes of acute pancreatitis
not ruled out.
c
Class II: at least four cases in the literature, consistent latency in ≥75% of cases (period between initiation
of drug and development of acute pancreatitis).
Adapted, with permission, from Badalov N, Baradarian R, Iswara K, et al. Drug-induced acute pancreatitis:
an evidence-based review. Clin Gastroenterol Hepatol. 2007 Jun;5(6):648–661.

»» Clinical Findings can be seen in cases of acute pancreatitis with hemorrhage

A. Symptoms and Signs
Abdominal pain is the most common symptom in patients
presenting with acute pancreatitis. The pain is typically
epigastric and radiates to the back. Patients also often pres-
ent with nausea and vomiting. In patients with severe acute
pancreatitis, signs and symptoms parallel the presence of
a systemic inflammatory response and organ dysfunction.
Patients with systemic inflammatory response syndrome
(SIRS) (temperature >33°C, respiratory rate >24 per minute,
heart rate >90 per minute, white blood count >12,000, or
>10% bands), which arises in response to proinflammatory
mediators, can present with fever, tachycardia, tachypnea, or
a combination of these findings. Other examination find-
ings include respiratory distress, crackles or absent breathe
sounds on lung auscultation, cool extremities, impaired
mental status, decreased bowel sounds, abdominal disten-
tion, oliguria, and anuria. Cullen sign (periumbilical ecchy-
moses) and Grey Turner sign (flank ecchymoses) are rare but
and are associated with increased mortality.
B. Laboratory Findings
Serum amylase and lipase are the principal laboratory tests
that aid in the diagnosis of acute pancreatitis. Elevations
greater than three times the upper limit of normal are
typically used to diagnose acute pancreatitis. However, both
enzymes can be elevated in other disease states. For example,
amylase is also produced by nonpancreatic organs such as
salivary glands, ovaries, and fallopian tubes; thus, diseases of
these organs can increase the serum amylase level. Pancreatic
amylase and lipase can be elevated in other intra-abdominal
disease states such as a perforated ulcer, intestinal obstruc-
tion, and mesenteric infarction. Both amylase and lipase are
elevated in patients with renal insufficiency or critical illness
in the absence of acute pancreatitis.
Serum amylase has rapid clearance and a short half-life
and therefore is best measured when there is a brief interval
between symptom onset and diagnosis. Serum lipase begins

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 338 CHAPTER 26

to rise later after symptom onset, but its longer half-life makes
it useful to measure when there has been a delay in seeking
care. Serum lipase is a more sensitive and specific indicator
of acute pancreatitis than serum amylase. The combination of
both serum amylase and lipase does not appear to increase the
accuracy of diagnosis. The degree of elevation of both serum
amylase and lipase does not correlate with severity of acute
pancreatitis, nor does the daily assessment of serum pancreatic
enzymes help to determine clinical deterioration or resolution.
Elevated findings on liver biochemical tests in a patient
with suspected acute pancreatitis usually signify a biliary
cause. A threefold elevation in alanine aminotransferase in
the setting of acute pancreatitis has been shown to have a
95% positive predictive value for gallstone pancreatitis.

C. Imaging Studies
In the early stages of illness, transabdominal ultrasound
is the most widely recommended diagnostic imaging test
for patients with acute pancreatitis, primarily in order to
evaluate for a potential biliary etiology. Contrast-enhanced
abdominal CT is not recommended for the initial evalua-
tion of acute pancreatitis unless the diagnosis is uncertain.
By contrast, in the setting of persistent abdominal pain or
clinical deterioration after 48–72 hours, a contrast-enhanced
CT can be useful to evaluate for local complications such as
necrosis or development of an acute fluid collection. Find-
ings of interstitial acute pancreatitis that are typically seen
on CT scan include enlargement of the pancreas with edema,
heterogeneous pancreatic parenchyma, peripancreatic fat
stranding, and peripancreatic fluid collections (Figure 26–1).
▲▲Figure 26–2. CT scan showing necrotizing acute pan-
creatitis. Pancreatic perfusion is diminished on contrast
enhancement.
Acute pancreatic necrosis typically appears as focal or diffuse
areas of nonenhanced pancreatic parenchyma (Figure 26–2).
Timing of CT imaging is important. If an admission diag-
nosis of acute pancreatitis can be made on the basis of his-
tory, physical examination, and elevated pancreatic enzymes,
a CT scan should generally be deferred. Given that some
patients will present with or develop renal failure, aggres-
sive fluid resuscitation with correction of renal function and
intravascular volume resuscitation should take place prior
to a contrast-enhanced CT due to the risk of inducing renal
insufficiency. Alternatively, a non–contrast-enhanced study
can be performed.
Magnetic resonance cholangiopancreatography (MRCP)
can be a helpful modality for further evaluation of a biliary
etiology or detection of a retained choledocholith. Gado-
linium should not be used in patients with renal impairment.

▲▲Figure 26–1. CT scan showing interstitial acute pan-
creatitis. There is uniform enhancement of the pancreatic
parenchyma, indicating that pancreatic perfusion is pre-
served. (Benign right renal cyst.)
D. Diagnostic Approach
1. Confirmation of the diagnosis—The diagnosis of
acute pancreatitis is usually made when there is a his-
tory of acute abdominal pain and a threefold elevation in
serum amylase or lipase, or both, or an abnormal abdomi-
nal CT scan demonstrating changes consistent with acute
pancreatitis.
2. Indications for more extensive evaluation—
Even after a careful history and physical examination,
laboratory evaluation, abdominal ultrasonography, and
CT scan, the cause of 20–30% of cases of acute pan-
creatitis cannot be elucidated. These cases are termed
idiopathic or unexplained. Recent reports suggest that

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 Acute Pancreatitis 339

nearly 70% of patient with a single or recurrent episode of
idiopathic acute pancreatitis have biliary microlithiasis or
sludge from cholesterol monohydrate crystals or calcium
bilirubinate granules.
There is considerable debate regarding which subgroup
of patients requires more extensive evaluation after being
diagnosed with idiopathic acute pancreatitis. It has been sug-
gested that patients younger than age 40, who have had only
a single episode of acute pancreatitis, need no further evalu-
ation as the recurrence rate is low. However, patients older
than 40 who have had a single episode and patients who have
had two or more episodes of idiopathic pancreatitis require
more extensive evaluation. Patients older than 40 years are
thought to have an increased risk of pancreatic malignancy.
Therefore, a contrast-enhanced CT scan should be part of
the evaluation. If the CT scan is negative, then attention is
directed at the pancreaticobiliary anatomy. Guidelines from
several societies recommend a repeat abdominal ultrasound
to evaluate for evidence of biliary sludge that can be missed
in the acute setting. In patients with recurrent episodes of
idiopathic acute pancreatitis, evaluation by a combination of
MRCP and endoscopic ultrasound has been shown to detect
additional causes of pancreatitis. Abnormalities noted on
either endoscopic ultrasound evaluation or magnetic reso-
nance imaging (MRI) should prompt consideration of endo-
scopic or surgical therapy (Figure 26–3). Causes of idiopathic
or unexplained acute pancreatitis commonly found during
endoscopic evaluation are listed in Table 26–3.
Tenner S, Baillie J, DeWitt J, et al. American College of Gastro-
enterology guideline: management of acute pancreatitis. Am J
Gastroenterol. 2013;108:1400–1415. [PMID: 23896955]
Wilcox CM, Varadarajulu S, Eloubeidi M. Role of endoscopic
evaluation in idiopathic pancreatitis: a systematic review. Gas-
trointest Endosc. 2006;63:1037–1045. [PMID: 16733122]

Idiopathic Pancreatitis
Negative CT
negative serology,
including lipids and
metabolic panel

MRCP,
EUS (if available)

CBD stones,
pancreatic divisum,
Gallbladder Autoimmune
choledochocele, Tumor Normal
stones/sludge pancreatitis
chronic pancreatitis
with PD stone

Endoscopic therapy Surgery Cholecystectomy Gallbladder in situ

Gallbladder out

ERCP with sphincter

of Oddi manometry,
Observation
sphincterotomy if
manometry abnormal

▲▲Figure 26–3. Algorithm for the evaluation and management of idiopathic pancreatitis. CBD, common bile duct; CT,
computed tomography; ERCP, endoscopic retrograde cholangiopancreatography; EUS, endoscopic ultrasound; MRCP,
magnetic resonance cholangiopancreatography; PD, pancreatic duct.

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 340 CHAPTER 26
Table 26–3. Causes of idiopathic or unexplained acute
pancreatitis diagnosed by endoscopic evaluation.a
Ampullary lesions
Choledocholithiasis
Chronic pancreatitis
Gallbladder microlithiasis or sludge
Pancreas divisum
Pancreatic cancer
Sphincter of Oddi dysfunction
a
Exclusion of hyperlipidemia and medications.
3. Criteria for assessing severity in acute pancreatitis—
Assessment of severity in patients with acute pancreatitis is
essential for appropriate triage and management. The basis
for the classification, severity, and complications of acute
pancreatitis was established at the International Symposium
held in Atlanta in 1992 and has been revised. The revision of
the Atlanta Classification of 2012 stratifies severity as mild,
moderately severe, or severe acute pancreatitis. Mild acute
pancreatitis is characterized by no organ failure and no local
or systemic complications. Moderately severe acute pancre-
atitis is characterized by transient organ failure and/or local
and/or systemic complications. Severe acute pancreatitis is
characterized by persistent organ failure (ie, organ failure
that lasts for more than 48 hours).
Early predictors of severity at 48 hours included three
or more Ranson signs and an APACHE II score of 8 or
higher. However, as illustrated in recent data from a large
multicenter study of intensive care units, the vast majority of
patients with acute pancreatitis who require admission to an
intensive care unit experience clinical deterioration within
the first 24 hours of hospitalization. Traditional severity indi-
ces such as APACHE II and Ranson criteria have not been as
useful clinically because they are cumbersome, require col-
lection of a large number of clinical and laboratory variables
over 48 hours, and do not have acceptable positive and nega-
tive predictive value for severe acute pancreatitis. A more
recently developed and widely validated clinical scoring
system for use during the initial 24 hours of hospitalization
for acute pancreatitis is the bedside index of severity in acute
pancreatitis (BISAP). This five-factor scoring system assigns
one point for the presence of each of the following, either
at admission or during the initial 24 hours of hospitaliza-
tion: BUN >25 mg/dL, Impaired mental status, SIRS, Age
>60, and a Pleural effusion. A score of ≥3 points has been
associated with increased risk of mortality and complications
such as necrosis as well as organ dysfunction.
Apart from the severity indices, additional factors can
be used to assess severity in acute pancreatitis. Patient-
related risk factors for severe acute pancreatitis include
older age (>60 years), obesity (basal metabolic index ≥30),
and comorbid disease. In terms of prognostic indices, the
persistence of SIRS for >48 hours or any rise in blood urea
Greenberger_CH26_p335-342.indd 340
nitrogen (BUN) during the initial period of resuscitation
indicate a poor prognosis marked by increased risk of in-
hospital mortality.
The importance of differentiating interstitial from nec-
rotizing acute pancreatitis has led to the development of a
CT severity index as another measure of severity. It is best
evaluated 2–3 days into hospitalization because it may not
be possible to distinguish interstitial from necrotizing pan-
creatitis on contrast-enhanced CT scan early in the disease
course. CT identification of local complications, particularly
necrosis, is essential because patients with infected and
sterile necrosis are at greatest risk of death, with a median
mortality rate of 30% and 12%, respectively. The median
prevalence of organ failure is 54% in necrotizing pancre-
atitis. The prevalence of organ failure is about the same
in infected versus sterile necrosis. A recent meta-analysis
found that both infected necrosis and organ dysfunction
were independent predictors of mortality in severe acute
pancreatitis, such that infected necrosis was associated with
pooled risk of mortality of 32%, organ failure alone 30%
whereas presence of both infected necrosis and organ failure
was associated with mortality >40%. Thus, patients with
infected necrosis and multisystem organ failure are most
likely to die.
»» Differential Diagnosis
It is important to exclude other potential intra-abdominal
diseases in patients for whom the diagnosis of acute pancre-
atitis is not certain, especially when management calls for
potential surgical intervention. Table 26–4 lists conditions of
which the clinician should be particularly aware.
»» Complications
The complications observed in acute pancreatitis can be
related either to local tissue injury or systemically mediated
effects. Potential local complications include development
of an acute fluid collection, and pancreatic ascites from a
pancreas duct disruption. Interventions on pancreatic fluid
collections should be considered only in the context of
Table 26–4. Differential diagnosis of acute pancreatitis.
Perforated viscus
Cholecystitis
Bowel obstruction
Vascular occlusion (especially mesentery venous disease)
Renal colic
Inferior myocardial infarction
Pneumonia
Diabetic ketoacidosis
Duodenal ulcer
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 Acute Pancreatitis 341

secondary infection or persistence of subsequent symptoms

such as abdominal pain or gastric obstruction. Recent lit-
erature suggests a benefit of a more conservative approach
to even infected necrosis with delayed surgical intervention,
temporizing measures such as percutaneous drainage, and in
some cases, antibiotic treatment alone. If drainage is consid-
ered, this can now be achieved safely by both an endoscopic
or surgical approach. Pancreatic ascites or pleural effusion
can be managed with endoscopic therapy if the disruption
can be “bridged” with a pancreatic stent. Otherwise, surgi-
cal therapy may be necessary. Bleeding complications from
esophagogastric varices can rarely occur from splenic vein
obstruction. In addition, bleeding from a pseudoaneurysm
can represent a life-threatening emergency in which angiog-
raphy is the preferred initial intervention.
Less-commonly seen complications include pancreatic A
encephalopathy, subcutaneous fat necrosis, or splenic com-
plications such as a subcapsular hematoma.

»» Treatment
A. Mild Acute Pancreatitis
The majority of patients with mild acute pancreatitis respond
to supportive care measures that include bowel rest, intrave-
nous hydration with crystalloid, and analgesia. Oral intake
can be resumed once the patient is pain free in the absence of
parenteral analgesia, has no nausea or vomiting, has normal
bowel sounds, and is hungry. Typically, a clear or full liquid
diet has been recommended for the initial meal, but a low-
fat solid diet is a reasonable choice following recovery from
mild acute pancreatitis. Patients discharged with continued
pain or tolerating less than a solid diet are at increased risk B
for early readmission for pancreatitis.
Patients with gallstone pancreatitis are also at increased
risk of recurrence. Therefore, following recovery from mild ▲▲Figure 26–4. CT scan in a patient with gallstone
pancreatitis, a laparoscopic cholecystectomy during the same pancreatitis. A. Axial image with walled-off necrosis and
admission is recommended as secondary prevention. An gallbladder stone. B. Coronal image showing extent of
alternative for patients who are not surgical candidates based necrosis and presence of a calcified gallstone.
on comorbid disease or local complications (Figure 26–4)
would be to perform an endoscopic biliary sphincterotomy.
increased serum creatinine) or nasal oxygen (to overcome
hypoxemia), as well as patients with labored respirations that
B. Severe Acute Pancreatitis
may herald respiratory failure, should be transferred to an
In addition to the aforementioned supportive measures, intensive care unit for close monitoring as these patients may
patients at increased risk of severe acute pancreati- require intubation with mechanical ventilation, hemodialy-
tis at admission based on obesity, hemoconcentration, or sis, and support of blood pressure.
azotemia should receive vigorous fluid resuscitation. A Once it is clear that a patient will not be able to toler-
decrease in hematocrit and/or fall in the BUN by at least ate oral feeding (a determination that can usually be made
5 mg/dL during the initial 12–24 hours suggest a favorable within 48–72 hours), enteral nutrition (rather than total
response to fluid resuscitation. If the hematocrit remains parenteral nutrition) should be considered. Enteral nutrition
elevated or the BUN rises during resuscitation, the patient maintains gut barrier integrity, thereby preventing bacterial
may require further hemodynamic monitoring to facilitate translocation, is less expensive, and is associated with fewer
adequate resuscitation. complications than parenteral nutrition. Recent data from
Patients with sustained organ failure that does not a large multicenter randomized controlled trial has refuted
respond to increased fluids (to counteract hypotension and earlier suggestions that probiotics may be helpful in the

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 342 CHAPTER 26
management of severe acute pancreatitis. Specifically, treat-
ment with probiotics was associated with increased mortal-
ity compared to placebo. The best route for administration
of enteral nutrition remains controversial. The nasogastric
route is easier to establish and may be as safe as the nasojeju-
nal route; however, enteral nutrition that bypasses the stom-
ach and duodenum is believed to produce less pancreatic
secretions. Both routes have been shown to alter morbidity
and possibly also mortality. When patients with necrotizing
pancreatitis begin oral intake of food, consideration should
also be given to the addition of pancreatic enzyme supple-
mentation to assist with fat digestion, and proton pump
inhibitor therapy to reduce gastric acid because of reduced
pancreatic bicarbonate secretion.
There is currently no role for prophylactic antibiotics in
either interstitial or necrotizing pancreatitis. Although previ-
ous small trials and meta-analyses had suggested benefit, the
two most recent adequately powered double-blind random-
ized controlled trials were unable to demonstrate any impact
on the rate of infected necrosis with use of prophylactic car-
bapenems or fluoroquinolone antibiotics. It is reasonable to
start antibiotics in a patient who is clinically unstable while
awaiting the results of cultures. If culture results are negative,
then antibiotics should be discontinued to minimize the risk
of developing fungal superinfection or Clostridium difficile.
Percutaneous aspiration of necrosis with Gram stain
and culture should generally not be performed until at least
7–10 days after establishing a diagnosis of necrotizing pan-
creatitis, and then only if there are ongoing signs of possible
pancreatic infection such as sustained leukocytosis, fever,
or organ failure. Once the diagnosis of infected necrosis is
established, appropriate antibiotics should be initiated and
surgical debridement should be considered. There exist
minimally invasive alternative therapies such as endoscopic,
percutaneous catheter, and retroperitoneal techniques for
necrosectomy. The optimal approach to management of
infected necrosis continues to evolve. There are currently no
large randomized studies supporting the use of one modality
over another. However, there has been an increasing trend
in favor of more conservative, less invasive approaches to
management. Temporizing measures such as percutaneous
catheter drainage have gained increasing acceptance for
Greenberger_CH26_p335-342.indd 342
management of critically ill patients. For patients with sterile
necrosis, medical management is preferred to surgical man-
agement unless patients continue to exhibit abdominal pain
and are unable to resume oral intake. Surgical debridement
should be delayed whenever possible to allow for resolution
of inflammation and the development of walled-off necrosis.
There are several clearly defined roles for ERCP in acute
pancreatitis. Urgent ERCP (within 24 hours) is indicated
in patients who have severe acute biliary pancreatitis with
organ failure or cholangitis, or both. Elective ERCP with
sphincterotomy can be considered in patients with persistent
or incipient biliary obstruction, those deemed to be poor
candidates for cholecystectomy, and those in whom there is
strong suspicion of bile duct stones after cholecystectomy.
ERCP also is indicated for pancreatic ductal disruptions that
occur as part of the inflammatory process and result in per-
sistent peripancreatic fluid collections.
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