In theClinic

In the Clinic

Acute
Pancreatitis
Prevention page ITC5-2

Diagnosis page ITC5-5

Treatment page ITC5-11

Practice Improvement page ITC5-13

Tool Kit page ITC5-14

Patient Information page ITC5-15

CME Questions page ITC5-16

Section Editors The content of In the Clinic is drawn from the clinical information and
Darren Taichman, MD, PhD education resources of the American College of Physicians (ACP), including PIER
Barbara J. Turner MD, MSED (Physicians’ Information and Education Resource) and MKSAP (Medical Knowledge
Sankey Williams, MD and Self-Assessment Program). Annals of Internal Medicine editors develop In the
Clinic from these primary sources in collaboration with the ACP’s Medical Education
Physician Writers and Publishing Division and with the assistance of science writers and physician writ-
Kapil Gupta, MD, MPH ers. Editorial consultants from PIER and MKSAP provide expert review of the content.
Bechien Wu, MD, MPH Readers who are interested in these primary resources for more detail can consult
http://pier.acponline.org, http://www.acponline.org/products_services/mksap/15/?pr31,
and other resources referenced in each issue of In the Clinic.

CME Objective: To revuew current evidence for the prevention, diagnosis, and
treatment of acute pancreatitis.

The information contained herein should never be used as a substitute for clinical
judgment.

© 2010 American College of Physicians

 cute pancreatitis is an acute inflammatory process of the pancreas

A that can occur as an isolated event or relapsing episodes. Acute pan-

creatitis is a heterogeneous disease ranging from minimal pancreatic
inflammation seen in mild interstitial pancreatitis to extensive pancreatic
necrosis and liquefaction of severe attacks. Diagnosis is based on the pres-
ence at least 2 of 3 features: abdominal pain; increased pancreatic enzyme,
amylase, and/or lipase levels to ≥3 times the upper limit of normal; and im-
aging tests showing characteristic findings of acute pancreatitis (1). Alcohol
and gallstones are the two most common causes, but there are many less
common causes. Acute pancreatitis accounts for more than 200 000 hospi-
tal admissions annually in the United States, and incidence has been in-
creasing (2). The rates of acute pancreatitis per 1000 Americans 40 to 59
years of age are the highest they have been in the past 20 years, and rates
are higher for blacks than for whites. Mortality from acute pancreatitis is
<5% overall, but severe attacks cause longer hospitalization and significant-
ly higher mortality (3). The annual relapse rate of acute pancreatitis ranges
from 0.6% to 5.6%, depending on the cause, and is highest when pancre-
atitis results from alcohol consumption (4).

Prevention
Who is at increased risk for acute those with common bile duct stones
pancreatitis? have them removed by endoscopic
Of the many causes of acute pancre- retrograde cholangiopancreatography
1. Bradley EL. A clinically
based classification atitis, gallstone disease (approximately (ERCP), an imaging and therapeutic
system for acute pan- 35% to 40% of cases) and excessive technique that combines endoscopy
creatitis: Summary of
the International alcohol consumption (approximately and fluoroscopy.
Symposium on Acute
Pancreatitis, Atlanta,
30% of cases) dominate (5) (Table 1).
Ga; September 11-13, Gallstone disease is among the most Alcohol-related pancreatitis usually
1992. Arch
Surg;1993;128:586-90. common disorders in the United occurs after long-term (>5 years),
[PMID: 8489394] States, affecting an estimated 6.3 mil- heavy alcohol consumption. Risk
2. Fagenholz PJ, Castillo
CF, Harris NS, Pelletier lion men and 14.2 million women 20 increases with the amount of alco-
AJ, Camargo CA Jr. In-
creasing United
to 74 years of age (6). It is difficult to hol consumed, indicative of a direct
States hospital ad- predict which patients with either toxic effect on the pancreas when
missions for acute
pancreatitis, 1988- symptomatic or asymptomatic gall- the alcohol is metabolized. Because
2003. Ann Epidemiol. stones will develop pancreatitis. One only about 5% of alcoholics develop
2007;17:491-7.
[PMID: 17448682] risk factor is the presence of stones in pancreatitis, additional unknown
3. Lowenfels AB,
Maisonneuve P, Sulli-
the common bile duct (choledo- genetic or other factors must in-
van T. The changing cholithiasis), especially small stones crease susceptibility. Smoking to-
character of acute
pancreatitis: epidemi- (<5 mm) or microlithiasis comprising bacco may play a role; it has been
ology, etiology, and
prognosis. Curr Gas-
stones that measure <2 mm because reported to accelerate progression
troenterol Rep. they can obstruct the orifice of the of established alcoholic pancreatitis
2009;11:97-103.
[PMID: 19281696]
pancreatic duct at the level of the am- (7). One study found an association
4. Lankisch PG, Breuer pulla. Pancreatitis occurs when gall- between high intake of beer (>14
N, Bruns A, et al. Nat-
ural history of acute stones pass into the bile duct and drinks per week) and pancreatitis,
pancreatitis: a long-
term population-
become trapped at the sphincter of but not for wine or spirits (8).
based study. Am J Oddi, stopping the flow of pancreatic
Gastroenterol.
2009;104:2797-805.
fluid containing digestive enzymes Hypertriglyceridemia is another
[PMID: 19603011] into the duodenum. If the blockage important risk factor for pancreati-
5. Forsmark CE, Baillie J.
AGA Institute Clinical continues, activated enzymes build up tis, especially during pregnancy (9).
Practice and Eco- in the pancreas and cause severe in- No clear risk profile can indicate
nomics Committee.
AGA Institute techni- flammation. To reduce the risk for which patients with elevated
cal review on acute
pancreatitis. Gas- such complications as pancreatitis, pa- triglycerides will develop pancreati-
troenterology. tients with symptomatic gallstones tis, but the complication occurs
2007;132:2022-44.
[PMID: 17484894] usually have cholecystectomy and rarely in the absence of significant

© 2010 American College of Physicians ITC5-2 In the Clinic Annals of Internal Medicine 2 November 2010
 Table 1. Causes of Acute Pancreatitis
More Common Causes
Gallstones and microlithiasis
Alcohol abuse
Drugs
ERCP
Hyperlipidemia
Hypercalcemia
Genetic
Autoimmune pancreatitis
Infections
Idiopathic
Less common causes
Cystic lesions of the pancreas
Cystic fibrosis
Pancreas divisum
Pancreatic cancer
Penetrating peptic ulcer
Postsurgical
Trauma
Tropical pancreatitis
Vasculitis
ERCP = endoscopic retrograde cholangiopancreatography; HSV = herpes simplex virus.
elevations, usually >1000 to
2000 mg/dL (10).
Several drugs have been linked to
development of acute pancreatitis
(Table 1), but the risk is generally
low. In one review, the authors as-
sessed the evidence for specific
drugs causing acute pancreatitis as
well as their clinical presentations
and proposed a classification of
drug-induced pancreatitis (11).
Patients who develop apparent
drug-induced acute pancreatitis
should still be evaluated for other
causes before attributing an
episode to particular medications.
While searching for another, more
common cause of acute pancreati-
2 November 2010 Annals of Internal Medicine
Comments
Most common cause
Alcohol-related disease usually occurs only occurs after
>5–10 y of heavy drinking
More common in older patients, HIV-positive persons, or in
those receiving immunomodulating agents
Can be a trigger, particularly if performed by an inexperienced
clinician or if the patient has sphincter of Oddi dysfunction
Usually with extremely elevated triglyceride levels (>1000 mg/dL)
Commonly caused by hyperparathyroidism or cancer, can be a
trigger by increasing activation of trypsinogen
Hereditary, and research has linked gene mutations in cationic
trypsinogen (PRSS1), SPINK1, or CFTR genes with acute and
chronic pancreatitis
Diffuse “sausage shaped” finding on imaging with rim enhance-
ment or ductal abnormalities.
Includes viruses: mumps, coxsackievirus, cytomegalovirus, varicella,
HSV, HIV; bacteria: Mycoplasma, Legionella, Leptospira, Salmonella;
Parasites: Toxoplasma, Cryptosporidium, Ascaris; and fungi:
Aspergillus
Accounts for approximately 15%–20% of cases; causes include 6. Everhart JE, Khare M,
sphincter of Oddi dysfunction, microlithiasis, and biliary sludge; Hill M, Maurer KR.
anatomical abnormalities Prevalence and eth-
nic differences in
gallbladder disease in
More likely if cysts involve the main duct, such as pancreatic the United States.
Gastroenterology.
intraductal papillary mucinous tumor 1999;117:632-9.
Rare, occurs when some viable pancreatic tissue remains [PMID: 10464139]
7. Yadav D, Whitcomb
Controversial as a cause so exclude all other causes first DC. The role of alco-
Focal pancreatitis can indicate an underlying mass hol and smoking in
pancreatitis. Nat Rev
Rare, clue is thickening of the duodenal wall Gastroenterol Hepa-
tol. 2010;7:131-45.
Such as ischemia related to bypass surgery [PMID: 20125091]
History is usually compelling 8. Kristiansen L, Grøn-
baek M, Becker U, Tol-
Endemic in some parts of Asia and Africa strup JS. Risk of pan-
Rare even in patients with vasculitis creatitis according to
alcohol drinking
habits: a population-
based cohort study.
Am J Epidemiol.
2008;168:932-7.
[PMID: 18779386]
9. Ewald N, Hardt PD,
Kloer HU. Severe hy-
pertriglyceridemia
tis, the temporal association of and pancreatitis:
medication use and development presentation and
management. Curr
of the episode should be evaluat- Opin Lipidol.
ed. The clinician needs to recog- 2009;20:497-504.
[PMID: 19770656]
nize that drug-induced pancreati- 10. Yadav D, Pitchumoni
tis can occur at any point in the CS. Issues in hyper-
lipidemic pancreati-
course of a medication regimen, tis. J Clin Gastroen-
terol. 2003;36:54-62.
ranging from at or shortly after [PMID: 12488710]
initiation to an idiosyncratic 11. Badalov N, Baradari-
an R, Iswara K, Li J,
reaction after prolonged use. It Steinberg W, Tenner
S. Drug-induced
may be necessary to rechallenge acute pancreatitis:
with the drug if it is critical for an evidence-based
review. Clin Gas-
the patient’s health. In general, troenterol Hepatol.
2007;5:648-61.
drug-induced acute pancreatitis is [PMID: 17395548]
less common than was previously 12. Nitsche CJ, Jamieson
N, Lerch MM, Mayer-
believed, and without strong evi- le JV. Drug induced
pancreatitis. Best
dence for drug-related pancreati- Pract Res Clin Gas-
tis, medications can usually be troenterol.
2010;24:143-55.
continued (12). [PMID: 20227028].
In the Clinic ITC5-3 © 2010 American College of Physicians

13. Cheng CL, Sherman
S, Watkins JL, et al.
Risk factors for post-
ERCP pancreatitis: a
prospective multi-
center study. Am J
Gastroenterol.
2006;101:139-47.
[PMID: 16405547]
14. Saad AM, Fogel EL,
McHenry L, et al.
Pancreatic duct
stent placement
prevents post-ERCP
pancreatitis in pa-
tients with suspect-
ed sphincter of Oddi
dysfunction but nor-
mal manometry re-
sults. Gastrointest
Endosc. 2008;67:
255-61.
[PMID: 18028920].
15. Nordback I, Pelli H,
Lappalainen-Lehto R,
et al. The recurrence
of acute alcohol-as-
sociated pancreatitis
can be reduced: a
randomized con-
trolled trial. Gas-
troenterology.
2009;136:848-55.
[PMID: 19162029]
© 2010 American College of Physicians
An important iatrogenic risk factor
for development of acute pancreati-
tis is ERCP. The risk for acute pan-
creatitis related to ERCP ranges
from 5% to 20%, depending on
physician-related factors, such as
the level of experience performing
the procedure, and patient charac-
teristics, especially sphincter of
Oddi dysfunction and a history of
previous ERCP-related pancreatitis
(13). From a technical standpoint,
the incidence of ERCP-related
pancreatitis seems to be decreased
by placement of a pancreatic duct
stent at the time of ERCP (14).
Careful patient selection and avoid-
ance of ERCP, unless clearly indi-
cated, will decrease the risk for
acute pancreatitis resulting from
this procedure.
Other less common causes of
acute pancreatitis are listed in
Table 1. Rare causes of unex-
plained acute pancreatitis include
cancer; mucinous neoplasm; re-
mote history of trauma; infections
caused by parasites, such as toxo-
plasmosis and cryptosporidiosis;
and viruses (cytomegalovirus,
Epstein Barr virus). Autoimmune
processes leading to pancreatitis,
such as vasculitis and autoimmune
pancreatitis, are well described but
underrecognized.
What behavioral advice should
clinicians give to a patient to
minimize the chance of a repeated
episode of acute pancreatitis?
After a clear cause of acute pan-
creatitis has been identified, ef-
forts should be made not only to
eliminate the cause but also to
provide counseling and education
for the patient about the need to
avoid known risk factors for the
disease. When alcohol consump-
tion has been identified as the
cause, patients should be evaluated
for alcohol abuse or dependence.
The patient should receive inten-
sive counseling about the exigency
of abstaining from alcohol to
avoid repeated episodes of acute
ITC5-4 In the Clinic
pancreatitis or chronic pancreati-
tis, as well as the other well-
known complications of alcohol
abuse and dependence. In this sit-
uation, one brief alcohol counsel-
ing session will not suffice.
In a randomized, controlled trial of 120
patients hospitalized for a first episode of
alcohol-associated acute pancreatitis, 59
patients received repeated 30-minute al-
cohol reduction and social stressor coun-
seling intervention both before discharge
and after 6-months while the 61 control
participants received only the initial
counseling session (15). Over the next
2 years, significantly fewer recurrent
episodes occurred in the patients with re-
peated alcohol counseling.
In addition, referral to alcohol spe-
cialty treatment will improve absti-
nence, ideally with support to
ensure that the patient receives
this care.
As noted, there are few drugs with
a definite link to acute pancreatitis
(12). Physicians should be alert
for drug-induced pancreatitis in
certain groups, such as the elderly
or patients with HIV infection or
cancer, who often take multiple
medications (16). However, even
when the association seems to be
clear, questions may linger with
regard to whether it was the drug
or the underlying condition for
which the drug was prescribed
that caused the pancreatitis.
Patients who develop acute pan-
creatitis because of hypertriglyc-
eridemia should be counseled
about lifestyle modifications, such
as reducing sugars and unhealthy
fats, and should have aggressive
medical interventions (fibrates or
nicotinic acid) to reduce triglyc-
eride levels to normal. When the
triglyceride level is ≥500 mg/dL,
the first priority is to prevent
acute pancreatitis by reducing the
level to <500; reducing the risk for
coronary heart disease is a second-
ary goal, according to an expert
panel report (17).
Annals of Internal Medicine 2 November 2010
 Prevention... Gallstones and excessive alcohol consumption are the two most
common causes of acute pancreatitis. It is not possible to predict which patients
with these conditions will develop this complication. Removal of gallstones and
alcohol cessation can help prevent recurrences. Other less common causes include
hypertriglyceridemia and side effects of medications, but alcohol and gallstones
should first be ruled out as sole or concurrent causes. Recurrent pancreatitis re-
lated to hypercalcemia is best prevented through treatment of the underlying
cause. Iatrogenic acute pancreatitis due to ERCP can be reduced by careful pa-
tient selection and possibly through placement of a pancreatic duct stent.

CLINICAL BOTTOM LINE

What elements of the history
and examination are helpful in
suggesting a diagnosis of acute
pancreatitis?
The most common presenting
symptom of acute pancreatitis is
abdominal pain, classically de-
scribed as occurring in the upper
abdomen and radiating to the back.
The pain is typically severe and
persistent without alleviating or
relieving factors and is usually asso-
ciated with nausea and vomiting.
When ileus is present, vomiting
reduces the pain associated with
acute pancreatitis only slightly.
In patients with suspected acute
pancreatitis, a detailed history
should address the potential causes
listed in Table 1. Previous cholecys-
tectomy for gallstones in a person
with no or minimal use of alcohol
increases the likelihood of pancre-
atitis due to retained gallstones.
Careful history should assess for
hyperlipidemia, abdominal trauma,
similar previous episodes, or prior
ERCP. A detailed list of medica-
tions must be reviewed, focusing on
the likelihood of a drug being the
cause as well as timing of use (11).
On physical examination, vital
signs including pulse, orthostatic
blood pressure, and respiratory rate
must be performed to evaluate hy-
dration status and indicate the
severity of pancreatitis. Tachycardia
and hypotension represent intravas-
cular depletion secondary to fluid
Diagnosis
sequestration seen in more severe
cases. Jaundice indicates biliary tree
obstruction. The clinician should
perform a careful abdominal exami-
nation focusing especially on aus-
cultation for bowel sounds, location
of pain, guarding (usually severe),
rebound, and distention. Distention
with absent bowel sounds indicates
ileus. Ecchymosis in the flanks
(Grey-Turner sign) or around the
umbilicus (Cullen sign) are indica-
tive of blood in the abdomen from
pancreatic necrosis. Mental status
impairment is also an indicator of
more severe pancreatitis and may
occur as a result of septicemia, hy-
poxemia, electrolyte imbalance, or
alcohol use. Multiorgan dysfunc-
tion signifies a more severe episode
with complications, such as pancre-
atic necrosis.
A patient with gallstones and a his-
tory of fever, chills, and/or rigors
suggests ascending cholangitis, but 16. Trivedi CD, Pitchu-
these symptoms may be due only to moni CS. Drug-in-
duced pancreatitis:
the inflammatory process associat- an update. J Clin
Gastroenterol.
ed with acute pancreatitis. 2005;39:709-16.
[PMID: 16082282]
What laboratory tests are useful 17. Third Report of the
Expert Panel on De-
in the evaluation of acute tection, Evaluation,
and Treatment of
pancreatitis? High Blood Choles-
Elevation of the serum amylase terol in Adults (ATP
III Final Report). Cir-
and/or lipase levels at least three culation.
2002;106:3143-421.
times the upper limit of normal is a [PMID: 12485966].
key component of diagnosing acute 18. Yadav D, Agarwal N,
Pitchumoni CS. A
pancreatitis. Measurement of serum critical evaluation of
laboratory tests in
amylase levels has good sensitivity acute pancreatitis.
but low specificity, signifying a high Am J Gastroenterol.
2002;97:1309-18.
false-positive rate (18). Other causes [PMID: 12094843]

2 November 2010 Annals of Internal Medicine In the Clinic ITC5-5 © 2010 American College of Physicians

19. Liu KJ, Atten MJ,
Lichtor T, et al.
Serum amylase and
lipase elevation is as-
sociated with in-
tracranial events. Am
Surg. 2001;67:215-9;
discussion 219-20.
[PMID: 11270877]
20. Seno T, Harada H,
Ochi K, et al. Serum
levels of six pancre-
atic enzymes as re-
lated to the degree
of renal dysfunction.
Am J Gastroenterol.
1995;90:2002-5.
21. Manjuck J, Zein J,
Carpati C, Astiz M.
Clinical significance
of increased lipase
levels on admission
to the ICU. Chest.
2005;127:246-50.
[PMID: 15653991]
22. Wachter RM, Gold-
man, L, Hollander H.
Hospital Medicine.
Philadelphia: Wolters
Kluwer Health; 2005.
© 2010 American College of Physicians
of elevated serum amylase levels in-
clude disorders of salivary glands and
fallopian tubes, intestinal ischemia,
perforated peptic ulcer, and chronic
renal insufficiency. To improve speci-
ficity, the level of the serum amylase
or lipase needs to be three times nor-
mal. Measurement of lipase levels is
more sensitive than that of amylase
levels in acute alcoholic pancreatitis
or when patients present to the
emergency department days after
disease onset because it remains ele-
vated for a longer period. However,
lipase can also be falsely elevated in
cases of renal insufficiency and head
trauma or an intracranial mass as
well as in patients receiving heparin
therapy (through activation of
lipoprotein lipase) (19, 20). Elevated
serum lipase levels are also common
among critically ill patients in the in-
tensive care unit (ICU) (21). Simul-
taneous measurement of amylase and
lipase levels does not seem to im-
prove diagnostic accuracy (18).
No enzyme assay can assess the
severity or cause of an episode of
acute pancreatitis. Serum C-reactive
protein at 48 hours is the best avail-
able laboratory marker of severity.
Liver enzymes should also be rou-
tinely checked. Elevated liver en-
zymes (alanine transaminase) >150
IU/L has a 95% positive predictive
value and a specificity of 96% but
sensitivity of less than 50%; the ac-
curacy of the aspartate transaminase
is similar (22). Elevations can sug-
gest gallstone pancreatitis. Triglyc-
eride levels should be checked
because levels above >1000 mg /dL
can precipitate acute pancreatitis that
is often severe. A low serum calcium
level can cause acute pancreatitis but
may also be a consequence of acute
pancreatitis due to other causes (23).
The presence of leukocytosis on
complete blood count may result
from the acute pancreatic inflam-
mation alone or point to an
underlying infectious process. In-
creased hematocrit and blood urea
nitrogen (BUN) levels may reveal
ITC5-6 In the Clinic
hemoconcentration, indicative of
fluid sequestration. Early changes
in the serial BUN levels provide the
most useful assessment of response
to initial resuscitation (24).
An acute drop in hemoglobin in an
unstable patient may represent he-
morrhagic pancreatitis. Patients
with pancreatitis may also develop
disseminated intravascular coagu-
lopathy, perhaps due to circulating
pancreatic enzymes or to vascular
injury precipitating consumption of
coagulation factors (25).
What other diagnoses should
clinicians consider in a patient
with possible acute pancreatitis?
The clinical presentation of upper
abdominal pain with nausea, vomit-
ing, and fever has a broad differential
(Table 2). Although peptic ulcer per-
foration often mimics this presenta-
tion, it is distinguished by free air
seen on imaging studies. Acute
cholecystitis, symptomatic choledo-
cholithiasis, and cholangitis are typi-
cally described as causing right upper
quadrant pain but can also present
with epigastric pain similar to that of
acute pancreatitis. Normal serum
amylase and lipase levels as well as
characteristic imaging findings, such
as gallbladder wall thickening
(cholecystitis) or common bile duct
stones (choledocholithiasis), help
differentiate biliary disease from
acute pancreatitis but, as noted, acute
pancreatitis may also present with
gallstone-related biliary obstruction.
Patients with intestinal obstruction
will have abdominal distention, col-
icky abdominal pain, and an obstruc-
tive bowel pattern on imaging. They
may also have elevated serum amy-
lase levels but these levels are usually
lower than those associated with
acute pancreatitis. Mesenteric vascu-
lar obstruction should be suspected
in patients with underlying vascular
or cardiac disease. Pain associated
with nonobstructive mesenteric is-
chemia is usually postprandial, and
on rare occasions an abdominal bruit
may be heard. Table 2 lists additional
Annals of Internal Medicine 2 November 2010
 Table 2. Differential Diagnosis of Acute Pancreatitis
Disease
Perforated viscus, especially peptic ulcer
Acute cholecystitis and biliary colic
Intestinal obstruction
Mesenteric vascular occlusion
Dissecting aortic aneurysm
Renal colic
Myocardial infarction
Connective tissue disorders with vasculitis Acute pancreatitis can be due to vasculitis
Appendicitis
Ectopic pregnancy
Pneumonia
AP = acute pancreatitis; ARDS = acute respiratory distress syndrome; CT = computed tomography; HCT = hematocrit.
causes of upper abdominal pain that
should be considered in the differen-
tial of acute pancreatitis.
What is the role of imaging
studies in the evaluation of
acute pancreatitis?
Imaging plays an important role in
identify the cause of the attack of
acute pancreatitis and in assessing
severity (26). A plain abdominal ra-
diograph may show nonspecific
signs of acute pancreatitis, such as a
sentinel loop (localized ileus involv-
ing the jejunum), colon cutoff sign
(isolated distention of the trans-
verse colon), duodenal distention
with air and fluid, and pleural effu-
sion localized to the left thorax. In
cases of abdominal distention with
acute pain, the X-ray may reveal
2 November 2010 Annals of Internal Medicine
Characteristics Findings
Sudden onset of pain that increases over 30-60 min Intraperitoneal air present
Epigastric or right upper quadrant pain that radiates Liver enzymes often elevated; ultrasonography
to right shoulder or shoulder blade may show thickened gallbladder, pericholecystic
fluid
Constant colicky pain Obstructive pattern can be seen on CT scan or
abdominal series
Classic triad is postprandial abdominal pain, Discrepancy between symptoms (severe pain) and
weight loss, and abdominal bruit examination (benign abdominal examination)
Sudden onset; pain may radiate to the lower
extremities
Flank pain radiates to the genitals; dysuria may Urinalysis with active sediment
be present
Upper abdominal or chest pain Electrocardiography usually abnormal
Other signs of vasculitis usually present (skin,
joint, eye, and kidney involvement)
Pain may start in epigastrium or periumbilical then Ultrasonography and and CT aid in diagnosis
migrate to right lower quadrant
Sudden onset of pain; menstrual abnormalities Rapid drop in hematocrit and intraperitoneal
often precede pain pelvic fluid on imaging should raise suspicion
Fever, malaise, and other respiratory symptoms Changes on physical examination of the chest
(dyspnea, cough, sputum production, chest pain) and abnormalities on chest X-ray possibly due to
usually present ARDS or pleural effusion
free air showing a perforated viscus
as the cause of pain.
23. Schütte K, Malfer-
theiner P. Markers for
However, the initial imaging study predicting severity
of choice is ultrasonography of the and progression of
acute pancreatitis.
right upper quadrant because it is Best Pract Res Clin
Gastroenterol.
readily available, noninvasive, inex- 2008;22:75-90.
pensive, and relatively sensitive [PMID: 18206814]
24. Wu BU, Johannes RS,
(95%) for diagnosing gallstone dis- Sun X, Conwell DL,
Banks PA. Early
ease. The presence of gallstones changes in blood
and/or dilatation of the common bile urea nitrogen pre-
dict mortality in
duct supports stones as the cause of acute pancreatitis.
acute pancreatitis. However, the dis- Gastroenterology.
2009;137:129-35.
tal common bile duct and pancreas [PMID: 19344722]
25. Saif MW. DIC sec-
are frequently obscured by overlying ondary to acute
bowel gas and limit the sensitivity of pancreatitis. Clin Lab
Haematol.
ultrasonography for diagnosing gall- 2005;27:278-82.
stone-associated pancreatitis. [PMID: 16048498]
26. Nichols MT, Russ PD,
Chen YK. Pancreatic
In this case, a contrast-enhanced, imaging: current and
emerging technolo-
thin-sliced, triple-phase computed gies. Pancreas.
2006;33:211-20.
tomography (CT) scan provides an [PMID: 17003640]
In the Clinic ITC5-7 © 2010 American College of Physicians
 excellent image of the pancreas and Which factors help to predict the
Atlanta Classification of Acute
can identify choledocholithiasis or prognosis of a patient with acute
Pancreatitis*
other causes of abdominal pain. CT pancreatitis?
Severe acute pancreatitis scanning can also be useful to assess Patients should be stratified by risk
• Organ failure (systolic blood pressure
<90 mm Hg, PaO2 the severity of the pancreatitis and in for severe morbidity and death relat-
<60 mm Hg, creatinine level identifying complications, such as ed to acute pancreatitis because of
>2 mg/dL, gastrointestinal bleeding necrosis (infected or not), pseudocyst the disease’s protean manifestations,
> 500 mL/24 h) unpredictable course, and the need
formation, and diffuse pancreatic flu-
• Local complications (pancreatic
necrosis, pseudocyst, or abscess) id collection (27). However, early in to identify persons who require in-
• ≥3 Ranson criteria. the course of disease a CT scan may tensive care. The Atlanta Classifica-
not show signs of pancreatitis or its tion of Acute Pancreatitis was
Mild acute pancreatitis
• Minimal organ dysfunction associated complications. In addi- developed in 1992 to standardize
• Uneventful recovery tion, intravenous contrast may accel- what was a heterogeneous set of cri-
• Lacks features of severe acute erate renal injury. When these fac- teria to diagnose the disease and to
pancreatitis. tors are a concern, magnetic assess severity (1). However, because
Notes: Consider determining APACHE II resonance imaging (MRI) offers an of a changing understanding of the
score and measuring C-reactive protein alternative at greater cost to diagnose pathophysiology and epidemiology
levels. Be aware of limited accuracy of
severity prediction. and evaluate the severity of acute of acute pancreatitis, in 2008 a revi-
*From reference 33. pancreatitis (28). sion was proposed to the Atlanta
Classification (still being reviewed
Among newer but even more costly with final approval expected by
27. Lankisch PG, Struck-
mann K, Assmus C, imaging modalities, the noninvasive 2011) that recognizes 2 phases of the
Lehnick D, Maison- magnetic resonance cholangiopan- disease that were not appreciated by
neuve P, Lowenfels
AB. Do we need a creatography (MRCP) has high the original classification (see the
computed tomogra-
phy examination in
sensitivity (>90%) for choledo- Box) (33). First, there is a peak in
all patients with cholithiasis and can identify other mortality usually within the first
acute pancreatitis
within 72 h after ad- anatomical abnormalities, such as week of onset and another 2 to 6
mission to hospital
for the detection of
pancreas divisum, pancreatic duct weeks after onset. In the first week,
pancreatic necrosis? abnormalities, and mucinous neo- the severity of the disease is usually
Scand J Gastroen-
terol. 2001;36:432-6. plasm in the pancreas (29). It can reflected by the extent of organ fail-
[PMID: 11336171] be useful to exclude the presence of
28. Arvanitakis M, Del- ure. After that, mortality can be pre-
haye M, De Maerte- a retained stone or debris if there is dicted more by the presence of
laere V, et al. Com-
puted tomography a high index of clinical suspicion. pancreatic necrosis and infection.
and magnetic reso-
nance imaging in
the assessment of Secretin-enhanced MRI is useful Therefore, when a patient first
acute pancreatitis. for evaluating pancreatic function presents, clinicians need to be alert
Gastroenterology.
2004;126:715-23. and anatomy when the patient is to the possibility of organ failure
[PMID: 14988825]
29. Makary MA, Duncan
suspected of having underlying (34). As expected, progression from
MD, Harmon JW, et chronic pancreatitis. However, since single to multiorgan failure is a pre-
al. The role of mag-
netic resonance secretin stimulates pancreatic secre- dictor of increased mortality (35).
cholangiography in
the management of
tion, it should not be obtained dur- Coagulopathy bodes poorly for pa-
patients with gall- ing an acute episode because it tients as indicated by platelet count
stone pancreatitis.
Ann Surg. could worsen the disease. <100 000/mm3, fibrinogen <100
2005;241:119-24.
[PMID: 15621999]
mg/dL, and fibrin split products
30. Liu CL, Lo CM, Chan Endoscopic ultrasonography is both >80 µg/mL. Similarly, low serum
JK, et al. Detection of
choledocholithiasis
sensitive and specific in identifying calcium levels (≤ 7.5 mg/dL) carry
by EUS in acute pan- small (e.g., ≤5 mm) gallstones in a poor prognosis.
creatitis: a prospec-
tive evaluation in the bile ducts (30) and can identify
100 consecutive pa- anatomical abnormalities of the The Atlanta symposium also
tients. Gastrointest
Endosc. 2001;54:325- pancreas. Although it is more inva- identified the development of lo-
30. [PMID: 11522972]
31. Lai R, Freeman ML,
sive than MRI, it can detect smaller cal complications (necrosis and
Cass OW, Mallery S. stones and can be used when MRI abscess and pseudocyst formation)
Accurate diagnosis
of pancreas divisum is not possible (e.g., in critically ill as indicative of severe acute pan-
by linear-array endo-
scopic ultrasonogra-
patients or when it is contraindicat- creatitis. Pancreatic necrosis is
phy. Endoscopy. ed, such as in patients with a car- demonstrated by poor perfusion
2004;36:705-9.
[PMID: 15280976] diac pacer) (31, 32). and nonenhancement on CT scan

© 2010 American College of Physicians ITC5-8 In the Clinic Annals of Internal Medicine 2 November 2010
of more than 3 cm or >30% of the
pancreas (but these dimensions
are being debated) (39). A
pseudocyst is a fluid collection
within the pancreas, separated by
a nonepithelized wall, that devel-
ops over a period of weeks (by
definition >4 wk). Infection of
either pancreatic necrosis or a
pseudocyst can lead to abscess for-
mation. Pancreatic fluid can also
extravasate as a result of the
inflammation. When both organ
failure and infected pancreatic
necrosis are present, relative risk
for mortality doubles (45).
A variety of other classifications
have been developed to assess the
severity of acute pancreatitis early
in the course of disease (Table 3),
including Ranson criteria; the
Acute Physiology and Chronic
Health Evaluation (APACHE-II

Table 3. Clinical Criteria for Determining Severity of Acute Pancreatitis

Classification
Ranson criteria
Acute Physiology and Chronic Daily: Based on diverse variables, Mortality: <4% for a score <8,
Health Evaluation
(APACHE) II scoring system
Modified Glasgow prognostic
criteria (Imrie scoring system) each): PaO2 < 60 mm Hg/7.9 kPa; 48 h
Bedside Index for Severity in
Acute Pancreatitis (BISAP)
score
Modified CT severity index
Predictors Outcomes Based on Score Comments
Admission measurements Mortality: 0%–3% for <3 criteria, Scoring on admission and at 48 h after
(1 point each): Age >55 years; 11%–15% for 3–5 criteria, presentation; limited predictive power reported in
leukocyte count >16 000/mm ; and 40% for ≥6 criteria (36)
3
meta-analysis (37)
glucose >200 mg/dL; LDH
>350 U/L; AST >250 U/L; fluid
sequestration >6 L
Measurement at 48 h (1 point
each): HCT decrease of 10
volume %; BUN increase of
5 mg/dL; calcium <8 mg/dL;
PaO2 <60 mm Hg; base deficit
>4 mEq/L
Requires data usually only available when
including age, physiology, and 11%–18% for a score ≥8 (39) patient is in ICU; an increasing APACHE-II
long-term health; equation score in the first few days of hospitalization
available at www.sfar.org/ indicates worsening severity whereas the oppo-
scores2/apache22.html#calcul; site indicates improvement (38); APACHE-II
Adding BMI to APACHE-II and APACHE-III have a similar performance
(the APACHE-O score)
increases discrimination (1 point
added for BMI 26-30; 2 points
for BMI >30) (38)
At 48 h after admission (1 point Severe episode: score ≥3 within Takes 48 h to complete; similar performance to
APACHE-III (40)
age >55 y; neutrophils (WBC
>15); calcium <2 mmoL/L; renal
function: urea >16 mmoL/L;
enzymes LDH >600 IU/L, AST
>200 IU/L; albumin <32 g/L
(serum); blood glucose level
>10 mmol/L
Within 24 h after presentation Mortality: <1% in the lowest Assessed at 24 h; prognostic accuracy similar to
(1 point each): BUN >25 mg/dL; risk group and >20% in the other scoring systems (42)
impaired mental status; systemic highest risk group.
inflammatory response syndrome
(see text for definition); age
>60 y; presence of pleural
effusion (41)
CT scan assessment of Correlated with length of stay Studied in small patient populations
pancreatic inflammation and and clinical complications (44)
necrosis, plus assessment of
extrapancreatic complications (43)

AST = aspartate transaminase; BMI = body mass index; BUN = blood urea nitrogen; CT = computed tomography; HCT = hematocrit; ICU = intensive care unit;
LDH = lactate dehydrogenase; WBC = white blood cells.

2 November 2010 Annals of Internal Medicine In the Clinic ITC5-9 © 2010 American College of Physicians
 and III) scale; the Modified Glas- includes aggressive intravenous fluid
gow prognostic criteria (also known resuscitation with no fluids or solids
as the Imrie scoring system); Bed- by mouth. Patients often require pain
side Index for Severity in Acute management with intravenous med-
Pancreatitis (BISAP) score; and the ications, typically opiates are used and
32. Sedlack R, Affi A, Modified CT Severity Index. must be monitored for side effects,
Vazquez-Sequeiros E, such as respiratory depression. Stable
Norton ID, Clain JE,
Wiersema MJ. Utility
It is important to note that neither patients having a mild episode who
of EUS in the evalua- serum amylase nor lipase levels are have a history of multiple episodes
tion of cystic pancre-
atic lesions. Gas- predictive of the severity of acute can sometimes be managed on an
trointest Endosc.
2002;56:543-7.
pancreatitis. On the other hand, outpatient basis.
[PMID: 12297771] C-reactive protein has been widely
33. Acute Pancreatitis
Classification Work- used to predict the severity of acute Such tests as ERCP are usually done
ing Group. Revision pancreatitis (18), and in critically ill in an inpatient setting when indicat-
of the Atlanta classi-
fication of acute patients, it has been shown to be ed. Severe acute pancreatitis requires
pancreatitis (3rd re-
vision). www.pan- associated with increased risk for close inpatient monitoring, and the
creasclub.com/re- organ failure and death (46). Pro- patient should be transferred to ICU
sources/AtlantaClass
ification.pdf. Ac- calcitonin has been associated with if organ failure develops (47). In eld-
cessed 16 Septem-
pancreatic infection and can be erly patients with underlying cardio-
ber 2010.
34. Johnson CD, Abu- used as an indicator of the need for vascular disease, aggressive fluid
Hilal M. Persistent or-
gan failure during fine-needle aspiration of pancreatic resuscitation should be administered
the first week as a necrosis (23). in an ICU and may require a central
marker of fatal out-
come in acute pan- venous catheter for more accurate
creatitis. Gut.
2004;53:1340-4.
What are the indications for fluid monitoring. Transfer to a spe-
[PMID: 15306596] hospitalization and for intensive cialized monitored unit, although
35. Brown A, Orav J,
Banks PA. Hemocon- care for a patient with acute not necessarily an ICU, should be
centration is an early pancreatitis? considered for patients with high
marker for organ fail-
ure and necrotizing Patients with acute pancreatitis body mass index (>30), decreased
pancreatitis. Pan-
creas. 2000;20:367-
should be hospitalized until they have urine output < 50 mL/h, tachycardia
72. [PMID: 10824690] been observed for a sufficient period (pulse rate > 120 beats/min), signs of
36. Blum T, Maison-
neuve P, Lowenfels to evaluate disease severity and pro- encephalopathy, and/or need for ad-
AB, Lankisch PG. Fa-
tal outcome in acute
gression. Essential management ditional narcotics (39).
pancreatitis: its oc-
currence and early
prediction. Pancre-
atology. 2001;1:237-
41. [PMID: 12120201] Diagnosis... In acute pancreatitis, diagnosis is based on the presence at least 2 of 3
37. De Bernardinis M, Vi- features: abdominal pain; increased pancreatic enzyme, amylase, and/or lipase levels
oli V, Roncoroni L,
Boselli AS, Giunta A,
to ≥3 times the upper limit of normal; and imaging tests showing characteristic
Peracchia A. Discrim- findings of acute pancreatitis. Ultrasonography of the right upper quadrant may re-
inant power and in- veal stones or biliary duct dilatation and CT scan can be useful to assess for pancre-
formation content of
Ranson’s prognostic atic edema, necrosis, or pseudocyst formation. MRI offers an alternative but is more
signs in acute pan- costly. Assessing the severity of the attack of acute pancreatitis using clinical labora-
creatitis: a meta-ana-
lytic study. Crit Care
tory parameters; imaging; and standard measurements, such as APACHE-II, BISAP, CT
Med. 1999;27:2272- severity index, or Ranson criteria, can guide management. Acute pancreatitis should
83. [PMID: 10548220] be managed in the inpatient setting with rare exceptions and patients with organ
38. Banks PA, Freeman
ML. Practice Parame- failure or severe comorbid conditions should be treated in the ICU.
ters Committee of
the American Col-
lege of Gastroen-
terology. Practice CLINICAL BOTTOM LINE
guidelines in acute
pancreatitis. Am J
Gastroenterol.
2006;101:2379-400.
[PMID: 17032204] Treatment
39. Johnson CD, Toh SK,
Campbell MJ. Com-
bination of APACHE- How should clinicians manage can experience a significant loss of
II score and an obe-
sity score
fluids in a patient with acute intravascular volume due to third
(APACHE-O) for the pancreatitis? spacing and increased permeability
prediction of severe
acute pancreatitis.
Fluid resuscitation is a critical com- from release of inflammatory media-
Pancreatology. ponent of management of patients tors. Compromised intravascular vol-
2004;4:1-6.
[PMID: 14988652] with acute pancreatitis because they ume can lead to decreased perfusion

© 2010 American College of Physicians ITC5-10 In the Clinic Annals of Internal Medicine 2 November 2010
of the pancreas and such complica- However, studies comparing naso-
tions as pancreatic necrosis and renal gastric with nasojejunal feeding
40. Chatzicostas C,
failure. Fluid administration should have not shown significant differ- Roussomoustakaki
be guided by vital signs, urine out- ences in outcomes, but larger com- M, Vlachonikolis IG,
et al. Comparison of
put, and change in hematocrit at ad- parative studies are required before Ranson, APACHE II
and APACHE III scor-
mission, 12 hours, and 24 hours practice recommendations are ing systems in acute
(39). Increasing hematocrit or BUN changed. pancreatitis. Pan-
creas. 2002;25:331-5.
is a poor prognostic sign and indi- [PMID: 12409825].
cates worsening severity. A meta-analysis of 6 studies showed a 41. Blamey SL, Imrie CW,
O’Neill J, Gilmour
lower incidence of infections, reduced WH, Carter DC. Prog-
How should clinicians manage the surgical intervention and shorter hospital nostic factors in
acute pancreatitis.
nutritional needs of a patient stay in patients with acute pancreatitis Gut. 1984;25:1340-46.
with acute pancreatitis? receiving nasojejunal feeding (50). In one 42. Wu BU, Johannes RS,
Sun X, et al. The ear-
study, nasojejunal feeding was associat-
In mild acute pancreatitis, nutri- ly prediction of mor-
ed with a shorter hospital stay and fewer tality in acute pan-
tional support is not necessary. complications than parental nutrition creatitis: a large
population-based
Once pain has diminished along (sepsis, 4% vs. 33%; metabolic complica- study. Gut.
with nausea and vomiting, oral nu- tions, 15% vs. 52%, respectively), and a 2008;57:1698-703.
[PMID: 18519429] 43.
trition can be started. It begins with savings of $2362 (51). Papachristou GI,
Muddana V, Yadav D,
clear liquids and clinical monitoring et al. Comparison of
for change in pain and symptoms of An ongoing National Institutes of BISAP, Ranson’s,
APACHE-II, and CTSI
nausea and vomiting. Resolution of Health multi-center trial, called the scores in predicting
imaging findings and normalization Study of Nutrition in Acute Pan- organ failure, com-
plications, and mor-
of amylase and lipase may not occur creatitis (SNAP), is evaluating na- tality in acute pan-
creatitis. Am J
for up to a week, so the diet should sogastric vs. nasojejunal feeding. Gastroenterol.
be advanced based on how the pa- Difficulty placing or maintaining a 2010;105:435-41;
quiz 442.
tient feels. There is no clear consen- nasojejunal tube also requires par- [PMID: 19861954]
44. Mortele KJ, Wiesner
sus about fat restriction. enteral nutrition. Notably, parenter- W, Intriere L, et al. A
al nutrition may be required in modified CT severity
index for evaluating
Patients with moderate or severe some critically ill patients as well as acute pancreatitis:
pancreatitis must usually abstain those with severe ileus. improved correla-
tion with patient
from solids and liquids for several outcome. AJR Am J
days to weeks. Although mortality What other supportive care may be Roentgenol.
2004;183:1261-5.
rates do not differ substantially be- beneficial for acute pancreatitis? [PMID: 15505289]
45. Petrov MS,
tween parenteral and enteral nutri- Oxygen may reduce the acute res- Shanbhag S,
tion, the latter has been shown to piratory distress syndrome that Chakraborty M, et al.
Organ failure and in-
reduce the rate of infection, surgical can occur in the early stages of fection of pancreatic
necrosis as determi-
interventions, and noninfectious acute pancreatitis. Pain manage- nants of mortality in
complications (48). United King- ment is another key aspect of patients with acute
pancreatitis. Gas-
dom guidelines for management of treatment. Due to the severity of troenterology. 2010
Jun 9. [Epub ahead
acute pancreatitis recommend en- pain with acute pancreatitis and of print]
teral nutrition for all patients with the inability to take pills, par- [PMID: 20540942]
46. Lobo SM, Lobo FR,
severe acute pancreatitis, but state enteral narcotic analgesics are es- Bota DP, et al. C-re-
that the nasogastric route is pre- sential. Opiates are usually admin- active protein levels
correlate with mor-
ferred for feeding because it is ef- istered every 2 to 4 hours. A tality and organ fail-
ure in critically ill pa-
fective in ≥ 80% of cases (49). patient-controlled analgesia pump tients. Chest.
However, the nasojejunal route is offers an alternative when boluses 2003;123:2043-9.
[PMID: 12796187]
increasingly being used in the of pain medications provide inad- 47. Zhang XP, Wang L,
Zhou YF. The patho-
United States. Although tube equate pain control. Morphine has genic mechanism of
placement is more difficult, enteral been theoretically implicated in severe acute pancre-
atitis complicated
feeding beyond the ligament of increasing pressure in the sphinc- with renal injury: a
review of current
Treitz may decrease the risk for in- ter of Oddi and potentially de- knowledge. Dig Dis
fectious complications that can oc- creasing pancreatic and biliary Sci. 2008;53:297-306.
[PMID: 17597411]
cur with feeding methods in which flow into the small bowel lumen, 48. Frossard J-L, Steer
ML, Pastor CM.
the small bowel can be affected by but this has not been confirmed in Acute pancreatitis.
edema and permeability from in- clinical studies. Meperidine, mor- Lancet.
2008;371:143-52.
flammatory mediators is increased. phine and hydromorphone are [PMID: 18191686]

2 November 2010 Annals of Internal Medicine In the Clinic ITC5-11 © 2010 American College of Physicians

49. UK Working Party on
Acute Pancreatitis.
UK guidelines for the
management of
acute pancreatitis.
Gut 2005;54(Suppl
III):iii1-iii9.
50. Louie BE, Noseworthy
T, Hailey D, Gramlich
LM, Jacobs P,
Warnock GL. 2004
MacLean-Mueller
prize enteral or par-
enteral nutrition for
severe pancreatitis: a
randomized con-
trolled trial and
health technology as-
sessment. Can J Surg.
2005;48:298-306.
[PMID: 16149365]
51.Abou-Assi S, Craig K,
O’Keefe SJ.
Hypocaloric jejunal
feeding is better
than total parenteral
nutrition in acute
pancreatitis: results
of a randomized
comparative study.
Am J Gastroenterol.
2002;97:2255-62.
[PMID: 12358242]
52. Villatoro E, Mulla M,
Larvin M. Antibiotic
therapy for prophy-
laxis against infec-
tion of pancreatic
necrosis in acute
pancreatitis.
Cochrane Database
Syst Rev. 2010 May
12;5:CD002941.
[PMID: 20464721]
53. Carter CR, McKay CJ,
Imrie CW. Percuta-
neous necrosectomy
and sinus tract en-
doscopy in the man-
agement of infected
pancreatic necrosis:
an initial experience.
Ann Surg.
2000;232:175-80.
[PMID: 10903593]
54. Connor S, Ghaneh P,
Raraty M, Sutton R,
Rosso E, Garvey CJ,
et al. Minimally inva-
sive retroperitoneal
pancreatic necrosec-
tomy. Dig Surg.
2003;20:270-7.
[PMID: 12748429].
55. van Santvoort HC,
Besselink MG, Bakker
OJ, et al. A step-up
approach or open
necrosectomy for
necrotizing pancre-
atitis. N Engl J Med.
2010;362:1491-502.
[PMID: 20410514]
© 2010 American College of Physicians
more commonly used narcotics for
pain control in acute pancreatitis.
What is the role of antibiotics in
the management of patients with
acute pancreatitis?
Antibiotics are not currently rec-
ommended for mild interstitial
pancreatitis or even for moderate to
severe pancreatitis with sterile
necrosis. Studies of prophylactic
administration of antibiotics to de-
crease infectious complications
have been largely nonsupportive.
A recent Cochrane review found no benefit
of antibiotics to prevent infection of pan-
creatic necrosis or mortality, with the pos-
sible exception of the β-lactam imipenem,
that was associated with a significant de-
crease in pancreatic infection (52). The re-
viewers concluded that better-designed
studies would be required before antibiotic
prophylaxis could be recommended.
However, antibiotics are definitely re-
quired to treat ascending cholangitis,
infected pancreatic necrosis, or an in-
fected pseudocyst. When the patient
seems to be septic or infection is sus-
pected, a fever workup should be con-
ducted with cultures and a chest
X-ray. If needed, CT-guided needle
aspiration of a necrotic area of the
pancreas should be cultured for bacte-
ria and fungi. If the workup is nega-
tive, continue antibiotics if the patient
has septicemia, organ failure, or ≥30%
necrosis of the pancreas (5).
For an infected necrotic pancreas,
the choice of antibiotic is guided by
the culture. For gram-negative or-
ganisms, options include imipenem,
meropenem, ofloxacin, or
ciprofloxacin with metronidazole, or
a third-generation cephalosporin
with metronidazole. Patients with
infected pancreatic necrosis should
be closely observed to assess for re-
sponse and surgical debridement
should be considered when the pa-
tient does not improve—mortality is
high if this disorder is not treated
aggressively (49).
There are multiple approaches for
debridement but no consensus on
ITC5-12 In the Clinic
which one is best. Open surgical
debridement has been a standard,
but debridement with a percuta-
neous nephroscope offers an alter-
native (53, 54).
A recent multicenter study randomly as-
signed 88 patients with necrotizing pan-
creatitis and suspected or confirmed in-
fected necrotic tissue to primary open
necrosectomy or a step-up treatment ap-
proach (percutaneous drainage followed
by minimally invasive retroperitoneal
necrosectomy if needed) (55). Major com-
plications or death occurred in 69% of pa-
tients in the open necrosectomy group vs.
40% in the step-up treatment group.
Case reports have also described
endoscopic transgastric endoscopic
debridement of an infected area of
necrosis in selected patients who
are poor surgical candidates (56).
This approach should be consid-
ered in advanced centers with ex-
pertise in these techniques.
When should clinicians consider
consultation with a gastro-
enterologist, a surgeon, or an
interventional radiologist?
For patients who have mild acute
pancreatitis with a known cause,
consultation is usually unneces-
sary. However, if the cause is un-
clear or pancreatitis tends to recur,
a gastroenterology consult may be
useful. In patients with more se-
vere attacks, gastroenterology
consultation can assist with man-
agement and monitoring for
complications. Further, when gall-
stone pancreatitis is suspected,
consultation for ERCP may be
necessary, as noted below.
When a patient develops necrotizing
pancreatitis or abscesses or pseudo-
cysts, or pancreatic fluid collection is
necessary, both a surgeon and a gas-
troenterologist should be consulted.
These patients usually require a team
approach because surgical, endoscop-
ic, and percutaneous drainage meth-
ods should be considered. Endoscopic
drainage of pseudocysts has been as-
sociated with better outcomes (57).
Because of limited data on endoscopic
Annals of Internal Medicine 2 November 2010
drainage of pancreatic necrosis but removal. Urgent ERCP is indi-
especially when infected, surgical in- cated if cholangitis is suspected.
tervention may be required. An inter- In the absence of these criteria,
ventional radiology consultation may studies have found that early
be useful for percutaneous CT-guided ERCP was associated with in-
catheter drainage of infected pancre- creased complications.
atic pseudocysts (58). A trial of per-
cutaneous drainage followed by A meta-analysis of 7 randomized trials
minimally invasive retroperitoneal found no significant reduction in overall
necrosectomy, if necessary, versus sur- complications or mortality from early
gery with open necrosectomy found ERCP in patients with predicted mild or se-
that the minimally invasive approach vere acute biliary pancreatitis without
had fewer major complications or acute cholangitis (59).
death (55). When gallstones are pres-
Several studies have shown an ad-
ent, patients need to be evaluated by a
vantage of ERCP in pancreatitis
surgeon for cholecystectomy.
from obstructive biliary disease. Pa-
What are the indications for ERCP? tients presenting with complicated
Presence of a retained bile duct acute pancreatitis due to a disrupted
56. Gupta K, Freeman
stone seen on imaging is an indi- pancreatic duct with a leak may also ML. Disconnected
cation for ERCP to perform bil- benefit from ERCP and placement pancreatic duct with
pancreas necrosis,
iary sphincterotomy and stone of a pancreatic duct stent. treated with trans-
gastric debridement
and pancreatic duct
stent. Clin Gastroen-
terol Hepatol.
2010;8:e51.
Treatment... Aggressive fluid resuscitation is the most important approach to manage [PMID: 20005979]
acute pancreatitis. Appropriate pain control and supportive care with oxygen supple- 57. Seewald S, Ang TL,
Teng KC, Soehendra
mentation are additional basic measures. In patients with a prolonged course, enteral N. EUS-guided
nutrition is preferred to parenteral nutrition whenever possible. Antibiotics are only drainage of pancre-
recommended for a documented infectious process or if there is ≥30% necrosis. If the atic pseudocysts, ab-
scesses and infected
cause of acute pancreatitis is unclear or ERCP reveals retained gallstones, consultation necrosis. Dig Endosc.
by a gastroenterologist is indicated. A team approach with both a gastroenterologist 2009;21 Suppl 1:S61-
5. [PMID: 19691738]
and surgeon is indicated for patients with organized necrosis (sterile or infected), 58. Maniatis P, Delis S,
pseudocyst, or abscess. In some cases, an interventional radiologist should be consult- Fagrezos D, et al. The
ed for specialized diagnostic and therapeutic imaging techniques. interventional radio-
logical procedures of
the infections of
pancreas. Infect Dis-
CLINICAL BOTTOM LINE ord Drug Targets.
2010;10:5-8.
[PMID: 20180752]
59. Petrov MS, van
Santvoort HC,
Practice Besselink MG, et al.
Early endoscopic ret-
rograde cholan-
What do professional
organizations recommend with
What is the role of patient
education in the management of
Improvement giopancreatography
versus conservative
management in
regard to the care of patients acute pancreatitis? acute biliary pancre-
atitis without
with acute pancreatitis? Patient education plays an impor- cholangitis: a meta-
A recent summary has assessed the tant role in preventing recurrent analysis of random-
ized trials. Ann Surg.
quality of 30 clinical guidelines re- acute pancreatitis. Lifestyle meas- 2008;247:250-7.
[PMID: 18216529]
garding management of acute pan- ures, such as cessation of alcohol 60. Loveday BPT, Srini-
creatitis that were published between consumption, are critical. Educa- vasa S, Vather R, et
al. High quantity and
1988 and 2008 (60). Among the tion about the risks of certain variable quality of
more recent U.S. clinical guidelines, medications if implicated in the guidelines for acute
pancreatitis: a sys-
those from the American Thoracic initial episode should also be pro- tematic review. Am J
Gastroenterol.
Society (2004), American College of vided with careful monitoring. 2010;105:1466-76.
Gastroenterology (2006), and the Dietary modification and adher- 61. Nathens AB, Curtis
JR, Beale RJ et al.
American Gastroenterological Asso- ence to lipid-lowering medica- Management of the
critically ill patient
ciation (2007) earned high quality tions are both necessary in with severe acute
scores (5, 39, 61). The Box summa- patients with pancreatitis due to pancreatitis. Crit
Care Med.
rizes the most recent 2 guidelines. hypertriglyceridemia. 2004;32:2524-36.

2 November 2010 Annals of Internal Medicine In the Clinic ITC5-13 © 2010 American College of Physicians
 American College of Gastroenterology Guidelines 2006
• Diagnosis of acute pancreatitis requires 2 of the following 3 criteria: abdominal pain, amylase and/or lipase levels ≥3 times upper limit of
normal, and/or CT scan findings of acute pancreatitis.
• Obesity, older age, and organ failure on admission; APACHE II score ≥8 and/or increasing in first 48 hours; and/or hematocrit ≥44 suggest
severe acute pancreatitis.
• CT scan with intravenous contrast and C-reactive protein > 150 mg/L help to identify necrotizing pancreatitis.
• Initial management includes aggressive intravenous hydration and supplemental oxygen. Patients with organ failure require ICU monitoring.
• Prolonged illness requires nutritional support. Enteral is preferred to total parenteral nutrition when possible.
• Antibiotics are not necessary for necrotizing pancreatitis, even with organ failure. If infection is suspected, CT-guided needle aspiration and
culture are recommended.
• MRCP and endoscopic ultrasonography can identify choledocholithiasis. If bile duct stone is confirmed, urgent ERCP is recommended.
• For complex necrotizing pancreatitis, pseudocyst, or infected necrosis, interventional options include open or laparoscopic surgery or
percutaneous or endoscopic drainage. Individualize management to the patient and available expertise.

American Gastroenterological Association Guidelines 2007

• Clinical presentation, increased serum amylase and lipase levels, and imaging—especially contrast-enhanced CT scan—assist in diagnosis of
acute pancreatitis.
• Organ failure and local pancreatic complications help to assess severity. Progressive organ failure predicts increased mortality.
• ICU monitoring is recommended if severe comorbidity or severe disease is diagnosed on the basis of imaging or APACHE II score ≥8.
• Identify the cause through imaging and laboratory studies, including liver enzyme and triglyceride levels.
• Specialized imaging, such as endoscopic ultrasonography, is needed when choledocholithiasis is a concern before proceeding with ERCP.
• Reserve ERCP for when less invasive methods are unavailable.
• Supportive care should include fluid resuscitation, supplemental oxygen, correction of electrolyte abnormalities, and pain control.
• Consider nutritional support with preference for enteral nutrition over total parenteral nutrition.
• Reserve antibiotic prophylaxis for patients with > 30% of necrosis. Use CT-guided aspiration to guide antibiotic selection.
• Base management of pseudocysts, fluid collections, and necrosis on symptoms and available expertise.

PIER Module

In the Clinic
In the Clinic www.pier.acponline.org
Access the PIER module on acute pancreatitis. PIER modules provide evidence-

Tool Kit based, updated information on current diagnosis and treatment in an electronic
format designed for rapid access at the point of care.
The PIER module on acute pancreatitis includes two tables to help guide diagnosis.

Patient Information
www.annals.org/intheclinic/toolkit-acutepancreatitis.html
Acute Access the Patient Information material that appears on the following page
for duplication and distribution to patients.
Pancreatitis http://digestive.niddk.nih.gov/ddiseases/pubs/pancreatitis/
Access information on pancreatitis from the NIDDK’s National Digestive
Diseases Information Clearinghouse.
www.nlm.nih.gov/medlineplus/ency/article/000287.htm
www.nlm.nih.gov/medlineplus/spanish/ency/article/000287.htm
Access information on acute pancreatitis in English and Spanish from the
National Library of Medicine’s Medline Plus.
www.gastro.org/patient-center/digestive-conditions/pancreatitis
Access “Understanding Pancreatitis” from the American Gastroenterological
Association.

Clinical Guidelines
www.acg.gi.org/physicians/guidelines/AcutePancreatitis.pdf
The American College of Gastroenterology published practice guidelines in
acute pancreatitis in 2006.
www.gastrojournal.org/article/S0016-5085%2807%2900592-6/fulltext
The American Gastroenterological Association Institute published a Medical Position
Statement on the management of acute pancreatitis in 2007.

The PIER module on acute pancreatitis includes two tablesto help guide diagnosis.

Quality Measures
There are currently no Centers for Medicare & Medicaid Services quality
measures for acute pancreatitis.

© 2010 American College of Physicians ITC5-14 In the Clinic Annals of Internal Medicine 2 November 2010
THINGS YOU SHOULD In the Clinic
Annals of Internal Medicine
KNOW ABOUT ACUTE
PANCREATITIS

What is acute pancreatitis?

• The pancreas is a gland that lies behind the stomach
and produces fluid that goes into the small intestine to
break down food.
• Acute pancreatitis occurs when something blocks the
flow of this fluid or attacks the tissues of the pancreas.
• Severe acute cases can be fatal.
What are symptoms of acute
pancreatitis?
• Severe, constant pain in the upper abdomen may
spread to the back.
• Nausea and vomiting can occur.
• Sweating, fast heart rate, and fever can occur.
Who gets acute pancreatitis?
• People with gallstone disease or who use alcohol
heavily are at risk.
• Other, less common causes include some medications,
injury to the pancreas, high triglyceride levels (often
checked with cholesterol), and pancreas deformities
from birth.
• Men are at higher risk than women.
How is it diagnosed?
• Your doctor will ask you about risk factors for acute
pancreatitis, review your medications, and examine
your stomach area as well as check your vital signs.

• Your doctor will order blood tests of enzymes from
the pancreas among other tests and do X-ray or
ultrasonography studies.
• Common tests used to diagnose acute pancreatitis
include ultrasonography, computed tomography (CT)
scan, and endoscopic retrograde cholangiopancrea-
tography (ERCP), which examines the pancreas
through a tube inserted down the throat into the
stomach and pancreas.
How is it treated?
• Hospitalization is necessary for nearly all patients
with acute pancreatitis. Sometimes intensive care is
needed.
Patient Information
• While in the hospital and under physician care, you
may need to stop eating for a few days to rest the
pancreas.
• Pain medications and intravenous fluids are often
needed.
• Treatment may be needed for the underlying cause,
such as for alcohol use or surgery to clear a bile duct
blocked by a gallstone.
• It is important to avoid anything that can cause
pancreatitis after an episode, such as alcohol, certain
medications, or foods that increase triglyceride levels
in order to prevent the disease from coming back.

For More Information

http://digestive.niddk.nih.gov/ddiseases/pubs/pancreatitis/
http://digestive.niddk.nih.gov/ddiseases/pubs/ercp/
National Institute of Diabetes and Digestive and Kidney Diseases
information on acute pancreatitis and ERCP.

www.nlm.nih.gov/medlineplus/ency/article/000287.htm
www.nlm.nih.gov/medlineplus/spanish/ency/article/000287.htm
Information on acute pancreatitis in English and in Spanish from
the National Library of Medicine’s MEDLINE Plus.
CME Questions
1. A 42-year-old woman is evaluated in the
emergency department for acute onset
of epigastric pain that radiates to the
back and is associated with nausea and
vomiting. The patient had previously
been healthy and has no history of
alcohol or tobacco use. Her only
medication is an oral contraceptive pill.
On physical examination, the
temperature is 37.2° C (99° F), the blood
pressure is 158/90 mm Hg, the pulse rate
is 101/min, and the respiration rate is
20/min. There is no scleral icterus or
jaundice. The abdomen is distended with
mid-epigastric tenderness without
rebound or guarding and with hypoactive
bowel sounds. The results of laboratory
studies are follows: leukocyte count,
13 500/µL (13.5 × 109/L); aspartate
aminotransferase, 131 U/L; alanine
aminotransferase, 567 U/L; bilirubin
(total), 1.1 mg/dL (18.8 µmol/L); amylase,
824 U/L; lipase, 1432 U/L.
Radiography of the abdomen shows mild
ileus.
Which of the following is the most
appropriate next step in the evaluation
of this patient?
A. CT scan of the abdomen and pelvis
B. Endoscopic retrograde
cholangiopancreatography
C. Esophagogastroduodenoscopy
D. Ultrasonography of the abdomen
2. A 34-year-old woman is evaluated for
continued severe mid-epigastric pain
that radiates to the back, nausea, and
vomiting 5 days after being hospitalized
for acute alcohol-related pancreatitis.
She has not been able eat or drink and
has not had a bowel movement since
being admitted.
On physical examination, the
temperature is 38.2° C (100.8° F), the
blood pressure is 132/84 mm Hg, the
pulse rate is 101/min, and the respiration
rate is 20/min. There is no scleral icterus
or jaundice. The abdomen is distended
Questions are largely from the ACP’s Medical Knowledge Self-Assessment Program (MKSAP, accessed at
http://www.acponline.org/products_services/mksap/15/?pr31). Go to www.annals.org/intheclinic/
to complete the quiz and earn up to 1.5 CME credits, or to purchase the complete MKSAP program.
© 2010 American College of Physicians
and diffusely tender with hypoactive
bowel sounds. The results of laboratory
studies are follows: leukocyte count, 15
400/µL (15.4 × 109/L); aspartate
aminotransferase, 189 U/L; alanine
aminotransferase, 151 U/L; bilirubin
(total), 1.1 mg/dL (18.8 µmol/L); amylase,
388 U/L; lipase, 924 U/L.
CT scan of the abdomen shows a
diffusely edematous pancreas with
multiple peripancreatic fluid collections,
and no evidence of pancreatic necrosis.
Which of the following is the most
appropriate next step in the
management of this patient?
A. Enteral nutrition by nasojejunal
feeding tube
B. Intravenous imipenem
C. Pancreatic débridement
D. Parenteral nutrition
3. A 68-year-old man with a history of
alcoholism is evaluated in the emergency
department for a 7-month history of
diarrhea during which he has noted an
increased volume of stool and decreased
consistency. He has had intermittent
abdominal pain but not severe enough to
prevent him from eating or drinking. He
is not taking any medications.
On physical examination, he is afebrile;
the blood pressure is 108/72 mm Hg, the
pulse rate is 80/min, and the respiration
rate is 16/min. The abdomen is soft with
mild periumbilical tenderness but no
distention. The results of laboratory
studies are follows: aspartate
aminotransferase, 155 U/L; alanine
aminotransferase, 88 U/L; alkaline
phosphatase, 96 U/L; bilirubin (total),
1.1 mg/dL (18.8 µmol/L); amylase, 65
U/L; lipase, 70 U/L.
CT scan of the abdomen shows
calcifications but no mass. There is fat in
the stool.
Which of the following is the most
appropriate management for this
patient?
ITC5-16 In the Clinic
A. Fiber
B. Cholestyramine
C. Loperamide
D. Pancreatic enzymes
4. A 51-year-old man is evaluated for an
8-month history of mid-epigastric pain
that is worse after eating, six to eight
bowel movements a day usually
occurring after a meal, and loss of 6.8 kg
(15 lb) over the past 6 months. The
patient drinks six to eight cans of beer a
day. He takes no medications.
On physical examination, the patient is
thin (BMI 21) and has normal bowel
sounds, mid-epigastric tenderness, but
no evidence of hepatosplenomegaly or
masses. Rectal examination reveals
brown stool that is occult blood
negative. The remainder of the
examination is normal. Plain radiograph
of the abdomen shows a normal bowel
gas pattern and is otherwise normal. The
results of laboratory studies are follows:
leukocyte count, 6800/µL (6.8 × 109/L);
platelet count, 69 000/µL (69 × 109/L);
fasting plasma glucose, 104 mg/dL
(5.77 mmol/L); aspartate amino-
transferase, 191 U/L; alanine amino-
transferase, 82 U/L; amylase, 122 U/L;
lipase, 289 U/L.
Which of the following tests is most
likely to establish the diagnosis in this
patient?
A. Colonoscopy
B. CT scan of the abdomen
C. Measurement of serum
antiendomysial antibodies
D. Stool for leukocytes, culture, ova,
and parasites
Annals of Internal Medicine 2 November 2010