nic Cli the In

Acute
Pancreatitis
Section Editors
Darren Taichman, MD, PhD
Barbara J. Turner MD, MSED
Sankey Williams, MD
Physician Writers
Kapil Gupta, MD, MPH
Bechien Wu, MD, MPH
In theClinic
In the Clinic
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
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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
A
cute pancreatitis is an acute inflammatory process of the pancreas
that can occur as an isolated event or relapsing episodes. Acute pancreatitis 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 presence 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 imaging 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 hospital admissions annually in the United States, and incidence has been increasing (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 significantly 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 pancreatitis results from alcohol consumption (4).
Prevention
1. Bradley EL. A clinically
based classification
system for acute pancreatitis: Summary of
the International
Symposium on Acute
Pancreatitis, Atlanta,
Ga; September 11-13,
1992. Arch
Surg;1993;128:586-90.
[PMID: 8489394]
2. Fagenholz PJ, Castillo
CF, Harris NS, Pelletier
AJ, Camargo CA Jr. Increasing United
States hospital admissions for acute
pancreatitis, 19882003. Ann Epidemiol.
2007;17:491-7.
[PMID: 17448682]
3. Lowenfels AB,
Maisonneuve P, Sullivan T. The changing
character of acute
pancreatitis: epidemiology, etiology, and
prognosis. Curr Gastroenterol Rep.
2009;11:97-103.
[PMID: 19281696]
4. Lankisch PG, Breuer
N, Bruns A, et al. Natural history of acute
pancreatitis: a longterm populationbased study. Am J
Gastroenterol.
2009;104:2797-805.
[PMID: 19603011]
5. Forsmark CE, Baillie J.
AGA Institute Clinical
Practice and Economics Committee.
AGA Institute technical review on acute
pancreatitis. Gastroenterology.
2007;132:2022-44.
[PMID: 17484894]
© 2010 American College of Physicians
Who is at increased risk for acute
pancreatitis?
Of the many causes of acute pancreatitis, gallstone disease (approximately
35% to 40% of cases) and excessive
alcohol consumption (approximately
30% of cases) dominate (5) (Table 1).
Gallstone disease is among the most
common disorders in the United
States, affecting an estimated 6.3 million men and 14.2 million women 20
to 74 years of age (6). It is difficult to
predict which patients with either
symptomatic or asymptomatic gallstones will develop pancreatitis. One
risk factor is the presence of stones in
the common bile duct (choledocholithiasis), especially small stones
(<5 mm) or microlithiasis comprising
stones that measure <2 mm because
they can obstruct the orifice of the
pancreatic duct at the level of the ampulla. Pancreatitis occurs when gallstones pass into the bile duct and
become trapped at the sphincter of
Oddi, stopping the flow of pancreatic
fluid containing digestive enzymes
into the duodenum. If the blockage
continues, activated enzymes build up
in the pancreas and cause severe inflammation. To reduce the risk for
such complications as pancreatitis, patients with symptomatic gallstones
usually have cholecystectomy and
ITC5-2
In the Clinic
those with common bile duct stones
have them removed by endoscopic
retrograde cholangiopancreatography
(ERCP), an imaging and therapeutic
technique that combines endoscopy
and fluoroscopy.
Alcohol-related pancreatitis usually
occurs after long-term (>5 years),
heavy alcohol consumption. Risk
increases with the amount of alcohol consumed, indicative of a direct
toxic effect on the pancreas when
the alcohol is metabolized. Because
only about 5% of alcoholics develop
pancreatitis, additional unknown
genetic or other factors must increase susceptibility. Smoking tobacco may play a role; it has been
reported to accelerate progression
of established alcoholic pancreatitis
(7). One study found an association
between high intake of beer (>14
drinks per week) and pancreatitis,
but not for wine or spirits (8).
Hypertriglyceridemia is another
important risk factor for pancreatitis, especially during pregnancy (9).
No clear risk profile can indicate
which patients with elevated
triglycerides will develop pancreatitis, but the complication occurs
rarely in the absence of significant
Annals of Internal Medicine
2 November 2010
Table 1. Causes of Acute Pancreatitis
More Common Causes
Comments
Gallstones and microlithiasis
Alcohol abuse
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 enhancement 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
sphincter of Oddi dysfunction, microlithiasis, and biliary sludge;
anatomical abnormalities
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
More likely if cysts involve the main duct, such as pancreatic
intraductal papillary mucinous tumor
Rare, occurs when some viable pancreatic tissue remains
Controversial as a cause so exclude all other causes first
Focal pancreatitis can indicate an underlying mass
Rare, clue is thickening of the duodenal wall
Such as ischemia related to bypass surgery
History is usually compelling
Endemic in some parts of Asia and Africa
Rare even in patients with 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 assessed 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
tis, the temporal association of
medication use and development
of the episode should be evaluated. The clinician needs to recognize that drug-induced pancreatitis can occur at any point in the
course of a medication regimen,
ranging from at or shortly after
initiation to an idiosyncratic
reaction after prolonged use. It
may be necessary to rechallenge
with the drug if it is critical for
the patient’s health. In general,
drug-induced acute pancreatitis is
less common than was previously
believed, and without strong evidence for drug-related pancreatitis, medications can usually be
continued (12).
In the Clinic
ITC5-3
6. Everhart JE, Khare M,
Hill M, Maurer KR.
Prevalence and ethnic differences in
gallbladder disease in
the United States.
Gastroenterology.
1999;117:632-9.
[PMID: 10464139]
7. Yadav D, Whitcomb
DC. The role of alcohol and smoking in
pancreatitis. Nat Rev
Gastroenterol Hepatol. 2010;7:131-45.
[PMID: 20125091]
8. Kristiansen L, Grønbaek M, Becker U, Tolstrup JS. Risk of pancreatitis according to
alcohol drinking
habits: a populationbased cohort study.
Am J Epidemiol.
2008;168:932-7.
[PMID: 18779386]
9. Ewald N, Hardt PD,
Kloer HU. Severe hypertriglyceridemia
and pancreatitis:
presentation and
management. Curr
Opin Lipidol.
2009;20:497-504.
[PMID: 19770656]
10. Yadav D, Pitchumoni
CS. Issues in hyperlipidemic pancreatitis. J Clin Gastroenterol. 2003;36:54-62.
[PMID: 12488710]
11. Badalov N, Baradarian R, Iswara K, Li J,
Steinberg W, Tenner
S. Drug-induced
acute pancreatitis:
an evidence-based
review. Clin Gastroenterol Hepatol.
2007;5:648-61.
[PMID: 17395548]
12. Nitsche CJ, Jamieson
N, Lerch MM, Mayerle JV. Drug induced
pancreatitis. Best
Pract Res Clin Gastroenterol.
2010;24:143-55.
[PMID: 20227028].
© 2010 American College of Physicians
An important iatrogenic risk factor
for development of acute pancreatitis is ERCP. The risk for acute pancreatitis related to ERCP ranges
from 5% to 20%, depending on
physician-related factors, such as
the level of experience performing
the procedure, and patient characteristics, 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 avoidance of ERCP, unless clearly indicated, will decrease the risk for
acute pancreatitis resulting from
this procedure.
13. Cheng CL, Sherman
S, Watkins JL, et al.
Risk factors for postERCP pancreatitis: a
prospective multicenter 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 patients with suspected sphincter of Oddi
dysfunction but normal manometry results. Gastrointest
Endosc. 2008;67:
255-61.
[PMID: 18028920].
15. Nordback I, Pelli H,
Lappalainen-Lehto R,
et al. The recurrence
of acute alcohol-associated pancreatitis
can be reduced: a
randomized controlled trial. Gastroenterology.
2009;136:848-55.
[PMID: 19162029]
© 2010 American College of Physicians
Other less common causes of
acute pancreatitis are listed in
Table 1. Rare causes of unexplained acute pancreatitis include
cancer; mucinous neoplasm; remote history of trauma; infections
caused by parasites, such as toxoplasmosis 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 pancreatitis has been identified, efforts 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 consumption has been identified as the
cause, patients should be evaluated
for alcohol abuse or dependence.
The patient should receive intensive counseling about the exigency
of abstaining from alcohol to
avoid repeated episodes of acute
ITC5-4
In the Clinic
pancreatitis or chronic pancreatitis, as well as the other wellknown complications of alcohol
abuse and dependence. In this situation, one brief alcohol counseling 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 alcohol reduction and social stressor counseling 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 repeated alcohol counseling.
In addition, referral to alcohol specialty treatment will improve abstinence, 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 pancreatitis because of hypertriglyceridemia 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 triglyceride 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 secondary 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 related to hypercalcemia is best prevented through treatment of the underlying
cause. Iatrogenic acute pancreatitis due to ERCP can be reduced by careful patient selection and possibly through placement of a pancreatic duct stent.
CLINICAL BOTTOM LINE
Diagnosis
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 described 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 associated 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 cholecystectomy for gallstones in a person
with no or minimal use of alcohol
increases the likelihood of pancreatitis due to retained gallstones.
Careful history should assess for
hyperlipidemia, abdominal trauma,
similar previous episodes, or prior
ERCP. A detailed list of medications 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 hydration status and indicate the
severity of pancreatitis. Tachycardia
and hypotension represent intravascular depletion secondary to fluid
2 November 2010
Annals of Internal Medicine
sequestration seen in more severe
cases. Jaundice indicates biliary tree
obstruction. The clinician should
perform a careful abdominal examination focusing especially on auscultation 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 indicative 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, hypoxemia, electrolyte imbalance, or
alcohol use. Multiorgan dysfunction signifies a more severe episode
with complications, such as pancreatic necrosis.
A patient with gallstones and a history of fever, chills, and/or rigors
suggests ascending cholangitis, but
these symptoms may be due only to
the inflammatory process associated with acute pancreatitis.
What laboratory tests are useful
in the evaluation of acute
pancreatitis?
Elevation of the serum amylase
and/or lipase levels at least three
times the upper limit of normal is a
key component of diagnosing acute
pancreatitis. Measurement of serum
amylase levels has good sensitivity
but low specificity, signifying a high
false-positive rate (18). Other causes
In the Clinic
ITC5-5
16. Trivedi CD, Pitchumoni CS. Drug-induced pancreatitis:
an update. J Clin
Gastroenterol.
2005;39:709-16.
[PMID: 16082282]
17. Third Report of the
Expert Panel on Detection, Evaluation,
and Treatment of
High Blood Cholesterol in Adults (ATP
III Final Report). Circulation.
2002;106:3143-421.
[PMID: 12485966].
18. Yadav D, Agarwal N,
Pitchumoni CS. A
critical evaluation of
laboratory tests in
acute pancreatitis.
Am J Gastroenterol.
2002;97:1309-18.
[PMID: 12094843]
© 2010 American College of Physicians
of elevated serum amylase levels include disorders of salivary glands and
fallopian tubes, intestinal ischemia,
perforated peptic ulcer, and chronic
renal insufficiency. To improve specificity, the level of the serum amylase
or lipase needs to be three times normal. 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 elevated 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 intensive care unit (ICU) (21). Simultaneous measurement of amylase and
lipase levels does not seem to improve diagnostic accuracy (18).
19. Liu KJ, Atten MJ,
Lichtor T, et al.
Serum amylase and
lipase elevation is associated with intracranial 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 pancreatic enzymes as related 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, Goldman, L, Hollander H.
Hospital Medicine.
Philadelphia: Wolters
Kluwer Health; 2005.
© 2010 American College of Physicians
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 available laboratory marker of severity.
Liver enzymes should also be routinely checked. Elevated liver enzymes (alanine transaminase) >150
IU/L has a 95% positive predictive
value and a specificity of 96% but
sensitivity of less than 50%; the accuracy of the aspartate transaminase
is similar (22). Elevations can suggest gallstone pancreatitis. Triglyceride 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 inflammation alone or point to an
underlying infectious process. Increased 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 hemorrhagic pancreatitis. Patients
with pancreatitis may also develop
disseminated intravascular coagulopathy, 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, vomiting, and fever has a broad differential
(Table 2). Although peptic ulcer perforation often mimics this presentation, it is distinguished by free air
seen on imaging studies. Acute
cholecystitis, symptomatic choledocholithiasis, and cholangitis are typically 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, colicky abdominal pain, and an obstructive bowel pattern on imaging. They
may also have elevated serum amylase levels but these levels are usually
lower than those associated with
acute pancreatitis. Mesenteric vascular obstruction should be suspected
in patients with underlying vascular
or cardiac disease. Pain associated
with nonobstructive mesenteric ischemia 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
Characteristics
Findings
Perforated viscus, especially peptic ulcer
Acute cholecystitis and biliary colic
Sudden onset of pain that increases over 30-60 min
Epigastric or right upper quadrant pain that radiates
to right shoulder or shoulder blade
Intestinal obstruction
Constant colicky pain
Intraperitoneal air present
Liver enzymes often elevated; ultrasonography
may show thickened gallbladder, pericholecystic
fluid
Obstructive pattern can be seen on CT scan or
abdominal series
Discrepancy between symptoms (severe pain) and
examination (benign abdominal examination)
Mesenteric vascular occlusion
Classic triad is postprandial abdominal pain,
weight loss, and abdominal bruit
Dissecting aortic aneurysm
Sudden onset; pain may radiate to the lower
extremities
Renal colic
Flank pain radiates to the genitals; dysuria may
be present
Myocardial infarction
Upper abdominal or chest pain
Connective tissue disorders with vasculitis Acute pancreatitis can be due to vasculitis
Appendicitis
Ectopic pregnancy
Pneumonia
Urinalysis with active sediment
Pain may start in epigastrium or periumbilical then
migrate to right lower quadrant
Sudden onset of pain; menstrual abnormalities
often precede pain
Fever, malaise, and other respiratory symptoms
(dyspnea, cough, sputum production, chest pain)
usually present
Electrocardiography usually abnormal
Other signs of vasculitis usually present (skin,
joint, eye, and kidney involvement)
Ultrasonography and and CT aid in diagnosis
Rapid drop in hematocrit and intraperitoneal
pelvic fluid on imaging should raise suspicion
Changes on physical examination of the chest
and abnormalities on chest X-ray possibly due to
ARDS or pleural effusion
AP = acute pancreatitis; ARDS = acute respiratory distress syndrome; CT = computed tomography; HCT = hematocrit.
causes of upper abdominal pain that
should be considered in the differential 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 radiograph may show nonspecific
signs of acute pancreatitis, such as a
sentinel loop (localized ileus involving the jejunum), colon cutoff sign
(isolated distention of the transverse colon), duodenal distention
with air and fluid, and pleural effusion 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
free air showing a perforated viscus
as the cause of pain.
However, the initial imaging study
of choice is ultrasonography of the
right upper quadrant because it is
readily available, noninvasive, inexpensive, and relatively sensitive
(95%) for diagnosing gallstone disease. The presence of gallstones
and/or dilatation of the common bile
duct supports stones as the cause of
acute pancreatitis. However, the distal common bile duct and pancreas
are frequently obscured by overlying
bowel gas and limit the sensitivity of
ultrasonography for diagnosing gallstone-associated pancreatitis.
In this case, a contrast-enhanced,
thin-sliced, triple-phase computed
tomography (CT) scan provides an
In the Clinic
ITC5-7
23. Schütte K, Malfertheiner P. Markers for
predicting severity
and progression of
acute pancreatitis.
Best Pract Res Clin
Gastroenterol.
2008;22:75-90.
[PMID: 18206814]
24. Wu BU, Johannes RS,
Sun X, Conwell DL,
Banks PA. Early
changes in blood
urea nitrogen predict mortality in
acute pancreatitis.
Gastroenterology.
2009;137:129-35.
[PMID: 19344722]
25. Saif MW. DIC secondary to acute
pancreatitis. Clin Lab
Haematol.
2005;27:278-82.
[PMID: 16048498]
26. Nichols MT, Russ PD,
Chen YK. Pancreatic
imaging: current and
emerging technologies. Pancreas.
2006;33:211-20.
[PMID: 17003640]
© 2010 American College of Physicians
Atlanta Classification of Acute
Pancreatitis*
Severe acute pancreatitis
• Organ failure (systolic blood pressure
<90 mm Hg, PaO2
<60 mm Hg, creatinine level
>2 mg/dL, gastrointestinal bleeding
> 500 mL/24 h)
• Local complications (pancreatic
necrosis, pseudocyst, or abscess)
• ≥3 Ranson criteria.
Mild acute pancreatitis
• Minimal organ dysfunction
• Uneventful recovery
• Lacks features of severe acute
pancreatitis.
Notes: Consider determining APACHE II
score and measuring C-reactive protein
levels. Be aware of limited accuracy of
severity prediction.
*From reference 33.
27. Lankisch PG, Struckmann K, Assmus C,
Lehnick D, Maisonneuve P, Lowenfels
AB. Do we need a
computed tomography examination in
all patients with
acute pancreatitis
within 72 h after admission to hospital
for the detection of
pancreatic necrosis?
Scand J Gastroenterol. 2001;36:432-6.
[PMID: 11336171]
28. Arvanitakis M, Delhaye M, De Maertelaere V, et al. Computed tomography
and magnetic resonance imaging in
the assessment of
acute pancreatitis.
Gastroenterology.
2004;126:715-23.
[PMID: 14988825]
29. Makary MA, Duncan
MD, Harmon JW, et
al. The role of magnetic resonance
cholangiography in
the management of
patients with gallstone pancreatitis.
Ann Surg.
2005;241:119-24.
[PMID: 15621999]
30. Liu CL, Lo CM, Chan
JK, et al. Detection of
choledocholithiasis
by EUS in acute pancreatitis: a prospective evaluation in
100 consecutive patients. Gastrointest
Endosc. 2001;54:32530. [PMID: 11522972]
31. Lai R, Freeman ML,
Cass OW, Mallery S.
Accurate diagnosis
of pancreas divisum
by linear-array endoscopic ultrasonography. Endoscopy.
2004;36:705-9.
[PMID: 15280976]
© 2010 American College of Physicians
excellent image of the pancreas and
can identify choledocholithiasis or
other causes of abdominal pain. CT
scanning can also be useful to assess
the severity of the pancreatitis and in
identifying complications, such as
necrosis (infected or not), pseudocyst
formation, and diffuse pancreatic fluid collection (27). However, early in
the course of disease a CT scan may
not show signs of pancreatitis or its
associated complications. In addition, intravenous contrast may accelerate renal injury. When these factors are a concern, magnetic
resonance imaging (MRI) offers an
alternative at greater cost to diagnose
and evaluate the severity of acute
pancreatitis (28).
Among newer but even more costly
imaging modalities, the noninvasive
magnetic resonance cholangiopancreatography (MRCP) has high
sensitivity (>90%) for choledocholithiasis and can identify other
anatomical abnormalities, such as
pancreas divisum, pancreatic duct
abnormalities, and mucinous neoplasm in the pancreas (29). It can
be useful to exclude the presence of
a retained stone or debris if there is
a high index of clinical suspicion.
Secretin-enhanced MRI is useful
for evaluating pancreatic function
and anatomy when the patient is
suspected of having underlying
chronic pancreatitis. However, since
secretin stimulates pancreatic secretion, it should not be obtained during an acute episode because it
could worsen the disease.
Endoscopic ultrasonography is both
sensitive and specific in identifying
small (e.g., ≤5 mm) gallstones in
the bile ducts (30) and can identify
anatomical abnormalities of the
pancreas. Although it is more invasive than MRI, it can detect smaller
stones and can be used when MRI
is not possible (e.g., in critically ill
patients or when it is contraindicated, such as in patients with a cardiac pacer) (31, 32).
ITC5-8
In the Clinic
Which factors help to predict the
prognosis of a patient with acute
pancreatitis?
Patients should be stratified by risk
for severe morbidity and death related to acute pancreatitis because of
the disease’s protean manifestations,
unpredictable course, and the need
to identify persons who require intensive care. The Atlanta Classification of Acute Pancreatitis was
developed in 1992 to standardize
what was a heterogeneous set of criteria to diagnose the disease and to
assess severity (1). However, because
of a changing understanding of the
pathophysiology and epidemiology
of acute pancreatitis, in 2008 a revision was proposed to the Atlanta
Classification (still being reviewed
with final approval expected by
2011) that recognizes 2 phases of the
disease that were not appreciated by
the original classification (see the
Box) (33). First, there is a peak in
mortality usually within the first
week of onset and another 2 to 6
weeks after onset. In the first week,
the severity of the disease is usually
reflected by the extent of organ failure. After that, mortality can be predicted more by the presence of
pancreatic necrosis and infection.
Therefore, when a patient first
presents, clinicians need to be alert
to the possibility of organ failure
(34). As expected, progression from
single to multiorgan failure is a predictor of increased mortality (35).
Coagulopathy bodes poorly for patients as indicated by platelet count
<100 000/mm3, fibrinogen <100
mg/dL, and fibrin split products
>80 µg/mL. Similarly, low serum
calcium levels (≤ 7.5 mg/dL) carry
a poor prognosis.
The Atlanta symposium also
identified the development of local complications (necrosis and
abscess and pseudocyst formation)
as indicative of severe acute pancreatitis. Pancreatic necrosis is
demonstrated by poor perfusion
and nonenhancement on CT scan
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 develops over a period of weeks (by
definition >4 wk). Infection of
either pancreatic necrosis or a
pseudocyst can lead to abscess formation. 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
Predictors
Outcomes Based on Score
Comments
Ranson criteria
Admission measurements
Mortality: 0%–3% for <3 criteria,
(1 point each): Age >55 years; 11%–15% for 3–5 criteria,
3
leukocyte count >16 000/mm ; and 40% for ≥6 criteria (36)
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
Acute Physiology and Chronic Daily: Based on diverse variables, Mortality: <4% for a score <8,
Health Evaluation
including age, physiology, and 11%–18% for a score ≥8 (39)
(APACHE) II scoring system
long-term health; equation
available at www.sfar.org/
scores2/apache22.html#calcul;
Adding BMI to APACHE-II
(the APACHE-O score)
increases discrimination (1 point
added for BMI 26-30; 2 points
for BMI >30) (38)
Modified Glasgow prognostic
At 48 h after admission (1 point Severe episode: score ≥3 within
criteria (Imrie scoring system) each): PaO2 < 60 mm Hg/7.9 kPa; 48 h
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
Bedside Index for Severity in
Within 24 h after presentation
Mortality: <1% in the lowest
Acute Pancreatitis (BISAP)
(1 point each): BUN >25 mg/dL; risk group and >20% in the
score
impaired mental status; systemic highest risk group.
inflammatory response syndrome
(see text for definition); age
>60 y; presence of pleural
effusion (41)
Modified CT severity index
CT scan assessment of
Correlated with length of stay
pancreatic inflammation and
and clinical complications (44)
necrosis, plus assessment of
extrapancreatic complications (43)
Scoring on admission and at 48 h after
presentation; limited predictive power reported in
meta-analysis (37)
Requires data usually only available when
patient is in ICU; an increasing APACHE-II
score in the first few days of hospitalization
indicates worsening severity whereas the opposite indicates improvement (38); APACHE-II
and APACHE-III have a similar performance
Takes 48 h to complete; similar performance to
APACHE-III (40)
Assessed at 24 h; prognostic accuracy similar to
other scoring systems (42)
Studied in small patient populations
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
32. Sedlack R, Affi A,
Vazquez-Sequeiros E,
Norton ID, Clain JE,
Wiersema MJ. Utility
of EUS in the evaluation of cystic pancreatic lesions. Gastrointest Endosc.
2002;56:543-7.
[PMID: 12297771]
33. Acute Pancreatitis
Classification Working Group. Revision
of the Atlanta classification of acute
pancreatitis (3rd revision). www.pancreasclub.com/resources/AtlantaClass
ification.pdf. Accessed 16 September 2010.
34. Johnson CD, AbuHilal M. Persistent organ failure during
the first week as a
marker of fatal outcome in acute pancreatitis. Gut.
2004;53:1340-4.
[PMID: 15306596]
35. Brown A, Orav J,
Banks PA. Hemoconcentration is an early
marker for organ failure and necrotizing
pancreatitis. Pancreas. 2000;20:36772. [PMID: 10824690]
36. Blum T, Maisonneuve P, Lowenfels
AB, Lankisch PG. Fatal outcome in acute
pancreatitis: its occurrence and early
prediction. Pancreatology. 2001;1:23741. [PMID: 12120201]
37. De Bernardinis M, Violi V, Roncoroni L,
Boselli AS, Giunta A,
Peracchia A. Discriminant power and information content of
Ranson’s prognostic
signs in acute pancreatitis: a meta-analytic study. Crit Care
Med. 1999;27:227283. [PMID: 10548220]
38. Banks PA, Freeman
ML. Practice Parameters Committee of
the American College of Gastroenterology. Practice
guidelines in acute
pancreatitis. Am J
Gastroenterol.
2006;101:2379-400.
[PMID: 17032204]
39. Johnson CD, Toh SK,
Campbell MJ. Combination of APACHEII score and an obesity score
(APACHE-O) for the
prediction of severe
acute pancreatitis.
Pancreatology.
2004;4:1-6.
[PMID: 14988652]
and III) scale; the Modified Glasgow prognostic criteria (also known
as the Imrie scoring system); Bedside Index for Severity in Acute
Pancreatitis (BISAP) score; and the
Modified CT Severity Index.
It is important to note that neither
serum amylase nor lipase levels are
predictive of the severity of acute
pancreatitis. On the other hand,
C-reactive protein has been widely
used to predict the severity of acute
pancreatitis (18), and in critically ill
patients, it has been shown to be
associated with increased risk for
organ failure and death (46). Procalcitonin has been associated with
pancreatic infection and can be
used as an indicator of the need for
fine-needle aspiration of pancreatic
necrosis (23).
What are the indications for
hospitalization and for intensive
care for a patient with acute
pancreatitis?
Patients with acute pancreatitis
should be hospitalized until they have
been observed for a sufficient period
to evaluate disease severity and progression. Essential management
includes aggressive intravenous fluid
resuscitation with no fluids or solids
by mouth. Patients often require pain
management with intravenous medications, typically opiates are used and
must be monitored for side effects,
such as respiratory depression. Stable
patients having a mild episode who
have a history of multiple episodes
can sometimes be managed on an
outpatient basis.
Such tests as ERCP are usually done
in an inpatient setting when indicated. Severe acute pancreatitis requires
close inpatient monitoring, and the
patient should be transferred to ICU
if organ failure develops (47). In elderly patients with underlying cardiovascular disease, aggressive fluid
resuscitation should be administered
in an ICU and may require a central
venous catheter for more accurate
fluid monitoring. Transfer to a specialized monitored unit, although
not necessarily an ICU, should be
considered for patients with high
body mass index (>30), decreased
urine output < 50 mL/h, tachycardia
(pulse rate > 120 beats/min), signs of
encephalopathy, and/or need for additional narcotics (39).
Diagnosis... In acute pancreatitis, diagnosis is based on the presence 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 imaging tests showing characteristic
findings of acute pancreatitis. Ultrasonography of the right upper quadrant may reveal stones or biliary duct dilatation and CT scan can be useful to assess for pancreatic edema, necrosis, or pseudocyst formation. MRI offers an alternative but is more
costly. Assessing the severity of the attack of acute pancreatitis using clinical laboratory parameters; imaging; and standard measurements, such as APACHE-II, BISAP, CT
severity index, or Ranson criteria, can guide management. Acute pancreatitis should
be managed in the inpatient setting with rare exceptions and patients with organ
failure or severe comorbid conditions should be treated in the ICU.
CLINICAL BOTTOM LINE
Treatment
© 2010 American College of Physicians
How should clinicians manage
fluids in a patient with acute
pancreatitis?
Fluid resuscitation is a critical component of management of patients
with acute pancreatitis because they
ITC5-10
In the Clinic
can experience a significant loss of
intravascular volume due to third
spacing and increased permeability
from release of inflammatory mediators. Compromised intravascular volume can lead to decreased perfusion
Annals of Internal Medicine
2 November 2010
of the pancreas and such complications as pancreatic necrosis and renal
failure. Fluid administration should
be guided by vital signs, urine output, and change in hematocrit at admission, 12 hours, and 24 hours
(39). Increasing hematocrit or BUN
is a poor prognostic sign and indicates worsening severity.
How should clinicians manage the
nutritional needs of a patient
with acute pancreatitis?
In mild acute pancreatitis, nutritional support is not necessary.
Once pain has diminished along
with nausea and vomiting, oral nutrition can be started. It begins with
clear liquids and clinical monitoring
for change in pain and symptoms of
nausea and vomiting. Resolution of
imaging findings and normalization
of amylase and lipase may not occur
for up to a week, so the diet should
be advanced based on how the patient feels. There is no clear consensus about fat restriction.
Patients with moderate or severe
pancreatitis must usually abstain
from solids and liquids for several
days to weeks. Although mortality
rates do not differ substantially between parenteral and enteral nutrition, the latter has been shown to
reduce the rate of infection, surgical
interventions, and noninfectious
complications (48). United Kingdom guidelines for management of
acute pancreatitis recommend enteral nutrition for all patients with
severe acute pancreatitis, but state
that the nasogastric route is preferred for feeding because it is effective in ≥ 80% of cases (49).
However, the nasojejunal route is
increasingly being used in the
United States. Although tube
placement is more difficult, enteral
feeding beyond the ligament of
Treitz may decrease the risk for infectious complications that can occur with feeding methods in which
the small bowel can be affected by
edema and permeability from inflammatory mediators is increased.
2 November 2010
Annals of Internal Medicine
However, studies comparing nasogastric with nasojejunal feeding
have not shown significant differences in outcomes, but larger comparative studies are required before
practice recommendations are
changed.
A meta-analysis of 6 studies showed a
lower incidence of infections, reduced
surgical intervention and shorter hospital
stay in patients with acute pancreatitis
receiving nasojejunal feeding (50). In one
study, nasojejunal feeding was associated with a shorter hospital stay and fewer
complications than parental nutrition
(sepsis, 4% vs. 33%; metabolic complications, 15% vs. 52%, respectively), and a
savings of $2362 (51).
An ongoing National Institutes of
Health multi-center trial, called the
Study of Nutrition in Acute Pancreatitis (SNAP), is evaluating nasogastric vs. nasojejunal feeding.
Difficulty placing or maintaining a
nasojejunal tube also requires parenteral nutrition. Notably, parenteral nutrition may be required in
some critically ill patients as well as
those with severe ileus.
What other supportive care may be
beneficial for acute pancreatitis?
Oxygen may reduce the acute respiratory distress syndrome that
can occur in the early stages of
acute pancreatitis. Pain management is another key aspect of
treatment. Due to the severity of
pain with acute pancreatitis and
the inability to take pills, parenteral narcotic analgesics are essential. Opiates are usually administered every 2 to 4 hours. A
patient-controlled analgesia pump
offers an alternative when boluses
of pain medications provide inadequate pain control. Morphine has
been theoretically implicated in
increasing pressure in the sphincter of Oddi and potentially decreasing pancreatic and biliary
flow into the small bowel lumen,
but this has not been confirmed in
clinical studies. Meperidine, morphine and hydromorphone are
In the Clinic
ITC5-11
40. Chatzicostas C,
Roussomoustakaki
M, Vlachonikolis IG,
et al. Comparison of
Ranson, APACHE II
and APACHE III scoring systems in acute
pancreatitis. Pancreas. 2002;25:331-5.
[PMID: 12409825].
41. Blamey SL, Imrie CW,
O’Neill J, Gilmour
WH, Carter DC. Prognostic factors in
acute pancreatitis.
Gut. 1984;25:1340-46.
42. Wu BU, Johannes RS,
Sun X, et al. The early prediction of mortality in acute pancreatitis: a large
population-based
study. Gut.
2008;57:1698-703.
[PMID: 18519429] 43.
Papachristou GI,
Muddana V, Yadav D,
et al. Comparison of
BISAP, Ranson’s,
APACHE-II, and CTSI
scores in predicting
organ failure, complications, and mortality in acute pancreatitis. Am J
Gastroenterol.
2010;105:435-41;
quiz 442.
[PMID: 19861954]
44. Mortele KJ, Wiesner
W, Intriere L, et al. A
modified CT severity
index for evaluating
acute pancreatitis:
improved correlation with patient
outcome. AJR Am J
Roentgenol.
2004;183:1261-5.
[PMID: 15505289]
45. Petrov MS,
Shanbhag S,
Chakraborty M, et al.
Organ failure and infection of pancreatic
necrosis as determinants of mortality in
patients with acute
pancreatitis. Gastroenterology. 2010
Jun 9. [Epub ahead
of print]
[PMID: 20540942]
46. Lobo SM, Lobo FR,
Bota DP, et al. C-reactive protein levels
correlate with mortality and organ failure in critically ill patients. Chest.
2003;123:2043-9.
[PMID: 12796187]
47. Zhang XP, Wang L,
Zhou YF. The pathogenic mechanism of
severe acute pancreatitis complicated
with renal injury: a
review of current
knowledge. Dig Dis
Sci. 2008;53:297-306.
[PMID: 17597411]
48. Frossard J-L, Steer
ML, Pastor CM.
Acute pancreatitis.
Lancet.
2008;371:143-52.
[PMID: 18191686]
© 2010 American College of Physicians
more commonly used narcotics for
pain control in acute pancreatitis.
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 parenteral nutrition for
severe pancreatitis: a
randomized controlled trial and
health technology assessment. 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 prophylaxis against infection of pancreatic
necrosis in acute
pancreatitis.
Cochrane Database
Syst Rev. 2010 May
12;5:CD002941.
[PMID: 20464721]
53. Carter CR, McKay CJ,
Imrie CW. Percutaneous necrosectomy
and sinus tract endoscopy in the management 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 invasive retroperitoneal
pancreatic necrosectomy. 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 pancreatitis. N Engl J Med.
2010;362:1491-502.
[PMID: 20410514]
© 2010 American College of Physicians
What is the role of antibiotics in
the management of patients with
acute pancreatitis?
Antibiotics are not currently recommended for mild interstitial
pancreatitis or even for moderate to
severe pancreatitis with sterile
necrosis. Studies of prophylactic
administration of antibiotics to decrease infectious complications
have been largely nonsupportive.
A recent Cochrane review found no benefit
of antibiotics to prevent infection of pancreatic necrosis or mortality, with the possible exception of the β-lactam imipenem,
that was associated with a significant decrease in pancreatic infection (52). The reviewers concluded that better-designed
studies would be required before antibiotic
prophylaxis could be recommended.
However, antibiotics are definitely required to treat ascending cholangitis,
infected pancreatic necrosis, or an infected pseudocyst. When the patient
seems to be septic or infection is suspected, a fever workup should be conducted with cultures and a chest
X-ray. If needed, CT-guided needle
aspiration of a necrotic area of the
pancreas should be cultured for bacteria and fungi. If the workup is negative, 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 organisms, 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 response and surgical debridement
should be considered when the patient 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 percutaneous nephroscope offers an alternative (53, 54).
A recent multicenter study randomly assigned 88 patients with necrotizing pancreatitis and suspected or confirmed infected necrotic tissue to primary open
necrosectomy or a step-up treatment approach (percutaneous drainage followed
by minimally invasive retroperitoneal
necrosectomy if needed) (55). Major complications or death occurred in 69% of patients 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 considered in advanced centers with expertise in these techniques.
When should clinicians consider
consultation with a gastroenterologist, a surgeon, or an
interventional radiologist?
For patients who have mild acute
pancreatitis with a known cause,
consultation is usually unnecessary. However, if the cause is unclear or pancreatitis tends to recur,
a gastroenterology consult may be
useful. In patients with more severe attacks, gastroenterology
consultation can assist with management and monitoring for
complications. Further, when gallstone pancreatitis is suspected,
consultation for ERCP may be
necessary, as noted below.
When a patient develops necrotizing
pancreatitis or abscesses or pseudocysts, or pancreatic fluid collection is
necessary, both a surgeon and a gastroenterologist should be consulted.
These patients usually require a team
approach because surgical, endoscopic, and percutaneous drainage methods should be considered. Endoscopic
drainage of pseudocysts has been associated with better outcomes (57).
Because of limited data on endoscopic
Annals of Internal Medicine
2 November 2010
drainage of pancreatic necrosis but
especially when infected, surgical intervention may be required. An interventional radiology consultation may
be useful for percutaneous CT-guided
catheter drainage of infected pancreatic pseudocysts (58). A trial of percutaneous drainage followed by
minimally invasive retroperitoneal
necrosectomy, if necessary, versus surgery with open necrosectomy found
that the minimally invasive approach
had fewer major complications or
death (55). When gallstones are present, patients need to be evaluated by a
surgeon for cholecystectomy.
What are the indications for ERCP?
Presence of a retained bile duct
stone seen on imaging is an indication for ERCP to perform biliary sphincterotomy and stone
removal. Urgent ERCP is indicated if cholangitis is suspected.
In the absence of these criteria,
studies have found that early
ERCP was associated with increased complications.
A meta-analysis of 7 randomized trials
found no significant reduction in overall
complications or mortality from early
ERCP in patients with predicted mild or severe acute biliary pancreatitis without
acute cholangitis (59).
Several studies have shown an advantage of ERCP in pancreatitis
from obstructive biliary disease. Patients presenting with complicated
acute pancreatitis due to a disrupted
pancreatic duct with a leak may also
benefit from ERCP and placement
of a pancreatic duct stent.
Treatment... Aggressive fluid resuscitation is the most important approach to manage
acute pancreatitis. Appropriate pain control and supportive care with oxygen supplementation are additional basic measures. In patients with a prolonged course, enteral
nutrition is preferred to parenteral nutrition whenever possible. Antibiotics are only
recommended for a documented infectious process or if there is ≥30% necrosis. If the
cause of acute pancreatitis is unclear or ERCP reveals retained gallstones, consultation
by a gastroenterologist is indicated. A team approach with both a gastroenterologist
and surgeon is indicated for patients with organized necrosis (sterile or infected),
pseudocyst, or abscess. In some cases, an interventional radiologist should be consulted for specialized diagnostic and therapeutic imaging techniques.
CLINICAL BOTTOM LINE
What do professional
organizations recommend with
regard to the care of patients
with acute pancreatitis?
A recent summary has assessed the
quality of 30 clinical guidelines regarding management of acute pancreatitis that were published between
1988 and 2008 (60). Among the
more recent U.S. clinical guidelines,
those from the American Thoracic
Society (2004), American College of
Gastroenterology (2006), and the
American Gastroenterological Association (2007) earned high quality
scores (5, 39, 61). The Box summarizes the most recent 2 guidelines.
2 November 2010
Annals of Internal Medicine
What is the role of patient
education in the management of
acute pancreatitis?
Patient education plays an important role in preventing recurrent
acute pancreatitis. Lifestyle measures, such as cessation of alcohol
consumption, are critical. Education about the risks of certain
medications if implicated in the
initial episode should also be provided with careful monitoring.
Dietary modification and adherence to lipid-lowering medications are both necessary in
patients with pancreatitis due to
hypertriglyceridemia.
In the Clinic
ITC5-13
Practice
Improvement
56. Gupta K, Freeman
ML. Disconnected
pancreatic duct with
pancreas necrosis,
treated with transgastric debridement
and pancreatic duct
stent. Clin Gastroenterol Hepatol.
2010;8:e51.
[PMID: 20005979]
57. Seewald S, Ang TL,
Teng KC, Soehendra
N. EUS-guided
drainage of pancreatic pseudocysts, abscesses and infected
necrosis. Dig Endosc.
2009;21 Suppl 1:S615. [PMID: 19691738]
58. Maniatis P, Delis S,
Fagrezos D, et al. The
interventional radiological procedures of
the infections of
pancreas. Infect Disord Drug Targets.
2010;10:5-8.
[PMID: 20180752]
59. Petrov MS, van
Santvoort HC,
Besselink MG, et al.
Early endoscopic retrograde cholangiopancreatography
versus conservative
management in
acute biliary pancreatitis without
cholangitis: a metaanalysis of randomized trials. Ann Surg.
2008;247:250-7.
[PMID: 18216529]
60. Loveday BPT, Srinivasa S, Vather R, et
al. High quantity and
variable quality of
guidelines for acute
pancreatitis: a systematic review. Am J
Gastroenterol.
2010;105:1466-76.
61. Nathens AB, Curtis
JR, Beale RJ et al.
Management of the
critically ill patient
with severe acute
pancreatitis. Crit
Care Med.
2004;32:2524-36.
© 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
In the Clinic
PIER Module
In the Clinic
• 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.
Tool Kit
www.pier.acponline.org
Access the PIER module on acute pancreatitis. PIER modules provide evidencebased, 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.
Acute
Pancreatitis
www.annals.org/intheclinic/toolkit-acutepancreatitis.html
Access the Patient Information material that appears on the following page
for duplication and distribution to patients.
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.
Patient Information
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
KNOW ABOUT ACUTE
PANCREATITIS
In the Clinic
Annals of Internal Medicine
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.
• 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 cholangiopancreatography (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.
• 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.
Patient Information
How is it diagnosed?
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
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.
A.
B.
C.
D.
Fiber
Cholestyramine
Loperamide
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 aminotransferase, 191 U/L; alanine aminotransferase, 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
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?
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
ITC5-16
In the Clinic
Annals of Internal Medicine
2 November 2010