In the Clinic

Acute Pancreatitis
Prevention Diagnosis Treatment Practice Improvement Tool Kit Patient Information CME Questions
Section Editors Darren Taichman, MD, PhD Barbara J. Turner MD, MSED Sankey Williams, MD Physician Writers Kapil Gupta, MD, MPH Bechien Wu, MD, MPH

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The content of In the Clinic is drawn from the clinical information and education resources of the American College of Physicians (ACP), including PIER (Physicians Information and Education Resource) and MKSAP (Medical Knowledge and Self-Assessment Program). Annals of Internal Medicine editors develop In the Clinic from these primary sources in collaboration with the ACPs Medical Education and Publishing Division and with the assistance of science writers and physician writers. Editorial consultants from PIER and MKSAP provide expert review of the content. 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

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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]

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

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

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Table 1. Causes of Acute Pancreatitis

More Common Causes Comments

Gallstones and microlithiasis Alcohol abuse Drugs ERCP Hyperlipidemia Hypercalcemia Genetic

Autoimmune pancreatitis Infections

Idiopathic

Most common cause Alcohol-related disease usually occurs only occurs after >510 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 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

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 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-

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 patients 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).

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, Grnbaek 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].

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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. 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

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).

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]

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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 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

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]

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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). 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

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

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.

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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 Constant colicky pain

Intestinal obstruction 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 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

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)

Urinalysis with active sediment 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

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
23. Schtte 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]

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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]

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).

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 diseases 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 g/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

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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

Admission measurements Mortality: 0%3% for <3 criteria, (1 point each): Age >55 years; 11%15% for 35 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)

Ranson criteria

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.

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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 Ransons 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
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 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

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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.

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

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, ONeill 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, Ransons, 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]

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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 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 -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.

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.

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, OKeefe 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]

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 improvemortality is high if this disorder is not treated aggressively (49). There are multiple approaches for debridement but no consensus on

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

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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.

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.

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.

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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 imagingespecially contrast-enhanced CT scanassist 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.

In the Clinic

Tool Kit
Acute Pancreatitis

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.

Patient Information
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 NIDDKs 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 Medicines 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.

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PIER Module

THINGS YOU SHOULD 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.

In the Clinic Annals of Internal Medicine

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?

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 Medicines MEDLINE Plus.

Patient Information

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.

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/L (13.5 109/L); aspartate aminotransferase, 131 U/L; alanine aminotransferase, 567 U/L; bilirubin (total), 1.1 mg/dL (18.8 mol/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?

and diffusely tender with hypoactive bowel sounds. The results of laboratory studies are follows: leukocyte count, 15 400/L (15.4 109/L); aspartate aminotransferase, 189 U/L; alanine aminotransferase, 151 U/L; bilirubin (total), 1.1 mg/dL (18.8 mol/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. 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/L (6.8 109/L); platelet count, 69 000/L (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. Enteral nutrition by nasojejunal feeding tube B. Intravenous imipenem C. Pancreatic dbridement 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 mol/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?

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

A. Colonoscopy B. CT scan of the abdomen C. Measurement of serum antiendomysial antibodies D. Stool for leukocytes, culture, ova, and parasites

Questions are largely from the ACPs 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.

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