Clinical manifestations and diagnosis of acute pancreatitis Author Santhi Swaroop Vege, MD Section Editor David C Whitcomb, MD,

PhD Deputy Editor Shilpa Grover, MD, MPH Disclosures All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jul 2013. | This topic last updated: may 6, 2013. INTRODUCTION Acute pancreatitis is an acute inflammatory process of the pancreas. Acute pancreatitis should be suspected in patients with severe acute upper abdominal pain but requires biochemical or radiologic evidence to establish the diagnosis. This topic will review the clinical manifestations and diagnosis of acute pancreatitis. The etiology, pathogenesis, assessment of severity, and management of acute pancreatitis are discussed separately. (See "Etiology of acute pancreatitis" and "Pathogenesis of acute pancreatitis" and "Predicting the severity of acute pancreatitis" and"Treatment of acute pancreatitis".) CLASSIFICATION Acute pancreatitis is divided into the following: Mild acute pancreatitis, which is characterized by the absence of organ failure and local or systemic complications Moderately severe acute pancreatitis, which is characterized by transient organ failure (resolves within 48 hours) and/or local or systemic complications without persistent organ failure (>48 hours) Severe acute pancreatitis, which is characterized by persistent organ failure that may involve one or multiple organs

The complications of acute pancreatitis are reviewed below. (See 'Natural history and complications' below.) The classification and predictors of severity are reviewed in more detail elsewhere. (See "Predicting the severity of acute pancreatitis".) CLINICAL FEATURES Most patients with acute pancreatitis have acute onset of persistent, severe epigastric abdominal pain [1]. In some patients, the pain may be in the right upper quadrant or, rarely, confined to the left side. In patients with gallstone pancreatitis, the pain is well localized and the onset of pain is rapid, reaching maximum intensity in 10 to 20 minutes. In contrast, in patients with pancreatitis due to hereditary or metabolic causes or alcohol, the onset of pain may be less abrupt and the pain may be poorly localized. In approximately 50 percent of patients, the pain radiates to the back [2]. The pain persists for several hours to days and may be partially relieved by sitting up or bending forward. (See "Etiology of acute pancreatitis".) Approximately 90 percent of patients have associated nausea and vomiting which may persist for several hours [3].

Patients with severe acute pancreatitis may have dyspnea due to diaphragmatic inflammation secondary to pancreatitis, pleural effusions, or adult respiratory distress syndrome. (See "Predicting the severity of acute pancreatitis", section on 'Classification of acute pancreatitis' and "Acute respiratory distress syndrome: Clinical features and diagnosis", section on 'Clinical features'.) Approximately 5 to 10 percent of patients with acute severe pancreatitis may have painless disease and have unexplained hypotension (eg, postoperative and critically ill patients, patients on dialysis, organophosphate poisoning, and Legionnaire's disease) [4-6]. (See "Sepsis and the systemic inflammatory response syndrome: Definitions, epidemiology, and prognosis" and "Shock in adults: Types, presentation, and diagnostic approach" and "Gastrointestinal disease in dialysis patients", section on 'Pancreatitis' and "Organophosphate and carbamate poisoning" and "Clinical manifestations and diagnosis of Legionella infection".) PHYSICAL EXAMINATION Physical findings vary depending upon the severity of acute pancreatitis. In patients with mild acute pancreatitis, the epigastrium may be minimally tender to palpation. In contrast, in patients with severe pancreatitis, there may be significant tenderness to palpation in the epigastrium or more diffusely over the abdomen. (See "History and physical examination in adults with abdominal pain", section on 'Abdominal examination'.) Patients may have abdominal distention and hypoactive bowel sounds due to an ileus secondary to inflammation (image 1). Patients may have scleral icterus due to obstructive jaundice due to choledocholithiasis or edema of the head of the pancreas. (See "Diagnostic approach to the adult with jaundice or asymptomatic hyperbilirubinemia" and "Approach to the patient with suspected choledocholithiasis", section on 'Clinical presentation'.) Patients with severe pancreatitis may have fever, tachypnea, hypoxemia, and hypotension. In 3 percent of patients with acute pancreatitis, ecchymotic discoloration may be observed in the periumbilical region (Cullens sign) or along the flank (Grey-Turner's sign) [7]. These findings, although nonspecific, suggest the presence of retroperitoneal bleeding in the setting of pancreatic necrosis [8]. (See "Evaluation of the adult with abdominal pain in the emergency department", section on 'Physical examination' and'Disease course' below.) In rare cases, patients may have subcutaneous nodular fat necrosis or panniculitis (picture 1) [9,10]. These lesions are tender red nodules that frequently occur on the distal extremities but may occur elsewhere. (See "Panniculitis: Recognition and diagnosis", section on 'Enzymatic destruction'.) Patient may also have findings suggestive of the underlying etiology (table 1). As examples, hepatomegaly may be present in patients with alcoholic pancreatitis, xanthomas in hyperlipidemic pancreatitis, and parotid swelling in patients with mumps (picture 2 and picture 3). (See "Etiology of acute pancreatitis" and"Hypertriglyceridemia-induced acute pancreatitis", section on 'Clinical features' and "Epidemiology, clinical manifestations, diagnosis and management of mumps", section on 'Clinical features'.) LABORATORY FINDINGS Pancreatic enzymes and products Early in the course of acute pancreatitis, there is a breakdown in the synthesis-secretion coupling of pancreatic digestive enzymes; synthesis continues while there is a blockade of secretion. As a result, digestive enzymes leak out of acinar cells through the basolateral membrane to the interstitial space and then enter the systemic

circulation. (See "Pathogenesis of acute pancreatitis", section on 'Intraacinar activation of proteolytic enzymes'.) Serum amylase Serum amylase rises within 6 to 12 hours of the onset of acute pancreatitis. Amylase has a short half-life of approximately 10 hours and in uncomplicated attacks returns to normal within three to five days. Serum amylase elevation of greater than three times the upper limit of normal has a sensitivity for the diagnosis of acute pancreatitis of 67 to 83 percent and a specificity of 85 to 98 percent [11]. However, elevations in serum amylase to more than three times the upper limit of normal may not be seen in approximately 20 percent of patients with alcoholic pancreatitis due to the inability of the parenchyma to produce amylase, and in 50 percent of patients with hypertriglyceridemia-associated pancreatitis as triglycerides interfere with the amylase assay [12]. Given the short half-life of amylase, the diagnosis of acute pancreatitis may be missed in patients who present >24 hours after the onset of pancreatitis. In addition, elevations in serum amylase are not specific for acute pancreatitis and may be seen in other conditions (table 2). (See "Approach to the patient with elevated serum amylase or lipase".) Serum lipase Serum lipase has a sensitivity and specificity for acute pancreatitis ranging from 82 to 100 percent [11]. Serum lipase rises within four to eight hours of the onset of symptoms, peaks at 24 hours, and returns to normal within 8 to 14 days [13]. Lipase elevations occur earlier and last longer as compared with elevations in amylase and are therefore especially useful in patients who present >24 hours after the onset of pain [14]. Serum lipase is also more sensitive as compared with amylase in patients with pancreatitis secondary to alcohol. However, nonspecific elevations of lipase have also been reported (table 3) [11,15]. (See "Approach to the patient with elevated serum amylase or lipase".) Other enzymes and products Trypsinogen activation peptide (TAP), a five amino-acid peptide that is cleaved from trypsinogen to produce active trypsin, is elevated in acute pancreatitis. Since activation of trypsin is likely an early event in the pathogenesis of acute pancreatitis, TAP may be useful in detection of early acute pancreatitis and as a predictor of the severity of acute pancreatitis [16-19]. (See "Predicting the severity of acute pancreatitis", section on 'Other serum markers'.) Urinary and serum trypsinogen-2 levels are elevated in early acute pancreatitis. However, additional studies are needed to determine their role in the diagnosis of acute pancreatitis [16,18,20-23]. (See "Post-ERCP pancreatitis", section on 'Early diagnosis'.) Other pancreatic digestive enzymes that leak into the systemic circulation and are elevated in serum include trypsin, phospholipase, carboxypeptidase, carboxylester lipase, colipase, and pancreatic isoamylase. Markers of immune activation Activation of granulocytes and macrophages in acute pancreatitis results in release of a number of cytokines and inflammatory mediators. Acute pancreatitis is associated with elevations in C-reactive protein (CRP), interleukin (IL)-6, IL-8, IL-10, tumor necrosis factor (TNF), and PMN elastase [24]. A CRP level above 150 mg/dL at 48 hours is associated with severe pancreatitis. (See "Predicting the severity of acute pancreatitis", section on 'C-reactive protein'.)

Other laboratory findings Patients with pancreatitis may have leukocytosis and an elevated hematocrit from hemoconcentration due to extravasation of intravascular fluid into third spaces. Metabolic abnormalities including elevated blood urea nitrogen (BUN), hypocalcemia, hyperglycemia, and hypoglycemia may also occur. (See"Pathogenesis of acute pancreatitis", section on 'Systemic response' and "Hypoglycemia in adults: Clinical manifestations, definition, and causes", section on 'Hypoglycemia in diabetes' and "Clinical features and diagnosis of diabetic ketoacidosis and hyperosmolar hyperglycemic state in adults", section on 'Precipitating factors'.) IMAGING Several features may be seen on imaging in patients with acute pancreatitis. Abdominal and chest radiographs The radiographic findings in acute pancreatitis range from unremarkable in mild disease to localized ileus of a segment of small intestine (sentinel loop) or the colon cutoff sign in more severe disease (image 1). The colon cut off sign reflects a paucity of air in the colon distal to the splenic flexure due to functional spasm of the descending colon secondary to pancreatic inflammation. A ground glass appearance may indicate the presence of an acute peripancreatic fluid collection (table 4). (See 'Local complications' below.) Approximately one-third of patients with acute pancreatitis have abnormalities visible on the chest roentgenogram such as elevation of a hemidiaphragm, pleural effusions, basal atelectasis, pulmonary infiltrates, or acute respiratory distress syndrome [25]. Abdominal ultrasound In patients with acute pancreatitis, the pancreas appears diffusely enlarged and hypoechoic on abdominal ultrasound. Gallstones may be visualized in the gallbladder or the bile duct (image 2). (See "Approach to the patient with suspected choledocholithiasis", section on 'Transabdominal ultrasound'.) Peripancreatic fluid appears as an anechoic collection on abdominal ultrasound. These collections may demonstrate internal echoes in the setting of pancreatic necrosis (table 4). (See 'Local complications' below.) However, in approximately 25 to 35 percent of patients with acute pancreatitis, bowel gas due to an ileus precludes evaluation of the pancreas or bile duct [16]. In addition, ultrasound cannot clearly delineate extrapancreatic spread of pancreatic inflammation or identify necrosis within the pancreas. Abdominal computed tomography Contrast-enhanced abdominal computed tomography (CT) scan findings of acute interstitial edematous pancreatitis (image 3) include focal or diffuse enlargement of the pancreas with heterogeneous enhancement with intravenous contrast. Necrosis of pancreatic tissue is recognized as lack of enhancement after intravenous contrast administration (image 4). If performed three or more days after the onset of abdominal pain, contrast-enhanced CT scan can reliably establish the presence and extent of pancreatic necrosis and local complications and predict the severity of the disease (table 4). (See 'Local complications' below and "Predicting the severity of acute pancreatitis", section on 'CT scan'and "Predicting the severity of acute pancreatitis", section on 'CT severity index'.) A common bile duct stone may occasionally be visualized on contrast-enhanced abdominal CT scan. A pancreatic mass may be seen in patients with an underlying pancreatic cancer, and diffuse dilation of the pancreatic duct or a cystic lesion may be seen in patients with an intraductal papillary mucinous neoplasia or cystic neoplasm. (See "Etiology of acute pancreatitis", section on

'Mechanical ampullary obstruction' and "Pathophysiology and clinical manifestations of intraductal papillary mucinous neoplasm of the pancreas", section on 'Clinical presentation' and "Clinical manifestations, diagnosis, and staging of exocrine pancreatic cancer", section on 'Clinical presentation'.) Magnetic resonance imaging On MR T1 weighted images with fat suppression, diffuse or focal enlargement of the pancreatic gland can be seen in patients with acute pancreatitis and the margins of the pancreas may be blurred. Due to pancreatic edema, the signal intensity of the pancreatic parenchyma might be hypointense relative to the liver on T1-weighted images, and hyperintense on T2-weighted images. On contrast-enhanced magnetic resonance imaging (MRI), failure of the pancreatic parenchyma to enhance indicates the presence of pancreatic necrosis. MRI has a higher sensitivity for the diagnosis of early acute pancreatitis as compared with contrastenhanced abdominal CT scan and can better characterize the pancreatic and bile ducts and complications of acute pancreatitis [26-28]. Magnetic resonance cholangiopancreatogram (MRCP) is comparable to endoscopic retrograde cholangiopancreatogram (ERCP) for the detection of choledocholithiasis [29]. MRI has the advantage of not requiring radiation, and gadolinium has a lower risk of nephrotoxicity as compared with iodinated contrast [28,30,31]. In addition, in patients with renal failure, a nonenhanced MRI can identify pancreatic necrosis. However, MRI has the disadvantage of being operator-dependent with consequent variability in quality and technique and its use is limited by the presence of local expertise and availability. In addition, MRI has a longer scanning time as compared with CT scan, making it more difficult to perform in critically ill patients. (See "Overview of indications for and complications of ERCP and endoscopic biliary sphincterotomy" and "Magnetic resonance cholangiopancreatography", section on 'Clinical use' and "Approach to the patient with suspected choledocholithiasis", section on 'Imaging tests'.) DIAGNOSIS The diagnosis of acute pancreatitis should be suspected in a patient with acute onset of a persistent, severe, epigastric pain with tenderness on palpation on physical examination. The diagnosis of acute pancreatitis requires the presence of two of the following three criteria: acute onset of persistent, severe, epigastric pain often radiating to the back, elevation in serum lipase or amylase to three times or greater than the upper limit of normal, and characteristic findings of acute pancreatitis on imaging (contrast-enhanced computed tomography [CT], magnetic resonance imaging [MRI], or transabdominal ultrasonography) [32]. (See 'Imaging' above.) In patients with characteristic abdominal pain and elevation in serum lipase or amylase to three times or greater than the upper limit of normal, no imaging is required to establish the diagnosis of acute pancreatitis. In patients with abdominal pain that is not characteristic for acute pancreatitis or serum amylase or lipase levels that are less than three times the upper limit of normal, or in whom the diagnosis is uncertain, we perform abdominal imaging with a contrast-enhanced abdominal CT scan to establish the diagnosis of acute pancreatitis and to exclude other causes of acute abdominal pain. In patients with severe contrast allergy or renal failure, we perform an abdominal MRI without gadolinium. Diagnostic evaluation Laboratory studies Elevation in serum lipase or amylase to three times or greater than the upper limit of normal is suggestive of acute pancreatitis. We evaluate levels of serum lipase and

amylase. Lipase remains elevated for a longer period of time and has a higher specificity as compared with amylase. (See 'Serum lipase' above and 'Serum amylase' above.) In addition, a complete blood count, electrolytes, alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, calcium, and albumin should be obtained to rule out other causes of acute abdominal pain. A pregnancy test should be performed in all women of childbearing age. (See 'Differential diagnosis' below.) Imaging The presence of focal or diffuse enlargement of the pancreas on contrast-enhanced abdominal CT or MRI is suggestive of acute pancreatitis. (See'Abdominal computed tomography' above and 'Magnetic resonance imaging' above.) DIFFERENTIAL DIAGNOSIS The differential diagnosis of acute pancreatitis includes other causes of epigastric abdominal pain. Acute pancreatitis can be distinguished from these causes based on the clinical features and laboratory studies. However, in some cases if the diagnosis of acute pancreatitis is still in doubt, we perform a contrast-enhanced abdominal computed tomography (CT) scan for further evaluation. (See 'Clinical features' above and 'Physical examination' above and 'Laboratory studies'above and 'Abdominal computed tomography' above.) Peptic ulcer disease Patients may have a history of longstanding epigastric pain that is usually intermittent. The pain does not radiate to the back. Patients may have a history of nonsteroidal antiinflammatory drug (NSAID) use or prior infection with Helicobacter pylori. On laboratory testing, patients with peptic ulcer disease have a normal amylase and lipase. (See "Clinical manifestations of peptic ulcer disease".) Choledocholithiasis or cholangitis Patients with choledocholithiasis and cholangitis may have a history of gallstones or biliary manipulation such as endoscopic retrograde cholangiopancreatography (ERCP). Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) concentrations are typically elevated early in the course of biliary obstruction. Later, patients have elevations in serum bilirubin, alkaline phosphatase, exceeding the elevations in serum ALT and AST. Serum amylase and lipase are normal. (See "Acute cholangitis", section on 'Clinical manifestations' and "Approach to the patient with suspected choledocholithiasis", section on 'Clinical presentation'.) Cholecystitis Patients with acute cholecystitis typically complain of abdominal pain, most commonly in the right upper quadrant or epigastrium that may radiate to the right shoulder or back. Unlike patients with acute pancreatitis, patients with acute cholecystitis commonly experience increased discomfort while the area around the gallbladder fossa is palpated and may have an associated inspiratory arrest (Murphys sign). Mild elevations in serum aminotransferases and amylase, along with hyperbilirubinemia may be seen but amylase or lipase elevations of greater than three times the upper limit of normal are not usually associated with cholecystitis. An abdominal CT scan shows gallbladder wall edema and pericholecystic stranding (image 5). (See "Pathogenesis, clinical features, and diagnosis of acute cholecystitis", section on 'Clinical manifestations' and "Pathogenesis, clinical features, and diagnosis of acute cholecystitis", section on 'Diagnosis'.) Perforated viscus Patients with a perforated viscus present with sudden onset abdominal pain and have peritoneal signs with guarding, rigidity and rebound tenderness that are not associated with acute pancreatitis. Patients may have an elevated amylase but elevations are unlikely to be three times the upper limit of normal. On upright chest film and abdominal films and abdominal CT scan, free air can be seen. Other possible findings on abdominal CT include free fluid, phlegmon, and bowel wall pathology with adjacent inflammation

(image 6 and image 7). (See "Surgical management of complications of peptic ulcer disease", section on 'Perforated ulcers'.) Intestinal obstruction Patients with intestinal obstruction have abdominal pain with anorexia, emesis, obstipation, or constipation and elevation in serum amylase and lipase. These patients may have a history of prior abdominal surgeries or Crohns disease. On physical examination, patients may have prior surgical scars or hernias. On abdominal CT scan in addition to dilated loops of bowel with air fluid levels, the etiology and site of obstruction (transition point) may be seen (image 8). (See "Small bowel obstruction: Clinical manifestations and diagnosis".) Mesenteric ischemia In patients with mesenteric ischemia, the pain is often periumbilical and out of proportion to findings on physical examination. Patients may have risk factors for mesenteric ischemia including advanced age, atherosclerosis, cardiac arrhythmias, severe cardiac valvular disease, recent myocardial infarction, and intra-abdominal malignancy. Although patients may have elevations in amylase or lipase these are usually less marked than elevations seen in acute pancreatitis. On abdominal CT scan there may be focal or segmental bowel wall thickening or intestinal pneumatosis with portal vein gas (image 9). In addition, arterial or venous thrombosis or hepatic or splenic infarcts may be seen. (See "Acute mesenteric ischemia", section on 'Clinical manifestations'.) Hepatitis Patients have acute right upper quadrant pain, anorexia, and general malaise. Patients may also note dark urine, acholic stool, jaundice, and pruritus. On physical findings, patients with acute hepatitis have scleral icterus and tender hepatomegaly. Laboratory studies are notable for marked elevations of serum aminotransferases (usually >1000 int. units/dL), serum total and direct bilirubin, and alkaline phosphatase with normal amylase and lipase. (See "Overview of hepatitis A virus infection in adults", section on 'Clinical evaluation' and "Clinical manifestations and natural history of hepatitis B virus infection", section on 'Acute hepatitis'.)

In patients who present with an elevated amylase or lipase without abdominal pain, the differential diagnosis is broad (table 2 and table 3). This topic is discussed separately. (See "Approach to the patient with elevated serum amylase or lipase".) ESTABLISHING THE ETIOLOGY Once the diagnosis of acute pancreatitis is established, the underlying etiology should be determined (table 1). An approach to identifying the cause of acute pancreatitis is discussed in detail separately. (See "Etiology of acute pancreatitis", section on 'Determining the etiology of acute pancreatitis'.) NATURAL HISTORY AND COMPLICATIONS Patients with acute pancreatitis usually present with acute onset of epigastric abdominal pain and elevated serum amylase and lipase. With supportive treatment, most patients recover without local or systemic complications or organ failure and do not have recurrent attacks. However, a small proportion of patients with acute pancreatitis have necrosis of the pancreas or peripancreatic tissue and complications due to pancreatitis. These patients have a high overall mortality. Disease course Approximately 85 percent of patients with acute pancreatitis have acute interstitial edematous pancreatitis characterized by an enlargement of the pancreas due to inflammatory edema [3]. Approximately 15 percent of patients have necrotizing pancreatitis with necrosis of the pancreatic parenchyma, the peripancreatic tissue, or both (table 4).

In most patients with acute pancreatitis, the disease is mild in severity and patients recover in three to five days without complications or organ failure. However, 20 percent of patients have moderately severe or severe acute pancreatitis with local or systemic complications or organ failure. (See 'Local complications' below and 'Systemic complications' below and 'Organ failure' below.) The overall mortality in acute pancreatitis is approximately 5 percent with a lower mortality in patients with interstitial pancreatitis as compared with those with necrotizing pancreatitis (3 versus 17 percent) [3]. Patients with acute pancreatitis may also have recurrent attacks [33]. In one observational study, in which 532 patients who were hospitalized for acute pancreatitis were followed for a mean duration of eight years, 17 percent of patients had a recurrent attack [34]. The rates of recurrence of acute pancreatitis varied based on etiology. The annual relapse rates were highest in patients with alcoholic pancreatitis as compared to patients with pancreatitis due to gallstones, other known causes (post-ERCP, hyperlipidemia, medications, trauma), or idiopathic causes (5.3, 1.5, and 1.9/100 patients per year, respectively). In this study, chronic pancreatitis developed only in patients with acute alcoholic pancreatitis with a cumulative incidence of 13 percent in 10 years. Local complications Local complications of acute pancreatitis include acute peripancreatic fluid collection (image 10), pancreatic pseudocyst, acute necrotic collection (image 11), and walled-off necrosis (table 4). While acute peripancreatic fluid collections and acute necrotic collections may develop less than four weeks after the onset of pancreatitis, pancreatic pseudocyst and walled off necrosis usually occurs >4 weeks after onset of acute pancreatitis. Both acute necrotic fluid collections and walled off necrosis may become infected. The management of infected pancreatic necrosis (image 12) is discussed in detail separately. (See "Pancreatic debridement", section on 'Infected pancreatic necrosis'.) Systemic complications According to the revised Atlanta classification of acute pancreatitis, a systemic complication of acute pancreatitis is defined as an exacerbation of an underlying comorbidity (eg, coronary artery disease or chronic lung disease) [32]. Organ failure In the Atlanta classification, organ failure is a distinct entity separate from a systemic complication [32]. Pancreatic inflammation results in the activation of a cytokine cascade that manifests clinically as a systemic inflammatory response syndrome (SIRS). Patients with persistent SIRS are at risk for failure of one or more organs. Organ failure (acute respiratory failure, shock, and renal failure) may be transient, resolving within 48 hours in patients with moderately severe pancreatitis or persistent for >48 hours in patients with severe acute pancreatitis (table 5). (See "Sepsis and the systemic inflammatory response syndrome: Definitions, epidemiology, and prognosis", section on 'Systemic inflammatory response syndrome'.) INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, th th at the 5 to 6 grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, th th more sophisticated, and more detailed. These articles are written at the 10 to 12 grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.) Basics topics (see "Patient information: Pancreatitis (The Basics)") Beyond the Basics topics (see "Patient information: Acute pancreatitis (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS The majority of patients with acute pancreatitis have acute onset of severe upper abdominal pain. Patients may have associated nausea and vomiting. On physical examination, patients have abdominal tenderness to palpation. Patients with severe acute pancreatitis may have fever, tachypnea, tachycardia, hypoxemia, and hypotension. (See 'Clinical features' above and 'Physical examination' above.) Early in the course of acute pancreatitis, pancreatic enzymes leak out of acinar cells to the interstitial space and then the systemic circulation. Patients with acute pancreatitis may therefore have acute elevations in serum amylase and lipase in addition to other pancreatic enzymes, breakdown products, and inflammatory mediators. (See 'Laboratory findings' above.) The diagnosis of acute pancreatitis is defined by the presence of two of the following: acute onset of persistent, severe, epigastric pain often radiating to the back, elevation in serum lipase or amylase to three times or greater than the upper limit of normal, or characteristic findings of acute pancreatitis on imaging (contrast-enhanced computed tomography, magnetic resonance imaging, or transabdominal ultrasonography). (See 'Diagnosis' above.) Serum lipase has a slightly higher sensitivity for acute pancreatitis, and elevations occur earlier and last longer as compared with elevations in amylase. Serum lipase is therefore especially useful in patients who present late to the physician. Serum lipase is also more sensitive as compared with amylase in patients with pancreatitis secondary to alcohol. (See 'Serum lipase' above and "Approach to the patient with elevated serum amylase or lipase".) In patients with characteristic abdominal pain and elevation in serum lipase or amylase to three times or greater than the upper limit of normal, no imaging is required to establish the diagnosis of acute pancreatitis. In patients with abdominal pain that is not characteristic for acute pancreatitis or a serum amylase and/or lipase activity that is less than three times the upper limit of normal, we perform abdominal imaging with a contrast-enhanced abdominal computed tomography scan to establish the diagnosis of acute pancreatitis and to exclude other causes of acute abdominal pain. (See 'Abdominal computed tomography' above and 'Differential diagnosis' above.) Approximately 85 percent of patients with acute pancreatitis have acute interstitial edematous pancreatitis (image 3) characterized by an enlargement of the pancreas due to inflammatory edema. Approximately 15 percent of patients have necrotizing pancreatitis (image 4)with necrosis of the pancreatic parenchyma, the peripancreatic tissue or both. (See 'Disease course' above.) In most patients with acute pancreatitis, the disease is mild in severity and patients recover in three to five days without complications or organ failure. However, 20 percent of patients

have moderately severe or severe acute pancreatitis with local or systemic complications or organ failure. (See 'Natural history and complications'above.) Use of UpToDate is subject to the Subscription and License Agreement. Treatment of acute pancreatitis Author Santhi Swaroop Vege, MD Section Editor David C Whitcomb, MD, PhD Deputy Editor Shilpa Grover, MD, MPH Disclosures All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jul 2013. | This topic last updated: abr 10, 2013. INTRODUCTION Acute pancreatitis can be divided into two broad categories [1]: Edematous, interstitial, or mild acute pancreatitis Necrotizing or severe acute pancreatitis

Treatment of acute pancreatitis is based upon the severity of the condition, as determined by the clinical, laboratory and a severity scoring system (algorithm 1). (See"Predicting the severity of acute pancreatitis".) Treatment is aimed at correcting any underlying predisposing factors and at the pancreatic inflammation itself. Most attacks of acute pancreatitis are mild with recovery occurring within five to seven days. Death is unusual in such patients. In contrast, severe necrotizing pancreatitis is associated with a high rate of complications and significant mortality. A subgroup of patients with severe pancreatitis has early severe acute pancreatitis or fulminant acute pancreatitis characterized by extended pancreatic necrosis with organ failure either at admission or within 72 hours. Early severe acute pancreatitis or fulminant acute pancreatitis has a high mortality of 25 to 30 percent [2-4]. An intermediate group of patients with "moderately severe acute pancreatitis", comprised of patients with local complications but no organ failure, has also been recognized [5]. Moderately severe acute pancreatitis has a low mortality like mild acute pancreatitis but morbidity (requiring prolonged hospital stay and interventions) similar to severe acute pancreatitis. This topic reviews the treatment of acute pancreatitis. Our recommendations are largely consistent with the American Gastroenterological Association (AGA) and the American College of Gastroenterology (ACG) guidelines for the treatment of acute pancreatitis [6,7]. The etiology, clinical manifestations, diagnosis of acute pancreatitis, methods to predict its severity, and the diagnosis and management of pancreatic pseudocysts are discussed separately. (See "Etiology of acute pancreatitis" and "Clinical manifestations and diagnosis of acute pancreatitis" and "Predicting the severity of acute pancreatitis" and "Diagnosis and management of pseudocysts of the pancreas".) PRETREATMENT ASSESSMENT OF DISEASE SEVERITY The first step in managing patients with acute pancreatitis is determining the severity. The severity of acute pancreatitis can be predicted based upon clinical, laboratory, and radiologic risk factors, severity grading systems, and

serum markers. Some of these can be performed on admission to assist in triage of patients, while others can only be obtained after the first 48 to 72 hours or later. Although measurement of amylase and lipase are useful for diagnosis of pancreatitis, serial measurements in patients with acute pancreatitis are not useful to predict prognosis or for altering management. (See "Predicting the severity of acute pancreatitis".) SUPPORTIVE CARE Mild acute pancreatitis is treated with supportive care including pain control, intravenous fluids, and correction of electrolyte and metabolic abnormalities. The majority of patients require no further therapy, and recover and eat within three to seven days. (See "Predicting the severity of acute pancreatitis" and'Pain management' below and 'Nutrition' below.) In severe acute pancreatitis, intensive care unit monitoring and support of pulmonary, renal, circulatory, and hepatobiliary function may minimize systemic sequelae [8]. Vital signs and urine output should be monitored every few hours in the first 24 to 48 hours. Patients with severe pancreatitis will need ongoing monitoring for other complications that might arise. (See "Abdominal compartment syndrome".) Sustained hypoxemia, hypotension refractory to a bolus of IV fluids, and possibly renal insufficiency that does not respond to a fluid bolus warrant prompt transfer to an intensive care unit for close monitoring. The importance of fluid replacement in the initial stages has been accepted as standard of care [9]. Fluid replacement is important because patients with necrotizing pancreatitis develop vascular leak syndrome [10]. At least one report suggested that inadequate fluid replacement (as evidenced by persistent hemoconcentration at 24 hours) was associated with development of necrotizing pancreatitis [11]. Inadequate hydration can lead to hypotension and acute tubular necrosis. In addition, fluid depletion damages pancreatic microcirculation and results in further pancreatic necrosis. Faster initial hydration was associated with decreased mortality [12]. The exact amount and composition of fluid resuscitation that is required has not been extensively studied but several approaches have been published [13,14]. After initial resuscitation with 20 cc/kg of intravenous fluid given over 60 to 90 minutes, approximately 250 to 300 cc of intravenous fluids per hour are typically required for 48 hours if the cardiac status permits [15]. Adequate fluid replacement can be assessed by improvement in vital signs and urine output and reduction in hematocrit and blood urea nitrogen (BUN) over 24 hours, particularly if they were high at the onset. Monitoring the BUN may be particularly important, as both the BUN at the time of admission and the change in BUN during the first 24 hours of hospitalization predict mortality [16]. Increased fluid resuscitation should be considered in patients whose BUN levels stay the same or increase. Fluids should be titrated to maintain urine output greater than 0.5 cc/kg/hour [17]. However, a low urine output may reflect the development of acute tubular necrosis rather than persistent volume depletion. In this setting, aggressive fluid replacement can lead to peripheral and pulmonary edema without improving the urine output. (See "Etiology and diagnosis of prerenal disease and acute tubular necrosis in acute kidney injury (acute renal failure)".) There is some evidence that fluid resuscitation with lactated Ringers solution may be

superior to normal saline [18]. In one small randomized trial of 40 patients, patients who received lactated Ringers had significantly lower mean C-reactive protein levels compared with patients who received normal saline (52 versus 104mg/dL) and a significant reduction in systemic inflammatory response syndrome (SIRS) after 24 hours (84 versus 0 percent). However, in rare patients with acute pancreatitis due to hypercalcemia, lactated Ringers is contraindicated because it contains 3 mEq/L calcium. In these patients normal saline is the preferred fluid for volume resuscitation. Oxygen saturation needs to be assessed routinely and supplemental oxygen administered to maintain arterial oxygen saturation of greater than 95 percent. Blood gas analysis should be done if oxygen saturation is less than 95 percent or if clinical situation demands. Hypoxia may be due to splinting, atelectasis, pleural effusions, opening of intrapulmonary shunts, or acute respiratory distress syndrome (ARDS). Persistent or progressive hypoxia may require mechanical ventilation. (See "Acute respiratory distress syndrome: Clinical features and diagnosis" and "Supportive care and oxygenation in acute respiratory distress syndrome".) Electrolytes should be monitored in patients with acute pancreatitis based on disease severity. Hypocalcemia should be corrected if ionized calcium is low or if there are signs of neuromuscular instability (Chvosteks or Trousseaus sign). Low magnesium levels may cause hypocalcemia and should be corrected. Serum glucose levels should be carefully monitored hourly in patients with severe pancreatitis and sliding scale insulin should be used to keep blood sugar levels under good control. Hyperglycemia may result from parenteral nutritional therapy, decreased insulin release, increased gluconeogenesis, and decreased glucose utilization, and may increase the risk of secondary pancreatic infections. Deep vein thrombosis prophylaxis should be considered in bedridden patients. (See "Prevention of venous thromboembolic disease in surgical patients".)

PAIN MANAGEMENT Abdominal pain is often the dominant symptom. Patients with hypovolemia from vascular leak and hemoconcentration may have ischemic pain. Markers of ischemia include metabolic acidosis and elevated serum lactate. Uncontrolled pain can contribute to the hemodynamic instability. Attention to adequate fluid resuscitation should be the first priority in addressing severe abdominal pain (see 'Supportive care' above). Adequate pain control requires the use of intravenous opiates, usually in the form of a patient controlled analgesia pump. (See "Pain control in the critically ill adult patient".) Hydromorphone or fentanyl (intravenous) may be used for pain relief in acute pancreatitis. Fentanyl is being increasingly used due to its better safety profile, especially in renal impairment. As with other opiates, fentanyl can depress respiratory function. It can be given both as boluses as well as constant infusion. The typical dose for bolus regimen ranges from 20 to 50 micrograms with a 10-minute lock-out period (time from the end of one dose infusion to the time the machine starts responding to another demand). Patients on patient-controlled analgesia should be carefully monitored for side effects. (See "Pain control in the critically ill adult patient", section on 'Opioid side effects'.) Meperidine has been favored over morphine for analgesia in pancreatitis because studies showed that morphine caused an increase in sphincter of Oddi pressure. However, there are no clinical studies to suggest that morphine can aggravate or cause pancreatitis or

cholecystitis [19]. It is important to note that meperidine has a short half-life and repeated doses can lead to accumulation of the metabolite normeperidine that causes neuromuscular irritation and, rarely, seizures. NUTRITION Patients with mild pancreatitis can often be managed with intravenous hydration alone since recovery often occurs rapidly, allowing patients to resume an oral diet within a week. Nutritional support is often required in patients with severe pancreatitis. Nutritional support should be provided to those who are unlikely to resume oral intake for more than five to seven days. Nasojejunal tube feeding (using an elemental or semi-elemental formula) is preferred to total parenteral nutrition. Early enteral nutrition (24 to 48 hours) should be initiated upon transfer to an intensive care unit, development of organ dysfunction, or systemic inflammatory response syndrome (SIRS) persisting for 48 hours if severe acute pancreatitis is confirmed [20-23]. Enteral Enteral feeding is recommended in patients with severe acute pancreatitis [6,7]. A benefit of enteral nutrition is its ability to maintain the intestinal barrier and prevent bacterial translocation from the gut, which may be a major cause of infection. (See"Pathogenesis of acute pancreatitis".) Another advantage is the avoidance of the complications associated with parenteral nutrition including catheter sepsis (which occurs in 2 percent even if the catheter is managed appropriately) and less frequent complications such as arterial laceration, pneumothorax, vein thrombosis, thrombophlebitis, and catheter embolism. In patients with a partial gastric outlet obstruction due to inflammation or a fluid collection, a few weeks of enteral feeding allows for the inflammation to subside or the fluid collection to mature and be drained, leading to resolution of the obstruction and resumption of oral feeding. Consistent with previous meta-analyses, a 2010 metaanalysis of eight trials demonstrated that enteral nutrition significantly reduced mortality, multiple organ failure, systemic infections, and the need for surgery compared with those who received parenteral nutrition [24-27]. Radiologic or endoscopic placement of a jejunal feeding tube beyond the ligament of Treitz and enteral feeding should be attempted. If this is not possible, nasogastric feeding has been proposed as an easier alternative. A controlled trial comparing nasogastric with nasojejunal feedings found no significant differences in APACHE II score, CRP measurement, pain levels, or analgesic requirement [28]. However, another small study comparing nasogastric feeding with TPN noted increased pulmonary and total complications in the nasogastric group [29]. Further studies are needed before the nasogastric approach can be recommended. We use high protein, low fat, semi-elemental feeding formulas (eg, Peptamen AF) because of a reduction in pancreatic digestive enzymes. We start at 25 cc per hour and advance as tolerated to at least 30 percent of the calculated daily requirement (25 kcal/kg ideal body weight), even in the presence of ileus. Signs that the formula is not tolerated include gastric residual volumes >400 cc (with nasogastric feeding), vomiting (with nasogastric feeding), bloating, or diarrhea (>5 watery stools or >500 mL per 24 hours with exclusion of C. difficile toxin and medication-induced diarrhea) that resolves if the feeding is held. The presence of fluid collections or elevated pancreatic enzymes is not necessarily a contraindication to oral or enteral feeding. However, in a subgroup of patients there is clear correlation of pain, recurrence of pancreatitis, or worsening of fluid collections, with feeding, either oral or enteral. These patients often have disrupted pancreatic ducts with fluid collections. Drainage of fluid collections may allow resumption of oral intake. If the fluid collections are not considered

suitable for drainage or if the target rate of enteral feeding is not achieved within 48 to 72 hours, supplemental parenteral nutrition should be provided. (See 'Parenteral' below.) Parenteral Parenteral nutrition should be initiated in patients who do not tolerate enteral feeding. The use of parenteral nutrition as an adjunct to enteral nutrition to improve provision of calories and protein to critically ill patients may be harmful according to two studies. The first study was a multicenter trial that randomly assigned 4640 critically ill adults who were already receiving enteral nutrition to have supplemental parenteral nutrition initiated early (within 48 hours of ICU admission) or late (after the eighth day of ICU admission) [30]. Those who received early parenteral nutrition were more likely to develop a new infection and had a longer duration of mechanical ventilation, ICU stay, and hospitalization. The second study was an observational study that compared three groups: enteral nutrition alone, enteral nutrition plus early parenteral nutrition, and enteral nutrition plus late parenteral nutrition in mechanically ventilated critically ill adults [31]. Enteral nutrition plus either early or late parenteral nutrition was associated with increased mortality compared with enteral nutrition alone. (See "Nutrition support in critically ill patients: An overview", section on 'Parenteral nutrition'.) Initiation of oral feeding When to begin oral feedings depends on the severity of the pancreatitis. In mild pancreatitis, in the absence of ileus, nausea or vomiting, oral feeds can be initiated as soon as the pain starts improving and narcotic requirements are decreasing. This usually occurs 24 to 48 hours after the onset of pancreatitis. Traditionally, patients have been advanced from a clear liquid diet to solid food as tolerated. More recent data suggest that early refeeding when patients are subjectively hungry, regardless of resolution of abdominal pain and normalization of pancreatic enzymes, may be safe [32,33]. In addition, starting first with a solid, low fat diet may also be safe, although it does not necessarily decrease length of stay [32,34-36]. In moderate to severe pancreatitis, oral feeding is frequently not tolerated due to postprandial pain, nausea, or vomiting, probably related to gastroduodenal inflammation and/or extrinsic compression from fluid collections leading to gastric outlet obstruction. Patients are generally placed on enteral or parenteral feeding as discussed above. When the local complications start improving, oral feeds are initiated and advanced as tolerated.

INFECTION The occurrence of pancreatic infection is a leading cause of morbidity and mortality in acute necrotizing pancreatitis. Approximately one-third of patients with pancreatic necrosis develop infected necrosis [6]. Patients who develop infection tend to have more extensive necrosis. Although infection can occur early in the course of necrotizing pancreatitis, it is more often seen late in the clinical course (after 10 days) [37,38]. The important organisms causing infection in necrotizing pancreatitis are predominantly gut-derived, including Escherichia coli, Pseudomonas, Klebsiella, andEnterococcus. The majority of infections (about 75 percent) are monomicrobial. Fungal infection and infection with gram-positive organisms are uncommon but occur more frequently in the setting of prophylactic antibiotic use for severe acute pancreatitis, especially when used for more than 10 to 14 days. Fungal infections occur in approximately 9 percent of necrotizing pancreatitis and it is not clear if they are associated with higher mortality [6].

Approaches taken to decrease bacterial infections in acute necrotizing pancreatitis include enteral feeding, systemic antibiotics, percutaneous computerized tomography (CT) guided aspiration, and necrosectomy. Our approach based upon these data is summarized in the following algorithm (algorithm 1). (See 'Percutaneous CT-guided aspiration' below and 'Necrosectomy' below.) Prophylactic antibiotics Although this is still an area of debate, in the author's practice, we initiate antimicrobial therapy with imipenem/meropenem and continue it for 7 to 10 days if there is necrotizing pancreatitis (involving more than approximately 30 percent of the pancreas). Because of the risk of fungal superinfection, antibiotics should be stopped after 7 to 10 days unless infection is documented. Given that the data are equivocal regarding a benefit to prophylactic antibiotics, it is also reasonable to withhold antibiotics until there is clinical evidence of infection (eg, fever, leukocytosis) or infection has been demonstrated after sampling the necrotic tissue [6]. We do not routinely recommend prophylactic antifungal therapy with fluconazole. Studies evaluating the benefits [39-42] and harms [43-48] of prophylactic antibiotics have produced disparate results. Contradictory results on the use of prophylactic antibiotics may be due to differences in methodological quality, inconsistent presence of organ failure in these studies, differences in antibiotic regimens and feeding used, and lack of data on adverse effects, making direct comparisons difficult [49-52]. One systematic review concluded prophylactic antibiotics decreased mortality in severe pancreatitis, but not the rate of infected pancreatic necrosis [53]. In contrast, a subsequent meta-analysis of seven trials detected no mortality benefit or reduction in the incidence of infected necrosis [43]. Further casting doubt on the benefit of prophylactic antibiotics is recognition that it can be associated with the selection of resistant organisms and the development of fungal infection [46-48].

Guidelines issued by multiple societies also differ in their recommendations: The American College of Gastroenterology guidelines [6] do not recommend prophylactic antibiotics. Guidelines from the American Gastroenterological Association [54] do not make a firm recommendation with regard to prophylactic antibiotics, but note that: "Antibiotic prophylaxis, if used, should be restricted to patients with substantial pancreatic necrosis (>30 percent of the gland necrotic by CT criteria) and should continue for no more than 14 days." Guidelines from the Italian Association for the Study of the Pancreas [55] recommend antibiotics for patients with CT-proven necrosis.

Whether there is a benefit to a specific class of antibiotics is also unclear. However, the authors suggest imipenem or meropenem for 14 days for patients with proven necrosis based on the following data: In a randomized controlled trial, 60 patients with severe acute pancreatitis with necrosis affecting at least 50 percent of the pancreas were randomly assigned to receive two weeks of pefloxacin, 400 mg twice daily, or imipenem, 500 mg three times daily, within 120 hours of symptom onset. Rates of infected necrosis were significantly lower in patients treated

with imipenem as compared with pefloxacin (10 and 34 percent, respectively), although mortality was not significantly different in the two groups. [52]. A meta-analysis of five trials showed reduced sepsis and mortality but not a reduction in prevention of necrosis with antibiotics (imipenem or meropenem) [56]. However, a subgroup of patients receiving prophylactic imipenem had reduction in infected necrosis.

Percutaneous CT-guided aspiration CT-guided percutaneous aspiration with Gram's stain and culture is recommended when infected pancreatic necrosis is suspected (clinical instability or sepsis physiology, increasing white blood cell count, fevers) [57,58]. Sterile necrosis does not usually require antibiotics and acute fluid collections do not require therapy in the absence of infection or obstruction of a surrounding hollow viscus [7]. Continued conservative management in a stable patient allows organization of necrotic fluid collections permitting a minimally invasive debridement either by endoscopic or percutaneous route to clear necrotic debris [59-62]. However, if there has been no improvement after one week of empiric antibiotics in a patient with >30 percent pancreatic necrosis and there are clinical signs of infection without another obvious site of infection, we perform a percutaneous CT-guided aspiration [63-65]. We repeat percutaneous CT-guided aspiration if the conditions of probable infection remain and no other source is found. If there is evidence of a bacterial infection, we consider performing a necrosectomy (see 'Necrosectomy' below) change the antibiotics according to the culture and sensitivity results (image 1) [37,66]. If the aspirated material is sterile, we continue conservative treatment for four to six weeks. A repeat aspiration in five to seven days may be indicated in patients with signs of systemic toxicity since a negative fine needle aspiration does not confidently exclude infection [67]. Necrosectomy Indications for necrosectomy include infected pancreatic necrosis and sterile symptomatic pancreatic necrosis with abdominal pain preventing oral intake. Surgical debridement of pancreatic necrosis (necrosectomy) can be accomplished by open surgery or a minimally invasive approach (endoscopic or percutaneous radiologic). In a randomized controlled trial, compared to open necrosectomy, a minimally invasive step-up approach consisting of percutaneous drainage followed, if necessary, by open necrosectomy, reduced the rate of the composite end point of major complications or death among patients with necrotizing pancreatitis and infected necrotic tissue [68,69]. (See "Pancreatic debridement".) Protease inhibitors The role of protease inhibitors in the treatment of acute pancreatitis remains unclear as evidence from clinical trials and a meta-analysis show only marginal benefit in patients with severe pancreatitis [66,67,70-72]. TREATMENT OF ASSOCIATED CONDITIONS In addition to the above treatment for pancreatic inflammation, treatment of acute pancreatitis is aimed at correcting any underlying predisposing factors, such as gallstones and hypertriglyceridemia, and treating complications such as splenic vein thrombosis and abdominal compartment syndrome. Gallstone pancreatitis Gallstone pancreatitis requires specific therapeutic considerations, in addition to the above recommendations. In this disorder, obstructive stones in the biliary tract or ampulla of Vater are responsible for the pancreatitis. (See "Etiology of acute pancreatitis".) The diagnosis of gallstone pancreatitis is discussed separately. (See "Clinical manifestations and diagnosis of acute pancreatitis".)

Endoscopic retrograde cholangiopancreatography Early endoscopic retrograde cholangiogram (ERCP) with papillotomy or surgical intervention to remove bile duct stones may lessen the severity of gallstone pancreatitis [73]. Multiple studies suggest that early endoscopic papillotomy is of benefit in patients with acute biliary pancreatitis [74-76]. Endoscopic papillotomy is typically accompanied by placement of a plastic biliary stent to decrease the risk of post-ERCP pancreatitis, which can occur in a patient who already has gallstone pancreatitis. (See "Endoscopic management of bile duct stones: Standard techniques and mechanical lithotripsy" and"Prophylactic pancreatic stents to prevent ERCP-induced pancreatitis: When do you use them?", section on 'Pancreatic sphincterotomy'.) In general, ERCP should be performed within 72 hours in those with a high suspicion of persistent bile duct stones (ie, visible common bile duct stone on noninvasive imaging, persistently dilated common bile duct, jaundice or rising liver chemistries) [7]. In the absence of cholangitis or a high suspicion of a persistent common bile duct stone, early ERCP (within 24 to 48 hours) is controversial. Three meta-analyses and one multicenter study reached different conclusions [75-78]. Two meta-analyses found that early ERCP in patients without cholangitis did not lead to a significant reduction in the risk of overall complications and mortality regardless of the predicted severity [76,78]. In another meta-analysis of five prospective randomized trials that included 702 patients, early ERCP reduced complications but not mortality in predicted severe pancreatitis; no benefit was observed in predicted mild pancreatitis [77]. We suggest early ERCP should be performed within 24 to 48 hours if there is concomitant cholangitis, persistently abnormal liver tests, or increasing liver tests (indicating the presence of a stone in the common bile duct). In the absence of persistent bile duct stones, cholangitis, persistently abnormal liver tests, or increasing liver tests, patients with biliary pancreatitis, can undergo ERCP before the cholecystectomy. Endoscopic ultrasound (EUS) or magnetic resonance cholangiopancreatogram (MRCP) to determine the need for ERCP should be considered in patients in whom the clinical course is not improving sufficiently to allow timely laparoscopic cholecystectomy and intraoperative cholangiogram, pregnant patients, patients with high risk of difficult ERCP (altered surgical anatomy or coagulopathy), or if there is intermediate concern regarding the possibility of a retained common bile duct stone, and the patient is not felt to be a good candidate for cholecystectomy with cholangiogram within the near future. Cholecystectomy Cholecystectomy should be performed after recovery in all patients with gallstone pancreatitis. Failure to perform a cholecystectomy is associated with a 25 to 30 percent risk of recurrent acute pancreatitis, cholecystitis, or cholangitis within 6 to 18 weeks [79]. The risk of recurrent pancreatitis is highest in patients who have not undergone a sphincterotomy. (See "Endoscopic management of bile duct stones: Standard techniques and mechanical lithotripsy", section on 'Cholecystectomy following sphincterotomy'.) In patients who have had mild pancreatitis, cholecystectomy can usually be performed safely within seven days after recovery [80]. In a randomized prospective study of 50 patients with mild gallstone pancreatitis, laparoscopic cholecystectomy performed within 48 hours of admission resulted in a shorter hospitalized stay than one performed after resolution of pain and laboratory abnormalities [81].

On the other hand, in patients who have had severe necrotizing pancreatitis, delaying cholecystectomy for at least three weeks may be reasonable because of an increased risk of infection [80]. Cholecystectomy after sphincterotomy in elderly and sick patients is controversial [82]. (See "Endoscopic management of bile duct stones: Standard techniques and mechanical lithotripsy", section on 'Safety of outpatient sphincterotomy'.) If the clinical suspicion of common bile duct stones is high (eg, in those with persistent or worsening liver test abnormalities or cholangitis), a preoperative ERCP is the best test as there is a high likelihood that therapeutic intervention (sphincterotomy, stone extraction) will be required (see 'Endoscopic retrograde cholangiopancreatography'above). On the other hand, if the suspicion of persistent common bile duct stones is low (eg, if liver tests normalize), an intraoperative cholangiogram during cholecystectomy may be preferable to avoid the morbidity associated with ERCP. MRCP and EUS are other imaging options that can exclude common bile duct stones [83]. A preoperative ERCP can then be performed only in those with stones or sludge in the common bile duct. (See "Magnetic resonance cholangiopancreatography" and"Endoscopic ultrasound in patients with suspected choledocholithiasis".) Biliary sludge Most patients with biliary sludge are asymptomatic. However, biliary sludge is commonly found in 20 to 40 percent of patients with acute pancreatitis with no other obvious cause. On ultrasound, sludge appears as a mobile, low-amplitude echo that layers in the most dependent part of the gallbladder and is not associated with shadowing. We recommend cholecystectomy in patients who have had an episode of pancreatitis and have biliary sludge because of the high risk of recurrence [32,36]. (See "Etiology of acute pancreatitis", section on 'Biliary sludge and microlithiasis'.) Although there are no randomized trials documenting that intervention in patients with pancreatitis and biliary sludge or microcrystals prevents further attacks of pancreatitis, two studies suggest that biliary sludge can lead to pancreatitis, and that these patients may benefit from intervention [84,85]. In one prospective study of 86 patients with acute pancreatitis of which 31 were idiopathic, 23 (74 percent) had either biliary sludge on ultrasonography (11 patients)and/or cholesterol monohydrate or calcium bilirubinate crystals on biliary microscopy [85]. Of the 21 patients in whom biliary sludge was the only finding (two patients also had dilated bile ducts when restudied), the 10 patients treated by cholecystectomy or papillotomy had fewer recurrences of acute pancreatitis during follow-up (up to seven years) than the 11 untreated patients. Another report evaluated the efficacy of biliary drainage in 51 patients recovering from an attack of acute "idiopathic" pancreatitis [84]. Clusters of cholesterol monohydrate crystals, calcium bilirubinate granules, and/or calcium carbonate microspheroliths were found in 67 percent. Examination of the gallbladder bile at cholecystectomy or serial ultrasonography of the gallbladder for up to 12 months showed that 73 percent of the patients with unexplained pancreatitis had biliary sludge or microlithiasis. Dissolution of gallstones by ursodeoxycholic acid (UDCA) or cholecystectomy prevented further attacks, while those with a delay in surgery or failed UDCA therapy continued to have episodes of pancreatitis.

Hypertriglyceridemic pancreatitis The treatment of hypertriglyceridemic pancreatitis is discussed separately. (See "Hypertriglyceridemia-induced acute pancreatitis".)

Hypercalcemia Hypercalcemia is a rare cause of acute pancreatitis. If present, treatment should be directed at normalizing serum calcium levels and determining the underlying etiology. It is important to note that Lactated Ringers solution is contraindicated in patients with hypercalcemia because it contains 3 mEq/L of calcium and normal saline is the preferred fluid for volume resuscitation. (See "Etiology of hypercalcemia" and "Diagnostic approach to hypercalcemia" and "Treatment of hypercalcemia".) Splenic vein thrombosis Splenic vein thrombosis is seen on imaging in up to 19 percent of patients with acute pancreatitis [86]. Treatment should focus on the underlying pancreatitis since the effective treatment may be associated with spontaneous resolution of the thrombosis. Anticoagulation may be needed if there is extension of the clot into the portal or superior mesenteric vein resulting in hepatic decompensation or compromise of bowel perfusion. However, this needs to be considered along with the theoretical possibility of hemorrhage into pancreatic necrosis or fluid collections. Complications such as variceal bleeding are uncommon (in contrast to chronic pancreatitis) and thus prophylactic splenectomy is not recommended [87]. Abdominal compartment syndrome Patients with severe pancreatitis are at increased risk for intraabdominal hypertension and abdominal compartment syndrome. Factors that can contribute to abdominal compartment syndrome in patients with acute pancreatitis include tissue edema from aggressive fluid resuscitation, peripancreatic inflammation, ascites, and ileus [88]. Abdominal compartment syndrome is a life threatening complication that results in visceral organ ischemia and tissue necrosis. Abdominal compartment syndrome occurs when intra-abdominal pressure rises above 21 mmHg. Patients in the ICU should be monitored for potential abdominal compartment syndrome with serial measures of urinary bladder pressures [89]. Most patients who develop abdominal compartment syndrome are critically ill and unable to communicate. The rare patient who is able to convey symptoms may complain of malaise, weakness, lightheadedness, dyspnea, abdominal bloating, or abdominal pain. Nearly all patients with abdominal compartment syndrome have a tensely distended abdomen. Progressive oliguria and increased ventilatory requirements are also common in patients with abdominal compartment syndrome. Other findings may include hypotension, tachycardia, an elevated jugular venous pressure, jugular venous distension, peripheral edema, abdominal tenderness, or acute pulmonary decompensation. There may also be evidence of hypoperfusion, including cool skin, obtundation, restlessness, or lactic acidosis. If abdominal compartment syndrome is confirmed, either percutaneous catheter-based or surgical decompression is indicated [90]. (See "Abdominal compartment syndrome", section on 'Surgical decompression'.) In patients with severe pancreatitis who require surgical decompression, this typically requires midline laparotomy. Following decompressive laparotomy, temporary abdominal closure is used until the need for an open abdomen has resolved. The abdomen is then closed primarily, functionally, or using skin grafts. (See "Management of the open abdomen in adults", section on 'Temporary abdominal closure' and "Abdominal compartment syndrome".) INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, th th at the 5 to 6 grade reading level, and they answer the four or five key questions a patient might

have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, th th more sophisticated, and more detailed. These articles are written at the 10 to 12 grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.) Basics topics (see "Patient information: Pancreatitis (The Basics)") Beyond the Basics topics (see "Patient information: Acute pancreatitis (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS Acute pancreatitis can be divided into two broad categories: edematous, interstitial or mild acute pancreatitis and necrotizing or severe acute pancreatitis. (See'Introduction' above.) Treatment varies depending on the severity of the condition. (See "Predicting the severity of acute pancreatitis".) Mild pancreatitis is treated for several days with supportive care including pain control, intravenous fluids, correction of electrolyte and metabolic abnormalities, and nothing by mouth. The majority of patients require no further therapy, and recover and eat within three to seven days. (See 'Supportive care' above.) In severe pancreatitis, intensive care unit monitoring and support of pulmonary, renal, circulatory, and hepatobiliary function may minimize systemic sequelae. (See'Supportive care' above.) Abdominal pain is often the dominant symptom. Adequate pain control requires the use of intravenous opiates, such as meperidine and fentanyl, usually in the form of a patient controlled analgesia pump. (See 'Pain management' above.) In patients with mild pancreatitis, recovery generally occurs quickly, making it generally unnecessary to initiate supplemental nutrition. Soft diet can be started after resolution of pain. (See 'Initiation of oral feeding' above.) In patients with severe pancreatitis, we recommend attempting to provide early enteral nutrition in the first 72 hours through a nasojejunal tube placed endoscopically or radiologically (Grade 1B). If the target rate is not achieved within 48-72 hours and if severe acute pancreatitis is not resolved, supplemental parenteral nutrition should be provided. (See 'Enteral' above.) The occurrence of pancreatic infection is a leading cause of morbidity and mortality in acute necrotizing pancreatitis. We suggest prophylactic imipenem ormeropenem in patients with necrosis that involves more than 30 percent of the pancreas ( Grade 2C). However, not all guidelines recommend the routine use of antibiotics and it is reasonable to withhold antibiotics unless there is clinical or microbiologic evidence of infection. (See 'Infection' above.) We suggest the following algorithm (algorithm 1), based upon clinical and CT findings, to direct percutaneous aspiration, antibiotic therapy, and minimally invasive or open surgical debridement as needed (Grade 2B). (See 'Infection' above.)

In patients with gallstone pancreatitis, we recommend early ERCP and sphincterotomy for those who have a high suspicion of cholestasis and those with cholangitis (Grade 1B). Cholecystectomy should be performed after recovery in all patients with gallstone pancreatitis. (See 'Gallstone pancreatitis' above.) Use of UpToDate is subject to the Subscription and License Agreement.

REFERENCES Predicting the severity of acute pancreatitis Author Santhi Swaroop Vege, MD Section Editor David C Whitcomb, MD, PhD Deputy Editor Shilpa Grover, MD, MPH Disclosures All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jul 2013. | This topic last updated: feb 13, 2013. INTRODUCTION Approximately 15 to 25 percent of all patients with acute pancreatitis (AP) develop severe AP. Between 1988 and 2003, mortality from acute pancreatitis decreased from 12 percent to 2 percent, according to a large epidemiologic study from the United States [1]. However, mortality rates remain much higher in subgroups of patients with severe disease. The ability to predict its severity can help identify patients at increased risk for morbidity and mortality, thereby assisting in appropriate early triage to intensive care units and selection of patients for specific interventions. This topic review will summarize methods for predicting the severity of AP. The clinical manifestations, diagnosis, and treatment of AP are discussed separately. (See"Clinical manifestations and diagnosis of acute pancreatitis" and "Treatment of acute pancreatitis".) GENERAL CONSIDERATIONS A multitude of predictive models have been developed to predict the severity of acute pancreatitis (AP) based upon clinical, laboratory, and radiologic risk factors, various severity grading systems, and serum markers [2]. Some of these can be performed on admission to assist in triage of patients, while others can only be obtained after the first 48 to 72 hours or later. However, these predictive models have low specificity (ie, high false positive rates), which when coupled with the low prevalence of severe AP (15 to 25 percent) results in low positive predictive values [3]. Future predictive models will need to incorporate additional factors (eg, biomarkers, genetic polymorphisms and mutations, and proteomic and metabolomic patterns) and methods of analyses [4]. CLASSIFICATION OF ACUTE PANCREATITIS The revised Atlanta classification system divides acute pancreatitis into two broad categories (table 1) [5,6]: Interstitial edematous acute pancreatitis, which is characterized by acute inflammation of the pancreatic parenchyma and peripancreatic tissues, but without recognizable tissue necrosis

Necrotizing acute pancreatitis, which is characterized by inflammation associated with pancreatic parenchymal necrosis and/or peripancreatic necrosis

According to the severity, acute pancreatitis is divided into the following: Mild acute pancreatitis which is characterized by the absence of organ failure and local or systemic complications Moderately severe acute pancreatitis which is characterized by transient organ failure (resolves within 48 hours) and/or local or systemic complications without persistent organ failure (>48 hours) Severe acute pancreatitis which is characterized by persistent organ failure that may involve one or multiple organs

Local complications of acute pancreatitis include acute peripancreatic fluid collection, pancreatic pseudocyst, acute necrotic collection, and walled-off necrosis (table 1). Organ failure is defined as a score of 2 or more for any one of three organ systems (respiratory, cardiovascular, or renal) using the modified Marshall scoring system (table 2) [7]. CLINICAL PREDICTORS Clinical judgment Clinical judgment based upon clinical and laboratory data at admission might underestimate the severity of acute pancreatitis (AP). In one review, the clinical judgment of experienced physicians at admission had a sensitivity, specificity, positive predictive value, and negative predictive value of 39, 93, 66, and 82 percent, respectively, for predicting severe AP [8]. Older age Several studies have concluded that older age is a predictor of a worse prognosis, although the age cutoff has varied from 55 to 75 years in different reports [9,10]. In an illustrative study, patients older than 75 years had more than a 15-fold greater chance of dying within two weeks and a more than 22-fold greater chance of dying within 91 days compared with patients aged 35 years or younger [10]. Sex The patient's sex has not been a predictor of outcome in most reports [9]. Alcoholic pancreatitis Alcohol as a cause of pancreatitis has been associated with an increased risk of pancreatic necrosis and need for intubation in some reports [10-12]. Short time interval to symptom onset A time interval between the onset of symptoms and hospital admission of less than 24 hours, as well as rebound tendernessand/or guarding were associated with increasing severity of pancreatitis in at least one report [13]. Obesity Many studies have found obesity (defined as a body mass index >30) to be a risk factor for severe AP. A meta-analysis that included 739 patients made the following estimates [14]: Severe acute pancreatitis, odds ratio (OR) 2.9 (95% CI 1.8-4.6) Systemic complications, OR 2.3 (95% CI 1.4-3.8) Local complications, OR 3.8 (95% CI 2.4-6.6) Mortality, OR 2.1 (95% CI 1.0-4.8)

Organ failure Early and persistent organ failure is a reliable indicator of a prolonged hospital stay and increased mortality. In one report, organ failure within 72 hours of admission was

associated with the presence of extended pancreatic necrosis and a mortality rate of 42 percent [15]. Several subsequent studies found that the evolution and clinical course of organ failure was a more accurate predictor of adverse outcomes. In one study, persistent and deteriorating (48 hours) organ failure were associated with mortality rates of 21 and 55 percent, respectively [16]. On the other hand, early organ dysfunction that was not persistent (<48 hours) was associated with a mortality rate of 0 percent. In a second study, transient organ failure was associated with a mortality rate of 1.4 percent, whereas persistent organ failure had a 35 percent mortality rate [17]. Persistent organ failure is widely accepted as a reliable criterion for severe AP. LABORATORY AND RADIOLOGIC PREDICTORS Hemoconcentration Acute pancreatitis (AP) results in significant third space losses, resulting in hemoconcentration and a high hematocrit. Studies evaluating the hematocrit as a predictor of the severity of AP have produced variable results [18-22]. The discrepancies may be due to differences in values chosen as a cutoff and the time that they were obtained. Despite these differences, it appears that a normal or low hematocrit at admission and during the first 24 hours is generally associated with a milder clinical course. C-reactive protein C-reactive protein (CRP) is one of the acute phase reactants made by the liver in response to interleukin-1 and interleukin-6. Levels of CRP above 150mg/dL at 48 hours discriminate severe from mild disease. At 48 hours, CRP above 150 mg/dL has a sensitivity, specificity, positive predictive value, and negative predictive value of 80, 76, 67, and 86 percent, respectively, for severe acute pancreatitis [8]. CRP rises steadily in relation to the severity of pancreatitis, is inexpensive to measure, and testing is readily available [23-25]. As a result, we suggest it be used to help predict the severity of pancreatitis, especially at 48 hours. Blood urea nitrogen In a large hospital-based cohort, serial blood urea nitrogen (BUN) measurements were the most reliable routine laboratory test to predict the mortality in AP [26]. For every increase in the BUN of 5 mg/dL during the first 24 hours, the adjusted odds ratio for mortality was 2.2. A subsequent study by the same group that included 1043 patients found that a BUN level of 20 mg/dL or higher at admission was associated with an increased risk of death compared with a BUN level of less than 20 mg/dL (OR 4.6) [27]. In addition, any increase in BUN at 24 hours was also associated with an increased risk of death (OR 4.3). Serum creatinine An elevated serum creatinine within the first 48 hours may predict the development of pancreatic necrosis. In one study of 129 patients, a peak creatinine of greater than 1.8 mg/dL during the first 48 hours had a positive predictive value of 93 percent for the development of pancreatic necrosis [22]. However, a study from Germany did not find this association, though it did show that a normal creatinine had a high negative predictive value for the development of pancreatic necrosis [28]. The authors suggested that a normal creatinine in the absence of complications obviated the need for an abdominal computed tomographic (CT) scan. The discrepancy between the two studies may have been due to a lower prevalence of pancreatic necrosis in the German study, which could have resulted in a lower positive predictive value. Other serum markers Multiple other serum markers have been studied for predicting the severity pancreatitis including: urinary trypsinogen activation peptide (TAP), procalcitonin, polymorphonuclear elastase, pancreatic-associated protein, amylase, lipase, serum glucose, serum

calcium, procarboxypeptidase-B, carboxypeptidase B activation peptide, serum trypsinogen-2, phospholipase A-2, serum amyloid protein-A, substance P, antithrombin III, platelet activating factor, interleukins 1, 6, and 8, tumor necrosis factor-alpha or soluble tumor necrosis factor receptor, and various genetic polymorphisms [22,29-31]. Tests for most of these markers are not widely available and their test characteristics are incompletely understood. Exceptions are a dipstick test for procalcitonin, an ELISA test for urine TAP, and a test for urine anionic trypsinogen, which are likely to become commercially available. Procalcitonin is the most rapid general acute-phase reactant. In a validation study, the procalcitonin strip test had an accuracy of 86 percent for predicting severe AP [32]. TAP is cleaved from the amino-terminal end of trypsinogen when trypsin is activated. TAP is the most studied activation peptide in AP. A European multicenter study found a sensitivity of 58 percent and specificity of 73 percent with urinary TAP within 24 hours of symptom onset [32].

Chest radiographs A pleural effusion and/or pulmonary infiltrates during the first 24 hours may be associated with necrosis and organ failure [33]. CT scan CT scan is probably the most frequently used radiologic investigation when severe AP is suspected. It is used to look for pancreatic necrosis and extrapancreatic inflammation. Intravenous contrast-enhanced CT distinguishes between edematous and necrotizing pancreatitis, since areas of necrosis and exudates do not enhance. CT is more accurate than ultrasonography for the diagnosis of severe pancreatic necrosis (90 versus 73 percent in one report) [34]. After assessment of the patient, a contrast-enhanced CT scan is indicated in patients who are deteriorating or have severe pancreatitis determined clinically and by APACHE II score (calculator 1). A CT scan is not required on the first day unless there are other diagnoses are being considered. A retrospective analysis of the performance of several CT scoring systems for the severity of acute pancreatitis found that none was statistically superior to the APACHE II or BISAP scoring systems [35]. In addition, it takes time for pancreatic necrosis to develop, and treatment is unlikely to be altered on the basis of CT findings on day one. Although there are some experimental data that suggest ionic contrast may worsen pancreatitis, the association is probably not strong and the information obtained from the CT scan justifies the potential risk. Perfusion CT can differentiate reversible from irreversible ischemic tissue in the brain and uses less contrast than the conventional contrast-enhanced CT. One report described the utility of perfusion CT in predicting pancreatic necrosis in early stages of AP [36]. Ten of 30 patients with AP had pancreatic ischemia on perfusion CT and nine patients were proven to have pancreatic necrosis subsequently on contrast-enhanced CT. MRI and MRCP Magnetic resonance imaging (MRI) and magnetic resonance cholangiopancreatography (MRCP) are being used increasingly to diagnose AP and to assess its severity [37]. MRI appears to be comparable to CT, if not better, in providing precise information regarding the severity of the disease [38-40]. MRI is as effective as CT in demonstrating the presence and extent of pancreatic necrosis and fluid collections, and is probably superior for indicating the suitability of such collections for nonsurgical drainage [39]. MRI can characterize the "pancreatic necrosis" seen on CT as necrotic pancreatic parenchyma, peripancreatic necrotic fluid collections, or hemorrhagic foci [40]. One study found that MRI was

reliable for staging the severity of AP and predicting prognosis with fewer contraindications than CT [41]. It can also detect pancreatic duct disruption, which can occur early in the course of AP. SCORING SYSTEMS Many scoring systems have been reported but none has proven to be perfect [42]. While they can be useful to group patients for the purpose of inter-institutional comparisons and reporting, none has high accuracy in predicting the severity of acute pancreatitis (AP) in a given patient at the bedside. On the other hand, they are superior to clinical judgment for triaging patients to more intensive care and aggressive therapy. (See 'Clinical judgment' above.) Many scoring systems (eg, Ranson, Glasgow) take 48 hours to complete, can be used only once, and do not have a high degree of sensitivity and specificity (table 3) [43-45]. In addition, some have limited utility since they focus on specific complications (eg, Banks) or are invasive (eg, Leeds diagnostic peritoneal lavage) [43]. As a result, many of these systems are not used routinely. Ranson's criteria A score based upon Ranson's criteria is one of the earliest scoring systems for severity in AP [44]. Ranson's criteria consist of 11 parameters. Five of the factors are assessed at admission and six are assessed during the next 48 hours (table 3) (calculator 2). A later modification for biliary pancreatitis included only 10 points [46]. Mortality increases with an increasing score. Using the 11 component score, mortality was 0 to 3 percent when the score was <3, 11 to 15 percent when the score was 3, and 40 percent when the score was 6 [ 9]. Although the system continues to be used, a meta-analysis of 110 studies found the Ranson score to be a poor predictor of severity [47]. The APACHE II score The acute physiology and chronic health examination (APACHE) II score was originally developed for critically ill patients in intensive care units. (See "Predictive scoring systems in the intensive care unit".) It has 12 physiologic measures and extra points based upon age and presence of chronic disease (calculator 1). It is probably the most widely studied severity scoring system in AP. It has good negative predictive value and modest positive predictive value for predicting severe AP and can be performed daily. Decreasing values during the first 48 hours suggest a mild attack, while increasing values suggest a severe attack. Studies suggest that mortality is less than 4 percent with a score <8 and is 11 to 18 percent with a score >8 [8,9]. Some limitations of the APACHE II score are that is complex and cumbersome to use, it does not differentiate between interstitial and necrotizing pancreatitis, and it does not differentiate between sterile and infected necrosis. Finally, it has a poor predictive value at 24 hours [9]. The addition of a body mass index (BMI) score to APACHE II (known as APACHE O) improved the prediction of severe pancreatitis compared with the conventional APACHE II score in one study [48]. One point was added for a BMI of >25 to 30 and two points were added for a BMI >30. However, the improved performance of APACHE O was not validated in a second study [49]. A simplified Acute Physiology Score II developed in ICU patients may be comparable to APACHE II [50]. (See "Predictive scoring systems in the intensive care unit".) Several additional variables were added to APACHE II to improve its accuracy leading to the development of APACHE III. Both APACHE II and III scores use physiology, age, and chronic health to calculate prognosis; they differ in total score, the number of physiologic variables (12 for APACHE II versus 17 for APACHE III), and the assessment of chronic health status. However, the APACHE III system does not appear to be as useful as APACHE II for distinguishing mild from severe attack [51].

Systemic inflammatory response syndrome score As noted above, the presence of the systemic inflammatory response syndrome (SIRS) is associated with increased mortality. A score based upon the systemic inflammatory response syndrome has been developed [52]. Initial studies suggest it can reliably predict the severity of pancreatitis and has the added advantage that it can be applied easily at the bedside every day (table 4) [16]. In one validation study, mortality rates were 25, 8, and 0 percent in those with persistent SIRS from admission, SIRS at admission but not persistent, and no SIRS, respectively [53]. Another study found that the severity of AP was greater among patients with AP and SIRS on day one, particularly in those with three or four SIRS criteria, compared with those without SIRS on day one [54]. Thus, it appears that the SIRS score is inexpensive, readily available, and compares favorably with other more complicated scores. BISAP score Development of the bedside index of severity in acute pancreatitis (BISAP) score was based upon 17,922 cases of AP from 2000 to 2001 and validated in 18,256 cases from 2004 to 2005 [55]. Patients are assigned 1 point for each of the following during the first 24 hours: BUN >25 mg/dL, impaired mental status, SIRS (using the same criteria as the SIRS score, (table 4)), age >60 years, or the presence of a pleural effusion (calculator 3) [55]. Patients with a score of zero had a mortality of less than one percent, whereas patients with a score of five had a mortality rate of 22 percent. In the validation cohort, the BISAP score had similar test performance characteristics for predicting mortality as the APACHE II score. As is a problem with many of the other scoring systems, the BISAP has not been validated for predicting outcomes such as length of hospital stay, need for ICU care, or need for intervention. A validation study of the BISAP score that included 185 patients found that its performance was similar to APACHE II, Ranson's criteria, and the CT severity index system [56]. While the BISAP score is meant to be easily calculated at the bedside, it has been noted that to do so is not as simple as was initially reported because four variables need to be considered to determine if SIRS is present [57]. Harmless acute pancreatitis score The harmless acute pancreatitis score can typically be calculated within 30 minutes of admission and takes into account three parameters: lack of rebound tenderness or guarding, normal hematocrit, and normal serum creatinine. It was derived on a cohort of 394 patients and validated in a cohort of 452 patients [58]. This score correctly identified 200 of 204 patients (98 percent) with a harmless course. Presumably patients were considered likely to have a harmless course if none of the three parameters were present, though this was not clearly defined in the report. Organ failure-based scores As noted above, organ failure is a marker of the severity of pancreatitis. While there are several scoring systems for organ failure, they do not directly measure the severity of AP, but rather measure the severity of the organ failure itself. (See 'Organ failure' above.) This distinction is potentially important as reflected in the limitations of Atlanta classification system described above [59,60]. Organ failure was listed as being present or absent, without specifying the number of organs failing or the severity of each organ failure, issues that are potentially clinically relevant. (See 'Classification of acute pancreatitis' above.) Organ failure scoring systems such as the Goris multiple organ failure score [61], the Marshall (or multiple) organ dysfunction score [7], the Bernard score [62], the sequential organ failure assessment (SOFA) [63], and the logistic organ dysfunction system score [64] have been described. All these scores take into account the number of organ systems involved and the degree

of dysfunction of each individual organ. Some also include the use of inotropic or vasopressor agents, mechanical ventilation, or dialysis [7]. As noted above, the presence of persistent organ failure lasting for more than 48 hours appears to be important [17]. (See 'Organ failure' above.) CT severity index A CT severity score (the Balthazar score) has been developed based upon the degree of necrosis, inflammation, and the presence of fluid collections (table 5) [65]. In an initial validation study, mortality was 23 percent with any degree of pancreatic necrosis and 0 percent with no necrosis. In addition, there was a strong association between necrosis >30 percent and morbidity and mortality [65]. The finding of necrotizing pancreatitis (or even infected necrosis) does not necessarily predict the occurrence of organ failure, but may alter the therapeutic approach [66]. In a retrospective study of 268 patients with AP assessed by the CT severity index, patients with a CT severity index >5 were eight times more likely to die, 17 times more likely to have a prolonged hospital course, and 10 times more likely to undergo necrosectomy than the patients with scores <5 [67]. While necrosis on CT predicts a severe attack, there was no uniform correlation with the extent of necrosis and organ failure and/or mortality. Such a correlation may become more apparent with newer scoring systems that measure the number of failing organ systems and the severity of each failing organ system. (See 'Organ failure-based scores' above.) AGA GUIDELINES The American Gastroenterological Association (AGA) has issued guidelines for assessing the severity of pancreatitis [29]. The AGA recommends: Prediction of severe disease be performed using the APACHE II system (using a cutoff of 8) (calculator 1). Those with actual or predicted severe disease and those with other severe comorbid conditions should be considered for triage to an intensive care or intermediate medical care unit. In patients with predicted severe disease (ie, APACHE II score of 8) and those with evidence of organ failure during the initial 72 hours, rapid-bolus CT should be performed after 72 hours of illness to assess the degree of pancreatic necrosis. CT should be used selectively based upon clinical features in patients who do not meet these criteria. Laboratory tests can be used as an adjunct to clinical judgment and the APACHE II score. A serum C-reactive protein level of >150 mg/L at 48 hours is preferred.

INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, th th at the 5 to 6 grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, th th more sophisticated, and more detailed. These articles are written at the 10 to 12 grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

Beyond the Basics topics (see "Patient information: Acute pancreatitis (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS During the initial 24 hours, severe acute pancreatitis can be predicted using clinical, laboratory, and radiologic risk factors, many of which have been incorporated into scoring systems such as the SIRS score, the APACHE II score, the BISAP score, and the CT severity index. We favor the SIRS score because it is simple, cheap, readily available, and as accurate as any other complex scoring system, especially persistent SIRS. (See 'Scoring systems' above.) We suggest a contrast-enhanced CT be performed in patients considered to have severe AP based upon clinical criteria or possibly the APACHE II score (calculator 1) to determine if necrotizing pancreatitis is present. A CT scan is not required on the first day unless other diagnoses are being considered. It takes time for pancreatic necrosis to develop, and thus CT may be normal in the first 48 hours. As noted above, a guideline issued by the American Gastroenterological Association suggests a CT be performed after 72 hours of illness in patients with predicted severe disease and those with evidence of organ failure during the initial 72 hours. Although there are some experimental data that ionic contrast may worsen pancreatitis, the association is probably not strong, and the information obtained from the CT scan justifies the potential risk. (See 'AGA guidelines' above.) MRI is emerging as a useful imaging tool in pancreatitis, especially to distinguish the contents of fluid collections seen on CT. However, experience remains inadequate in the setting of acute pancreatitis primarily because of its high cost and need for prolonged examination time. (See 'MRI and MRCP' above.) Laboratory tests have an adjunctive role in predicting the severity of acute pancreatitis. We agree with the guideline issued by the AGA, which suggests that of the available tests, a Creactive protein level of >150 mg/L at 48 hours after disease onset is preferred for discriminating patients with severe disease. (See 'Laboratory and radiologic predictors' above and 'AGA guidelines' above.) Use of UpToDate is subject to the Subscription and License Agreement.