* This is the Professional Version. *
Acute pancreatitis is inflammation of the pancreas (and, sometimes, adjacent tissues) caused by the release of activated pancreatic enzymes. The most common triggers are biliary tract disease and chronic heavy alcohol intake. The condition ranges from mild (abdominal pain and vomiting) to severe (pancreatic necrosis and a systemic inflammatory process with shock and multiorgan failure). Diagnosis is based on clinical presentation and serum amylase and lipase levels. Treatment is supportive, with IV fluids, analgesics, and fasting.
Biliary tract disease and alcoholism account for ≥ 80% of acute pancreatitis cases. The remaining 20% result from myriad causes (see Some Causes of Acute Pancreatitis).
Some Causes of Acute Pancreatitis
The precise mechanism by which obstruction of the sphincter of Oddi by a gallstone or microlithiasis (sludge) causes pancreatitis is unclear, although it probably involves increased ductal pressure. Prolonged alcohol intake (> 100 g/day for > 3 to 5 yr) may cause the protein of pancreatic enzymes to precipitate within small pancreatic ductules. Ductal obstruction by these protein plugs may cause premature activation of pancreatic enzymes. An alcohol binge in such patients can trigger pancreatitis, but the exact mechanism is not known.
A number of genetic mutations predisposing to pancreatitis have been identified. One, an autosomal dominant mutation of the cationic trypsinogen gene, causes pancreatitis in 80% of carriers; an obvious familial pattern is present. Other mutations have lesser penetrance and are not readily apparent clinically except through genetic testing. The genetic abnormality responsible for cystic fibrosis increases the risk of recurrent acute as well as chronic pancreatitis.
Regardless of the etiology, pancreatic enzymes (including trypsin, phospholipase A2, and elastase) become activated within the gland itself. The enzymes can damage tissue and activate the complement system and the inflammatory cascade, producing cytokines. This process causes inflammation, edema, and sometimes necrosis. In mild pancreatitis, inflammation is confined to the pancreas; the mortality rate is < 5%. In severe pancreatitis, there is significant inflammation, with necrosis and hemorrhage of the gland and a systemic inflammatory response; the mortality rate is 10 to 50%. After 5 to 7 days, necrotic pancreatic tissue may become infected by enteric bacteria.
Activated enzymes and cytokines that enter the peritoneal cavity cause a chemical burn and third spacing of fluid; those that enter the systemic circulation cause a systemic inflammatory response that can result in acute respiratory distress syndrome and renal failure. The systemic effects are mainly the result of increased capillary permeability and decreased vascular tone, which result from the released cytokines and chemokines. Phospholipase A2 is thought to injure alveolar membranes of the lungs.
In about 40% of patients, collections of enzyme-rich pancreatic fluid and tissue debris form in and around the pancreas. In about half, the collections resolve spontaneously. In others, the collections become infected or form pseudocysts. Pseudocysts have a fibrous capsule without an epithelial lining. Pseudocysts may hemorrhage, rupture, or become infected.
Death during the first several days is usually caused by cardiovascular instability (with refractory shock and renal failure) or respiratory failure (with hypoxemia and at times adult respiratory distress syndrome). Occasionally, death results from heart failure secondary to an unidentified myocardial depressant factor. Death after the first week is usually caused by multiorgan system failure.
An acute attack causes steady, boring upper abdominal pain, typically severe enough to require large doses of parenteral opioids. The pain radiates through to the back in about 50% of patients; rarely, pain is first felt in the lower abdomen. Pain usually develops suddenly in gallstone pancreatitis; in alcoholic pancreatitis, pain develops over a few days. The pain usually persists for several days. Sitting up and leaning forward may reduce pain, but coughing, vigorous movement, and deep breathing may accentuate it. Nausea and vomiting are common.
The patient appears acutely ill and sweaty. Pulse rate is usually 100 to 140 beats/min. Respiration is shallow and rapid. BP may be transiently high or low, with significant postural hypotension. Temperature may be normal or even subnormal at first but may increase to 37.7 to 38.3° C (100 to 101° F) within a few hours. Sensorium may be blunted to the point of semicoma. Scleral icterus is occasionally present. The lungs may have limited diaphragmatic excursion and evidence of atelectasis.
About 20% of patients experience upper abdominal distention caused by gastric distention or displacement of the stomach by a pancreatic inflammatory mass. Pancreatic duct disruption may cause ascites (pancreatic ascites). Marked abdominal tenderness occurs, most often in the upper abdomen. There may be mild tenderness in the lower abdomen, but the rectum is not tender and the stool is usually negative for occult blood. Mild-to-moderate muscular rigidity may be present in the upper abdomen but is rare in the lower abdomen. Rarely, severe peritoneal irritation results in a rigid and boardlike abdomen. Bowel sounds may be hypoactive. The Grey Turner sign (ecchymoses of the flanks) and the Cullen sign (ecchymoses of the umbilical region) indicate extravasation of hemorrhagic exudate.
Infection in the pancreas or in an adjacent fluid collection should be suspected if the patient has a generally toxic appearance with elevated temperature and WBC count or if deterioration follows an initial period of stabilization.
Pancreatitis is suspected whenever severe abdominal pain occurs, especially in a patient with significant alcohol use or known gallstones. Conditions causing similar symptoms include perforated gastric or duodenal ulcer, mesenteric infarction, strangulating intestinal obstruction, dissecting aneurysm, biliary colic, appendicitis, diverticulitis, inferior wall MI, and hematoma of the abdominal muscles or spleen.
Diagnosis is made by clinical suspicion, serum markers (amylase and lipase), and the absence of other causes for the patient’s symptoms. Thus, a broad range of tests is done, typically including CBC, electrolytes, Ca, Mg, glucose, BUN, creatinine, amylase, and lipase. Other routine tests include ECG and an abdominal series (chest, flat, and upright abdomen). A urine dipstick for trypsinogen-2 has sensitivity and specificity of > 90% for acute pancreatitis. Ultrasonography and CT are not generally done specifically to diagnose pancreatitis but are often used to evaluate acute abdominal pain (see Testing).
Serum amylase and lipase concentrations increase on the first day of acute pancreatitis and return to normal in 3 to 7 days. Lipase is more specific for pancreatitis, but both enzymes may be increased in renal failure and various abdominal conditions (eg, perforated ulcer, mesenteric vascular occlusion, intestinal obstruction). Other causes of increased serum amylase include salivary gland dysfunction, macroamylasemia, and tumors that secrete amylase. Both amylase and lipase levels may remain normal if destruction of acinar tissue during previous episodes precludes release of sufficient amounts of enzymes. The serum of patients with hypertriglyceridemia may contain a circulating inhibitor that must be diluted before an elevation in serum amylase can be detected.
Amylase:creatinine clearance ratio does not have sufficient sensitivity or specificity to diagnose pancreatitis. It is generally used to diagnose macroamylasemia when no pancreatitis exists. In macroamylasemia, amylase bound to serum immunoglobulin falsely elevates the serum amylase level.
Fractionation of total serum amylase into pancreatic type (p-type) isoamylase and salivary-type (s-type) isoamylase increases the accuracy of serum amylase. However, the level of p-type also increases in renal failure and in other severe abdominal conditions in which amylase clearance is altered.
The WBC count usually increases to 12,000 to 20,000/μL. Third-space fluid losses may increase the Hct to as high as 50 to 55%, indicating severe inflammation. Hyperglycemia may occur. Serum Ca concentration falls as early as the first day because of the formation of Ca “soaps” secondary to excess generation of free fatty acids, especially by pancreatic lipase. Serum bilirubin increases in 15 to 25% of patients because pancreatic edema compresses the common bile duct.
Plain x-rays of the abdomen may disclose calcifications within pancreatic ducts (evidence of prior inflammation and hence chronic pancreatitis), calcified gallstones, or localized ileus in the left upper quadrant or the center of the abdomen (a “sentinel loop” of small bowel, dilation of the transverse colon, or duodenal ileus). Chest x-ray may reveal atelectasis or a pleural effusion (usually left-sided or bilateral but rarely confined to the right pleural space).
Ultrasonography should be done if gallstone pancreatitis is suspected (and another etiology is not obvious) to detect gallstones or dilation of the common bile duct (which indicates biliary tract obstruction). Edema of the pancreas may be visualized, but overlying gas frequently obscures the pancreas.
CT with IV contrast is generally done to identify necrosis, fluid collections, or pseudocysts once pancreatitis has been diagnosed. It is particularly recommended for severe pancreatitis or if a complication ensues (eg, hypotension or progressive leukocytosis and elevation of temperature). IV contrast facilitates the recognition of pancreatic necrosis; however, it may cause pancreatic necrosis in areas of low perfusion (ie, ischemia). Thus, contrast-enhanced CT should be done only after the patient has been adequately hydrated.
If pancreatic infection is suspected, fluid obtained by percutaneous CT-guided needle aspiration of cysts or areas of fluid collection or necrosis may reveal organisms on Gram stain or culture. The diagnosis is supported by positive blood cultures and, particularly, by the presence of air bubbles in the retroperitoneum on abdominal CT. The advent of magnetic resonance cholangiopancreatography (MRCP) may make the selection of pancreatic imaging simpler.
In edematous pancreatitis, mortality is < 5%. In pancreatitis with necrosis and hemorrhage, mortality is 10 to 50%. In pancreatic infection, mortality is usually 100% without extensive surgical debridement or drainage of the infected area.
CT findings correlate with prognosis. If CT is normal or shows only mild pancreatic edema (Balthazar class A or B), the prognosis is excellent. Patients with peripancreatic inflammation or one area of fluid collection (classes C and D) have a 10 to 15% incidence of abscess formation; the incidence is over 60% in patients with two or more areas of fluid collection (class E).
Ranson's prognostic signs help predict the prognosis of acute pancreatitis. Five of the signs can be documented at admission:
The rest of Ranson’s signs are determined within 48 h of admission:
Mortality increases with the number of positive signs: If < 3 signs are positive, the mortality rate is < 5%; if ≥ 3 are positive, mortality is 15 to 20%.
The APACHE II index (see Table: Acute Physiologic Assessment and Chronic Health Evaluation (APACHE) II Scoring System*), calculated on the second hospital day, also correlates with prognosis.
Adequate fluid resuscitation is essential; up to 6 to 8 L/day of fluid containing appropriate electrolytes may be required. Inadequate fluid therapy increases the risk of pancreatic necrosis.
Fasting is indicated until acute inflammation subsides (ie, cessation of abdominal tenderness and pain, normalization of serum amylase, return of appetite, feeling better). Fasting can last from a few days in mild pancreatitis to several weeks. In severe cases, TPN should be initiated within the first few days to prevent undernutrition.
Pain relief requires parenteral opioids, which should be given in adequate doses. Although morphine may cause the sphincter of Oddi to contract, this is of doubtful clinical significance. Antiemetic agents (eg, prochlorperazine 5 to 10 mg IV q 6 h) should be given to alleviate vomiting. An NGT is required only if significant vomiting persists or ileus is present.
Parenteral H2 blockers or proton pump inhibitors are given. Efforts to reduce pancreatic secretion with drugs (eg, anticholinergics, glucagon, somatostatin, octreotide) have no proven benefit.
Severe acute pancreatitis should be treated in an ICU, particularly in patients with hypotension, oliguria, Ranson’s score ≥ 3, APACHE II ≥ 8, or pancreatic necrosis on CT > 30%. In the ICU, vital signs and urine output are monitored hourly; metabolic parameters (Hct, glucose, and electrolytes) are reassessed every 8 h; ABG is determined as needed; central venous pressure line or Swan-Ganz catheter measurements are determined every 6 h if the patient is hemodynamically unstable or if fluid requirements are unclear. CBC, platelet count, coagulation parameters, total protein with albumin, BUN, creatinine, Ca, and Mg are measured daily.
Hypoxemia is treated with humidified O2 via mask or nasal prongs. If hypoxemia persists or adult respiratory distress syndrome develops, assisted ventilation may be required. Glucose > 170 to 200 mg/dL (9.4 to 11.1 mmol/L) should be treated cautiously with sc or IV insulin and carefully monitored. Hypocalcemia generally is not treated unless neuromuscular irritability occurs; 10 to 20 mL of 10% Ca gluconate in 1 L of IV fluid is given over 4 to 6 h. Chronic alcoholics and patients with documented hypomagnesemia should receive Mg sulfate 1 g/L of replacement fluid for a total of 2 to 4 g, or until levels normalize. If renal failure occurs, serum Mg levels are monitored and IV Mg is given cautiously. With restoration of normal Mg levels, serum Ca levels usually return to normal.
Heart failure should be treated (see Heart Failure : Treatment). Prerenal azotemia should be treated by increased fluid replacement. Renal failure may require dialysis (usually peritoneal).
Antibiotic prophylaxis with imipenem can prevent infection of sterile pancreatic necrosis, although the effect on reducing mortality is unclear. Infected areas of pancreatic necrosis require surgical debridement, but infected fluid collections outside the pancreas may be drained percutaneously. A pseudocyst that is expanding rapidly, infected, bleeding, or likely to rupture requires drainage. Whether drainage is percutaneous, surgical, or endoscopic depends on location of the pseudocyst and institutional expertise. Peritoneal lavage to wash out activated pancreatic enzymes and inflammatory mediators has no proven benefit.
Surgical intervention during the first several days is justified for severe blunt or penetrating trauma or uncontrolled biliary sepsis. Although > 80% of patients with gallstone pancreatitis pass the stone spontaneously, ERCP with sphincterotomy and stone removal is indicated for patients who do not improve after 24 h of treatment. Patients who spontaneously improve generally undergo elective laparoscopic cholecystectomy. Elective cholangiography remains controversial.
There are many causes of acute pancreatitis but the most common are biliary disease and chronic, heavy alcohol intake.
Inflammation is confined to the pancreas in mild cases but, with increasing severity, pancreatic necrosis, pseudocysts, and/or a severe systemic inflammatory response may develop.
Once pancreatitis is diagnosed, CT is done to diagnose pancreatic necrosis or pseudocyst.
CT results and Ranson's signs help establish prognosis.
Treatment is with IV fluid resuscitation, fasting, parenteral analgesics, and acid-blockers.
Identified complications are treated as needed (eg, drainage of pseudocysts, antibiotics for infected pancreatic necrosis).
* This is the Professional Version. *