Acute Pancreatitis

Gallstones and alcohol abuse account for most cases in the United States. A cause cannot be identified in some patients (idiopathic pancreatitis).

• Many medications have been implicated, but a causal association is difficult to confirm because ethical and practical considerations prevent rechallenge.
• AP is initiated by premature activation of trypsinogen to trypsin within the pancreas, leading to activation of other digestive enzymes and autodigestion of the gland.
• Activated pancreatic enzymes released into the pancreas and surrounding tissues produce damage and necrosis to pancreatic tissue, surrounding fat, vascular endothelium, and adjacent structures. Lipase damages fat cells, producing noxious substances that cause further pancreatic and peripancreatic injury.

CLINICAL PRESENTATION

• Clinical presentation depends on severity of the inflammatory process and whether damage is confined to the pancreas or involves local and systemic complications.
• The initial presentation ranges from moderate abdominal discomfort to excruciating pain, shock, and respiratory distress. Abdominal pain occurs in 95% of patients and is usually epigastric, often radiating to the upper quadrants or back. Onset is usually sudden, and intensity is often described as “knife-like” or “boring.” Pain usually reaches maximum intensity within 30 minutes and may persist for hours or days. Nausea and vomiting occur in 85% of patients and usually follow onset of pain.
• Signs associated with widespread pancreatic inflammation and necrosis include marked epigastric tenderness, abdominal distention, hypotension, tachycardia, and low-grade fever. In severe disease, bowel sounds are diminished or absent. Dyspnea and tachypnea are signs of acute respiratory complications.

DIAGNOSIS

• Contrast-enhanced computed tomography (CECT) of the abdomen may confirm the diagnosis; magnetic resonance imaging and ultrasonography are sometimes useful.
• AP may be associated with leukocytosis, hyperglycemia, and hypoalbuminemia. Hepatic transaminases, alkaline phosphatase, and bilirubin are usually elevated in gallstone pancreatitis and in patients with intrinsic liver disease. Marked hypocalcemia indicates severe necrosis and is a poor prognostic sign.
• Serum amylase usually rises 4 to 8 hours after symptom onset, peaks at 24 hours, and returns to normal over the next 8 to 14 days. Concentrations greater than three times the upper limit of normal are highly suggestive of AP.
• Serum lipase is specific to the pancreas, and concentrations are elevated and parallel the serum amylase elevations. Increases persist longer than serum amylase elevations and can be detected after the amylase has returned to normal.
• Hematocrit may be normal, but hemoconcentration results from multiple factors (e.g., vomiting). Hematocrit greater than 47% predicts severe AP, and hematocrit less than 44% predicts mild disease.
• C-reactive protein levels greater than 150 mg/dL at 48 to 72 hours predict severe AP.
• Thrombocytopenia and increased international normalized ratio (INR) occur in some patients with severe AP and associated liver disease
• Diagnosis should be made within 48 hours based on characteristics of abdominal pain and elevation of amylase, lipase, or both to at least three times the upper limit of normal.

TREATMENT

• Goals of Treatment: Relieve abdominal pain and nausea; replace fluids; correct electrolyte, glucose, and lipid abnormalities; minimize systemic complications; and prevent pancreatic necrosis and infection. Nonpharmacologic Therapy
• Nutritional support is important because AP creates a catabolic state that promotes nutritional depletion. Patients with mild AP can begin oral feeding when bowel sounds have returned, and pain has resolved. Nutritional support should begin when it is anticipated that oral nutrition will be withheld for longer than 1 week. Enteral feeding is preferred over parenteral nutrition (PN) in severe AP, if it can be tolerated. If enteral feeding is not possible or is inadequate, PN should be implemented before protein and calorie depletion become advanced.
• Endoscopic retrograde cholangiopancreatography (ERCP) is performed to remove any biliary tract stones.
• Surgery is indicated in patients with pancreatic pseudocyst or abscess or to drain the pancreatic bed if hemorrhagic or necrotic material is present. Pharmacologic Therapy
• Patients with AP often require IV antiemetics for nausea. Patients with severe AP should be treated with antisecretory agents to prevent stress-related mucosal bleeding. Appropriate fluid resuscitation and pain management are also necessary.
• Vasodilation from the inflammatory response, vomiting, and nasogastric suction contribute to hypovolemia and fluid and electrolyte abnormalities, necessitating replacement. Because there is a lack of objective data, treatment guidelines call for rapid replacement of fluid without details on the optimal rate or type of fluid. Some patients require aggressive fluid resuscitation, whereas others may require gradual fluid administration.
• Parenteral opioid analgesics are used to control abdominal pain. Morphine is often used, and patient-controlled analgesia should be considered in patients who require frequent opioid dosing (e.g., every 2–3 hours). Meperidine is no longer recommended as a first-line agent because of adverse effects (e.g., seizures) and dosing limitations.
• There are insufficient data to support routine use of somatostatin or octreotide for treatment of AP.
• Prophylactic antibiotics offer no benefit in mild AP or when there is no necrosis. Use of antibiotics in severe AP (with or without necrosis) but without infection is not supported by controlled trials.
• Use of antibiotics in necrotizing AP is only recommended in the presence of known or suspected infection.
• Surgical debridement is required once infection develops in patients with necrotic AP. Because the source of bacterial contamination in AP is most likely the colon, broad-spectrum antibiotics that cover enteric aerobic gram-negative bacilli and anaerobic organisms should be started within 48 hours and continued for 2 to 3 weeks when infection is present. Imipenem–cilastatin (500 mg IV every 8 hours) has been widely used but has been replaced on many formularies by newer carbapenems (e.g., meropenem).
• A fluoroquinolone (e.g., ciprofloxacin or levofloxacin) combined with metronidazole should be considered for penicillin-allergic patients.