Acute pancreatitis is an inflammatory disorder of the pancreas characterized by severe pain in the upper abdomen and increased serum concentrations of pancreatic lipase and amylase. Most patients with mild Acute pancreatitis recover completely, but severe Acute pancreatitis is associated with local complications such as acute fluid collection, pancreatic necrosis, abscess, and pseudocyst. Exocrine and endocrine pancreatic functions may remain impaired for variable periods after an acute attack, but Acute pancreatitis rarely progresses to chronic pancreatitis.
Chronic pancreatitis is a syndrome of destructive and inflammatory conditions resulting from long-standing pancreatic injury. It is characterized by irreversible fibrosis and destruction of exocrine and endocrine tissue but is not invariably progressive. Most patients have periods of intractable abdominal pain. Progressive pancreatic insufficiency leads to maldigestion and diabetes mellitus.
Gallstone-associated biliary tract disease and ethanol use 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.
Table Medications Associated with Acute Pancreatitis lists medications according to their certainty of causing Acute pancreatitis. A definite association implies a temporal relationship of drug administration to abdominal pain and hyperamylasemia or to a positive response to rechallenge. Suggestive evidence exists for drugs with a probable association, whereas evidence is inadequate or contradictory for drugs having a possible associa- tion.
Acute pancreatitis is initiated by premature activation of pancreatic zymogens (inactive enzymes) within the acinar cells, pancreatic ischemia, or pancreatic duct obstruction.
Release of active pancreatic enzymes directly causes local or distant tissue damage. Trypsin digests cell membranes and leads to the activation of other pancreatic enzymes. Lipase damages fat cells, producing noxious substances that cause further pancreatic and peripancreatic injury.
Release of cytokines injures the acinar cell and enhances the inflammatory response. Injured acinar cells liberate chemoattractants that attract neutrophils, macrophages, and other cells to the area of inflammation, and increased vascular permeability promotes tissue edema.
Pancreatic infection may result from increased intestinal permeability and translocation of colonic bacteria.
Local complications include acute fluid collection, pancreatic necrosis, abscess, pseudocyst formation, and pancreatic ascites.
Systemic complications include cardiovascular, renal, pulmonary, metabolic, hemorrhagic, and central nervous system abnormalities.
|TABLE. Medications Associated with Acute Pancreatitis|
In most individuals, chronic pancreatitis is progressive and loss of pancreatic function is irreversible. Permanent destruction of pancreatic tissue usually leads to exocrine and endocrine insufficiency.
Prolonged ethanol consumption accounts for 70% of all cases in the United States; 10% result from other causes, and 20% are idiopathic.
Ethanol-induced pancreatitis appears to progress from inflammation to cellular necrosis, and fibrosis occurs over time. Chronic alcohol ingestion causes changes in pancreatic fluid that create intraductal protein plugs that block small ductules. This results in progressive structural damage in the ducts and acinar tissue. Calcium complexes with the protein plugs, eventually resulting in destruction of pancreatic tissue.
Abdominal pain may be related in part to increased intraductal pressure secondary to continued pancreatic secretion, pancreatic inflammation, and abnormalities of pancreatic nerves.
Malabsorption of protein and fat occurs when the capacity for enzyme secretion is reduced by 90%. Lipase secretion decreases more rapidly than the proteolytic enzymes. Reduced bicarbonate secretion may lead to a duodenal pH of less than 4.
A minority of patients develop complications including pancreatic pseudocyst, abscess, and ascites or common bile duct obstruction leading to cholangitis or secondary biliary cirrhosis.
The clinical presentation depends on the severity of the inflammatory process and whether damage is confined to the pancreas or involves contiguous organs.
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. The onset is usually sudden and the intensity is often described as «knifelike» or «boring.» The pain tends to be steady and usually persists for several days. Nausea and vomiting occur in 85% of patients and usually follow the onset of pain.
Clinical signs associated with widespread pancreatic inflammation and necrosis include marked epigastric tenderness, abdominal distention, hypotension, and low-grade fever. In severe disease, bowel sounds are diminished or absent. Dyspnea and tachypnea are signs of acute respiratory complications.
The main features are abdominal pain, malabsorption, weight loss, and diabetes. Jaundice occurs in about 10% of patients.
Patients typically report dull epigastric or abdominal pain that radiates to the back. It may be either consistent or episodic. The pain is deep-seated, positional, frequently nocturnal, and unresponsive to medication. Nausea and vomiting often accompany the pain. Severe attacks last from several days to weeks and may be aggravated by eating and relieved by abstinence from alcohol.
Steatorrhea (excessive loss of fat in the feces) and azotorrhea (excessive loss of protein in the feces) are seen in most patients. Steatorrhea is often associated with diarrhea and bloating. Weight loss may occur.
Pancreatic diabetes is usually a late manifestation that is commonly associated with pancreatic calcification. Neuropathy is sometimes seen.
A definitive diagnosis of Acute pancreatitis is made by surgical examination of the pancreas or pancreatic histology. In the absence of these procedures, the diagnosis depends on recognition of an etiologic factor, clinical signs and symptoms, abnormal laboratory tests, and imaging techniques that predict disease severity.
Acute pancreatitis and its complications may be associated with leukocytosis, hyperglycemia, hypoalbuminemia, mild hyperbilirubinemia, and elevations in serum alkaline phosphatase and hepatic transaminases.
Dehydration may lead to hemoconcentration with elevated hemoglobin, hematocrit, BUN, and serum creatinine.
Marked hypocalcemia indicates severe necrosis and is a poor prognostic sign.
Some patients with severe pancreatitis develop thrombocytopenia and a prolonged prothrombin time.
C-reactive protein increases by 48 hours after the onset of symptoms and may be useful in distinguishing mild from severe pancreatitis.
The serum amylase concentration usually rises 4 to 8 hours of symptom onset, peaks at 24 hours, and returns to normal over the next 8 to 14 days. Serum amylase elevations do not correlate with disease etiology or severity.
Serum lipase is specific to the pancreas, and concentrations are usually elevated. Serum lipase elevations persist longer than serum amylase elevations and can be detected after the amylase has returned to normal.
Contrast-enhanced computed tomography distinguishes interstitial from necrotizing pancreatitis. Endoscopic retrograde cholangiopancreatography is used to visualize and remove bile duct stones in patients with gallstone pancreatitis.
Most patients have a history of heavy ethanol use and attacks of recurrent upper abdominal pain. The classic triad of calcification, steatorrhea, and diabetes usually confirms the diagnosis.
Serum amylase and lipase concentrations usually remain normal unless the pancreatic duct is blocked or a pseudocyst is present.
The white blood cell count, fluid balance, and electrolyte concentrations usually remain normal unless fluids and electrolytes are lost due to vomiting and diarrhea.
Malabsorption of fat can be detected by Sudan staining of the feces or a 72-hour quantitative measurement of fecal fat.
Surgical biopsy of pancreatic tissue through laparoscopy or laparotomy is the gold standard for confirming the diagnosis of chronic pancreatitis.
In the absence of histologic samples, imaging techniques are helpful in detecting calcification of the pancreas and other causes of pain (ductal obstruction secondary to stones, strictures, or pseudocysts) and in differentiating chronic pancreatitis from pancreatic cancer. Ultrasound is the simplest and least expensive technique, and abdominal computed tomography is often used if the ultrasound examination is negative or unsatisfactory.
Endoscopic retrograde cholangiopancreatography is the most sensitive and specific diagnostic test, but it is reserved for patients in whom the diagnosis cannot be established by imaging techniques because of its expense and the potential for complications.
Treatment of Acute pancreatitis is aimed at relieving abdominal pain, replacing fluids, minimizing systemic complications, and preventing pancreatic necrosis and infection.
The goal of treatment of uncomplicated chronic pancreatitis is directed at control of chronic pain and correction of malabsorption and glucose intolerance.
Medications listed in Table Medications Associated with Acute Pancreatitis should be discontinued whenever possible.
Initial treatment usually involves withholding food or liquids to minimize exocrine stimulation of the pancreas.
Nasogastric aspiration is beneficial in patients with profound pain, severe disease, paralytic ileus, and intractable vomiting.
Patients predicted to follow a severe course require treatment of any cardiovascular, respiratory, renal, and metabolic complications. Aggressive fluid resuscitation is essential to correct intravascular volume depletion and maintain blood pressure. Intravenous colloids may be required because fluid losses are rich in protein. Drotrecogin alfa may benefit patients with pancreatitis and systemic inflammatory response syndrome. Intravenous potassium, calcium, and magnesium are used to correct deficiency states. Insulin is used to treat hyperglycemia. Patients with necrotizing pancreatitis may require antibiotics and surgical intervention.
Nutritional support with enteral or parenteral nutrition should be initiated if it is anticipated that oral nutrition will be withheld for more than 1 week.
Analgesics are given to reduce abdominal pain. In the past, treatment was usually initiated with parenteral meperidine (50 to 100 mg) every 3 to 4 hours because it causes less spasm of the sphincter of Oddi than other narcotics. Meperidine is used less frequently today because it is not as effective as other opioids and is contraindicated in renal failure. Parenteral morphine is sometimes used, but it can cause spasm of the sphincter of Oddi, increase serum amylase and rarely pancreatitis. Although it is less well studied, hydromorphone has a longer half-life than meperidine and can be given parenterally by a patient-controlled analgesia pump.
There is no evidence that inhibition of gastric acid secretion by antisecretory drugs prevents exacerbations of abdominal pain, but they may be used to prevent stress-related mucosal bleeding.
Although there are conflicting data, octreotide, 0.1 mg subcutaneously every 8 hours, may decrease sepsis, length of hospital stay, and perhaps mortality in patients with severe Acute pancreatitis.
Only patients with severe Acute pancreatitis complicated by necrosis should receive infection prophylaxis with broad-spectrum antibiotics. Agents that cover the range of enteric aerobic gram-negative bacilli and anaerobic organisms should be started within the first 48 hours and continued for 2 to 3 weeks. Imipenem-cilastatin (500 mg every 8 hours) may be most effective; a fluoroquinolone (e.g., ciprofloxacin, levofloxacin) with metronidazole should be considered for penicillin-allergic patients.
In patients with ethanol-induced chronic pancreatitis, abstinence is the most important factor in preventing abdominal pain in the early stages of the disease.
Small and frequent meals (6 meals/day) and a diet restricted in fat (50 to 75 g/day) are recommended to minimize postprandial pancreatic secretion and pain.
Pain management should begin with nonnarcotic analgesics such as acetaminophen or nonsteroidal anti-inflammatory drugs given on a scheduled basis before meals to prevent postprandial exacerbation of pain. If these agents are ineffective, consideration should be given to using tramadol or adding a low-dose opioid (e.g., acetaminophen and codeine). If pain persists, the response to exogenous pancreatic enzymes should be evaluated in patients with mild to moderate chronic pancreatitis.
If these measures fail, an oral opioid should be added to the regimen. Parenteral opioids are reserved for patients with severe pain unresponsive to oral analgesics. In patients with pain that is difficult to manage, nonnarcotic modulators of chronic pain (e.g., selective serotonin reuptake inhibitors, tricyclic antidepressants) may be considered.
Most patients with malabsorption require pancreatic enzyme supplementation. The combination of pancreatic enzymes (lipase, amylase, and protease) and a reduction in dietary fat (to less than 25 g/meal) enhances nutritional status and reduces steatorrhea. An initial dose containing about 30,000 IU of lipase and 10,000 IU of trypsin should be given with each meal.
Oral pancreatic enzyme supplements are available as powders, uncoated or coated tablets, capsules, enteric-coated spheres and microspheres, or enteric-coated microtablets encased in a cellulose or gelatin capsul. Microencapsulated enteric-coated products are not superior to recommended doses of conventional nonenteric-coated enzyme preparations. The quantity of active lipase delivered to the duodenum appears to be a more important determinant in pancreatic enzyme replacement therapy than the dosage form. Gastrointestinal side effects appear to be dose-related but occur less frequently with enteric-coated products.
The concurrent use of antisecretory drugs (H2-receptor antagonists or proton pump inhibitors) may improve the efficacy of pancreatic enzyme supplementation by both increasing pH and decreasing intragastric volume. Antacids appear to have little or no added effect in reducing steatorrhea. Addition of an H2 -receptor antagonist may be beneficial for symptomatic patients whose steatorrhea is not corrected by enzyme replacement therapy and reducing dietary fat. A proton pump inhibitor should be considered in patients who fail to benefit from an H2-receptor antagonist.
Removal of an underlying biliary tract gallstone with Endoscopic retrograde cholangiopancreatography or surgery usually resolves Acute pancreatitis and reduces the risk of recurrence. Surgery may be indicated in
Acute pancreatitis to treat pseudocyst, pancreatic abscess, and to drain the pancreatic bed if hemorrhagic or necrotic material is present.
The most common indication for surgery in chronic pancreatitis is abdominal pain refractory to medical therapy. Surgical procedures that alleviate pain include a subtotal pancreatectomy, decompression of the main pancreatic duct, or interruption of the splanchnic nerves.
Evaluation of therapeutic outcomes
In patients with mild Acute pancreatitis, pain control, fluid and electrolyte status, and nutrition should be assessed periodically depending on the degree of abdominal pain and fluid loss.
Patients with severe Acute pancreatitis should be transferred to an intensive care unit for close monitoring of vital signs, prothrombin time, fluid and electrolyte status, white blood cell count, blood glucose, lactate dehydrogenase, aspartate aminotransferase, serum albumin, hematocrit, BUN, and serum creatinine. Continuous hemodynamic and arterial blood gas monitoring is essential. Serum lipase, amylase, and bilirubin require less frequent monitoring. The patient should be monitored for signs of infection, relief of abdominal pain, and adequate nutritional status.
|TABLE. Enzyme content of selected pancreatic enzyme preparations|
The severity and frequency of abdominal pain should be assessed periodically to determine the efficacy of the analgesic regimen.
The effectiveness of pancreatic enzyme supplementation is measured by improvement in body weight and stool consistency or frequency. The 72-hour stool test for fecal fat may be used when the adequacy of treatment is in question.
Serum uric acid and folic acid concentrations should be monitored yearly in patients prone to hyperuricemia or folic acid deficiency. Blood glucose must be monitored carefully in diabetic patients.