Acute Pancreatitis

1 What is acute pancreatitis (AP)?

AP is an inflammatory condition of the pancreas that has a broad spectrum of severity ranging from mild and self-limited to severe and associated with multiorgan failure. Clinically it is associated with the acute onset of abdominal pain and elevation of serum biochemical markers. The underlying pathophysiology is early and inappropriate activation of digestive enzymes within acinar cells.

2 What are the different degrees of AP, and how are they defined?

Mild AP is defined as pancreatic inflammation (of any cause) without persistent organ failure or local complications. Severe acute pancreatitis (SAP) is associated with systemic complications, including multiple-organ failure, and local complications, such as necrosis, abscess, and/or pseudocyst. This degree of pancreatitis requires aggressive therapy in an intensive care setting to prevent significant morbidity or mortality.

3 What are the causes of AP?

Gallstone-related disease and excessive alcohol intake are the two most common causes of AP in the developed world, comprising 70% of all cases. Beyond these, a number of independent factors are thought to cause pancreatitis, including hypertriglyceridemia (serum triglyceride level above 1500 mg/dL), trauma, and hypercalcemia. Evidence is growing that smoking is a risk factor for AP in a time- and dose-dependent manner. A large number of medications have been implicated in causing AP, including angiotensin-converting enzyme inhibitors, furosemide, tetracycline, aminosalicylic acid, corticosteroids, procainamide, thiazides, metronidazole, and ranitidine. Because of the varied duration between exposure and development of symptoms, and the usual lack of a clear mechanism, it is often difficult to identify a drug as the sole cause of AP. True idiopathic cases of AP are diminishing as more genetic causes of the disease are discovered. Endoscopic retrograde cholangiopancreatography (ERCP) causes pancreatitis in approximately 5% of individuals who undergo this procedure.

4 What are the presenting signs and symptoms of AP?

AP is characterized by the sudden onset of abdominal pain, classically located in the epigastrium and usually associated with nausea and/or vomiting. Radiation of pain from the epigastrium through to the back that is alleviated with the patient leaning forward is a typical but not a necessary feature. Tachycardia related to pain or volume depletion and low-grade fever may be present. Two additional findings associated with severe pancreatitis may be present, the Grey Turner and Cullen signs. The Grey Turner sign is an ecchymosis of the flank due to retroperitoneal hemorrhage. When present, it usually occurs 3 to 7 days after the onset of pain and is indicative of severe pancreatitis. The Cullen sign is periumbilical ecchymosis associated with both severe necrotizing pancreatitis and retroperitoneal hemorrhage of various causes.

5 Are amylase and/or lipase measurements helpful in the diagnosis?

The most commonly used diagnostic markers are serum amylase and lipase. Although serum amylase levels have a high sensitivity in the first 24 hours the specificity is very low. In addition to pancreatitis, elevated amylase levels are seen with many other conditions including bowel infarction, renal failure, perforated peptic ulcer, trauma to the salivary glands, and macroamylasemia. In contrast, serum lipase levels are both more specific and more sensitive than amylase measurements. Of note, no correlation exists between the absolute levels of amylase and lipase and the severity of pancreatitis.

6 What is the role of imaging in the diagnosis of AP?

Abdominal plain radiographs may be nonspecific or reveal an ileus if the pancreatitis is severe. Ultrasound evaluation of the pancreas itself is often limited by overlying bowel gas and/or patient discomfort. This test may, however, detect signs of biliary abnormalities in cases where this cause is suspected.

Computed tomography (CT) with oral and intravenous (IV) contrast can offer information regarding severity of disease (see question 9) and development of complications. Features that may be identified on CT include evidence of inflammation (pancreatic parenchymal edema or peripancreatic fat stranding), peripancreatic or intrapancreatic fluid collections, pancreas perfusion, and presence and extent of pancreatic necrosis.

7 Should all patients have imaging studies done at the time of presentation?

The timing of performing CT in the evaluation of AP has been frequently debated and studied. Obtaining CT early in the course of illness has not been shown to establish alternative diagnoses or change clinical management. The need for cross-sectional imaging should be evaluated on a case-by-case basis and reserved for those who do not improve clinically after several days of supportive therapy and/or in whom worrisome symptoms such as fever or leukocytosis develop. Advanced imaging should be considered early in a patient’s course of illness if the diagnosis itself is uncertain or if suspicion exists of a complication from AP that, if identified, would significantly alter management, or if alternative diagnoses requiring surgical management are considered.

8 What if the patient cannot receive contrast for imaging?

Magnetic resonance imaging (MRI) has a growing role in the diagnosis and management of AP and is a reasonable option in patients who cannot receive iodinated contrast for CT. Enhanced MRI requires the administration of gadolinium, which has been implicated in severe toxic side effects (nephrogenic systemic fibrosis) in patients with compromised renal function. Good correlation has been noted, however, when comparing magnetic resonance cholangiopancreatography (MRCP), with or without gadolinium contrast, with CT in the evaluation AP. MRCP also has the added benefit of being able to better define the pancreatic and biliary ductal system in cases where this cause is suspected but the pretest probability is too low to proceed directly to ERCP.

9 How do you determine the severity and prognosis of AP?

Recognizing and differentiating mild AP from SAP is important so that patients can be triaged to the appropriate setting and treatment plan. Over decades, several clinical predictors have emerged. Although all are imperfect, they are considered superior to clinical judgment alone.

Ranson criteria (Table 47-1) were one of the earliest and widely used scoring systems. Their major disadvantage was that they required 48 hours to complete. The Acute Physiology and Chronic Health Evaluation (APACHE) II system, developed to evaluate critically ill patients, has also been used to differentiate mild AP from SAP. The major disadvantage of this system is that many find it cumbersome as it requires 12 physiologic measures to calculate. A CT severity index (Balthazar score, Table 47-2), has been developed and often used to predict severity of pancreatitis on the basis of radiographic features. The bedside index of severity in AP (BISAP) score (Table 47-3) integrates the systemic inflammatory response syndrome (SIRS) criteria and can be calculated relatively quickly on admission.

^{Table 47-1} Ranson Prognostic Signs

NA, Not applicable.

Modified from Ranson JH, Rifkind KM, Roses DF, et al: Prognostic signs and the role of operative management in acute pancreatitis. Surg Gynecol Obstet 139:69-81, 1974; and Ranson JH: Etiological and prognostic factors in human acute pancreatitis: a review. Am J Gastroenterol 77:633-638, 1982.

^{Table 47-3} Bisap Score

BUN, Blood urea nitrogen; WBC, white blood cells.

Modified from Wu BU, Johannes RS, Sun X, et al: The early prediction of mortality in acute pancreatitis: a large population-based study. Gut 57:1698-1703, 2008.

10 What is the treatment for AP?

The mainstay of treatment in AP is aggressive supportive and symptomatic therapy that includes volume repletion, pain control, nutritional support, correction of electrolyte abnormalities, treatment of infection (if present), and treatment of associated or causative conditions.

Adequate volume repletion and restoration of perfusion to pancreatic microcirculation is imperative to stave off progression of disease and development of local complications. Inadequate volume repletion is associated with higher rates of pancreatic necrosis. No randomized trials exist to guide rate or volume of fluid administration. Most experts recommend isotonic crystalloid infusion rates of 250 to 300 mL/hr or greater for the first 48 hours or enough to maintain urine output at 0.5 mL/kg/hr. Narcotics are usually necessary to establish pain control. IV morphine or hydromorphone at 2- to 4-hour intervals should be considered. Occasionally, continuous infusion with additional patient-administered boluses is necessary.

Antisecretory agents have been considered for use in pancreatitis. The inhibitory effect of octreotide, a pharmaceutical analog of somatostatin, on pancreatic enzyme secretion has led to its study in the treatment of AP. The largest randomized trial comparing placebo with octreotide in the treatment of moderate or severe pancreatitis found no significant difference with regard to mortality, rate of new complications, rate of surgical intervention, duration of pain, or length of hospital stay.

11 How should patients with pancreatitis be fed?

Enteral feeding is the preferred method of nutritional support for all patients who are seen with pancreatitis. It is thought to help maintain the intestinal mucosal barrier, thereby preventing translocation, which is thought to be a major source of infection. No strong evidence exists that nasojejunal feeding is advantageous over nasogastric feeding. Still, many experts recommend fluoroscopic or endoscopic placement of a jejunal, or postpyloric, feeding tube if possible. Parenteral nutrition should be initiated in patients unable to tolerate oral feeding because of pain, ileus, and/or nausea. Opinion with regard to the timing of initiation of parenteral nutrition ranges from 2 to 5 days after presentation.

12 Should all patients with AP receive antibiotics?

No. The use of prophylactic antibiotics to prevent infection of pancreatic necrosis has been controversial but is not currently recommended. No significant benefit has been found with regard to mortality, rates of infected necrosis, need for operative treatment, or overall infections when administering prophylactic antibiotics.

Broad-spectrum antibiotics should be administered if objective evidence exists of infected necrosis on the basis of clinical status (i.e., fever) or cultured aspirate. Some experts believe antibiotics are warranted when evidence is seen on CT of necrosis in > 30% of the pancreas. In such cases, the use of antibiotics should be limited to 7 to 14 days because of the risk of fungal superinfection. If the patient’s condition continues to deteriorate, he or she should be evaluated for minimally invasive and/or surgical debridement or necrosectomy (see question 14).

13 What are the most common bacteria responsible for infected pancreatic necrosis?

Culprit infective agents are usually gut derived, including Escherichia coli, Bacteroides, and Enterococcus. Staphylococcus and Pseudomonas are also potential pathogens and should be considered. Fungal infection of necrosis is rare but more common when prophylactic antibiotics are given. It is unclear whether fungal superinfection has any impact on mortality.

14 What is the role of surgery for AP?

Surgery may be necessary for delayed complications of AP (i.e., pancreatic pseudocysts, persistent sterile necrosis) or for cholecystectomy to prevent future episodes of biliary pancreatitis. Surgical necrosectomy is the gold standard treatment for infected pancreatic necrosis resulting from severe AP. Retrospective reviews addressing timing of intervention found that postponing surgery until 4 or 6 weeks after admission correlated with decreased mortality compared with earlier intervention. Expert panels recommend delaying necrosectomy at least 3 to 4 weeks after hospitalization if possible, while administering antibiotics and allowing the necrosis to organize.

Principles of surgical management of infected pancreatic necrosis include debridement of all infected necrotic material and drainage of the remaining pancreatic bed. Debridement is done bluntly and gently, with hydrosonic irrigation frequently used, to avoid vascular injury. Adequate debridement may require multiple trips to the operating room. The current favored drainage option includes closure of the abdomen over multiple large closed sump drains with or without irrigation. These patients are usually critically ill and require vigorous supportive care.

15 When should minimally invasive or image-guided therapy be considered?

Although surgical necrosectomy remains the gold standard for definitive management of pancreatic necrosis, percutaneous and endoscopic therapies have a growing role in at least adjunctive management. Percutaneous drainage (followed by surgery if necessary) has been associated with fewer major complications than open necrosectomy alone but did not offer any mortality benefit. One third to one half of patients who undergo percutaneous drainage have no need for surgical necrosectomy. CT-guided percutaneous drainage of necrotizing pancreatic collections may be considered as a bridge to necrosectomy in patients with sepsis who are too ill to proceed directly to surgery. Drainage of a walled-off necrotic cavity by endoscopic ultrasonography (EUS) via transgastric or transduodenal approach has been shown to be effective; however, this modality should be considered only in a carefully selected patient population and is dependent on local expertise.

16 Are there additional treatment options for acute biliary pancreatitis?

Early ERCP has previously been the standard of care for patients with AP suspected to be due to gallstones. All patients who have signs or symptoms of cholangitis should have early ERCP to relieve biliary obstruction. Other patients with AP in which cholangitis is not present should be evaluated on a case-by-case basis with the understanding that investigations have shown that early ERCP in patients with predicted mild or severe pancreatitis does not significantly reduce the risk for overall complications or mortality.

17 What are pancreatic pseudocysts?

Pancreatic pseudocysts are localized fluid collections rich in amylase and other pancreatic enzymes surrounded by a wall of fibrous tissue that are not lined by epithelium. Pseudocysts can form as a result of pancreatic necrosis during an episode of pancreatitis or because of disruption in the normal duct anatomy due to stenosis, calculus, or trauma. Pancreatic pseudocysts may be asymptomatic, present with pain alone, or present with a variety of other clinical complications including bleeding, infection, or rupture. Rare complications include gastric outlet and/or biliary obstruction and thrombosis of splenic or portal veins with development of gastric varices. Diagnosis is usually made on the basis of clinical and radiographic evidence.

18 What is the best approach to the management of pseudocysts?

Pancreatic pseudocysts require treatment if they become symptomatic or develop a complication (see question 17). Surgical, percutaneous, and endoscopic approaches have all been used to manage these collections. No randomized trials have been performed to compare these modalities. Endoscopic drainage has advantages of being less invasive, more cost-effective, and associated with lower lengths of stay than surgery, but its use may be limited on the basis of anatomy. Modality of treatment for pancreatic pseudocysts should be based on a combination of factors including patient comorbidities and clinical status, site and characteristics of the lesion, and available local expertise.