Special Feature: Severe Acute Pancreatitis: A Focused Review
July 1, 2009 7 minutes read
Special Feature
Severe Acute Pancreatitis: A Focused Review
By Saadia R. Akhtar, MD, MSc, Idaho Pulmonary Associates, Boise, is Associate Editor for Critical Care Alert.
Dr. Akhtar reports no financial relationship to this field of study.
Acute pancreatitis was described by surgeon Berkely Moynihan in 1925 as "… the most terrible of all calamities that occur in connection with the abdominal viscera." Although our understanding and management of this condition has progressed considerably since then, this description remains apt at least for the most advanced and complex cases of severe acute pancreatitis.1
Acute pancreatitis is a condition in which inappropriate activation of digestive pancreatic enzymes leads to pancreatic inflammation and destruction. This process may further trigger a systemic inflammatory response and multiorgan dysfunction; that is, it may become a severe acute pancreatitis.
More than 230,000 Americans are admitted annually for acute pancreatitis.2 Excessive alcohol intake and gallstones are the typical etiologies; about 20% of cases are idiopathic. Other known causes include hyperlipidemia, hypercalcemia, a variety of drugs, infections, duodenal or ampullary strictures, ischemia, genetic mutations (such as those of cystic fibrosis transmembrane conductance regulator), and other.3
Most cases of acute pancreatitis are mild with resolution within 1 week and very low (< 1%) mortality; about 15-20% of cases are severe. Patients with severe acute pancreatitis have a mean hospital stay of 1 month. Mortality is up to 15% with any pancreatic necrosis and up to 30-50% with infected pancreatic necrosis.4
Risk Assessment
There is a wide spectrum of disease severity in acute pancreatitis. A variety of scoring systems aim to identify severe acute pancreatitis (or those at highest risk of it) with the hope of implementing protocol-driven aggressive early resuscitation and care and preventing (or at least quickly controlling) local and systemic complications; that is, ultimately improving patient outcomes.5
The "classic" scoring system is Ranson's criteria, initially described in the 1970s in patients with alcoholic pancreatitis. Ranson's criteria use initial data points (age, white blood cell count [WBC], glucose, lactate dehydrogenase [LDH], aspartate aminotransferase [AST]) and characteristics at 48 hours (hematocrit, blood urea nitrogen [BUN], calcium, oxygenation, base deficit and net fluid intake) to determine a score. A score of 1 or 2 is consistent with mild disease and ≥ 3 is severe disease (correlating with adverse outcomes including increased mortality).6
There are multiple newer classification systems. For example, the Glasgow/Imrie system tries to simplify the Ranson's criteria: It uses the presence of 3 or more of 9 criteria at 48 hours of illness to define severe acute pancreatitis (age > 55 years and specific levels of WBC, glucose, BUN, calcium, albumin, LDH, AST, and oxygenation). The Glasgow/Imrie score appears to be predictive for acute pancreatitis of any etiology.7 A 1992 International Symposium on Acute Pancreatitis proposed the Atlanta criteria: ≥ 3 Ranson's criteria, an APACHE II score of ≥ 8, or evidence of organ failure and intrapancreatic pathology.8
It is clear that pancreatic necrosis and sepsis with associated organ failures are directly associated with mortality from severe acute pancreatitis. Thus, trends in nonspecific measures of severity of illness such as APACHE II score and C-reactive protein over the first 48 hours are useful indicators of severity and expected ICU mortality. Finally, the computed tomographic (CT) severity index grades pancreatic appearance and degree of necrosis to define severe acute pancreatitis.9
Other data points of interest include initial hemoconcentration (admission hematocrit > 47%), which is suggestive of severe acute pancreatitis. Furthermore, lack of improvement in hemoconcentration over the first 24 hours is predictive of local and systemic complications. Obesity (BMI > 30 kg/m2) is an independent predictor of death from acute pancreatitis. Serum amylase and lipase levels are useful in initial diagnosis, but they do not correlate with severity of acute pancreatitis.
Although not ready for widespread clinical use at this point, a variety of other serum markers are of interest as potential predictors of severe acute pancreatitis and outcomes: interleukin (IL)-6, IL-8, tumor necrosis factor alpha, procalcitonin, and markers of trypsinogen activity. Monocyte chemotactic protein-1 (MCP-1) polymorphisms may predict susceptibility to severe acute pancreatitis, and level of MCP-1 correlates with severity and multiorgan failure.10
Diagnosis
Usual presenting symptoms of acute pancreatitis include abdominal pain (often upper quadrant or epigastric), nausea, and vomiting.3,4 Elevated serum amylase and lipase levels (> 3 times the upper limits of normal) are consistent with the diagnosis.
Underlying etiology may be clear from the history (such as alcohol abuse or recent initiation of a new medication associated with acute pancreatitis). A markedly elevated alanine aminotransferase in the absence of alcohol abuse has a positive predictive value of 95% for gallstone pancreatitis. Measurement of calcium and triglyceride levels is also useful.
Initial imaging with transabdominal ultrasound or abdominal CT should be strongly considered if the diagnosis is uncertain or if gallstone pancreatitis is suspected and biliary obstruction must be ruled out. Otherwise, in patients with severe acute pancreatitis, delayed abdominal CT at 48-72 hours should be considered to assess for local complications. Pancreatic fluid collections occur in more than 50% of patients hospitalized with acute pancreatitis; most may be managed conservatively. There is, however, risk of enlargement, infection, and pseudocyst formation. Pancreatic necrosis with subsequent infection is one of the most dreaded complications. Ultrasound- or CT-guided needle aspiration to rule out infected pancreatic necrosis should be considered if necrosis or fluid collections are found.
Abdominal CT findings in severe acute pancreatitis include pancreatic enlargement, loss of peri-pancreatic fat planes, decreased density within the pancreas, and presence of variable ill-defined collections. Failure of pancreatic enhancement with contrast is consistent with pancreatic necrosis.
Management
Treatment of severe acute pancreatitis is primarily supportive: hydration, analgesia, and close monitoring for development of organ dysfunction. Standard critical care practice obviously applies: appropriate glucose control, prophylaxis for deep venous thrombosis, stress gastritis prophylaxis when indicated, etc.3,4
There does not appear to be a role for antibiotics when pancreatic infection has not been confirmed bacteriologically. Multiple small trials (typically < 50 patients) have evaluated prophylactic antibiotic therapy for acute pancreatitis: Most are flawed studies (due to lack of blinding, variable definition of acute pancreatitis, inclusion of patients with mild pancreatitis, etc.) that have not demonstrated decreases in pancreatic infections or other adverse outcomes. Only one trial found a mortality benefit of prophylactic antibiotics in severe acute pancreatitis but the results were greatly weakened because of excessive mortality in the control group. Thus, currently, prophylactic antibiotics are not recommended for acute pancreatitis of any severity. Similarly, there is no good support for empiric antifungals in patients with severe acute pancreatitis.11,12
Early surgical drainage/intervention is almost never indicated and usually worsens outcomes.1 Delayed surgical resection of infected pancreatic necrosis should be considered, ideally at least 2-3 weeks after initial presentation to allow full demarcation of viable tissue. Otherwise, there is no role for surgery for severe acute pancreatitis.
Early (< 72 hours) endoscopic retrograde cholangiopancreatography with endoscopic sphincterotomy and stone removal should be considered in patients with severe acute pancreatitis, gallstones, and persistent biliary obstruction with obstructive jaundice. This considerably lowers risk of local and systemic complications.13 Following resolution of the acute illness, definitive treatment to prevent recurrence must be considered; for gallstone pancreatitis, cholecystectomy should be undertaken within a few weeks to no more than a few months following the episode of acute pancreatitis.
Nutrition
Aggressive nutritional support is essential in the treatment of severe acute pancreatitis. Traditionally, bowel rest and parenteral nutrition were utilized due to concerns that enteral feeding would stimulate pancreatic enzyme release and worsen pancreatic inflammation. Over time, an understanding of the risks of parenteral nutrition (e.g., infection and hyperglycemia) and potential benefits of enteral feeding (e.g., maintenance of gut mucosal integrity) have led to a change in practice.
Although there have been no large randomized controlled trials of enteral vs parenteral nutrition for severe acute pancreatitis, meta-analyses of smaller such trials (< 100 patients) suggest good tolerance of and, sometimes, improved outcomes (lower rates of infection and surgical intervention) with enteral nutrition.14 The majority of these studies have instituted jejunal feedings and this remains the preferred route, but gastric feedings may be similarly well-tolerated.15
Animal studies and some small clinical human studies have suggested that enteric administration of probiotics in patients with acute pancreatitis may reduce risk of pancreatic necrosis and infectious complications. Larger multicenter controlled trials are needed to confirm these findings before any specific recommendations can be made for probiotics in this setting.16
Conclusion
Severe acute pancreatitis remains a relatively common diagnosis and a challenging management dilemma in any intensive care unit. Although specific scoring systems and predictors of severity may be helpful, ultimately, careful clinical care is the key to achieving the best possible patient outcomes. This includes close monitoring, identification of the trigger (with definitive treatment of that if indicated), aggressive hydration, repeated clinical assessment for progressive symptoms or organ dysfunction, and high suspicion for local complications with repeat abdominal imaging as indicated.
References
- Rocha FG, et al. A historic perspective on the contributions of surgeons to the understanding of acute pancreatitis. Am J Surg 2008;196:442-449.
- Center for Disease Control and Prevention. National Center for Health Statistics. Available at: www.cdc.gov/nchs/. Accessed June 8, 2009.
- Whitcomb DC. Clinical practice. Acute pancreatitis. N Engl J Med 2006;354:2142-2150.
- Nathens AB, et al. Management of the critically ill patient with severe acute pancreatitis. Crit Care Med 2004;32:2524-2536.
- Mofidi R, et al. Risk assessment in acute pancreatitis. Br J Surg 2009;96:137-150.
- Ranson JH, et al. Prognostic signs and the role of operative management in acute pancreatitis. Surg Gynecol Obstet 1974;139:69-81.
- Imrie CW. Prognostic indicators in acute pancreatitis. Can J Gastroenterol 2003;17:325-328.
- Bradley EL 3rd. A clinically based classification system for acute pancreatitis. Summary of the International Symposium on Acute Pancreatitis, Atlanta, Ga, September 11 through 13, 1992. Arch Surg 1993;128:586-590.
- Balthazar EJ, et al. Acute pancreatitis: Value of CT in establishing prognosis. Radiology 1990;174:331-336.
- Papachristou GI. Prediction of severe acute pancreatitis: Current knowledge and novel insights. World J Gastroenterol 2008;14:6273-6275.
- Villatoro E, et al. Antibiotic therapy for prophylaxis against infection of pancreatic necrosis in acute pancreatitis. Cochrane Database Syst Rev 2006;(4):CD002941.
- Nathens AB, et al. Executive summary: Management of the critically ill patient with severe acute pancreatitis. Proc Am Thorac Soc 2004;1:289-290.
- Ayub K, et al. Endoscopic retrograde cholangiopancreatography in gallstone-associated acute pancreatitis. Cochrane Database Syst Rev 2004;(4):CD003630.
- Marik PE, Zaloga GP. Meta-analysis of parenteral nutrition vs. enteral nutrition in patients with acute pancreatitis. BMJ 2004;328:1407.
- Petrov MS, et al. Nasogastric tube feeding in predicted severe acute pancreatitis. A systematic review of the literature to determine safety and tolerance. JOP 2008;9:440-448.
- Capurso G, et al. Probiotics and severe acute pancreatitis. J Clin Gastroenterol 2008;42(Suppl 3 Pt 1):S148-S151.
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