Keywords
acute pancreatitis, emergency care, infusion therapy, pain relief, nutritional support
How to Cite
Tsys, O. V. (2026). TREATMENT OF ACUTE PANCREATITIS IN THE EMERGENCY DEPARTMENT: STRATEGIES IN THE FIRST HOURS OF THE DISEASE. Herald of Pancreatic Club, 72(3), 4-10. Retrieved from https://vkp.org.ua/index.php/journal/article/view/360
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Abstract
The diagnosis of acute pancreatitis (AP) is established in the presence of at least two of the following signs: 1) typical pancreatic pain; 2) an increase in serum amylase and/or lipase levels more than 3 times above the upper limit of normal; and/or 3) characteristic changes in the pancreas according to radiological examination methods. Gallstones and alcohol consumption are the two most common causes of AP. It is believed that gallstones are the cause of the disease in 40–70% of cases. In this regard, all patients with AP admitted to the emergency department should undergo a transabdominal ultrasound examination. Alcohol consumption is the second most common cause, occurring in 25–40% of patients.
It is extremely important to identify patients who require admission to the intensive care unit, as opposed to the therapeutic ward, as well as those who need to be referred to specialists.
Early initiation of adequate infusion therapy to prevent hypovolaemia and organ hypoperfusion is a critical element in the management of patients with AP. Current clinical guidelines recommend a strategy of “targeted infusion therapy”, which involves administering intravenous fluids while monitoring heart rate, mean arterial pressure, central venous pressure, diuresis, blood urea nitrogen concentration, and hematocrit. Ringer’s solution with lactate has advantages. Currently, routine prescription of antibiotics to patients with AP is not recommended. Mild abdominal pain can be relieved by intravenous administration of acetaminophen or tramadol, but most patients require opioid analgesics for effective pain control.
Early enteral nutrition has been shown to be associated with a lower incidence of infectious complications and a reduced risk of adverse clinical outcomes compared to parenteral nutrition.
References
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2. Bakker O. J., van Brunschot S., van Santvoort H. C. et al. Early versus on-demand nasoenteric tube feeding in acute pancreatitis. N Engl J Med. 2014; 371: 1983–93.
3. Banks P. A., Bollen T. L., Dervcnis C. et al. Classification of acute pancreatitis — 2012: revision of the Atlanta classification and definitions by international consensus. Gut. 2013; 62: 102–11.
4. Brown A., Baillargeon J. D., Hughes M. D., Banks P. A. Can fluid resuscitation prevent pancreatic necrosis in severe acute pancreatitis? Pancreatology. 2002; 2: 104–7.
5. Brown A., Orav J., Banks P. A. Hemoconcentration is an early marker for organ failure and necrotizing pancreatitis. Pancreas. 2000; 20: 367–72.
6. Buxbaum J., Quezada M., Chong B. et al. The Pancreatitis Activity Scoring System predicts clinical outcomes in acute pancreatitis: findings from a prospective cohort study. Am J Gastroenterol. 2018; 113: 755–64.
7. Chebli J. M., Gaburri P. D., De Souza A. F. et al. Oral refeeding in patients with mild acute pancreatitis: prevalence and risk factors of relapsing abdominal pain. J Gastroenterol Hepatol. 2005; 20: 1385–9.
8. Crockett S. D., Wani S., Gardner Т. В. et al. American Gastroenterological Association Institute Guideline on initial management of acute pancreatitis. Gastroenterology. 2018; 154: 1096–101.
9. De Waele J. J., Leppaniemi A. K. Intra-abdominal hypertension in acute pancreatitis. World J Surg. 2009; 33: 1128–33.
10. de-Madaria E., Herrera-Marante I., Gonzalez-Camacho V. et al. Fluid resuscitation with lactated Ringer’s solution vs normal saline in acute pancreatitis: a triple-blind, randomized, controlled trial. United European Gastroenterol J. 2018; 6: 63–72.
11. de-Madaria E., Soler-Sala G., Sanchez-Paya J. et al. Influence of fluid therapy on the prognosis of acute pancreatitis: a prospective cohort study. Am J Gastroenterol. 2011; 106: 1843–50.
12. DiMagno M. J. Oktoberfest binge drinking and acute pancreatitis: is there really no relationship? Clin Gastroenterol Hepatol. 2011; 9: 920–2.
13. Eckerwall G. E., Tingstedt B. B., Bergenzaun P. E., Andersson R. G. Immediate oral feeding in patients with mild acute pancreatitis is safe and may accelerate recovery: a randomized clinical study. Clin Nutr. 2007; 26: 758–63.
14. Fagenholz P. J., Castillo C. F., Harris N. S. et al. Increasing United States hospital admissions for acute pancreatitis, 1988–2003. Ann Epidemiol. 2007; 17: 491–7.
15. Gardner Т. В., Vege S. S., Pearson R. K., Chari S. T. Fluid resuscitation in acute pancreatitis. Clin Gastroenterol Hepatol. 2008; 6: 1070–6.
16. Gullo L., Migliori M., Olah A. et al. Acute pancreatitis in five European countries: etiology and mortality. Pancreas. 2002; 24: 223–7.
17. Gumaste V. V., Roditis N., Mehta D., Dave P. B. Serum lipase levels in nonpancreatic abdominal pain versus acute pancreatitis. Am J Gastroenterol. 1993; 88: 2051–5.
18. Gupta R., Patel K., Calder P. C. et al. A randomised clinical trial to assess the effect of total enteral and total parenteral nutritional support on metabolic, inflammatory and oxidative markers in patients with predicted severe acute pancreatitis (APACHE II >6). Pancreatology. 2003; 3: 406–13.
19. Iqbal U., Anwar H., Scribani M. Ringer’s lactate versus normal saline in acute pancreatitis: a systematic review and meta-analysis. J Dig Dis. 2018; 19: 335–41.
20. Jacobs M. L., Daggett W. M., Civette J. M. et al. Acute pancreatitis: analysis of factors influencing survival. Ann Surg. 1977; 185: 43–51.
21. Kesavan C. R., Pitchumoni C. S., Marino W. D. Acute painless pancreatitis as a rare complication in Legionnaires disease. Am J Gastroenterol. 1993; 88: 468–9.
22. Kochar B., Akshintala V. S., Afghani E. et al. Incidence, severity, and mortality of post-ERCP pancreatitis: a systematic review by using randomized, controlled trials. Gastrointest Endosc. 2015; 81: 143–9.e9.
23. Lankisch P. G., Mahlke R., Blum T. et al. Hemoconcentration: an early marker of severe and/or necrotizing pancreatitis? A critical appraisal. Am J Gastroenterol. 2001; 96: 2081–5.
24. Lankisch P. G., Muller C. H., Niederstadt H., Brand A. Painless acute pancreatitis subsequent to anticholinesterase insecticide (parathion) intoxication. Am J Gastroenterol. 1990; 85: 872–5.
25. Lankisch P. G., Schirren C. A., Kunze E. Undetected fatal acute pancreatitis: why is the disease so frequently overlooked? Am J Gastroenterol. 1991; 86: 322–6.
26. Lim C. L., Lee W., Liew Y. X. et al. Role of antibiotic prophylaxis in necrotizing pancreatitis: a meta-analysis. J Gastrointest Surg. 2015; 19: 480–91.
27. Louie B. E., Noseworthy T., Hailey D. et al. 2004 MacLean-Mueller Prize. Enteral or parenteral nutrition for severe pancreatitis: a randomized controlled trial and health technology assessment. Can J Surg. 2005; 48: 298–306.
28. Lowenfels A. B., Maisonneuve P., Sullivan T. The changing character of acute pancreatitis: epidemiology, etiology, and prognosis. Curr Gastroenterol Rep. 2009; 11: 97–103.
29. Moreau J. A., Zinsmeister A. R., Melton L. J. III, DiMagno E. P. Gallstone pancreatitis and the effect of cholecystectomy: a population-based cohort study. Mayo Clin Proc. 1988; 63: 466–73.
30. Muniraj T., Dang S., Pitchumoni C. S. Pancreatitis or not? Elevated lipase and amylase in ICU patients. J Crit Care. 2015; 30: 1370–5.
31. Pandol S. J., Saluja A. K., Imrie C. W., Banks P. A. Acute pancreatitis: bench to the bedside. Gastroenterology. 2007; 132: 1127–51.
32. Pederzoli P., Bassi C., Vesentini S., Campedelli A. A randomized multicenter clinical trial of antibiotic prophylaxis of septic complications in acute necrotizing pancreatitis with imipenem. Surg Gynecol Obstet. 1993; 176: 480–3.
33. Peery A. F., Crockett S. D., Murphy C. C. et al. Burden and cost of gastrointestinal, liver, and pancreatic diseases in the United States: update 2018. Gastroenterology. 2019; 156: 254–72.e11.
34. Petrov M. S., Kukosh M. V., Emelyanov N. V. A randomized controlled trial of enteral versus parenteral feeding in patients with predicted severe acute pancreatitis shows a significant reduction in mortality and in infected pancreatic complications with total enteral nutrition. Dig Surg. 2006; 23: 336–44.
35. Phillip V., Huber W., Hagemes F. et al. Incidence of acute pancreatitis does not increase during Oktoberfest, but is higher than previously described in Germany. Clin Gastroenterol Hepatol. 2011; 9: 995–1000.e3.
36. Radadiya D., Devani K., Arora S. et al. Peri-procedural aggressive hydration for post endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis prophylaxis: meta-analysis of randomized controlled trials. Pancreatology. 2019; 19(6): 819–27.
37. Rivers E., Nguyen B., Havstad S. et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001; 345: 1368–77.
38. Singh N., Sharma B., Sharma M. et al. Evaluation of early enteral feeding through nasogastric and nasojejunal tube in severe acute pancreatitis: a noninferiority randomized controlled trial. Pancreas. 2012; 41: 153–9.
39. Singh V. K., Gardner Т. В., Papachristou G. I. et al. An international multicenter study of early intravenous fluid administration and outcome in acute pancreatitis. United European Gastroenterol J. 2017; 5: 491–8.
40. Singh V. K., Wu B. U., Bollen T. L. et al. Early systemic inflammatory response syndrome is associated with severe acute pancreatitis. Clin Gastroenterol Hepatol. 2009; 7: 1247–51.
41. Stimac D., Miletic D., Radic M. et al. The role of nonenhanced magnetic resonance imaging in the early assessment of acute pancreatitis. Am J Gastroenterol. 2007; 102: 997–1004.
42. Tenner S., Baillie J., DeWitt J., Vege S. S. American College of Gastroenterology guideline: management of acute pancreatitis. Am J Gastroenterol. 2013; 108: 1400–16.
43. Trna J., Vege S. S., Pribramska V. et al. Lack of significant liver enzyme elevation and gallstones and/or sludge on ultrasound on day 1 of acute pancreatitis is associated with recurrence after cholecystectomy: a population-based study. Surgery. 2012; 151: 199–205.
44. Vasudevan S., Goswami P., Sonika U. et al. Comparison of various scoring systems and biochemical markers in predicting the outcome in acute pancreatitis. Pancreas. 2018; 47: 65–71.
45. Vege S. S., DiMagno M. J., Forsmark C. E. et al. Initial medical treatment of acute pancreatitis: American Gastroenterological Association Institute Technical Review. Gastroenterology. 2018; 154: 1103–39.
46. Villatoro E., Mulla M., Larvin M. Antibiotic therapy for prophylaxis against infection of pancreatic necrosis in acute pancreatitis. Cochrane Database Syst Rev. 2010; 2010(5): CD002941.
47. Wall I., Badalov N., Baradarian R. et al. Decreased mortality in acute pancreatitis related to early aggressive hydration. Pancreas. 2011; 40: 547–50.
48. Warndorf M. G., Kurtzman J. T., Bartel M. J. et al. Early fluid resuscitation reduces morbidity among patients with acute pancreatitis. Clin Gastroenterol Hepatol. 2011; 9: 705–9.
49. Whitcomb D. C., LaRusch J., Krasinskas A. M. et al. Common genetic variants in the CLDN2 and PRSS1-PRSS2 loci alter risk for alcohol-related and sporadic pancreatitis. Nat Genet. 2012; 44: 1349–54.
50. Whitlock T. L., Tignor A., Webster E. M. et al. A scoring system to predict readmission of patients with acute pancreatitis to the hospital within thirty days of discharge. Clin Gastroenterol Hepatol. 2011; 9: 175–80.
51. Windsor A. C., Kanwar S., Li A. G. et al. Compared with parenteral nutrition, enteral feeding attenuates the acute phase response and improves disease severity in acute pancreatitis. Gut. 1998; 42: 431–5.
52. Working Group IAP/APA Acute Pancreatitis Guidelines. IAP/APA evidence-based guidelines for the management of acute pancreatitis. Pancreatology. 2013; 13(4 Suppl 2): e1–e15.
53. Wu B. U., Hwang J. Q., Gardner T. H. et al. Lactated Ringer’s solution reduces systemic inflammation compared with saline in patients with acute pancreatitis. Clin Gastroenterol Hepatol. 2011; 9: 710–7.e1.
54. Yadav D., Lowenfels A. B. Trends in the epidemiology of the first attack of acute pancreatitis: a systematic review. Pancreas. 2006; 33: 323–30.
55. Yadav D., Pitchumoni C. S. Issues in hyperlipidemic pancreatitis. J Clin Gastroenterol. 2003; 36: 54–62.
2. Bakker O. J., van Brunschot S., van Santvoort H. C. et al. Early versus on-demand nasoenteric tube feeding in acute pancreatitis. N Engl J Med. 2014; 371: 1983–93.
3. Banks P. A., Bollen T. L., Dervcnis C. et al. Classification of acute pancreatitis — 2012: revision of the Atlanta classification and definitions by international consensus. Gut. 2013; 62: 102–11.
4. Brown A., Baillargeon J. D., Hughes M. D., Banks P. A. Can fluid resuscitation prevent pancreatic necrosis in severe acute pancreatitis? Pancreatology. 2002; 2: 104–7.
5. Brown A., Orav J., Banks P. A. Hemoconcentration is an early marker for organ failure and necrotizing pancreatitis. Pancreas. 2000; 20: 367–72.
6. Buxbaum J., Quezada M., Chong B. et al. The Pancreatitis Activity Scoring System predicts clinical outcomes in acute pancreatitis: findings from a prospective cohort study. Am J Gastroenterol. 2018; 113: 755–64.
7. Chebli J. M., Gaburri P. D., De Souza A. F. et al. Oral refeeding in patients with mild acute pancreatitis: prevalence and risk factors of relapsing abdominal pain. J Gastroenterol Hepatol. 2005; 20: 1385–9.
8. Crockett S. D., Wani S., Gardner Т. В. et al. American Gastroenterological Association Institute Guideline on initial management of acute pancreatitis. Gastroenterology. 2018; 154: 1096–101.
9. De Waele J. J., Leppaniemi A. K. Intra-abdominal hypertension in acute pancreatitis. World J Surg. 2009; 33: 1128–33.
10. de-Madaria E., Herrera-Marante I., Gonzalez-Camacho V. et al. Fluid resuscitation with lactated Ringer’s solution vs normal saline in acute pancreatitis: a triple-blind, randomized, controlled trial. United European Gastroenterol J. 2018; 6: 63–72.
11. de-Madaria E., Soler-Sala G., Sanchez-Paya J. et al. Influence of fluid therapy on the prognosis of acute pancreatitis: a prospective cohort study. Am J Gastroenterol. 2011; 106: 1843–50.
12. DiMagno M. J. Oktoberfest binge drinking and acute pancreatitis: is there really no relationship? Clin Gastroenterol Hepatol. 2011; 9: 920–2.
13. Eckerwall G. E., Tingstedt B. B., Bergenzaun P. E., Andersson R. G. Immediate oral feeding in patients with mild acute pancreatitis is safe and may accelerate recovery: a randomized clinical study. Clin Nutr. 2007; 26: 758–63.
14. Fagenholz P. J., Castillo C. F., Harris N. S. et al. Increasing United States hospital admissions for acute pancreatitis, 1988–2003. Ann Epidemiol. 2007; 17: 491–7.
15. Gardner Т. В., Vege S. S., Pearson R. K., Chari S. T. Fluid resuscitation in acute pancreatitis. Clin Gastroenterol Hepatol. 2008; 6: 1070–6.
16. Gullo L., Migliori M., Olah A. et al. Acute pancreatitis in five European countries: etiology and mortality. Pancreas. 2002; 24: 223–7.
17. Gumaste V. V., Roditis N., Mehta D., Dave P. B. Serum lipase levels in nonpancreatic abdominal pain versus acute pancreatitis. Am J Gastroenterol. 1993; 88: 2051–5.
18. Gupta R., Patel K., Calder P. C. et al. A randomised clinical trial to assess the effect of total enteral and total parenteral nutritional support on metabolic, inflammatory and oxidative markers in patients with predicted severe acute pancreatitis (APACHE II >6). Pancreatology. 2003; 3: 406–13.
19. Iqbal U., Anwar H., Scribani M. Ringer’s lactate versus normal saline in acute pancreatitis: a systematic review and meta-analysis. J Dig Dis. 2018; 19: 335–41.
20. Jacobs M. L., Daggett W. M., Civette J. M. et al. Acute pancreatitis: analysis of factors influencing survival. Ann Surg. 1977; 185: 43–51.
21. Kesavan C. R., Pitchumoni C. S., Marino W. D. Acute painless pancreatitis as a rare complication in Legionnaires disease. Am J Gastroenterol. 1993; 88: 468–9.
22. Kochar B., Akshintala V. S., Afghani E. et al. Incidence, severity, and mortality of post-ERCP pancreatitis: a systematic review by using randomized, controlled trials. Gastrointest Endosc. 2015; 81: 143–9.e9.
23. Lankisch P. G., Mahlke R., Blum T. et al. Hemoconcentration: an early marker of severe and/or necrotizing pancreatitis? A critical appraisal. Am J Gastroenterol. 2001; 96: 2081–5.
24. Lankisch P. G., Muller C. H., Niederstadt H., Brand A. Painless acute pancreatitis subsequent to anticholinesterase insecticide (parathion) intoxication. Am J Gastroenterol. 1990; 85: 872–5.
25. Lankisch P. G., Schirren C. A., Kunze E. Undetected fatal acute pancreatitis: why is the disease so frequently overlooked? Am J Gastroenterol. 1991; 86: 322–6.
26. Lim C. L., Lee W., Liew Y. X. et al. Role of antibiotic prophylaxis in necrotizing pancreatitis: a meta-analysis. J Gastrointest Surg. 2015; 19: 480–91.
27. Louie B. E., Noseworthy T., Hailey D. et al. 2004 MacLean-Mueller Prize. Enteral or parenteral nutrition for severe pancreatitis: a randomized controlled trial and health technology assessment. Can J Surg. 2005; 48: 298–306.
28. Lowenfels A. B., Maisonneuve P., Sullivan T. The changing character of acute pancreatitis: epidemiology, etiology, and prognosis. Curr Gastroenterol Rep. 2009; 11: 97–103.
29. Moreau J. A., Zinsmeister A. R., Melton L. J. III, DiMagno E. P. Gallstone pancreatitis and the effect of cholecystectomy: a population-based cohort study. Mayo Clin Proc. 1988; 63: 466–73.
30. Muniraj T., Dang S., Pitchumoni C. S. Pancreatitis or not? Elevated lipase and amylase in ICU patients. J Crit Care. 2015; 30: 1370–5.
31. Pandol S. J., Saluja A. K., Imrie C. W., Banks P. A. Acute pancreatitis: bench to the bedside. Gastroenterology. 2007; 132: 1127–51.
32. Pederzoli P., Bassi C., Vesentini S., Campedelli A. A randomized multicenter clinical trial of antibiotic prophylaxis of septic complications in acute necrotizing pancreatitis with imipenem. Surg Gynecol Obstet. 1993; 176: 480–3.
33. Peery A. F., Crockett S. D., Murphy C. C. et al. Burden and cost of gastrointestinal, liver, and pancreatic diseases in the United States: update 2018. Gastroenterology. 2019; 156: 254–72.e11.
34. Petrov M. S., Kukosh M. V., Emelyanov N. V. A randomized controlled trial of enteral versus parenteral feeding in patients with predicted severe acute pancreatitis shows a significant reduction in mortality and in infected pancreatic complications with total enteral nutrition. Dig Surg. 2006; 23: 336–44.
35. Phillip V., Huber W., Hagemes F. et al. Incidence of acute pancreatitis does not increase during Oktoberfest, but is higher than previously described in Germany. Clin Gastroenterol Hepatol. 2011; 9: 995–1000.e3.
36. Radadiya D., Devani K., Arora S. et al. Peri-procedural aggressive hydration for post endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis prophylaxis: meta-analysis of randomized controlled trials. Pancreatology. 2019; 19(6): 819–27.
37. Rivers E., Nguyen B., Havstad S. et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001; 345: 1368–77.
38. Singh N., Sharma B., Sharma M. et al. Evaluation of early enteral feeding through nasogastric and nasojejunal tube in severe acute pancreatitis: a noninferiority randomized controlled trial. Pancreas. 2012; 41: 153–9.
39. Singh V. K., Gardner Т. В., Papachristou G. I. et al. An international multicenter study of early intravenous fluid administration and outcome in acute pancreatitis. United European Gastroenterol J. 2017; 5: 491–8.
40. Singh V. K., Wu B. U., Bollen T. L. et al. Early systemic inflammatory response syndrome is associated with severe acute pancreatitis. Clin Gastroenterol Hepatol. 2009; 7: 1247–51.
41. Stimac D., Miletic D., Radic M. et al. The role of nonenhanced magnetic resonance imaging in the early assessment of acute pancreatitis. Am J Gastroenterol. 2007; 102: 997–1004.
42. Tenner S., Baillie J., DeWitt J., Vege S. S. American College of Gastroenterology guideline: management of acute pancreatitis. Am J Gastroenterol. 2013; 108: 1400–16.
43. Trna J., Vege S. S., Pribramska V. et al. Lack of significant liver enzyme elevation and gallstones and/or sludge on ultrasound on day 1 of acute pancreatitis is associated with recurrence after cholecystectomy: a population-based study. Surgery. 2012; 151: 199–205.
44. Vasudevan S., Goswami P., Sonika U. et al. Comparison of various scoring systems and biochemical markers in predicting the outcome in acute pancreatitis. Pancreas. 2018; 47: 65–71.
45. Vege S. S., DiMagno M. J., Forsmark C. E. et al. Initial medical treatment of acute pancreatitis: American Gastroenterological Association Institute Technical Review. Gastroenterology. 2018; 154: 1103–39.
46. Villatoro E., Mulla M., Larvin M. Antibiotic therapy for prophylaxis against infection of pancreatic necrosis in acute pancreatitis. Cochrane Database Syst Rev. 2010; 2010(5): CD002941.
47. Wall I., Badalov N., Baradarian R. et al. Decreased mortality in acute pancreatitis related to early aggressive hydration. Pancreas. 2011; 40: 547–50.
48. Warndorf M. G., Kurtzman J. T., Bartel M. J. et al. Early fluid resuscitation reduces morbidity among patients with acute pancreatitis. Clin Gastroenterol Hepatol. 2011; 9: 705–9.
49. Whitcomb D. C., LaRusch J., Krasinskas A. M. et al. Common genetic variants in the CLDN2 and PRSS1-PRSS2 loci alter risk for alcohol-related and sporadic pancreatitis. Nat Genet. 2012; 44: 1349–54.
50. Whitlock T. L., Tignor A., Webster E. M. et al. A scoring system to predict readmission of patients with acute pancreatitis to the hospital within thirty days of discharge. Clin Gastroenterol Hepatol. 2011; 9: 175–80.
51. Windsor A. C., Kanwar S., Li A. G. et al. Compared with parenteral nutrition, enteral feeding attenuates the acute phase response and improves disease severity in acute pancreatitis. Gut. 1998; 42: 431–5.
52. Working Group IAP/APA Acute Pancreatitis Guidelines. IAP/APA evidence-based guidelines for the management of acute pancreatitis. Pancreatology. 2013; 13(4 Suppl 2): e1–e15.
53. Wu B. U., Hwang J. Q., Gardner T. H. et al. Lactated Ringer’s solution reduces systemic inflammation compared with saline in patients with acute pancreatitis. Clin Gastroenterol Hepatol. 2011; 9: 710–7.e1.
54. Yadav D., Lowenfels A. B. Trends in the epidemiology of the first attack of acute pancreatitis: a systematic review. Pancreas. 2006; 33: 323–30.
55. Yadav D., Pitchumoni C. S. Issues in hyperlipidemic pancreatitis. J Clin Gastroenterol. 2003; 36: 54–62.