A Prospective, Randomized, Placebo-Controlled Trial of Prednisone and Allopurinol in the Prevention of ERCP-Induced Pancreatitis

Background and Study Aims: Acute pancreatitis is the most frequent and difficult-to-avoid complication of endoscopic retrograde cholangiopancreatography (ERCP). Corticosteroids, potent anti-inflammatory drugs, and allopurinol - a xanthine oxidase inhibitor that blocks the generation of oxygen-derived free radicals - may be potentially effective in preventing post-ERCP pancreatitis. The aim of this prospective study was to determine the effect of prophylactic oral corticosteroids and allopurinol on the incidence and severity of procedure-induced pancreatitis.

Patients and Methods: 300 patients were randomly assigned to receive oral prednisone (40 mg), allopurinol (200 mg), or placebo 15 h and 3 h prior to ERCP. The diagnosis and grading of ERCP complications were based on commonly accepted criteria. Patients receiving prednisone or allopurinol were compared with the placebo group in a search for differences in pancreatitis rates associated with endoscopic techniques.

Results: The overall incidence of pancreatitis was 10.7 %, with 12 % in the prednisone group, 12.1 % in the allopurinol group, and 7.9 % in the placebo group. There were no statistical differences in the incidence or distribution of severity grades between the groups, although severe pancreatitis occurred only in the prednisone and allopurinol groups. Multiple cannulations and prolonged manipulations of the papilla of Vater were identified as risk factors for ERCP-induced pancreatitis.

Conclusions: Neither prednisone nor allopurinol showed a beneficial influence on the incidence and severity of post-ERCP pancreatitis.

References

• 1 Sherman S, Lehman G A. ERCP - and endoscopic sphincterotomy-induced pancreatitis.  Pancreas. 1991;  6 350-367
• 2 Tulassay Z, Papp J. The effect of long-lasting somatostatin analogue on enzyme changes after endoscopic pancreatography.  Gastrointest Endosc. 1991;  37 48-50
• 3 Binmoeller K F, Harris A G, Dumas R, et al. Does the somatostatin analogue octreotide protect against ERCP-induced pancreatitis?.  Gut. 1992;  33 1129-1133
• 4 Sternlieb J M, Aronchick C A, Retig J N, et al. A multicenter, randomized controlled trial to evaluate the effect of prophylactic octreotide on ERCP-induced pancreatitis.  Am J Gastroenterol. 1992;  87 1561-1566
• 5 Arcidiacono R, Gambitta P, Rossi A, et al. The use of long-acting somatostatin analogue (octreotide) for prophylaxis of acute pancreatitis after endoscopic sphincterotomy.  Endoscopy. 1994;  26 715-718
• 6 Testoni P A, Cicardi M, Bergamaschini L, et al. Infusion of C1-inhibitor plasma concentrate prevents hyperamylasemia induced by endoscopic sphincterotomy.  Gastrointest Endosc. 1995;  42 301-305
• 7 Cavallini G, Tittobello A, Frulloni L, et al. Gabexate for the prevention of pancreatic damage related to endoscopic retrograde cholangiopancreatography.  N Engl J Med. 1996;  335 919-923
• 8 Rabenstein T, Schneider H T, Bulling D, et al. Analysis of the risk factors associated with endoscopic sphincterotomy techniques: preliminary results of a prospective study, with emphasis on the reduced risk of acute pancreatitis with low-dose anticoagulation treatment.  Endoscopy. 2000;  32 10-19
• 9 Sanfey H, Bulkley G .B, Cameron J L. The pathogenesis of acute pancreatitis: the source and role of oxygen-derived free radicals in three different experimental models.  Ann Surg. 1985;  201 633-638
• 10 Wisner J R, Renner I G. Allopurinol attenuates caerulein-induced acute pancreatitis in the rat.  Gut. 1988;  29 926-929
• 11 Sarr M G, Bulkley G B, Cameron J L. Temporal efficacy of allopurinol during the induction of pancreatitis in the ex vivo perfused canine pancreas.  Surgery. 1987;  101 342-346
• 12 Lasser E C, Lang J H, Lyon S G, et al. Glucocorticoid-induced elevations of C-1-esterase inhibitor: a mechanism for protection against lethal dose range contrast challenge in rabbits.  Invest Radiol. 1981;  16 20-23
• 13 Bettinger J R, Grendell J H. Intracellular events in the pathogenesis of acute pancreatitis.  Pancreas. 1991;  6 (Suppl 1) S2-6
• 14 Weiner G R, Geenen J E, Hogan W J, Catalano M F. Use of corticosteroids in the prevention of post-ERCP pancreatitis.  Gastrointest Endosc. 1995;  42 579-583
• 15 De Palma G D, Catanzano C. Use of corticosteroids in the prevention of post-ERCP pancreatitis: results of a controlled prospective study.  Am J Gastroenterol. 1999;  94 982-985
• 16 Dumot J A, Conwell D L, O’Connor B, et al. Pretreatment with methylprednisolone to prevent ERCP-induced pancreatitis: a randomized, multicenter, placebo-controlled clinical trial.  Am J Gastroenterol. 1998;  93 61-65
• 17 Cotton P B, Lehman G, Vennes J, et al. Endoscopic sphincterotomy complications and their management: an attempt at consensus.  Gastrointest Endosc. 1991;  37 383-393
• 18 Huibregtse K, Katon R M, Tytgat G NJ. Precut papillotomy via fine needle-knife papillotome: a safe and effective technique.  Gastrointest Endosc. 1986;  32 403-405
• 19 Freeman M L, Nelson D B, Sherman S, et al. Complications of endoscopic biliary sphincterotomy.  N Engl J Med. 1996;  335 909-918
• 20 Tarnasky P, Cunningham J, Cotton P, et al. Pancreatic sphincter hypertension increases the risk of post-ERCP pancreatitis.  Endoscopy. 1997;  29 252-257
• 21 Sherman S, Hawes R H, Scott W, et al. Post-ERCP pancreatitis: randomized, prospective study comparing a low- and high-osmolality contrast agent.  Gastrointest Endosc. 1994;  40 422-427
• 22 Lankisch P G, Pohl U, Otto J, et al. Xanthine oxidase inhibitor in acute experimental pancreatitis in rats and mice.  Pancreas. 1989;  4 436-440
• 23 Gough D B, Boyle B, Joyce W P, et al. Free radical inhibition and serial chemiluminescence in evolving experimental pancreatitis.  Br J Surg. 1990;  77 1256-1259
• 24 Rinderknecht H. Fatal pancreatitis, a consequence of excessive leukocyte stimulation?.  Int J Pancreatol. 1988;  3 105-112
• 25 Sherman S, Lehman G, Earle D, et al. Does prophylactic oral steroid administration reduce the frequency and severity of post-ERCP pancreatitis?.  Gastrointest Endosc. 1997;  45 AB165, A561
• 26 Runzi M, Layer P. Drug-associated pancreatitis: facts and fiction.  Pancreas. 1996;  13 100-109
• 27 Sherman S, Ruffolo T A, Hawes R H, Lehman G A. Complications of endoscopic sphincterotomy: a prospective series with emphasis on the increased risk associated with sphincter of Oddi dysfunction and nondilated bile ducts.  Gastroenterology. 1991;  101 1068-1075
• 28 Chen Y K, Foliente R L, Santoro M J, et al. Endoscopic sphincterotomy-induced pancreatitis: increased risk associated with nondilated bile ducts and sphincter of Oddi dysfunction.  Am J Gastroenterol. 1994;  89 327-333