Intramuscular diclofenac for the prevention of post-ERCP pancreatitis: a randomized trial

Background and study aims: Rectal nonsteroidal anti-inflammatory drugs have been shown to reduce the incidence of postendoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP). The aim of this study was to determine whether intramuscular diclofenac reduces the risk of PEP.

Patients and methods: Patients who underwent ERCP were randomized to receive either 90 mg of diclofenac or placebo by intramuscular injection immediately after the procedure. PEP was defined as elevated serum amylase levels (at least three times the upper limit of normal 24 hours after the procedure) associated with new or worsened upper abdominal, epigastric, or back pain.

Results: In total, 380 patients were randomized, and 343 were eligible for analysis. The two groups were similar regarding clinical and demographic factors, as well as patient- and procedure-related risk factors for PEP. PEP developed in 20/170 patients (11.8 %) in the placebo group and in 22/173 patients (12.7 %) in the diclofenac group (P = 0.87). Multivariate regression analysis failed to illustrate that intramuscular diclofenac prevented PEP (odds ratio 0.79; 95 % confidence interval 0.39 – 1.25; P = 0.51).

Conclusion: Prophylactic intramuscular diclofenac had no beneficial preventive effect on PEP.

Clinicaltrials.gov NCT01717599.

• References

• 1 Andriulli A, Loperfido S, Napolitano G et al. Incidence rates of post-ERCP complications: a systematic survey of prospective studies. Am J Gastroenterol 2007; 102: 1781-1788
• 2 Freeman ML, Guda NM. Prevention of post-ERCP pancreatitis: a comprehensive review. Gastrointest Endosc 2004; 59: 845-864
• 3 Makela A, Kuusi T, Schroder T. Inhibition of serum phospholipase-A2 in acute pancreatitis by pharmacological agents in vitro. Scand J Clin Lab Invest 1997; 57: 401-407
• 4 Yuhara H, Ogawa M, Kawaguchi Y et al. Pharmacologic prophylaxis of post-endoscopic retrograde cholangiopancreatography pancreatitis: protease inhibitors and NSAIDs in a meta-analysis. J Gastroenterol 2014; 49: 388-399
• 5 Elmunzer BJ, Waljee AK, Elta GH et al. A meta-analysis of rectal NSAIDs in the prevention of post-ERCP pancreatitis. Gut 2008; 57: 1262-1267
• 6 Ding X, Chen M, Huang S et al. Nonsteroidal anti-inflammatory drugs for prevention of post-ERCP pancreatitis: a meta-analysis. Gastrointest Endosc 2012; 76: 1152-1159
• 7 Dai HF, Wang XW, Zhao K. Role of nonsteroidal anti-inflammatory drugs in the prevention of post-ERCP pancreatitis: a meta-analysis. Hepatobiliary Pancreat Dis Int 2009; 8: 11-16
• 8 Dumonceau JM, Andriulli A, Deviere J et al. European Society of Gastrointestinal Endoscopy (ESGE) Guideline: prophylaxis of post-ERCP pancreatitis. Endoscopy 2010; 42: 503-515
• 9 Anderson MA, Fisher L. ASGE Standards of Practice Committee et al. Complications of ERCP. Gastrointest Endosc 2012; 75: 467-473
• 10 Senol A, Saritas U, Demirkan H. Efficacy of intramuscular diclofenac and fluid replacement in prevention of post-ERCP pancreatitis. World J Gastroenterol 2009; 15: 3999-4004
• 11 Elmunzer BJ, Scheiman JM, Lehman GA et al. A randomized trial of rectal indomethacin to prevent post-ERCP pancreatitis. N Engl J Med 2012; 366: 1414-1422
• 12 Cotton P, Lehman G, Vennes J et al. Endoscopic sphincterotomy complications and their management: an attempt at consensus. Gastrointest Endosc 1991; 37: 383-393
• 13 Loperfido S, Angelini G, Benedetti G et al. Major early complications from diagnostic and therapeutic ERCP: a prospective multicenter study. Gastrointest Endosc 1998; 48: 1-10
• 14 Masci E, Toti G, Mariani A et al. Complications of diagnostic and therapeutic ERCP: a prospective multicenter study. Am J Gastroenterol 2001; 96: 417-423
• 15 Freeman ML, DiSario JA, Nelson DB et al. Risk factors for post-ERCP pancreatitis: a prospective, multicenter study. Gastrointest Endosc 2001; 54: 425-434
• 16 Otsuka T, Kawazoe S, Nakashita S et al. Low-dose rectal diclofenac for prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis: a randomized controlled trial. J Gastroenterol 2012; 47: 912-917
• 17 Montano LozaA, Rodriguez LomeliX, Garcia CorreaJE et al. [Effect of the administration of rectal indomethacin on amylase serum levels after endoscopic retrograde cholangiopancreatography, and its impact on the development of secondary pancreatitis episodes]. Rev Esp Enferm Dig 2007; 99: 330-336
• 18 Murray B, Carter R, Imrie C et al. Diclofenac reduces the incidence of acute pancreatitis after endoscopic retrograde cholangiopancreatography. Gastroenterology 2003; 124: 1786-1791
• 19 Sotoudehmanesh R, Khatibian M, Kolahdoozan S et al. Indomethacin may reduce the incidence and severity of acute pancreatitis after ERCP. Am J Gastroenterol 2007; 102: 978-983
• 20 Khoshbaten M, Khorram H, Madad L et al. Role of diclofenac in reducing post-endoscopic retrograde cholangiopancreatography pancreatitis. J Gastroenterol Hepatol 2008; 23: e11-16
• 21 Masci E, Mariani A, Curioni S et al. Risk factors for pancreatitis following endoscopic retrograde cholangiopancreatography: a meta-analysis. Endoscopy 2003; 35: 830-834
• 22 Singh P, Das A, Isenberg G et al. Does prophylactic pancreatic stent placement reduce the risk of post-ERCP acute pancreatitis? A meta-analysis of controlled trials. Gastrointest Endosc 2004; 60: 544-550
• 23 Sofuni A, Maguchi H, Itoi T et al. Prophylaxis of post-endoscopic retrograde cholangiopancreatography pancreatitis by an endoscopic pancreatic spontaneous dislodgement stent. Clin Gastroenterol Hepatol 2007; 5: 1339-1346
• 24 Mazaki T, Masuda H, Takayama T. Prophylactic pancreatic stent placement and post-ERCP pancreatitis: a systematic review and meta-analysis. Endoscopy 2010; 42: 842-853
• 25 Messmann H, Vogt W, Holstege A et al. Post-ERP pancreatitis as a model for cytokine induced acute phase response in acute pancreatitis. Gut 1997; 40: 80-85
• 26 Karne S, Gorelick FS. Etiopathogenesis of acute pancreatitis. Surg Clin North Am 1999; 79: 699-710
• 27 Diaz-Gonzalez F, Sanchez-Madrid F. Inhibition of leukocyte adhesion: an alternative mechanism of action for anti-inflammatory drugs. Immunol Today 1998; 19: 169-172
• 28 Gross V, Leser HG, Heinisch A et al. Inflammatory mediators and cytokines – new aspects of the pathophysiology and assessment of severity of acute pancreatitis?. Hepatogastroenterology 1993; 40: 522-530
• 29 Zeitlinger M, Rusca A, Oraha AZ et al. Pharmacokinetics of a new diclofenac sodium formulation developed for subcutaneous and intramuscular administration. Int J Clin Pharmacol Ther 2012; 50: 383-390
• 30 Shep D, Ojha A, Patel S et al. Comparative bioavailability study of a new formulation of injection of 75 mg diclofenac sodium in 1 ml with the conventional injection of 75 mg diclofenac sodium given in 3 ml volume. Curr Clin Pharmacol 2011; 6: 26-29
• 31 Kim MH, Lee SK, Chang YH et al. The clinical characteristics of 16 patients with sphincter of Oddi dyskinesia. Korean J Gastrointest Endosc 1996; 16: 585-590