Combination of Diclofenac and Sublingual Nitrates Is Superior to Diclofenac Alone in Preventing Pancreatitis After Endoscopic Retrograde Cholangiopancreatography.

BACKGROUND & AIMS Acute pancreatitis is a major adverse event of endoscopic retrograde cholangiopancreatography (ERCP). Rectal administration of nonsteroidal anti-inflammatory drugs (NSAIDs) decreases the incidence of post-ERCP pancreatitis (PEP). Little is known about the combined effects of sublingual nitrate and NSAIDs. We performed a randomized trial to assess whether the combination of NSAIDs and sublingual nitrate is more effective than NSAIDs alone in preventing PEP. METHODS In a prospective superiority trial, eligible patients underwent ERCP at 12 endoscopic units in Japan, from March 2015 through May 2018. Patients were randomly assigned to groups given diclofenac suppositories (50 mg) within 15 minutes after the endoscopic procedure alone (diclofenac-alone group, n = 442) or in combination with sublingual isosorbide dinitrate (5 mg) 5 minutes before the endoscopic procedure (combination group, n = 444). The primary endpoint was the occurrence of PEP. RESULTS PEP developed in 25 patients in the combination group (5.6%), and in 42 patients in the diclofenac-alone group (9.5%) (relative risk 0.59; 95% confidence interval 0.37-0.95; P = .03). Moderate to severe pancreatitis developed in 4 patients (0.9%) in the combination group, and 10 patients (2.3%) in the diclofenac-alone group (relative risk 0.12; 95% confidence interval 0.13-1.26; P = .12). There was no serious adverse event related to the additional administration of sublingual nitrate. CONCLUSIONS In a randomized controlled trial, we found that prophylaxis with rectal diclofenac and sublingual nitrate significantly reduces the overall incidence of PEP compared with diclofenac suppository alone. ClinicalTrials.gov, no: UMIN 000016274.

[1]  Masahiro Yoshida,et al.  Japanese guidelines for the management of acute pancreatitis: Japanese Guidelines 2015 , 2015, Journal of hepato-biliary-pancreatic sciences.

[2]  A. Asgari,et al.  A Randomized Trial of Rectal Indomethacin and Sublingual Nitrates to Prevent Post-ERCP Pancreatitis , 2014, The American Journal of Gastroenterology.

[3]  X. Calvet,et al.  How and When Should NSAIDs Be Used for Preventing Post-ERCP Pancreatitis? A Systematic Review and Meta-Analysis , 2013, PloS one.

[4]  M. Freeman Current Status of Endoscopic Stenting of the Pancreatic Duct as Prophylaxis Against Post-ERCP Pancreatitis. , 2012, Gastroenterology & hepatology.

[5]  Richard S. Kwon,et al.  A randomized trial of rectal indomethacin to prevent post-ERCP pancreatitis. , 2012, The New England journal of medicine.

[6]  T. Noda,et al.  Low-dose rectal diclofenac for prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis: a randomized controlled trial , 2012, Journal of Gastroenterology.

[7]  A. Irisawa,et al.  Endoscopic pancreatic duct stents reduce the incidence of post-endoscopic retrograde cholangiopancreatography pancreatitis in high-risk patients. , 2011, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[8]  Chun-Hui Wang,et al.  A meta-analysis for the effect of prophylactic GTN on the incidence of post-ERCP pancreatitis and on the successful rate of cannulation of bile ducts , 2010, BMC gastroenterology.

[9]  A. Andriulli,et al.  European Society of Gastrointestinal Endoscopy (ESGE)Guideline: Prophylaxis of post-ERCP pancreatitis , 2010, Endoscopy.

[10]  B. Petersen,et al.  A lexicon for endoscopic adverse events: report of an ASGE workshop. , 2010, Gastrointestinal endoscopy.

[11]  P. Andersen,et al.  Meta‐analysis: nitroglycerin for prevention of post‐ERCP pancreatitis , 2009, Alimentary pharmacology & therapeutics.

[12]  Ji-Young Park,et al.  Can wire-guided cannulation prevent post-ERCP pancreatitis? A prospective randomized trial. , 2009, Gastrointestinal endoscopy.

[13]  H. Dai,et al.  Role of nonsteroidal anti-inflammatory drugs in the prevention of post-ERCP pancreatitis: a meta-analysis. , 2009, Hepatobiliary & pancreatic diseases international : HBPD INT.

[14]  Ying-xin Gao,et al.  Prophylactic effect of glyceryl trinitrate on post-endoscopic retrograde cholangiopancreatography pancreatitis: a randomized placebo-controlled trial. , 2009, World journal of gastroenterology.

[15]  H. Xia,et al.  Rectal administration of NSAIDs in the prevention of post-ERCP pancreatitis: a complementary meta-analysis. , 2008, Gut.

[16]  M. Khoshbaten,et al.  Role of diclofenac in reducing post‐endoscopic retrograde cholangiopancreatography pancreatitis , 2008, Journal of gastroenterology and hepatology.

[17]  M. Bourke,et al.  A prospective randomized trial of cannulation technique in ERCP: effects on technical success and post-ERCP pancreatitis , 2008, Endoscopy.

[18]  P. Higgins,et al.  A meta-analysis of rectal NSAIDs in the prevention of post-ERCP pancreatitis , 2008, Gut.

[19]  J. Kountouras,et al.  A comparative study of standard ERCP catheter and hydrophilic guide wire in the selective cannulation of the common bile duct , 2008, Endoscopy.

[20]  Atul Kumar,et al.  Guidewire Cannulation Reduces Risk of Post-ERCP Pancreatitis and Facilitates Bile Duct Cannulation , 2007, The American Journal of Gastroenterology.

[21]  A. Ojeda,et al.  Efecto de la administración de indometacina rectal sobre los niveles séricos de amilasa posteriores a colangiopancreatografía retrógrada endoscópica y su impacto en la aparición de episodios de pancreatitis secundaria , 2007 .

[22]  M. Nouraie,et al.  Indomethacin May Reduce the Incidence and Severity of Acute Pancreatitis After ERCP , 2007, The American Journal of Gastroenterology.

[23]  E. Colombo,et al.  A simple way of avoiding post-ERCP pancreatitis. , 2004, Gastrointestinal endoscopy.

[24]  R. Carter,et al.  Diclofenac reduces the incidence of acute pancreatitis after endoscopic retrograde cholangiopancreatography. , 2003, Gastroenterology.

[25]  J. van Dam,et al.  Risk factors for complications after performance of ERCP. , 2002, Gastrointestinal endoscopy.

[26]  E. G. Hahn,et al.  Post-ERCP Pancreatitis: New Momentum , 2002, Endoscopy.

[27]  P. Edwards,et al.  Prospective randomized double‐blind placebo‐controlled trial of glyceryl trinitrate in endoscopic retrograde cholangiopancreatography‐induced pancreatitis , 2001, The British journal of surgery.

[28]  W. Caspary,et al.  Topical application of nitrates onto the papilla of Vater: manometric and clinical results. , 2001, Endoscopy.

[29]  C. Crosta,et al.  Complications of diagnostic and therapeutic ERCP: a prospective multicenter study , 2001, American Journal of Gastroenterology.

[30]  M. E. Ryan,et al.  Risk factors for post-ERCP pancreatitis: a prospective, multicenter study. , 1997, Gastrointestinal endoscopy.

[31]  M E Ryan,et al.  Complications of endoscopic biliary sphincterotomy. , 1996, The New England journal of medicine.

[32]  N. Fujita,et al.  Endoscopic Biliary Drainage without Endoscopic Sphincterotomy , 1995 .

[33]  C Liguory,et al.  Endoscopic sphincterotomy complications and their management: an attempt at consensus. , 1991, Gastrointestinal endoscopy.

[34]  StephenD. Williams,et al.  ENDOSCOPIC SPHINCTEROTOMY IN 1000 CONSECUTIVE PATIENTS , 1989, The Lancet.

[35]  J. Azuma,et al.  Usefulness of Isosorbide Dinitrate Spray as an Angina Attack Relieving Agent , 1987 .

[36]  K. Ewe,et al.  Effect of glyceryl trinitrate on the sphincter of Oddi motility and baseline pressure. , 1985, Gut.

[37]  E. McFadden,et al.  Toxicity and response criteria of the Eastern Cooperative Oncology Group , 1982, American journal of clinical oncology.

[38]  Jian-ting Cai,et al.  Nitroglycerin in the Prevention of Post-ERCP Pancreatitis: A Meta-Analysis , 2008, Digestive Diseases and Sciences.

[39]  A. González Ojeda,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]. , 2007, Revista espanola de enfermedades digestivas : organo oficial de la Sociedad Espanola de Patologia Digestiva.