Nitroglycerin in the Prevention of Post-ERCP Pancreatitis: A Meta-Analysis

  • Li-Ming Shao
  • Qing-Yu Chen
  • Miao-Yan Chen
  • Jian-Ting Cai


The objective of this research paper is to evaluate the effect of prophylactic nitroglycerin in the prevention of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) by performing a meta-analysis of randomized controlled trials (RCTs). Electronic databases, including PubMed, EMBASE, the Cochrane library, and the Science Citation Index, were searched to retrieve relevant trials. Outcome measures were the incidence of PEP. Four RCTs, enrolling a total of 856 patients, were included. Meta-analysis of these trials indicated a significant association between the use of nitroglycerin and the reduction of PEP (RR 0.60; 95%CI: 0.39–0.92; P = 0.02). However, subsequent sensitive analysis failed to confirm that nitroglycerin was statistically superior to a placebo in reducing PEP (RR 0.68; 95%CI: 0.41–1.11; P = 0.12). Based on the limitations in this meta-analysis, prophylactic use of nitroglycerine for all patients who underwent ERCP is not recommended. Further clinical trials are required to confirm the effect of nitroglycerin in the prevention of PEP.


Nitroglycerin Post-ERCP pancreatitis Meta-analysis 



We are indebted to the authors of the primary studies.


  1. 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. doi: 10.1111/j.1572-0241.2007.01279.x.CrossRefPubMedGoogle Scholar
  2. 2.
    Cotton PB, Lehman G, Vennes J, et al. Endoscopic sphincterotomy complications and their management: an attempt at consensus. Gastrointest Endosc. 1991;37:383–393. doi: 10.1016/S0016-5107(91)70740-2.CrossRefPubMedGoogle Scholar
  3. 3.
    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. doi: 10.1016/S0016-5107(98)70121-X.CrossRefPubMedGoogle Scholar
  4. 4.
    Freeman ML, DiSario JA, Nelson DB, et al. Risk factors for post-ERCP pancreatitis: a prospective, multicenter study. Gastrointest Endosc. 2001;54:425–434. doi: 10.1067/mge.2001.117550.CrossRefPubMedGoogle Scholar
  5. 5.
    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. doi: 10.1111/j.1572-0241.2001.03594.x.CrossRefPubMedGoogle Scholar
  6. 6.
    Christensen M, Matzen P, Schulze S, Rosenberg J. Complications of ERCP: a prospective study. Gastrointest Endosc. 2004;60:721–731. doi: 10.1016/S0016-5107(04)02169-8.CrossRefPubMedGoogle Scholar
  7. 7.
    Elmunzer BJ, Waljee AK, Elta GH, Taylor JR, Fehmi SM, Higgins PD. A meta-analysis of rectal NSAIDs in the prevention of post-ERCP pancreatitis. Gut. 2008;57:1262–1267. doi: 10.1136/gut.2007.140756.CrossRefPubMedGoogle Scholar
  8. 8.
    Andriulli A, Leandro G, Federici T, et al. Prophylactic administration of somatostatin or gabexate does not prevent pancreatitis after ERCP: an updated meta-analysis. Gastrointest Endosc. 2007;65:624–632. doi: 10.1016/j.gie.2006.10.030.CrossRefPubMedGoogle Scholar
  9. 9.
    Bai Y, Gao J, Zou DW, Li ZS. Prophylactic octreotide administration does not prevent post-ERCP pancreatitis: a meta-analysis of randomized controlled trials. Pancreas. 2008;37:241–246. doi: 10.1097/MPA.0b013e31816c90a1.CrossRefPubMedGoogle Scholar
  10. 10.
    Zheng M, Bai J, Yuan B, et al. Meta-analysis of prophylactic corticosteroid use in post-ERCP pancreatitis. BMC Gastroenterol. 2008;8:6. doi: 10.1186/1471-230X-8-6.CrossRefPubMedGoogle Scholar
  11. 11.
    Bai Y, Gao J, Zhang W, Zou D, Li Z. Meta-analysis: allopurinol in the prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis. Aliment Pharmacol Ther. 2008;28:557–564. doi: 10.1111/j.1365-2036.2008.03756.x.CrossRefPubMedGoogle Scholar
  12. 12.
    Staritz M, Poralla T, Ewe K, Meyer zum Büschenfelde KH. Effect of glyceryl trinitrate on the sphincter of Oddi motility and baseline pressure. Gut. 1985;26:194–197. doi: 10.1136/gut.26.2.194.CrossRefPubMedGoogle Scholar
  13. 13.
    Staritz M, Poralla T, Dormeyer HH, Meyer zum Büschenfelde KH. Endoscopic removal of common bile duct stones through the intact papilla after medical sphincter dilation. Gastroenterology. 1985;88:1807–1811.PubMedGoogle Scholar
  14. 14.
    Sudhindran S, Bromwich E, Edwards PR. Prospective randomized double-blind placebo-controlled trial of glyceryl trinitrate in endoscopic retrograde cholangiopancreatography-induced pancreatitis. Br J Surg. 2001;88:1178–1182. doi: 10.1046/j.0007-1323.2001.01842.x.CrossRefPubMedGoogle Scholar
  15. 15.
    Moretó M, Zaballa M, Casado I, et al. Transdermal glyceryl trinitrate for prevention of post-ERCP pancreatitis: a randomized double-blind trial. Gastrointest Endosc. 2003;57:1–7. doi: 10.1067/mge.2003.29.CrossRefPubMedGoogle Scholar
  16. 16.
    Kaffes AJ, Bourke MJ, Ding S, Alrubaie A, Kwan V, Williams SJ. A prospective, randomized, placebo-controlled trial of transdermal glyceryl trinitrate in ERCP: effects on technical success and post-ERCP pancreatitis. Gastrointest Endosc. 2006;64:351–357. doi: 10.1016/j.gie.2005.11.060.CrossRefPubMedGoogle Scholar
  17. 17.
    Jadad AR, Moore RA, Carroll D, et al. Assessing the quality of reports of randomized clinical trials: Is blinding necessary? Control Clin Trials. 1996;17:1–12. doi: 10.1016/0197-2456(95)00134-4.CrossRefPubMedGoogle Scholar
  18. 18.
    Moher D, Pham B, Jones A, et al. Does quality of reports of randomised trials affect estimates of intervention efficacy reported in meta-analyses? Lancet. 1998;352:609–613. doi: 10.1016/S0140-6736(98)01085-X.CrossRefPubMedGoogle Scholar
  19. 19.
    Begg CB, Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics. 1994;50:1088–1101. doi: 10.2307/2533446.CrossRefPubMedGoogle Scholar
  20. 20.
    Egger M, Davey Smith G, Schneider M, Minder C. Bias in metaanalysis detected by a simple, graphical test. BMJ. 1997;315:629–634.PubMedGoogle Scholar
  21. 21.
    Donnellan I, Hallissey M, Nwokolo C, Loft D, Fraser I. Sublingual GTN spray improves success at ERCP cannulation. Gut. 1994;35(Suppl 5):S36. (abstract).Google Scholar
  22. 22.
    Wehrmann T, Schmitt T, Stergiou N, Caspary WF, Seifert H. Topical application of nitrates onto the papilla of Vater: manometric and clinical results. Endoscopy. 2001;33:323–328. doi: 10.1055/s-2001-13687.CrossRefPubMedGoogle Scholar
  23. 23.
    Ghori A, Hallisey M, Nwokolo C, Loft D, Fraser I. The secret (GTN) of successful ERCP cannulation: a prospective randomised controlled study. J R Coll Surg Edinb. 2002;47:634–637.PubMedGoogle Scholar
  24. 24.
    Talwar A, Dare C, Pain J. Does topical GTN on the sphincter of Oddi facilitate ERCP? A double-blind randomized control trial. Surg Endosc. 2005;19:902–904. doi: 10.1007/s00464-004-9166-5.CrossRefPubMedGoogle Scholar
  25. 25.
    Beauchant M, Ingrand P, Favriel JM, et al. Intravenous nitroglycerin for prevention of pancreatitis after therapeutic endoscopic retrograde cholangiography: a randomized, double-blind, placebo-controlled multicenter trial. Endoscopy. 2008;40:631–636. doi: 10.1055/s-2008-1077362.CrossRefPubMedGoogle Scholar
  26. 26.
    Ranson JH, Rifkind KM, Turner JW. Prognostic signs and nonoperative peritoneal lavage in acute pancreatitis. Surg Gynecol Obstet. 1976;143:209–219.PubMedGoogle Scholar
  27. 27.
    Cooper ST, Slivka A. Incidence, risk factors, and prevention of post-ERCP pancreatitis. Gastroenterol Clin North Am. 2007;36:259–276. doi: 10.1016/j.gtc.2007.03.006.CrossRefPubMedGoogle Scholar
  28. 28.
    Freeman ML. Pancreatic stents for prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis. Clin Gastroenterol Hepatol. 2007;5:1354–1365. doi: 10.1016/j.cgh.2007.09.007.CrossRefPubMedGoogle Scholar
  29. 29.
    Freeman ML, Guda NM. Prevention of post-ERCP pancreatitis: a comprehensive review. Gastrointest Endosc. 2004;59:845–864. doi: 10.1016/S0016-5107(04)00353-0.CrossRefPubMedGoogle Scholar
  30. 30.
    Sand J, Nordback I. Prospective randomized trial of the effect of nifedipine on pancreatic irritation after endoscopic retrograde cholangiopancreatography. Digestion. 1993;54:105–111.CrossRefPubMedGoogle Scholar
  31. 31.
    Prat F, Amaris J, Ducot B, et al. Nifedipine for prevention of post-ERCP pancreatitis: a prospective, double-blind randomized study. Gastrointest Endosc. 2002;56:202–208. doi: 10.1016/S0016-5107(02)70178-8.CrossRefPubMedGoogle Scholar
  32. 32.
    Schwartz JJ, Lew RJ, Ahmad NA, et al. The effect of lidocaine sprayed on the major duodenal papilla on the frequency of post-ERCP pancreatitis. Gastrointest Endosc. 2004;59:179–184. doi: 10.1016/S0016-5107(03)02540-9.CrossRefPubMedGoogle Scholar
  33. 33.
    Bogaert MG. Clinical pharmacokinetics of nitrates. Cardiovasc Drugs Ther. 1994;8:693–699. doi: 10.1007/BF00877116.CrossRefPubMedGoogle Scholar
  34. 34.
    Hashimoto S, Kobayashi A. Clinical pharmacokinetics and pharmacodynamics of glyceryl trinitrate and its metabolites. Clin Pharmacokinet. 2003;42:205–221. doi: 10.2165/00003088-200342030-00001.CrossRefPubMedGoogle Scholar
  35. 35.
    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. doi: 10.1016/S0016-5107(04)02013-9.CrossRefPubMedGoogle Scholar
  36. 36.
    Testoni PA. Facts and fiction in the pharmacologic prevention of post-ERCP pancreatitis: a never-ending story. Gastrointest Endosc. 2006;64:732–734. doi: 10.1016/j.gie.2006.07.004.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Li-Ming Shao
    • 1
  • Qing-Yu Chen
    • 1
  • Miao-Yan Chen
    • 1
  • Jian-Ting Cai
    • 1
  1. 1.Department of GastroenterologySecond Affiliated Hospital, College of Medicine, Zhejiang UniversityHangzhouChina

Personalised recommendations