Indian Journal of Gastroenterology

, Volume 37, Issue 2, pp 120–126 | Cite as

Pre-endoscopic retrograde cholangiopancreatography (ERCP) administration of rectal indomethacin in unselected patients to reduce post-ERCP pancreatitis: A systematic review and meta-analysis

  • Rajat Garg
  • Babu P. Mohan
  • Rajesh Krishnamoorthi
  • Tarun Rustagi
Original Article



Previous studies have reported that peri-procedural administration of rectal indomethacin reduces the risk of pancreatitis in patients undergoing endoscopic retrograde cholangiopancreatography (ERCP). Based on these studies, gastrointestinal (GI) societies recommend prophylactic rectal indomethacin for all patients undergoing ERCP. However, recent studies have reported contradictory results. The aim of this study was to perform a systematic review and meta-analysis to estimate the pooled relative risk (RR) of post-ERCP pancreatitis (PEP) in unselected patients who received rectal indomethacin before the ERCP (pre-ERCP) compared to patients who received pre-ERCP rectal placebo.


We conducted a comprehensive search of multiple electronic databases and conference proceedings (from inception through September 1, 2017) to identify randomized control trials (RCTs) investigating the role of pre-ERCP rectal indomethacin in reducing the risk of PEP in unselected patients undergoing ERCP. The databases included Ovid, Medline, In-Process, and Other Non-Indexed Citations, Ovid MEDLINE, Ovid EMBASE, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, Scopus, and Web of Science. We calculated a pooled estimate of the RR of PEP in patients who received pre-ERCP rectal indomethacin compared to patients who received pre-ERCP rectal placebo. The meta-analysis was performed using the random effects model.


Six RCTs with a total of 2229 patients were included in the final meta-analysis. There were 1143 patients in the rectal indomethacin group and 1086 patients in the rectal placebo group. There were 71 events of PEP in the rectal indomethacin group and 114 events of PEP in the rectal placebo group. Pre-ERCP administration of rectal indomethacin significantly reduced the risk of PEP compared to pre-ERCP rectal placebo (RR 0.60, 95% CI, 0.45–0.80; p<0.0001). There was no heterogeneity between the studies (I2 = 0).


The results of this meta-analysis support the routine pre-ERCP administration of rectal indomethacin in unselected patients to prevent PEP.


Endoscopic retrograde cholangiopancreatography ERCP High-risk Indomethacin NSAIDS Pancreatic stent Pancreatitis Post-ERCP pancreatitis Rectal 


Authors’ contributions

Garg R acquisition of data, drafting the article, final approval; Mohan BP acquisition of data, analysis and interpretation of data, drafting the article, final approval; Krishnamoorthi R revising the article, final approval; Rustagi T conception and design of the study, drafting the article, critical revision, and final approval.

Compliance with ethical standards

Conflict of interest

RG, BPM, RK, and TR declare that they have no conflicts of interest.


  1. 1.
    Rustagi T, Jamidar PA. Endoscopic retrograde cholangiopancreatography (ERCP)-related adverse events: post-ERCP pancreatitis. Gastrointest Endosc Clin N Am. 2015;25:107–21.CrossRefPubMedGoogle Scholar
  2. 2.
    Andriulli A, Loperfido S, Napolitano G, et al. Incidence rates of post-ERCP complications: a systematic survey of prospective studies. Am J Gastroenterol. 2007;102:1781–8.Google Scholar
  3. 3.
    Rustagi T, Jamidar PA. Endoscopic retrograde cholangiopancreatography-related adverse events: general overview. Gastrointest Endosc Clin N Am. 2015;25:97–106.CrossRefPubMedGoogle Scholar
  4. 4.
    Rustagi T, Njei B. Factors affecting the efficacy of nonsteroidal anti-inflammatory drugs in preventing post-endoscopic retrograde cholangiopancreatography pancreatitis: a systematic review and meta-analysis. Pancreas. 2015;44:859–67.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Kochar B, Akshintala VS, 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. e9Google Scholar
  6. 6.
    Montaño Loza A, Rodriguez Lomeli X, Garcia Correa JE, 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;99:330–6.CrossRefPubMedGoogle Scholar
  7. 7.
    Elmunzer BJ, Scheiman JM, Lehman GA, et al. A randomized trial of rectal indomethacin to prevent post-ERCP pancreatitis. N Engl J Med. 2012;366:1414–22.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Patai A, Solymosi N, Mohacsi L, Patai AV. Indomethacin and diclofenac in the prevention of post-ERCP pancreatitis: a systematic review and meta-analysis of prospective controlled trials. Gastrointest Endosc. 2017;85:1144–56. e1CrossRefPubMedGoogle Scholar
  9. 9.
    Dumonceau JM, Andriulli A, Deviere J, et al. European Society of Gastrointestinal Endoscopy (ESGE) Guideline: prophylaxis of post-ERCP pancreatitis. Endoscopy. 2010;42:503–15.Google Scholar
  10. 10.
    Mine T, Morizane T, Kawaguchi Y, et al. Clinical practice guideline for post-ERCP pancreatitis. J Gastroenterol. 2017;52:1013–22.Google Scholar
  11. 11.
    ASGE Standards of Practice Committee, Chandrasekhara V, Khashab MA, et al. Adverse events associated with ERCP. Gastrointest Endosc. 2017;85:32–47.CrossRefGoogle Scholar
  12. 12.
    Levenick JM, Gordon SR, Fadden LL, et al. Rectal indomethacin does not prevent post-ERCP pancreatitis in consecutive patients. Gastroenterology. 2016;150:911–7. quiz e19Google Scholar
  13. 13.
    Inamdar S, Han D, Passi M, Sejpal DV, Trindade AJ. Rectal indomethacin is protective against post-ERCP pancreatitis in high-risk patients but not average-risk patients: a systematic review and meta-analysis. Gastrointest Endosc. 2017;85:67–75.CrossRefPubMedGoogle Scholar
  14. 14.
    Feng Y, Navaneethan U, Zhu X, et al. Prophylactic rectal indomethacin may be ineffective for preventing post-endoscopic retrograde cholangiopancreatography pancreatitis in general patients: a meta-analysis. Dig Endosc. 2016;29:272–80.Google Scholar
  15. 15.
    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.Google Scholar
  16. 16.
    Moher D, Jadad AR, Tugwell P. Assessing the quality of randomized controlled trials. Current issues and future directions. Int J Technol Assess Health Care. 1996;12:195–208.CrossRefPubMedGoogle Scholar
  17. 17.
    Dobronte Z, Toldy E, Mark L, Sarang K, Lakner L. Effects of rectal indomethacin in the prevention of post-ERCP acute pancreatitis. Orv Hetil. 2012;153:990–6.CrossRefPubMedGoogle Scholar
  18. 18.
    Sotoudehmanesh R, Khatibian M, Kolahdoozan S, Ainechi S, Malboosbaf R, Nouraie M. Indomethacin may reduce the incidence and severity of acute pancreatitis after ERCP. Am J Gastroenterol. 2007;102:978–83.CrossRefPubMedGoogle Scholar
  19. 19.
    Dobronte Z, Szepes Z, Izbeki F, et al. Is rectal indomethacin effective in preventing of post-endoscopic retrograde cholangiopancreatography pancreatitis? World J Gastroenterol. 2014;20:10151–7.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Patai A, Solymosi N, Patai AV. Effect of rectal indomethacin for preventing post-ERCP pancreatitis depends on difficulties of cannulation: results from a randomized study with sequential biliary intubation. J Clin Gastroenterol. 2015;49:429–37.CrossRefPubMedGoogle Scholar
  21. 21.
    Hosseini M, Shalchiantabrizi P, Yektaroudy K, Dadgarmoghaddam M, Salari M. Prophylactic effect of rectal indomethacin administration, with and without intravenous hydration, on development of endoscopic retrograde cholangiopancreatography pancreatitis episodes: a randomized clinical trial. Arch Iran Med. 2016;19:538–43.PubMedGoogle Scholar
  22. 22.
    Sethi S, Sethi N, Wadhwa V, Garud S, Brown A. A meta-analysis on the role of rectal diclofenac and indomethacin in the prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis. Pancreas. 2014;43:190–7.CrossRefPubMedGoogle Scholar
  23. 23.
    Ding X, Chen M, Huang S, Zhang S, Zou X. Nonsteroidal anti-inflammatory drugs for prevention of post-ERCP pancreatitis: a meta-analysis. Gastrointest Endosc. 2012;76:1152–9.CrossRefPubMedGoogle Scholar
  24. 24.
    Patai AV, Patai A. Rectal indomethacin for the prevention of post-ERCP pancreatitis. Gastroenterology. 2016;151:565–6.CrossRefPubMedGoogle Scholar
  25. 25.
    Luo H, Zhao L, Leung J, et al. Routine pre-procedural rectal indometacin versus selective post-procedural rectal indometacin to prevent pancreatitis in patients undergoing endoscopic retrograde cholangiopancreatography: a multicentre, single-blinded, randomised controlled trial. Lancet. 2016;387:2293–301.Google Scholar
  26. 26.
    Shen C, Shi Y, Liang T, Su P. Rectal NSAIDs in the prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis in unselected patients: systematic review and meta-analysis. Dig Endosc. 2017;29:281–90.CrossRefPubMedGoogle Scholar

Copyright information

© Indian Society of Gastroenterology 2018

Authors and Affiliations

  • Rajat Garg
    • 1
  • Babu P. Mohan
    • 2
  • Rajesh Krishnamoorthi
    • 3
  • Tarun Rustagi
    • 4
  1. 1.Department of Internal MedicineSt. John Hospital and Medical CenterDetroitUSA
  2. 2.Department of Internal MedicineUniversity of AlabamaTuscaloosaUSA
  3. 3.Department of Gastroenterology and HepatologyVirginia Mason Medical CenterSeattleUSA
  4. 4.Division of Gastroenterology and HepatologyUniversity of New MexicoAlbuquerqueUSA

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