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Diclofenac Does Not Reduce the Risk of Post-endoscopic Retrograde Cholangiopancreatography Pancreatitis in Low-Risk Units

  • Original Article
  • Published:
Journal of Gastrointestinal Surgery Aims and scope

Abstract

Background

Nonsteroidal anti-inflammatory drugs have an inhibitory role in pathogenesis of pancreatitis. Guidelines from the European Society of Gastrointestinal Endoscopy recommend routine rectal administration of 100 mg of diclofenac or indomethacin immediately before or after ERCP for all patients without contraindications.

Aims

Our aim was to evaluate the effect of diclofenac in preventing post-ERCP pancreatitis (PEP) in a high-volume, low-PEP-risk ERCP unit.

Methods

The rate and severity of PEP were compared in groups of 1000 historical controls prior to the routine use of diclofenac and in 1000 patients receiving 100 mg diclofenac before ERCP.

Results

PEP occurred in 56 (2.8%) of the 2000 patients, and the rate of the pancreatitis was 2.8% in control group and 2.8% in diclofenac group (p = 1.000). The PEP rate among the native papilla patients was 3.9% in control group and 3.6% in diclofenac group (p = 0.803). In subgroup analysis of patients with a high risk of PEP, diclofenac neither prevented PEP nor made its course milder.

Conclusions

In an unselected patient population in a center with a low incidence of PEP, diclofenac seems to have no beneficial effect.

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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.

    Article  PubMed  Google Scholar 

  2. Freeman ML, DiSario JA, Nelson DB, et al. Risk factors for post-ERCP pancreatitis: A prospective, multicenter study. Gastrointest Endosc. 2001;54:425–434.

    Article  CAS  PubMed  Google Scholar 

  3. Rabenstein T, Hahn EG. Post-ERCP pancreatitis: New momentum. Endoscopy. 2002;34:325–329. doi:10.1055/s-2002-23651.

    Article  CAS  PubMed  Google Scholar 

  4. Vandervoort J, Soetikno RM, Tham TC, et al. Risk factors for complications after performance of ERCP. Gastrointest Endosc. 2002;56:652–656. doi:10.1067/mge.2002.129086.

    Article  PubMed  Google Scholar 

  5. Freeman ML, Nelson DB, Sherman S, et al. Complications of endoscopic biliary sphincterotomy. N Engl J Med. 1996;335:909–918. doi:10.1056/NEJM199609263351301.

    Article  CAS  PubMed  Google Scholar 

  6. 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.

    Article  CAS  PubMed  Google Scholar 

  7. 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. doi:10.3109/00365519709084587.

    Article  CAS  PubMed  Google Scholar 

  8. Davies NM, Anderson KE. Clinical pharmacokinetics of diclofenac. therapeutic insights and pitfalls. Clin Pharmacokinet. 1997;33:184–213. doi:10.2165/00003088-199733030-00003.

    Article  CAS  PubMed  Google Scholar 

  9. Dumonceau J, Andriulli A, Elmunzer BJ, et al. Prophylaxis of post-ERCP pancreatitis: European society of gastrointestinal endoscopy (ESGE) guideline - updated june 2014. Endoscopy. 2014;46:799–815.

    Article  PubMed  Google Scholar 

  10. 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.

    CAS  PubMed  Google Scholar 

  11. 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;76:1152–1159. doi:10.1016/j.gie.2012.08.021.

    Article  PubMed  Google Scholar 

  12. 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.

    Article  CAS  PubMed  Google Scholar 

  13. 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;43:190–197. doi:10.1097/MPA.0000000000000090.

    Article  CAS  PubMed  Google Scholar 

  14. Sun H, Han B, Zhai H, Cheng X, Ma K. Rectal NSAIDs for the prevention of post-ERCP pancreatitis: A meta-analysis of randomized controlled trials. The Surgeon. 2014;12:141–147. doi:10.1016/j.surge.2013.10.010.

    Article  PubMed  Google Scholar 

  15. Yaghoobi M, Rolland S, Waschke KA, et al. Meta-analysis: Rectal indomethacin for the prevention of post-ERCP pancreatitis. Aliment Pharmacol Ther. 2013;38:995–1001. doi:10.1111/apt.12488.

    Article  CAS  PubMed  Google Scholar 

  16. Yuhara H, Ogawa M, Kawaguchi Y, Igarashi M, Shimosegawa T, Mine T. Pharmacologic prophylaxis of post-endoscopic retrograde cholangiopancreatography pancreatitis: Protease inhibitors and NSAIDs in a meta-analysis. J Gastroenterol. 2014;49:388–399. doi:10.1007/s00535-013-0834-x.

    Article  CAS  PubMed  Google Scholar 

  17. Zheng MH, Xia HH, Chen YP. Rectal administration of NSAIDs in the prevention of post-ERCP pancreatitis: A complementary meta-analysis. Gut. 2008;57:1632–1633.

    PubMed  Google Scholar 

  18. 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. doi:10.1056/NEJMoa1111103.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Khoshbaten M, Khorram H, Madad L, Ehsani Ardakani MJ, Farzin H, Zali MR. Role of diclofenac in reducing post-endoscopic retrograde cholangiopancreatography pancreatitis. J Gastroenterol Hepatol. 2008;23:e11–6.

    Article  CAS  PubMed  Google Scholar 

  20. Murray B, Carter R, Imrie C, Evans S, O’Suilleabhain C. Diclofenac reduces the incidence of acute pancreatitis after endoscopic retrograde cholangiopancreatography. Gastroenterology. 2003;124:1786–1791.

  21. 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. doi:10.1007/s00535-012-0554-7.

    Article  CAS  PubMed  Google Scholar 

  22. Lua GW, Muthukaruppan R, Menon J. Can rectal diclofenac prevent post endoscopic retrograde cholangiopancreatography pancreatitis?. Digestive Diseases & Sciences. 2015;60:3118–3123.

    Article  CAS  Google Scholar 

  23. 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;102:978–983.

    Article  CAS  PubMed  Google Scholar 

  24. Cheon YK, Cho KB, Watkins JL, et al. Efficacy of diclofenac in the prevention of post-ERCP pancreatitis in predominantly high-risk patients: A randomized double-blind prospective trial. Gastrointest Endosc. 2007;66:1126–1132.

    Article  PubMed  Google Scholar 

  25. Murray WR. Reducing the incidence and severity of post ERCP pancreatitis. Scand J Surg. 2005;94:112–116.

    Article  CAS  PubMed  Google Scholar 

  26. Sotoudehmanesh R, Eloubeidi MA, Asgari AA, Farsinejad M, Khatibian M. A randomized trial of rectal indomethacin and sublingual nitrates to prevent post-ERCP pancreatitis. Am J Gastroenterol. 2014;109:903–909. doi:10.1038/ajg.2014.9.

    Article  CAS  PubMed  Google Scholar 

  27. ASGE Standards of Practice Committee, Chandrasekhara V, Khashab MA, et al. Adverse events associated with ERCP. Gastrointest Endosc. 2017;85:32–47.

    Article  Google Scholar 

  28. Isaji S, Takada T, Mayumi T, et al. Revised japanese guidelines for the management of acute pancreatitis 2015: Revised concepts and updated points. J Hepatobiliary Pancreat Sci. 2015;22:433–445. doi:10.1002/jhbp.260.

    Article  PubMed  Google Scholar 

  29. Halttunen J, Kylanpaa L. A prospective randomized study of thin versus regular-sized guide wire in wire-guided cannulation. Surg Endosc. 2013;27:1662–1667. doi:10.1007/s00464-012-2653-1.

    Article  PubMed  Google Scholar 

  30. Kylanpaa L, Boyd S, Ristimaki A, Lindstrom O, Udd M, Halttunen J. A prospective randomised study of dense infinity cytological brush versus regularly used brush in pancreaticobiliary malignancy. Scand J Gastroenterol. 2016;51:590–593. doi:10.3109/00365521.2015.1121514.

    Article  PubMed  Google Scholar 

  31. Cotton PB, Eisen G, Romagnuolo J, et al. Grading the complexity of endoscopic procedures: Results of an ASGE working party. Gastrointest Endosc. 2011;73:868–874. doi:10.1016/j.gie.2010.12.036.

    Article  PubMed  Google Scholar 

  32. Cotton PB, Garrow DA, Gallagher J, Romagnuolo J. Risk factors for complications after ERCP: A multivariate analysis of 11,497 procedures over 12 years. Gastrointest Endosc. 2009;70:80–88. doi:10.1016/j.gie.2008.10.039.

    Article  PubMed  Google Scholar 

  33. Sarr MG, Banks PA, Bollen TL, et al. The new revised classification of acute pancreatitis 2012. Surg Clin North Am. 2013;93:549–562. doi:10.1016/j.suc.2013.02.012.

    Article  PubMed  Google Scholar 

  34. Leerhoy B, Nordholm-Carstensen A, Novovic S, Hansen MB, Jorgensen LN. Diclofenac is associated with a reduced incidence of post-endoscopic retrograde cholangiopancreatography pancreatitis: Results from a danish cohort study. Pancreas. 2014;43:1286–1290. doi:10.1097/MPA.0000000000000169.

    Article  CAS  PubMed  Google Scholar 

  35. Dobronte Z, Szepes Z, Izbeki F, et al. Is rectal indomethacin effective in preventing of post-endoscopic retrograde cholangiopancreatography pancreatitis? World J Gastroenterol. 2014;20:10151–10157. doi:10.3748/wjg.v20.i29.10151.

    Article  PubMed  PubMed Central  Google Scholar 

  36. 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 e19. doi:10.1053/j.gastro.2015.12.040.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Halttunen J, Keranen I, Udd M, Kylanpaa L. Pancreatic sphincterotomy versus needle knife precut in difficult biliary cannulation. Surg Endosc. 2009;23:745–749. doi:10.1007/s00464-008-0056-0.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Gastrointestinal Surgery, University of Helsinki, Helsinki University Hospital, Haartmaninkatu 4, 00290, Helsinki, Finland

    Mia Rainio, Outi Lindström, Marianne Udd, Johanna Louhimo & Leena Kylänpää

Authors
  1. Mia Rainio
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  2. Outi Lindström
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  3. Marianne Udd
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  4. Johanna Louhimo
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  5. Leena Kylänpää
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Contributions

MR collected clinical data, performed a part of the data analysis, and drafted the manuscript. OL and LK participated in designing and coordinating the study, collected clinical data, and provided supervision. MU collected clinical data and provided supervision. JL performed statistical analysis. All authors critically revised the manuscript and read and approved the final version.

Corresponding author

Correspondence to Mia Rainio.

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Conflict of Interest

The authors declare that they have no conflict of interest.

Funding

This study was supported by the Helsinki University Hospital Research Funds, Helsinki, Finland.

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Rainio, M., Lindström, O., Udd, M. et al. Diclofenac Does Not Reduce the Risk of Post-endoscopic Retrograde Cholangiopancreatography Pancreatitis in Low-Risk Units. J Gastrointest Surg 21, 1270–1277 (2017). https://doi.org/10.1007/s11605-017-3412-3

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  • DOI: https://doi.org/10.1007/s11605-017-3412-3

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