Elsevier

Gastrointestinal Endoscopy

Volume 85, Issue 6, June 2017, Pages 1144-1156.e1
Gastrointestinal Endoscopy

Systematic review and meta-analysis
Indomethacin and diclofenac in the prevention of post-ERCP pancreatitis: a systematic review and meta-analysis of prospective controlled trials

https://doi.org/10.1016/j.gie.2017.01.033Get rights and content

Background and Aims

Diclofenac and indomethacin are the most studied drugs for preventing post-ERCP pancreatitis (PEP). However, there are no prospective, randomized multicenter trials with a sufficient number of patients for correct evaluation of their efficacy. Our aim was to evaluate all prospective trials published in full text that studied the efficacy of diclofenac or indomethacin and were controlled with placebo or non-treatment for the prevention of PEP in adult patients undergoing ERCP.

Methods

Systematic search of databases (PubMed, Scopus, Web of Science, Cochrane) for relevant studies published from inception to 30 June 2016.

Results

Our meta-analysis of 4741 patients from 17 trials showed that diclofenac or indomethacin significantly decreased the risk ratio (RR) of PEP to 0.60 (95% confidence interval [CI], 0.46-0.78; P = .0001), number needed to treat (NNT) was 20, and the reduction of RR of moderate to severe PEP was 0.64 (95% CI, 0.43-0.97; P = .0339). The efficacy of indomethacin compared with diclofenac was similar (P = .98). The efficacy of indomethacin or diclofenac did not differ according to timing (P = .99) or between patients with average-risk and high-risk for PEP (P = .6923). The effect of non-rectal administration of indomethacin or diclofenac was not significant (P = .1507), but the rectal route was very effective (P = .0005) with an NNT of 19. The administration of indomethacin or diclofenac was avoided in patients with renal failure. Substantial adverse events were not detected.

Conclusions

The use of rectally administered diclofenac or indomethacin before or closely after ERCP is inexpensive and safe and is recommended in every patient (without renal failure) undergoing ERCP. (Registration number: CRD42016042726, http://www.crd.york.ac.uk/prospero/.)

Introduction

One of the greatest challenges for endoscopists performing ERCP is to decrease the frequency of post-ERCP pancreatitis (PEP). Since 1978, several basic studies and clinical recommendations have dealt with pharmacologic agents in the prevention of PEP. Diclofenac and indomethacin seem to be the most promising drugs for preventing PEP1, 2, 3, 4, 5, 6, 7, 8; nevertheless, a comprehensive consensus has not emerged with regard to their efficacy. The results of trials with too few patients9 differ; therefore a multicenter, carefully planned prospective, randomized, double-blind trial or meta-analysis with a sufficient number of patients can resolve this contradiction. In the absence of such original works, we have collected all prospective trials studying the efficacy of diclofenac or indomethacin for all routes of administration controlled with placebo or non-treatment for the prevention of PEP in adult patients undergoing ERCP.

Section snippets

Protocol and registration

This study was conducted and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement.10 The review protocol is registered at the International Prospective Register of Systematic Reviews (PROSPERO), which can be accessed at http://www.crd.york.ac.uk/prospero/ under registration number CRD42016042726.

Eligibility criteria

Studies were included if they were prospective, controlled studies published in full text irrespective of language or publication status.

Information sources and search strategy

Study selection

A total of 540 publications were found using the search strategy outlined earlier (Fig. 1). After excluding duplicates (n = 352), 188 publications were screened by title and abstract. After thorough review, an additional 167 records were excluded, resulting in the full text of 21 publications to be assessed for eligibility. Four studies15, 16, 17, 18 were excluded: 2 were retrospective and in 2 trials the allocation to the placebo or non-treated and to the treated groups was not clearly

Discussion

The intention to improve the success rate of ERCP to over 90% goes hand in hand with a high adverse event rate that casts shadows on its excellent results.19, 38 All-cause mortality at 30 days is 5.3% in unselected patients,39 and therapeutic ERCP-specific mortality occurs in between 0.4% and 0.5% of patients.40, 41 The most common adverse event of ERCP is PEP40, 41 with an estimated rate of between 1.6% and 15.7%.42 In a recent meta-analysis including 13,296 patients, the PEP rate was 9.7%

Acknowledgments

The authors would like to thank Dr Eliane Coffler and Dr Andrea Fekete for their help with linguistic review.

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    DISCLOSURE: All authors disclosed no financial relationships relevant to this publication.

    See CME section; p. 1284.

    If you would like to chat with an author of this article, you may contact Dr Patai at [email protected].

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