Per-rectal diclofenac decreases the risk of post-ERCP pancreatitis: What about intramuscular diclofenac?

 

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We read with interest the article by Park et al. [1] about the effect of intramuscular diclofenac for the prevention of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP). In this prospective trial, the authors found that PEP developed in 11.8 % (20/170) of the placebo group and in 12.7 % (22/173) of the intramuscular diclofenac group. The difference was not significant, and the authors concluded that prophylactic intramuscular diclofenac does not have any beneficial preventive effect on PEP.

To date, there have been eight randomized controlled trials and several meta-analyses published, which have all indicated a consistent beneficial role of per-rectal diclofenac administration in decreasing the incidence, and possibly the severity, of PEP [2]. Although the recent guideline issued by the European Society of Gastrointestinal Endoscopy suggests routine administration of diclofenac via the rectal route immediately before or after ERCP [3], there are some issues surrounding the routine use of per-rectal diclofenac for all patients undergoing ERCP. For example, per-rectal diclofenac is more expensive than its intramuscular formulation and it is not available in some countries. Furthermore, most patients do not prefer rectal suppository formulations and are more used to receiving the intramuscular or intravenous form of this drug. Therefore, it is reasonable to investigate other routes of diclofenac administration to scrutinize their effects on PEP development.

To the best of our knowledge, apart from the Park et al. study, only one other study, which was conducted by our group, has investigated the role of intramuscular diclofenac on preventing PEP in average- and high-risk patients, including those with sphincter of Oddi dysfunction (SOD) [4]. Our study revealed a statistically significant difference in PEP rates between the 37 patients (3 with SOD excluded) who received intramuscular diclofenac prophylaxis and the 30 control patients (10 with SOD excluded) who received placebo (2.7 % vs. 16.7 %, respectively; P = 0.04). Our result was therefore not consistent with the Park paper.

The Park paper includes some important details, which could explain the different results. In our study, we used vigorous fluid infusion just after the injection of intramuscular 75 mg diclofenac. We believe that post-ERCP fluid infusion is necessary and important to achieve sufficient pancreatic microcirculation, which ensures that diclofenac reaches the pancreatic tissue. In the Park study, no post-ERCP fluid replacement protocol is mentioned. In addition, more than 50 % of patients in each group in the Park study had pancreatic acinerization. Although there is controversy about the role of pancreatic acinerization in the development of PEP [5], we do not usually observe such a high percentage of acinerization in routine clinical practice, and in fact, in our study, no cases of pancreatic acinerization were observed [4]. Although Park et al. did not show a difference in the rate of PEP in cases with and without acinerization, acinerization may have limited the potential for preventive effects of intramuscular diclofenac administration in the study. Interestingly, the authors also revealed some findings that were contradictory to current literature, such as the risk of PEP being higher in the male sex and with pancreatic stenting.

Admittedly, we should accept that the small sample size was the main limitation in our study, and type II error due to adjustment of many confounding factors might be responsible for the lack of beneficial effect of intramuscular diclofenac on PEP in the Park study. Finally, we agree with the authors that larger, comparative, randomized, controlled trials are definitely needed to confirm the beneficial role of non-rectal administrations of diclofenac.

• References

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