Rectal NSAIDs to Prevent Post ERCP Pancreatitis: All Comers or High Risk Only?

Introduction: One of the most common complications of ERCP is post-ERCP pancreatitis. Prior randomized control trials have shown a protective effect with the use of prophylactic rectal NSAIDs. The goal of our systematic review and meta-analysis was to evaluate the types of patients in which rectal NSAIDs have the most impact. Methods: In collaboration with a health sciences librarian, a systematic search of Ovid Medline, Embase, the Cochrane Library, Web of Science, Clinical Trials.gov, and Google Scholar was performed. Studies were reviewed and screened using the Covidence system by two independent reviewers. Only randomized controlled studies including patients receiving rectal NSAIDs vs no rectal NSAIDs were included. A subgroup of interest were studies which restricted enrollment to those at high risk of developing post-ERCP pancreatitis. Patients were deemed to be high-risk using validated patient and procedure-related risk factors. The primary outcome was development of post-ERCP pancreatitis and severity of pancreatitis scored using Cotton’s criteria. The random effects model was used for quantitative harmonization. Results: Among 270 abstracts and manuscripts which were critically reviewed, we identified 11 RCTs evaluating rectal NSAIDs in high risk patients and 31 studies overall (high and indeterminate risk). Among high-risk patients, there was a reduction in the rates of post-ERCP pancreatitis associated with rectal NSAID use compared to placebo (OR 0.607, 95% CI 0.351-1.050) and a reduction of moderate to severe pancreatitis (OR 0.534, 95% CI 0.237-1.199) though these findings narrowly missed statistical significance (Table 1). For the overall group of studies which included both high risk and unselected patients there was a reduction of post-ERCP pancreatitis associated with rectal NSAID use compared to placebo (OR 0.595, 95% CI 0.466-0.760) as well as reduction of moderate to severe pancreatitis (OR 0.498, 95% CI 0.359-0.691). Conclusion: In patients undergoing ERCP, the use of rectal NSAIDs reduces the risk of post-ERCP pancreatitis and moderate to severe pancreatitis. Systematic review of all randomized trials and the subgroup restricted to high risk patients suggests that its effect is not dominated by studies in the latter category. Its use should be considered in all patients.Table 1.: Main Outcomes for Studies Including High Risk versus All Patients.