Allopurinol for Prophylaxis Against Post ERCP Pancreatitis: A Metaanalysis of Randomized Controlled Trials

Abstract

Purpose: Post-ERCP pancreatitis is a common complication after ERCP and contributes significantly to the morbidity and mortality of the procedure. A number of pharmacologic agents have been evaluated in an attempt to identify a strategy to reduce post ERCP pancreatitis with only mixed success. Based upon data from animal studies, allopurinol, a free radical scavenger, may prevent the cascade of inflammation in post ERCP pancreatitis. Since 1991, a number of large randomized controlled trials have been conducted to evaluate this effect with mixed results. We conducted a meta-analysis of the randomized controlled trials (RCTs) to evaluate the efficacy of prophylactic allopurinol in the prevention of post-ERCP pancreatitis. Methods: Medline, Cochrane Central Register of Controlled Trials & Database of Systemic Reviews, PubMed, and recent abstracts from major conference proceedings were searched through 11/10. RCTs comparing prophylactic allopurinol to placebo in patients undergoing ERCP were included. Standard forms were used to extract the data by two independent reviewers. The effects of prophylactic allopurinol were analyzed by calculating pooled estimates of post ERCP pancreatitis. Summary odds ratio was calculated using Comprehensive Meta-Analysis software. Publication bias was assessed by funnel plot. (Figure 1) Heterogeneity among studies was assessed by calculating 12 measures of inconsistency. Results: Seven RCT (N=2305) met the inclusion criteria. The studies were reported from the U.S., Canada, Mexico, Greece and Poland. Heterogenity was present and thus a random effect model was used for the analysis. Overall prophylactic allopurinol did not decrease the odds of developing post ERCP pancreatitis OR 0.70(95% CI: 0.36-1.36 p=0.29). (Figure 2) In subgroup analysis no differences were noted in the incidence of post ERCP pancreatitis with respect to the dosing of allopurinol. High dose allopurinol (1.2 g administered within 24hrs of the procedure) did not reduce the incidence of post ERCP pancreatitis OR 0.87 CI 0.61-1.24 p= 0.431), nor did low dose allopurinol (400 mg or less administered within 24hr of the procedure (OR 1.41, 95%CI 0.81-2.46)). The time of administration of allopurinol also did not have an effect on the rate of post ERCP pancreatitis. Loading the patient > 5 hrs prior to the procedure did not affect the rate of post-ERCP pancreatitis (OR 0.44, 95% CI: 0.14-1.39 p=0.16). Similarly drug dosing <5hrs prior to the procedure had no effect on the rate of pancreatitis. Publication bias was not present. Pooling of data from high quality studies (Jadad score >3) also did not reveal a reduction in the odds of pancreatitis. Conclusion: Prophylactic allopurinol does not prevent post ERCP pancreatitis.