How to select patients and timing for rectal indomethacin to prevent post-ERCP pancreatitis: a systematic review and meta-analysis

BACKGROUND Acute pancreatitis is a severe complication of endoscopic retrograde cholangiopancreatography (ERCP). Previous meta-analyses have shown that indomethacin effectively prevents this complication; however, the data are limited. We performed a systematic review and meta-analysis to clarify the applications for rectal indomethacin. METHODS A systematic search was performed in June 2016. Human prospective, randomized, placebo-controlled trials that compared rectally administered indomethacin with a placebo for the prevention of post-ERCP pancreatitis (PEP) were included. A meta-analysis was performed using a random-effects model to assess the outcomes (PEP) using Review Manager 5.0. RESULTS Seven randomized controlled trials met the inclusion criteria (n = 3013). The overall incidence of PEP was significantly lower after prophylactic administration of rectal indomethacin than after administration of the placebo (RR, 0.58, 95% CI, 0.40-0.83; P = 0.004). A subgroup analysis was performed for rectal indomethacin administration compared to a placebo in high-risk patients (RR, 0.46; 95% CI, 0.32-0.65; P < 0.00001) and average-risk patients (RR, 0.75; 95% CI, 0.46-1.22; P = 0.25) and for administration before ERCP (RR, 0.56; 95% CI, 0.39-0.79; P = 0.001) and after the procedure (RR, 0.61; 95% CI, 0.26-1.44; P = 0.26). CONCLUSIONS This meta-analysis indicated that prophylactic rectal indomethacin is not suitable for all patients undergoing ERCP but it is safe and effective to prevent PEP in high-risk patients. In addition, rectal indomethacin administration before ERCP is superior to its administration after ERCP for the prevention of PEP.