Meta-analysis: rectal indomethacin for the prevention of post-ERCP pancreatitis

Despite initial evidence in the literature, nonsteroidal anti-inflammatory drugs (NSAIDs) have not been widely used to prevent post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP).

To complete a meta-analysis of high-quality RCTs that included the latest available literature published after past meta-analytical efforts

A comprehensive electronic literature search was carried out for RCTs comparing peri-procedural rectal indomethacin and placebo in preventing PEP. Methodological quality was assessed by the Cochrane risk of bias tool. Fixed model Mantel-Haenszel meta-analysis, Q test and I(2) index were used. Several subgroup and sensitivity analyses were planned.

A total of four of 61 retrieved trials between 2007 and 2012 (n = 1470) were included. No significant publication bias existed. All studies used similar criteria to detect pancreatitis. The pooled proportion estimate of the rate of pancreatitis was 5.1% with indomethacin and 10.3% with placebo. After excluding the high-risk patients, the rates were 3.9% and 7.9% respectively. Fixed model meta-analysis showed that the rate of pancreatitis was significantly lower using indomethacin as compared with placebo [OR = 0.49(0.34-0.71); P = 0.0002]. Number needed to treat was 20. There was no significant statistical or clinical heterogeneity. In subgroup analysis, the difference remained unchanged for average-risk population [OR = 0.49(0.28-0.85); P = 0.01] or in preventing severe PEP [OR = 0.41(0.21-0.78); P = 0.007]. The result of the main outcome remained robust in multiple sensitivity analyses.

Rectal indomethacin used immediately before or after ERCP significantly reduces the risk of PEP to half in both low- and high-risk patients, and with both statistically and clinically significant conclusions. These results suggest that a possible change in routine practice for patients at both low and high risk of developing PEP should be advocated.