“Take two and call me in the morning” may now apply to the use of indomethacin in preventing post-ERCP pancreatitis. A multicenter, randomized, placebo-controlled, double-blind clinical trial has shown that rectal indomethacin (two 50 mg suppositories) can reduce the rate of post-ERCP pancreatitis (NEJM 2012; 366: 1414-22).
A total of 602 adult patients were enrolled. Patient selection favored those at increased risk for post-ERCP pancreatitis (eg. suspicion of sphincter of Oddi dysfunction) and excluded those at low risk for this complication (eg. routine biliary stent exchange, chronic calcific pancreatitis, or a pancreatic head mass). Other exclusion criteria included active pancreatitis, elevated creatinine (>1.4 mg/dL), active peptic ulcer disease, and those already receiving a NSAID.
The suppositories (or placebo) were administered immediately after ERCP while the patient remained in the procedure room.
Post-ERCP pancreatitis developed in 27 of 295 patients (9.2%) in indomethacin group and in 52 of 307 patients (16.9%) in placebo group. In addition, moderate-to-severe pancreatitis was reduced as well 4.4% compared with 8.8% respectively. In addition, there were no increased adverse events in the treatment arm; there was no increased risk of bleeding in particular.
While the mechanism of improvement is unclear, NSAIDs are potent inhibitors of phospholipase A2, cyclooxygenase, and neutrophil-endothelial interactions, all of which are known to play a role in the pathogenesis of acute pancreatitis.
- -Am J Gastroenterol 2007; 102: 978-83. Use of indomethacin to reduce pancreatitis after ERCP
- -Gut 2008; 57: 1262-7. Meta-analysis of rectal NSAIDs to prevent post-ERCP pancreatitis