Background: The most common serious complication of endoscopic retrograde cholangiopancreatography (ERCP) is acute pancreatitis. Currently, temporary pancreatic stenting is the only intervention proven to reduce the risk of post-ERCP pancreatitis. Nonsteroidal anti-inflammatory drugs (NSAIDs), administered as a single rectal dose, have shown preliminary promise in a meta-analysis, although no definitive evidence is available. Elmunzer and colleagues conducted a multicenter, randomized controlled trial of rectal indomethacin (Indocin) for preventing post-ERCP pancreatitis in high-risk patients.
The Study: Patients were randomized to receive two 50-mg indomethacin suppositories or placebo immediately after undergoing ERCP. Patients were then observed in the recovery area for at least 90 minutes, and were followed for 30 days to monitor for post-procedure events and complications. Patients were eligible if they met at least one of the major criteria for post-ERCP pancreatitis: previous post-ERCP pancreatitis, pancreatic or precut sphincterotomy, clinical suspicion of sphincter of Oddi dysfunction, pneumatic dilatation of an intact biliary sphincter, ampullectomy, or more than eight cannulation attempts. Eligibility also could be met with two or more minor criteria: women younger than 50 years, history of recurrent pancreatitis, multiple contrast injections into the pancreatic duct with at least one injection to the pancreatic tail, opacification of pancreatic acini caused by excessive contrast injection, or the brush acquisition of a pancreatic duct cytologic specimen. Patients were excluded if they had active pancreatitis or peptic ulcer disease, were already using NSAIDs, or had a serum creatinine level greater than 1.4 mg per dL (123.76 μmol per L). The primary outcome was the development of post-ERCP pancreatitis.
Results: Investigators enrolled 602 patients (295 were randomized to receive indomethacin and 307 to receive placebo), of whom most (82.3 percent) were suspected to have sphincter of Oddi dysfunction. Post-ERCP pancreatitis developed in 79 patients overall, with significantly fewer episodes occurring in the indomethacin group compared with the placebo group (9.2 versus 16.9 percent; P = .005; absolute risk reduction = 7.7 percentage points; relative risk reduction = 46 percent). The number needed to treat to prevent one episode of post-ERCP pancreatitis was 13. Secondary outcome analysis found that patients in the indomethacin group were less likely to experience moderate or severe post-ERCP pancreatitis (4.4 versus 8.8 percent; P = .03), and had a shorter median length of hospital stay (3.5 versus 4.0 days; P < .001). Adverse events, such as clinically significant bleeding, were similar between groups. No myocardial infarctions, strokes, or deaths were reported at the 30-day follow-up.
Conclusion: Compared with placebo, a single dose of rectal indomethacin significantly reduced the likelihood of post-ERCP pancreatitis, the likelihood of moderate or severe pancreatitis, and the length of hospital stay in patients at high risk of this complication.