Effect of Rectal Indomethacin for Preventing Post-ERCP Pancreatitis Depends on Difficulties of Cannulation Results from a Randomized Study With Sequential Biliary Intubation

Goals and Background: The greatest challenges for endoscopists performing biliary therapy in endoscopic retrograde cholangiopancreatography (ERCP) are to achieve selective biliary cannulation and prevent post-ERCP pancreatitis (PEP). Nonsteroidal anti-inflammatory drugs have proven prophylactic effect in PEP. However, the patient population that would benefit from this approach has not been defined. Study: A total of 539 patients undergoing our cannulation protocol with early precut were randomized into a placebo-controlled, prospective, double-blind study to rectally receive either 100 mg indomethacin or placebo. The effect of indomethacin on PEP was stratified based on difficulties of cannulation and analyzed in patients with different risks. Results: In 70.3% of patients, biliary intubation was successful in the first 5 atraumatic attempts, PEP rate was low, and indomethacin was ineffective (7.4% in the placebo group and 5.2% in the indomethacin group, P = 0.406). In the next phase of intubation using guidewire, the success rate increased up to 83.5%, and PEP rate rose up to 8.7%, the effect of indomethacin was significant (11.9% vs. 5.4%, P = 0.018). Applying early precut success rate of biliary cannulation increased up to 98.1% and overall indomethacin diminished the frequency of PEP from 13.8% to 6.7% (P= 0.007). Preventive effect of indomethacin was demonstrated in cases with defined procedure-related risk (28.3% vs. 13.8%, P= 0.028) and with defined patient-related risk (16.3% vs. 7.0%, P= 0.004), but not in patients without risk factors. Conclusions: Rectally administered 100 mg indomethacin results in significantly lower PEP rate, particularly in cases with difficult cannulation and with identifiable patient-related or procedure-related risk factors.