To determine the optimal timing, dosage, and efficacy of combination NSAID therapy in preventing post-ERCP pancreatitis.

A total of 866 patients undergoing ERCP between December 2021 and December 2023 were enrolled and randomly assigned to an observation group or a control group, with further subgrouping into combination therapy or monotherapy groups. The observation group received NSAIDs such as indomethacin suppositories and/or diclofenac sodium before ERCP, while the control group received NSAIDs postoperatively. The combination therapy group received both diclofenac sodium and indomethacin suppositories, whereas the monotherapy group received only diclofenac sodium. Primary endpoints included the incidence and severity of pancreatitis, as well as the occurrence of post-procedural complications such as perforation, bleeding, cholangitis, and pain scores. These outcomes were compared between groups to evaluate differences in the incidence and severity of PEP.

The group receiving pre-procedural NSAIDs had a significantly lower risk of adverse reactions compared with the post-procedural group. Combination therapy showed superior PEP risk reduction compared to monotherapy. Independent risk factors for PEP included female sex, age > 60 years, a history of gallstones or pancreatitis, hypertension, five cannulation attempts > 5, and non-dilated extrahepatic bile ducts.

Prophylactic combination therapy with indomethacin suppositories and diclofenac sodium before ERCP significantly reduces PEP incidence and severity, while concurrently decreasing risks of perforation, hemorrhage, cholangitis, and postoperative pain scores.