Confounding by Indication in Real-World Indomethacin Use for Post-ERCP Pancreatitis: Implications for Severity and Cost.

BACKGROUND AND AIMS: Rectal indomethacin is recommended for PEP prevention, but real-world effectiveness may differ due to selective use in higher-risk patients. This study evaluated the association between indomethacin use and PEP, severity, and cost implications of selective versus routine prophylaxis. METHODS: A retrospective cohort study of 332 ERCP procedures at a level III community hospital compared two endoscopists: selective versus routine administration. Firth penalized logistic regression evaluated PEP predictors. Severity was classified using Cotton and Revised Atlanta criteria. Cost analysis incorporated institutional acquisition and estimated hospitalization costs. RESULTS: Indomethacin was administered in 100 cases (30.1%). PEP occurred in 19 patients (5.7%), with no significant difference between groups. In adjusted analysis, indomethacin was not associated with PEP (odds ratio [OR] 1.26, 95% confidence interval [CI] 0.32-4.56, p = 0.74), while guidewire passage into the pancreatic duct (OR 5.25, p = 0.004) and prior PEP (OR 5.68, p = 0.001) were significant predictors. Indomethacin use was strongly associated with procedural difficulty, consistent with confounding by indication. Severe pancreatitis occurred only in the non-indomethacin group, though underpowered. Acquisition costs ranged from $262 to $532 per dose ($79-$160 per ERCP). At base-case PEP hospitalization cost of $20,000, mean total cost per ERCP was $1,263 for selective versus $1,173 for routine use; across all assumptions, costs were driven by PEP incidence rather than medication utilization. CONCLUSION: Indomethacin use was driven by procedural risk factors and not independently associated with reduced PEP. Economic outcomes were more sensitive to complication rates than drug costs.