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

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.

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.

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.

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.