← Issue №6/ week of Aug 9, 2026/Endoscopy

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

From GI Signals issue №6: what this paper found, what it changes, and where it sits against the current standard of care, reviewed by Simon Mathews, MD.

Endoscopy retrospective · n=332 · Aug 10, 2026 · Dig Dis Sci · IF 2.5

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

New evidenceERCPacute pancreatitiscost-effectivenesshealth services
Clinical takeawayThis observational study cannot reliably determine indomethacin's protective effect due to confounding by indication (drug use associated with procedural difficulty rather than independent risk reduction). While severe pancreatitis occurred only in the non-indomethacin group (underpowered), confounding precludes attributing this to the drug. RCT-based guidelines recommending indomethacin should continue to direct practice.
What it foundRectal indomethacin (30% of cases) was not independently associated with PEP in adjusted analysis (OR 1.26, 95% CI 0.32-4.56, p=0.74); use was strongly driven by procedural difficulty, indicating confounding by indication. True independent predictors of PEP were guidewire passage into the pancreatic duct (OR 5.25, p=0.004) and prior PEP (OR 5.68, p=0.001).
ContextRCTs support indomethacin for PEP prevention in high-risk cases. This real-world cohort demonstrates confounding by indication: drug administration correlates with procedural difficulty rather than independently reducing PEP. Selective prophylaxis cannot be evaluated observationally when drug use is driven by baseline risk.
Reinforcessuggested applicable standard· American Society for Gastrointestinal Endoscopy (ASGE), 'American Society for Gastrointestinal Endoscopy guideline on post-ERCP pancreatitis prevention strategies: summary and recommendations' (Buxbaum JL et al., Gastrointest Endosc 2023;97(2):153-162). DOI 10.1016/j.gie.2022.10.005, PMID 36517310.

Decision at stakeGive periprocedural rectal NSAID prophylaxis to all patients undergoing ERCP

For ALL patients undergoing ERCP (average-risk and high-risk alike), give periprocedural rectal NSAID prophylaxis (100 mg indomethacin or diclofenac) unless contraindicated (e.g., recent PUD, renal insufficiency), this is now a strong recommendation for unselected patients, not just high-risk ones.

From our summary of this standard, unedited — the part the paper bears on. marks omitted text. Our wording, not the guideline's; read the source for its own text.

Our full summary of this standard

For ALL patients undergoing ERCP (average-risk and high-risk alike), give periprocedural rectal NSAID prophylaxis (100 mg indomethacin or diclofenac) unless contraindicated (e.g., recent PUD, renal insufficiency), this is now a strong recommendation for unselected patients, not just high-risk ones. For high-risk patients undergoing repeated or deep pancreatic-duct access or ampullectomy, add a prophylactic small-caliber pancreatic duct stent (3-5Fr, preferably 5Fr, 3-7cm, removed within 5-10 days), strong recommendation; for other high-risk scenarios (difficult cannulation, prior PEP, precut sphincterotomy without fistulotomy), PD stenting is a conditional recommendation when PD access is easily achieved. Aggressive periprocedural/postprocedural IV hydration with lactated Ringer's (20 mL/kg bolus, then 3 mL/kg/h for 8h) is a conditional suggestion for unselected patients (most practical for inpatients), and wire-guided cannulation is conditionally favored over contrast-guided to reduce PEP risk. The SVI trial (Elmunzer, Lancet 2024) found rectal indomethacin alone did NOT meet non-inferiority versus indomethacin+stent in high-risk patients (PEP 14.9% vs 11.3%), supporting continued use of the combination bundle in high-risk cases rather than dropping the stent. Post-procedure, monitor for the major complications (pancreatitis, sphincterotomy bleeding, perforation, cholangitis) and manage by type, PEP by Cotton criteria with fluids/analgesia, bleeding with repeat endoscopic hemostasis, perforation by Stapfer classification with surgical consult for Type I, and cholangitis with empiric antibiotics (Tokyo Guidelines TG18) plus biliary drainage; these complication-management elements are unchanged from ESGE 2020.

American Society for Gastrointestinal Endoscopy (ASGE), 'American Society for Gastrointestinal Endoscopy guideline on post-ERCP pancreatitis prevention strategies: summary and recommendations' (Buxbaum JL et al., Gastrointest Endosc 2023;97(2):153-162). DOI 10.1016/j.gie.2022.10.005, PMID 36517310. · reviewed 2026-07-21 ↗
Eshov A … Datta S · Digestive Diseases and Sciences · IF 2.5 · PubMed ↗Permalink
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