A 58-year-old man presents with painless progressive jaundice, pale stools, and dark urine for 3 weeks. Imaging shows a dilated common bile duct (12 mm) with a distal stricture suspicious for pancreatic head malignancy. He is scheduled for ERCP. Which drug should be administered prophylactically before the procedure to reduce the risk of post-ERCP pancreatitis?

Explanation

## Prophylaxis of Post-ERCP Pancreatitis **Key Point:** Indomethacin (or diclofenac) administered rectally immediately before or after ERCP is the most effective pharmacological agent for preventing post-ERCP pancreatitis (PEP), reducing incidence from ~5% to ~2–3%. ### Mechanism of Indomethacin in PEP Prevention Indomethacin is a non-selective NSAIDs that: - Inhibits phosphodiesterase and increases intracellular cAMP in pancreatic acinar cells - Reduces inflammatory cascade and protease activation - Decreases pancreatic ductal pressure and edema - Most effective when given as a single 100 mg rectal suppository immediately after ERCP ### Evidence & Guidelines **High-Yield:** Multiple RCTs (PREVENT, POISED) demonstrate indomethacin reduces PEP risk by 50–60%, particularly in high-risk patients (age <50, SOD dysfunction, difficult cannulation, pancreatic sphincterotomy). ### Dosing & Administration | Parameter | Details | | --- | --- | | **Drug** | Indomethacin 100 mg (or diclofenac 50 mg) | | **Route** | Rectal suppository | | **Timing** | Immediately before or after ERCP | | **Contraindications** | Active GI bleeding, NSAIDs allergy, renal failure | | **Efficacy** | NNT ≈ 17–25 to prevent one case of PEP | ### Alternative Agents (Less Effective Alone) - **Octreotide:** Modest benefit (NNT ~30); used as adjunct in high-risk cases - **Gabapentin:** No proven role in PEP prevention - **Metoclopramide:** No evidence for PEP reduction **Clinical Pearl:** In high-risk patients (age <50, SOD, difficult cannulation), combine indomethacin + aggressive hydration (normal saline bolus + post-ERCP IV fluids) for additive benefit. **Warning:** Do NOT use indomethacin if patient has active peptic ulcer disease or severe renal impairment; consider alternative prophylaxis (aggressive hydration alone) in such cases.