Effective sedation is critical for endoscopic retrograde cholangiopancreatography (ERCP). While pethidine (meperidine) has traditionally been used for procedural analgesia, many centers are shifting toward fentanyl due to its favorable pharmacokinetic profile. We aimed to compare ERCP success rates and sedation characteristics between patients receiving fentanyl versus pethidine in a real-world endoscopy unit setting.

We retrospectively analyzed 2,871 ERCP procedures performed between 2004 and 2025 at our tertiary endoscopy center. Patients were grouped based on analgesic received (pethidine or fentanyl). Primary outcome was procedural success. Secondary outcomes included the total intravenous midazolam dose administered during the procedure, as well as procedural complexity indicators such as the need for needle-knife precut sphincterotomy and the presence of difficult biliary cannulation, as defined by ESGE criteria. Multivariable logistic regression and inverse probability of treatment weighting (IPTW) using propensity scores were applied to adjust for confounding (covariates: age, gender, year, procedure difficulty, precut use, midazolam dose).

Fentanyl was used in 348 cases (12.1%), primarily in 2024–2025, while pethidine was used in 2,523 (87.9%). Despite higher rates of difficult cannulation (37.1% vs 23.5%, p<0.001), fentanyl cases had significantly higher unadjusted success rates (95.4% vs 89.6%, p=0.0008). In adjusted logistic regression, fentanyl was independently associated with increased ERCP success (OR 7.08, 95% CI 3.58–14.03, p<0.001). IPTW analysis confirmed this association. Median midazolam dose was higher in fentanyl cases (3 mg vs 2 mg, p<0.001), likely reflecting the greater procedural complexity and evolving sedation practices during the study period. 

Fentanyl use during ERCP was independently associated with significantly higher procedural success, even in cases with increased technical difficulty. While fentanyl is typically associated with reduced midazolam requirements in procedural sedation, our finding of higher midazolam dosing in the fentanyl group likely reflects the significantly higher procedural complexity and case difficulty. Fentanyl was introduced in the most recent period, coinciding with more advanced therapeutic ERCPs, often requiring precut sphincterotomy and prolonged cannulation attempts, necessitating deeper sedation. Furthermore, evolving practice patterns may have permitted more aggressive midazolam titration when using fentanyl, due to its rapid onset and shorter duration of action. These findings suggest that fentanyl may offer clinical advantages over pethidine in achieving successful outcomes, particularly in challenging ERCPs, and support its adoption as the preferred analgesic in modern endoscopy sedation protocols.