Pharmacological and procedural strategies to prevent post-ERCP pancreatitis: an umbrella review of meta-analyses of randomized controlled trials

Background Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) is the most common complication following ERCP, and its prevention remains a major concern for biliopancreatic endoscopists. This umbrella review aims to assess existing meta-analytic evidence on the effectiveness of pharmacological interventions (PIs) and procedural technical modifications (PTMs) in reducing the incidence and severity of PEP. Methods We searched multiple databases to identify meta-analyses of randomized controlled trials (RCTs) that assessed the impacts of PIs or PTMs on the incidence and severity of PEP, from database inception to September 24, 2024. Evidence credibility was classified based on pre-specified criteria as: convincing (Class I), highly suggestive (Class II), suggestive (Class III), weak (Class IV), or non-significant evidence. Furthermore, the GRADE approach was employed to assess the quality of the evidence, categorizing it into four levels: high, moderate, low, and very low. Results A review of 47 meta-analyses (137,391 participants; 25 on PIs, 22 on PTMs) identified five PIs with suggestive evidence for PEP prevention: indomethacin (odds ratio [OR] 0.52, 95% confidence interval [CI] 0.39–0.71), epinephrine (risk ratio [RR] 0.34, 95% CI 0.18–0.62), nafamostat mesylate (RR 0.50, 0.38–0.66), NSAIDs (RR 0.65, 0.52–0.81), and aggressive hydration (OR 0.40, 0.26–0.63). For PTMs, one intervention was classified as highly suggestive evidence: pancreatic stent placement (RR 0.37, 0.27–0.51), while guidewire-assisted cannulation was suggestive (RR 0.51, 0.36–0.72). For high-risk patients, both indomethacin (RR 0.46, 0.32–0.65) and pancreatic stent placement (RR 0.41, 0.30–0.56) were suggestive. No interventions exceeded Class III evidence for preventing moderate to severe PEP. Conclusions Pancreatic stent placement and NSAIDs, such as indomethacin, have been confirmed as effective measures for PEP prevention in both unselected and high-risk patients.