For the prevention of postendoscopic retrograde cholangiopancreatography pancreatitis (PEP), the combination of aggressive hydration and rectal indomethacin appears to be the best intervention.

A systematic review and network meta-analysis was carried out to assess the effectiveness of various interventions for PEP prevention, the most commonly reported complication of endoscopic retrograde cholangiopancreatography pancreatitis (ERCP).

Databases like Cochrane databases, PubMed, and EMBASE were explored to find out the RCTs assessing guideline-recommended interventions and their combinations [rectal nonsteroidal anti-inflammatory drugs: diclofenac or indomethacin, aggressive hydration, pancreatic stent, sublingual nitrate) to prevent PEP.

For ranking the interventions, the surface under the cumulative ranking curve, and the direct and Bayesian network meta-analysis were carried out. The subgroup network meta-analysis for high-risk populations was also carried out.

Overall, 38 RCTs with 10 different interventions were recognized. In comparison with controls, each intervention was found to be protective against PEP on network and direct meta-analysis. Except for aggressive hydration+diclofenac and NSAIDs+ sublingual nitrate, aggressive hydration+indomethacin was linked with a profound drop in PEP risk when compared to the pancreatic stent, indomethcin+pancreatic stent, diclofenac, aggressive hydration, sublingual nitrate, and indomethacin.

Aggressive hydration with either rectal NSAIDs or sublingual nitrate had comparable effectiveness. For the prevention of PEP, aggressive hydration+indomethacin was the best strategy that exhibited a 95.3% probability of being ranked first. In the case of high-risk people, although the effectiveness of pancreatic stent and indomethacin were similar, pancreatic stent exhibited an 80.8% probability of being ranked first. For PEP prevention, aggressive hydration+indomethacin appears to be the best intervention. For high-risk people, pancreatic stent appears to be the most effective strategy.

Combining rectal indomethacin with aggressive hydration may be beneficial to prevent PEP.