Bridging evidence gaps in opioid-sparing postoperative pain control for percutaneous nephrolithotomy: a network meta-analysis identifying optimal strategies.

Percutaneous nephrolithotomy (PCNL) is the gold standard for large renal calculi, yet postoperative pain from tract dilation, capsule injury, and inflammation often delays recovery, prolongs hospital stays, and reduces patient satisfaction. Amid the opioid crisis, reliance on opioids for pain control raises concerns over adverse effects like respiratory depression, nausea, and dependence. This has spurred interest in opioid-sparing multimodal strategies, with recent studies suggesting feasibility of opioid-free discharge and comparable relief from NSAIDs with fewer side effects. However, robust comparative evidence remains scarce. This systematic review and network meta-analysis (NMA) evaluates and ranks postoperative analgesic strategies in PCNL, aiming to highlight approaches that may reduce opioid use while improving clinical outcomes in endourology. We searched PubMed, Embase, Web of Science, and Cochrane Library up to March 11, 2025 for RCTs assessing VAS pain in adults undergoing PCNL. Interventions grouped: local anesthesia/nerve blocks, intravenous analgesics, local instillation, intrathecal anesthesia, aromatherapy. Bayesian NMA used ADDIS v1.16.8/R v4.0.5, with MCMC simulations, node-splitting for consistency, SMAA for benefit-risk of VAS (<24h, ≥24h) and complications. 45 RCTs (2,626 patients) formed consistent network without significant inconsistency/heterogeneity. Levobupivacaine outperformed bupivacaine/ropivacaine in VAS reduction (<24h, ≥24h) via erector spinae plane block/local infiltration. Non-opioid analgesics (NSAIDs/paracetamol) showed superior efficacy; opioids excelled short-term but not long-term. IV paracetamol plus LI-levobupivacaine ranked highest in the multicriteria analysis, although the benefit-risk ranking should be interpreted cautiously because the safety component was based on sparse and imprecise data. Limitations: RCT protocol variability (e.g., pain assessment), moderate bias in 21 studies, limited data for high-risk subgroups (e.g., renal impairment, obesity). Comparative safety could not be established because complication data were sparse and estimates were highly imprecise. This NMA supports levobupivacaine and NSAID-based IV analgesics for PCNL pain management, positioning IV-Paracetamol+LI-Levobupivacaine as a leading opioid-sparing multimodal option to address complex pain profiles. These findings encourage safer practices amid opioid concerns, potentially accelerating recovery, shortening stays, and enhancing endourology patient outcomes.Trial registration: PROSPERO CRD42024600872.