Efficacy and safety of oliceridine versus sufentanil in perioperative anesthesia and analgesia: a systematic review and meta-analysis with trial sequential analysis.

BACKGROUND: Perioperative pain management is a significant challenge when using conventional µ opioid agonists, which often require careful balancing of efficacy and safety. Oliceridine, a G-protein-biased µ-opioid receptor agonist, may provide comparable analgesia while offering a potentially improved safety profile. METHODS: Randomized controlled trials (RCTs) comparing perioperative oliceridine and sufentanil in adult patients were systematically identified from PubMed, Scopus, Embase, Web of Science, and the Cochrane Library from inception to March 21, 2026. Primary outcomes included respiratory depression, hypotension, and postoperative nausea and vomiting (PONV). Secondary outcomes comprised Quality of Recovery-15 (QoR-15) scores at 24 h, recovery time, extubation time, rescue analgesic requirements, 48-hour pain scores at rest, dizziness, bradycardia, and hospital length of stay. Random-effects models were used to estimate risk ratios (RRs) for dichotomous outcomes and mean differences (MDs) for continuous outcomes. Trial sequential analysis (TSA) evaluated the robustness of the evidence. RESULTS: Seven RCTs (n = 1,327 patients; 1,242 in quantitative synthesis) showed that oliceridine reduced respiratory depression (RR = 0.48, 95% CI: 0.31-0.76; I² = 0%) and PONV (RR = 0.48, 95% CI: 0.36-0.65; I² = 0%), with TSA supporting conclusive evidence. Hypotension showed no difference between groups (RR = 0.83, 95% CI: 0.53-1.30; I² = 0%). Oliceridine significantly improved 24-hour QoR-15 scores (MD = 6.27, 95% CI: 4.33-8.20). Other secondary outcomes demonstrated no significant differences. CONCLUSIONS: These preliminary findings indicate that oliceridine reduces the risks of respiratory depression and PONV compared with sufentanil, while analgesic efficacy and hemodynamic stability were comparable in Chinese adults. Larger, multicenter trials in diverse populations and surgical contexts are required to confirm these findings and address existing gaps.