Comparison of Oliceridine and Hydromorphone for Postoperative Analgesia in Adults Undergoing Lower Limb Fracture Surgery: A Randomized Controlled Non-Inferiority Trial.

PURPOSE: This study aimed to compare the efficacy and safety of oliceridine versus hydromorphone for patient-controlled intravenous analgesia (PCIA) following lower limb fracture surgery. METHODS: A total of 126 adult patients scheduled for lower limb fracture surgery were enrolled and randomly assigned (1:1) to receive PCIA with either oliceridine or hydromorphone, both combined with flurbiprofen axetil. The study was double-blinded. The primary outcome was the non-inferiority of the resting Numeric Rating Scale (NRS) pain score at 48 hours postoperatively, with a pre-specified non-inferiority margin of 1.0. Secondary outcomes included resting NRS scores at 1, 12, 24 hours postoperatively, incidences of postoperative nausea and vomiting (PONV) and pruritus, and total analgesic consumption. RESULTS: Analysis of the primary endpoint revealed that the median 48-hour NRS score in the oliceridine group was non-inferior to that in the hydromorphone group within the per-protocol population (n=118). Using the Hodges-Lehmann estimator, the median difference was -0.0001 (95% CI: -0.0000, 0.0001). Since the upper confidence limit (0.0001) was less than the non-inferiority margin of 1.0, non-inferiority was established. Sensitivity analysis using a bootstrap method supported this conclusion, yielding a mean difference of 0.072 (95% CI: -0.183, 0.326). Secondary analyses indicated a significantly reduced rate of PONV in the oliceridine group within the intention-to-treat cohort (4.8% vs 15.9%, p=0.040), although this difference was marginal in the per-protocol cohort (p=0.092). No clinically relevant differences were noted in pruritus or rescue analgesia requirements. CONCLUSION: For post-operative analgesia after lower limb fracture surgery, oliceridine provides analgesic efficacy comparable to hydromorphone. Observations suggest a potential for a lower incidence of PONV with oliceridine, which may offer a favorable opioid option within multimodal analgesic regimens for this population.