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.