Tegileridine, a Biased μ-Opioid Receptor Agonist, versus Oxycodone for Postoperative Analgesia and Postoperative Nausea and Vomiting After Total Laparoscopic Hysterectomy: A Randomized, Double-Blind, Single-Center, Controlled Trial

Background: Patients undergoing total laparoscopic hysterectomy (TLH) commonly experience postoperative pain and are at relatively high risk of postoperative nausea and vomiting (PONV). Tegileridine is a recently developed biased μ-opioid receptor (MOR) agonist that may preserve analgesic efficacy while being associated with a lower incidence of opioid-related adverse effects. Objective: To evaluate whether tegileridine, compared with oxycodone at prespecified study doses, is associated with a lower incidence of PONV while providing similar early postoperative analgesic efficacy in patients undergoing TLH. Methods: This randomized, double-blind, single-center trial planned to enroll 66 adult women undergoing TLH. Participants were randomly assigned to the tegileridine group (group T) or the oxycodone group (group O). According to the study protocol, all patients received standardized anesthesia and surgery and were given intravenous tegileridine 0.01 mg·kg − 1 (group T) or oxycodone 0.06 mg·kg − 1 (group O) 20 minutes before the end of surgery. Data collected within 48 hours after surgery included the incidence and ordinal symptom grade of PONV, postoperative analgesic success rate, mean arterial pressure at predefined time points, the incidence of other adverse events, use of vasoactive medications, time to first patient-controlled intravenous analgesia (PCIA) demand, and the total number of PCIA demands within 24 and 48 hours. Results: A total of 68 patients were enrolled, with comparable baseline characteristics between groups. Compared with oxycodone, tegileridine was associated with a lower incidence of PONV (27.3% vs 54.3%; RR, 0.50; 95% CI, 0.27– 0.95; P = 0.024), a lower ordinal PONV symptom grade [0 (0– 1) vs 1 (0– 3); P = 0.012], and a lower overall incidence of other adverse events (27.3% vs 60.0%; P = 0.007). Postoperative analgesic success rates were similar between groups (87.9% vs 94.3%; P = 0.615). No significant between-group differences were observed in mean arterial pressure, vasoactive medication use, time to first PCIA demand, or total PCIA demands within 24 and 48 hours. Conclusion: In patients undergoing TLH, tegileridine was associated with a similar postoperative analgesic success rate and a lower risk of PONV compared with oxycodone. Trial Registration: This trial was retrospectively registered at ClinicalTrials.gov after patient enrollment had begun (NCT07326683).