Effect of oliceridine on hypoxia during sedated hysteroscopy: a Phase 4 randomized clinical trial

Abstract

Background: Hypoxia is a common complication in hysteroscopic surgery under sedation with conventional opioids. Oliceridine, a novel G protein-biased μ-opioid receptor agonist, provides effective analgesia with fewer opioid-related adverse events, but its impact on intraoperative hypoxia in hysteroscopy remains unclear. Methods: This is a single-center, prospective, double-blind, randomized clinical trial (TRN: ChiCTR2400090351), patients scheduled for hysteroscopic surgery under sedation were enrolled. Participants were randomized (1:1) to receive sufentanil (0.15 μg·kg⁻¹) or oliceridine (40 μg·kg⁻¹), combined with propofol (1.5 mg·kg⁻¹). The primary outcome was the incidence of intraoperative hypoxia from sedative drug initiation to hysteroscopy completion. Secondary outcomes included subclinical respiratory depression, severe hypoxia, airway interventions, supplemental propofol requirements, pain scores, arterial blood gas analysis, and patient and surgeon satisfaction. Results: Among 492 randomized patients, 482 (98%) completed the trial. The incidence of intraoperative hypoxia is significantly lower in the oliceridine group (24 [9.8%] of 246 patients) than that in the sufentanil group (48 [19.5%] of 246 patients; RR, 0.50 [95% CI, 0.32–0.79]; P = 0.002). The lowest oxygen saturation is higher in the oliceridine group (99.0 [94.0, 100.0] vs 97.0 [90.0, 100.0], P < 0.001). Compared to sufentanil group, oliceridine group requires less propofol intraoperatively (median difference: 10.0 mg, 95% CI: 0.0 to 14.5; P = 0.03), has lower PaCO2 in Post-Anesthesia Care Unit (median difference: 1.0 mmHg, 95% CI: 0.0 to 2.0; P = 0.02) and a reduced base excess (mean difference: 0.34 mmol/L, 95% CI: 0.03 to 0.66; P = 0.03). In addition, both patient satisfaction and surgeon satisfaction are significantly higher (P = 0.003 and P = 0.002) in oliceridine group. Conclusions: Oliceridine reduces the incidence of intraoperative hypoxia during hysteroscopic surgery under sedation, suggesting it may be a safer alternative to sufentanil.