Estimation of median effective doses and 95% effective doses of oliceridine combined with propofol for day-case hysteroscopy under total intravenous anesthesia with preserved spontaneous breathing: an up-and-down sequential allocation trial

Background Oliceridine is a newly developed G protein-biased µ-opioid receptor agonist, offering a significant reduction in the risk of opioid-related respiratory depression and a lower incidence of gastrointestinal adverse reactions. This sequential dose-finding study was employed to determine the median effective doses (ED₅₀) and 95% effective doses (ED₉₅) of oliceridine coadministered with propofol during day-case hysteroscopy under total intravenous anesthesia (TIVA) with preserved spontaneous breathing (PSB), to support the optimization of clinical anesthesia protocols. Methods In the study, 31 women undergoing day-case hysteroscopy were included. All patients were given a specific dose of oliceridine combined with 2.5 mg/kg propofol. A modified Dixon up-and-down sequential approach was adopted, with the starting dose of oliceridine set at 1.5 mg. The dosage of oliceridine was adjusted according to the response of the previous patient: a positive response led to an increased dose, while a negative response prompted a decrease, with a fixed dose ratio of 1:1.2. The positive response was defined as the patient exhibited involuntary movements, frown, or a MOAA/S score > 1 point during cervical dilatation. The formal trial commenced from the first crossover and continued until seven crossovers were observed. Using the probit model, the ED₅₀ and ED₉₅ with 95% confidence intervals (95% CI) were calculated. Furthermore, the following data is also recorded, including the anesthesia recovery time, the Visual Analogue Scale (VAS) scores, and the incidence of postoperative nausea and vomiting (PONV) both at the time of anesthesia recovery and discharge from the post-anesthesia care unit (PACU). Results For day-case hysteroscopy, the estimated ED₅₀ and ED₉₅ of oliceridine in combination with 2.5 mg/kg propofol were 1.309 mg (95% CI: 1.165–1.477 mg) and 1.675 mg (95% CI: 1.497–2.508 mg), respectively. All patients maintained spontaneous respiration throughout the procedure, with no episodes of respiratory depression observed. The mean anesthesia recovery time ranged from 3 to 4 minutes. Pain assessment using the VAS revealed scores under 3 during anesthetic recovery or in the PACU, and none of the patients required additional analgesics. No patients reported gastrointestinal side effects in the PACU. Conclusions Given its lower incidence of opioid-related adverse effects, oliceridine combined with propofol appears suitable for day-case hysteroscopy under TIVA with PSB. The estimated ED₅₀ and ED₉₅ of oliceridine in combination with 2.5 mg/kg propofol were 1.309 mg (95% CI: 1.165–1.477 mg) and 1.675 mg (95% CI: 1.497–2.508 mg), respectively, providing a reference for optimized dosing in clinical practice. Trial registration The trial was officially registered in the Chinese Clinical Trial Registry ( https://www.chictr.org.cn/bin/project/edit?pid=252762 ) on December 25, 2024, with the registration number ChiCTR2400094657.