Abstract
BACKGROUND: Oliceridine is a novel 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 effects. This sequential dose-finding study was conducted 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), thereby supporting 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 propofol (2.5 mg/kg). 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. A positive response was defined as the occurrence of involuntary movement, frowning, or an MOAA/S score > 1 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. Secondary outcome measures included the time to anesthesia emergence, the VAS scores at PACU entry and discharge, the incidence of PONV, and the number of patients requiring analgesics in the 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, and no episodes of respiratory depression were observed. The mean time to anesthesia emergence ranged from 3 to 4 min. The VAS scores at PACU entry and discharge remained below 3 in all patients, and no supplemental analgesics were required. No gastrointestinal adverse events were observed in the PACU. CONCLUSIONS: Given its lower incidence of opioid-related adverse effects, oliceridine combined with propofol may offer a promising and well-tolerated approach for day-case hysteroscopy under TIVA with PSB. The estimated ED₅₀ and ED₉₅ of oliceridine in combination with propofol (2.5 mg/kg) were 1.309 mg (95% CI: 1.165–1.477 mg) and 1.675 mg (95% CI: 1.497–2.508 mg), respectively. These findings provide a reference for optimizing clinical dosing strategies. 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12871-025-03411-5.