Sequential method for determining the effective dose of remimazolam combined with sufentanil for cervical dilation in hysteroscopic surgery

Abstract

This study investigated the 50% and 95% effective doses (ED50 and ED95) of remimazolam combined with sufentanil for cervical dilation during hysteroscopic surgery. Prospective single-center dose-finding study using a modified Dixon up-and-down sequential method. Twenty-five patients who underwent hysteroscopic surgery were enrolled in 2024. All patients received an intravenous injection of sufentanil at 0.15 μg/kg for intraoperative analgesia. We used a modified Dixon sequential method. The initial dose of remimazolam was 0.15 mg/kg. The dose of remimazolam administered to each patient was determined by whether hysteroscope placement had failed. Failure was defined as inadequate cervical dilation and difficulty in hysteroscope placement, accompanied by patient manifestations such as limb movements, frowning, or a Modified Observer's Assessment of Alertness/Sedation (MOAA/S) score ≥1. If cervical dilation failed (i.e., a positive response), the dose of remimazolam was increased by 0.02 mg/kg for subsequent subjects. Conversely, in the case of a negative response, the dose was decreased by the same gradient. Formal testing started from the first crossover point and continued until the eighth crossover point appeared. Statistical analysis: The probit method was used to calculate the 50% and 95% effective doses (ED50 and ED95) of remimazolam combined with sufentanil for cervical dilation during intravenous anesthesia, along with their corresponding 95% confidence intervals (95% CIs). The ED50 and ED95 of remimazolam combined with 0.15 μg/kg sufentanil for cervical dilation were 0.18 mg/kg (95% CI: 0.17–0.20) and 0.22 mg/kg (95% CI: 0.19–0.25), respectively. Administering 0.22 mg/kg remimazolam combined with 0.15 μg/kg sufentanil is safe and effective for intravenous anesthesia during cervical dilation in hysteroscopic surgery.