Effect of sex differences on the median effective dose of remimazolam combined with remifentanil in gastroscopy: an up-and-down sequential allocation trial

Background With the continuous popularization of comfortable medical treatments, the application of gastroscopy under sedation is becoming increasingly common, and moderate to deep sedation is often required. Remimazolam is an ultra-short-acting intravenous benzodiazepine anesthetic, which can produce better clinical effects when combined with analgesics. Moreover, it is not known whether gender differences influence the response to remimazolam in gastroscopy. Therefore, we set out to determine the median effective dose (ED50) for this drug when combined with the analgesic remifentanil in gastroscopy and compare the dosage requirements of remimazolam in male and female patients. Methods Using Dixon’s up-and-down sequential allocation method, seventy-six patients presenting for gastroscopy were prospectively enrolled. All patients were slowly injected with 0.5 µg/kg of remifentanil in advance, followed by the specific dose of remimazolam. The initial dose of remimazolam was 0.2 mg/kg, and the interval dose between patients was 0.05 mg/kg. Gastroscopy was performed after the MOAA/S score was ≤ 3. The standard positive responses in patients undergoing gastroscopy were coughing, swallowing, frowning, and physical movement affecting the operation during the examination. The dose of remimazolam was deemed to be ineffective if a positive reaction occurred, and the dose would be increased for the next patient. Otherwise, the dose would be decreased. Results The ED50 of remimazolam was 0.19 mg/kg (95% confidence interval 0.11–0.26 mg/kg); the 95% effective dose (ED95) was 0.30 mg/kg (95% CI 0.24–1.17 mg/kg). The ED50 of remimazolam was 0.16 mg/kg (95% CI 0.11–0.21 mg/kg) in males, and 0.22 mg/kg (95% CI 0.15–0.30 mg/kg) in females. Conclusion The ED50 and ED95 of remimazolam combined with remifentanil for gastroscopy respectively are 0.19 mg/kg and 0.30 mg/kg. The ED50 in male patients is lower than that of female patients, but the difference was not significant. Trial registration Retrospectively registered at the Clinicaltrials.gov, registration number: NCT05357430, date of registration: 14/04/2022