The influence of sex on the dosage of remimazolam co-administered with remifentanil for loss of consciousness in adult patients: an up-and-down sequential allocation trial

Abstract

Background: This study aimed to determine the 50% effective dose of remimazolam co-administered with remifentanil for loss of consciousness in men and women as well as to investigate whether there are between-sex differences. Methods: Using a modified Dixon’s up-and-down allocation approach, we sequentially enrolled male and female patients aged 19–60 years with American Society of Anesthesiologists class I or II who were scheduled for robotic surgery. For both sexes, the starting remimazolam dose was 0.15 mg/kg, with a step size of 0.05 mg/kg. After achievement of a target effect-site concentration 2.0 ng/ml of remifentanil, and administration of a bolus dose of remimazolam, we assessed whether adequate loss of consciousness (defined as a Modified Observer’s Assessment of Alertness/Sedation scale score < 2 within 2 min) was achieved. Results: We included 22 male and 22 female patients. Based on Dixon’s up-and-down method, the 50% effective dose of remimazolam (mean ± standard error) was 0.13 ± 0.01 mg/kg and 0.17 ± 0.01 mg/kg in the male and female groups, respectively (P = 0.34). Isotonic regression analysis revealed that the 95% effective dose (95% confidence interval) was 0.19 (0.18–0.20) mg/kg in the male group and 0.29 (0.29–0.30) mg/kg in the female group. Conclusions: There was no between-sex difference in the 50% effective dose of remimazolam for loss of consciousness; however, the 95% effective dose was significantly higher in female patients than in male patients. Trial registration: This study protocol was registered at Clinical Research Information Service (CRIS No. KCT0007951, 02/12/2022).