Isobolographic Analysis of the Interaction Between Remimazolam and Etomidate in General Anesthesia Induction: A Prospective, Sequential Allocation Study Based on the Dixon Up-and-Down Method.

PURPOSE: This study aimed to investigate the sedative interaction between the new benzodiazepine derivative remimazolam and etomidate during general anesthesia induction and determine the appropriate dose ratio for their combined use.

PATIENTS AND

METHODS

Patients scheduled for general anesthesia, aged 18 to 60 years with a BMI of 18 to 28 kg/m2 and American Society of Anesthesiologists (ASA) physical status I-II, were randomly divided into five groups using a random number table. The modified Dixon up-and-down method was employed to determine the median effective dose (ED5 0) of remimazolam in Group A (remimazolam group) and etomidate in Group B (etomidate group). For the combined medication groups: Group C (0.25 ED5 0 remimazolam + 0.75 ED5 0 etomidate), Group D (0.5 ED5 0 remimazolam + 0.5 ED5 0 etomidate), and Group E (0.75 ED5 0 remimazolam + 0.25 ED5 0 etomidate), the dose of remimazolam was fixed in each group, and the ED5 0 of etomidate in each group was calculated. Isobolographic analysis was utilized to assess the sedative interaction between the two drugs, and the interaction index and optimal dose ratio for synergism were calculated.

RESULTS

The ED5 0 of remimazolam and its 95% confidence interval (95% CI) in Group A were 0.193 (0.167-0.253) mg/kg, while those of etomidate in Group B were 0.155 (0.118-0.20) mg/kg. Isobolographic analysis revealed remimazolam and etomidate produced a synergistic effect in Groups C and D, and an additive effect in Group E. When combined at 0.048 mg/kg remimazolam and 0.062 mg/kg etomidate, the optimal dose ratio for the strongest synergism was 1:1.29.

CONCLUSION

During general anesthesia induction, when the dose ratios of remimazolam to etomidate are approximately 1:1.29 and 1:0.39, the two drugs exert a synergistic sedative effect, with the strongest synergism observed at the dose ratio of 1:1.29.