Effect-site Concentration of Remimazolam at Loss and Recovery of Responsiveness During General Anesthesia: a Simulation Study

Background: The objective of this study was to investigate the effect-site concentration (Ce) of remimazolam at loss of response (LOR) and recovery of response (ROR) in patients underwent general anesthesia using simulation. In addition, the relationships between patient's factors and simulated Ce at LOR and ROR were examined.

Methods: The medical records of 81 patients who underwent elective surgery under general anesthesia using remimazolam with simulation of Ce between August 4, 2021 and October 12, 2021, were retrospectively reviewed. Remimazolam was administered as an induction dose of 6 or 12 mg/kg/h until the patient became unresponsive, followed by 0.3-2 mg/kg/ h to maintain BIS values below 60. Simultaneously, simulations of manual infusion mode were performed using Asan Pump software and the Ce of remimazolam was simulated using the Schüttler model. Whenever infusion rate of remimazolam was manually changed, the simulated Ce was confirmed almost simultaneously. LOR and ROR, defined as unresponsive and eye-opening to verbal commands, respectively, were recorded in the Asan Pump program.

Results: The median (1Q, 3Q) simulated Ce at LOR and ROR were 0.7 (0.5, 0.9) and 0.3 (0.2, 0.4) μg/ml, respectively. LOR was achieved in 1.9 min after remimazolam infusion with cumulative doses of 0.3 mg/kg. There was a significant relationship between age and simulated Ce at ROR (Ce at ROR = -0.0043 × age + 0.57, r = 0.30, P = 0.014).

Conclusions: For optimal dosage adjustment, simulating Ce while administering remimazolam with a weight-based dose during anesthesia is helpful. Elderly patients may recover from anesthesia at lower Ce of remimazolam.