Electroencephalographic Features of Elderly Patients during Anesthesia Induction with Remimazolam: A Substudy of a Randomized Controlled Trial

Background: Although remimazolam is used as a general anesthetic in elderly patients due to its hemodynamic stability, the electroencephalogram characteristics of remimazolam are not well known. The purpose of this study was to identify the electroencephalographic features of remimazolam-induced unconsciousness in elderly patients and compare them with propofol. Methods: Remimazolam (n = 26) or propofol (n = 26) were randomly administered for anesthesia induction in surgical patients. The hypnotic agent was blinded only to the patients. During the induction of anesthesia, remimazolam was administered at a rate of 6 mg · kg^-1 · h^-1, and propofol was administered at a target effect-site concentration of 3.5 μg/ml. The electroencephalogram signals from eight channels (Fp1, Fp2, Fz, F3, F4, Pz, P3, and P4, referenced to A2, using the 10 to 20 system) were acquired during the induction of anesthesia and in the postoperative care unit. Power spectrum analysis was performed, and directed functional connectivity between frontal and parietal regions was evaluated using normalized symbolic transfer entropy. Functional connectivity in unconscious processes induced by remimazolam or propofol was compared with baseline. To compare each power of frequency over time of the two hypnotic agents, a permutation test with t statistic was conducted. Results: Compared to the baseline in the alpha band, the feedback connectivity decreased by averages of 46% and 43%, respectively, after the loss of consciousness induced by remimazolam and propofol (95% CI for the mean difference: -0.073 to -0.044 for remimazolam [P < 0.001] and -0.068 to -0.042 for propofol [P < 0.001]). Asymmetry in the feedback and feedforward connectivity in the alpha band was suppressed after the loss of consciousness induced by remimazolam and propofol. There were no significant differences in the power of each frequency over time between the two hypnotic agents (minimum q value = 0.4235). Conclusions: Both regimens showed a greater decrease in feedback connectivity compared to a decrease in feedforward connectivity after loss of consciousness, leading to a disruption of asymmetry between the frontoparietal connectivity.