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Background Remimazolam is a novel short-acting benzodiazepine characterized by metabolism independent from organ function. We report intraoperative MEP responses of two patients who underwent spine surgery under general anesthesia using remimazolam. Case presentation In case 1, MEP monitoring was successfully performed with the use of a fixed dose of remimazolam at 0.5 mg/kg/h and remifentanil at 0.2 μg/kg/min. In case 2, an increasing dose of remimazolam from 0.5 to 1.5 mg/kg/h during the operation did not affect MEP signals. In both cases, remimazolam was titrated to maintain the values of entropy electroencephalogram (EEG) monitoring at 40–60. Conclusions General anesthesia using remimazolam and remifentanil can be a valuable alternative for spine surgery with MEP monitoring by EEG to assess the optimal dose.

Background. We investigated the potential safety of remimazolam and propofol in malignant hyperthermia- (HM-) susceptible patients using ryanodine receptor 1- (RYR1-) expressing human embryonic kidney- (HEK-) 293 cells. Methods. We compared the enhanced responsiveness of HEK-293 cells expressing wild-type RYR1 with that of mutant RYR1 to caffeine following perfusion with remimazolam or propofol. Furthermore, we investigated whether RYR1 enhanced the responsiveness of cells to remimazolam or propofol and compared the median effective concentration (EC50; i.e., the concentration required to reach half-maximal activation) using an unpaired two-tailed t -test while a P < 0.05 was considered significant. Results. Remimazolam and propofol did not promote the caffeine-induced increase in intracellular Ca2+ levels in HEK-293 cells expressing mutant RYR1 even with exposure to approximately 100-fold the clinically used concentration. In wild-type RYR1, EC50 values of remimazolam following refusion vs. nonperfusion were 2.86 mM vs. 2.75 mM ( P = 0.76 ) while for propofol perfusion vs. nonperfusion, they were 2.76 mM vs. 2.75 mM, respectively ( P = 0.83 ). In mutant RYR1, EC50 values of remimazolam refusion vs. nonperfusion were 1.58 mM vs. 1.71 mM, respectively ( P = 0.63 ) while for propofol perfusion vs. nonperfusion, they were 1.65 mM vs. 1.71 mM, respectively ( P = 0.73 ). Remimazolam and propofol increased intracellular Ca2+ levels in a concentration-dependent manner, but the effect was not enhanced by RYR1. EC50 values of remimazolam with non-RYR1 vs. wild-type RYR1 were 1.00 mM vs. 0.92 mM, respectively ( P = 0.91 ) while those of propofol were 1.09 mM vs. 1.05 mM, respectively ( P = 0.84 ). Conclusions. The increase in intracellular Ca2+ concentration caused by remimazolam or propofol was not considered an RYR1-mediated reaction. We conclude that remimazolam and propofol can be safely used as an anesthetic in MH-susceptible patients with RYR1-mutation without causing MH and may be safely substituted for an MH-triggering anesthetic when RYR1-mediated MH occurs.

Introduction. We compared the hemodynamics during general anesthesia with remimazolam and conventional anesthetics in patients with severe aortic stenosis (AS). Methods. This was a retrospective single-center analysis. We reviewed the records of 42 patients who underwent transcatheter aortic valve implantation with a transfemoral artery approach under general anesthesia from January to December 2020. Patients were divided into three groups based on the general anesthetic used for (induction/maintenance) remimazolam/remimazolam (Group R/R), propofol/sevoflurane (Group P/S), and midazolam/propofol (Group M/P). Vasopressor use (ephedrine, phenylephrine, and noradrenaline) was compared among the groups. Results. The number of patients in each group was 15 (Group R/R), 13 (Group P/S), and 14 (Group M/P), with no significant difference in background characteristics and intraoperative vital signs. For anesthesia induction, doses of ephedrine and phenylephrine used were significantly lower in Group R/R (ephedrine [mg]: Group R/R 2 [0–4] vs. Group P/S 8 [8–12], P < 0.001 , Group R/R vs. Group M/P 5 [0–15], P = 0.39 ; phenylephrine (mg): Group R/R 0 [0–0.08] vs. Group P/S 0.15 [0.10–0.20], P = 0.03 , Group M/P 0.21 [0.04–0.40], P = 0.08 ). For anesthesia maintenance, the noradrenaline dose used was low in the Group R/R (noradrenaline [μg/kg/min]: Group R/R 0.019 [0.015–0.039], Group P/S 0.042 [0.035–0.045], P = 0.02 , Group M/P 0.048 [0.040–0.059], P < 0.01 ). Conclusion. In patients with severe AS, induction and maintenance of anesthesia with remimazolam resulted in less overall vasopressor use than conventional general anesthetics.

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