Effect-Site Concentration of Remimazolam by Age Groups During Target-Controlled Infusion for Total Intravenous Anesthesia: A Retrospective Comparative Study

Purpose: Pharmacokinetic and pharmacodynamic (PKPD) models exist for remimazolam, but data for target-controlled infusion (TCI) are limited. The Schüttler PKPD model, a three-compartment model including body weight as a covariate, does not account for age as a variable. This study aimed to investigate remimazolam’s effect-site concentration (Ce) in different age groups during sedation and general anesthesia with TCI using Schüttler PKPD model. Patients and methods: Records of patients who underwent remimazolam TCI with the Schüttler model were reviewed. During anesthesia induction, the target Ce of remimazolam was gradually increased until loss of responsiveness, and it was titrated to maintain bispectral index of 40–70 during operation. Patients were categorized into young (20–40 years, n=24), middle-aged (41–60 years, n=27), and elderly (61–80 years, n=35) groups. Bispectral index and hemodynamic variables were also assessed. Results: The elderly group had significantly lower remimazolam Ce compared to the young and middle-aged groups at all sedation levels, intubation, and surgery. Mean highest intraoperative Ce was 0.78±0.10, 0.71±0.07, and 0.61±0.10 µg/mL in young, middle-aged, and elderly groups, respectively (P<0.001). The recovery of responsiveness during emergence occurred at significantly lower Ce in the elderly group (0.28±0.06 µg/mL) than in the young (0.41±0.07 µg/mL) and middle-aged groups (0.35±0.07 µg/mL, P<0.001). Ce during sedation and general anesthesia was comparable between the young and middle-aged groups. The bispectral index was similar across groups but fluctuated more in the elderly group during general anesthesia. Elderly patients also showed the greatest systolic blood pressure suppression (18.4 ± 13.29% before intubation and 34.31 ± 14.91% during surgery). Conclusion: Older patients may require lower target Ce during remimazolam TCI for sedation and anesthesia, with emergence occurring at lower Ce. Blood pressure suppression may be greater in elderly patients under deep sedation or general anesthesia.