Blood Pressure Reduction During Anesthetic Induction with Remimazolam versus Propofol in Elderly Patients: Pharmacodynamic Modeling of Remimazolam

Juyeon Oh,1 Kyung Mi Kim,1 Ji-Hoon Sim,1 Eun-Kyung Lee,2 Byung-Moon Choi1 1Department of Anesthesiology and Pain Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea; 2Department of Statistics, Ewha Womans University, Seoul, KoreaCorrespondence: Eun-Kyung Lee, Department of Statistics, Ewha Womans University, 52, Ewhayeodae-Gil, Seodaemun-Gu, Seoul, 03760, Korea, Tel +82-2-3277-6857, Fax +82-2-3277-3607, Email [email protected] Byung-Moon Choi, Department of Anesthesiology and Pain Medicine, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-Ro 43-Gil, Songpa-Gu, Seoul, 05505, Korea, Tel +82-2-3010-1704, Fax +82-2-3010-6790, Email [email protected]: Remimazolam, a novel hypnotic agent, has demonstrated superior hemodynamic stability compared with propofol during general anesthesia, particularly in elderly patients. However, the dose-dependent reduction in blood pressure associated with remimazolam has not been quantitatively modeled in this population.Patients and Methods: We analyzed data from 432 patients aged ≥ 65 years who underwent elective gastrectomy as part of a randomized trial comparing remimazolam with propofol. Remimazolam was administered via zero-order infusion at 6 mg/kg/h, whereas propofol was delivered using target-controlled infusion (TCI) guided by the Schnider model. Blood pressure data were transformed into fractional changes in mean arterial pressure (MBP) relative to baseline. A modified simple logistic regression model was developed to characterize the relationship between cumulative remimazolam dose and MBP reduction, with body weight evaluated as a covariate.Results: A total of 209 patients were analyzed in each group. The modified logistic model effectively described the dose-dependent MBP reduction associated with remimazolam. Body weight was identified as a significant covariate that improved model performance. Although the remimazolam group exhibited a statistically greater MBP reduction before intubation than the propofol group (28.0 ± 9.9% vs 25.8 ± 10.1% reduction from baseline, P = 0.024), the difference was not considered clinically meaningful.Conclusion: In elderly patients undergoing general anesthesia with remimazolam, the relationship between dose and MBP reduction during induction was well characterized using a modified logistic model, with body weight as a significant covariate. TCI may represent an effective dosing strategy for maintaining hemodynamic stability during anesthetic induction.Trial Registration: This study was registered at the Clinical Research Information Service of the Korean National Institute of Health (CRIS, http://cris.nih.go.kr), with registration number KCT0006877, on December 27, 2021.Keywords: remimazolam, anesthesia, hemodynamics, aged, pharmacodynamics