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Background: Patients with obstructive sleep apnea (OSA) are highly vulnerable to airway obstruction and respiratory depression under anesthesia. Understanding the pharmacodynamic behavior of remimazolam, a short-acting benzodiazepine, in this specific population is essential for optimizing dosing and minimizing anesthetic risk.
Methods: Forty-four participants received stepwise escalating remimazolam infusions. Pharmacodynamic analyses of Modified Observer’s Assessment of Alertness and Sedation (MOAA/S) and Bispectral Index (BIS) data utilized nonlinear mixed-effects modeling. Three classes of models were evaluated for MOAA/S data, and clinical responses for 0.1, 0.15, and 0.2 mg/kg intravenous bolus regimens were simulated to evaluate efficacy.
Results: For MOAA/S data, a discrete-time Markov model (DTMM) provided the best fit compared to ordinal logistic and sigmoid probability models, identifying OSA as a significant covariate. BIS data were best described by an Emax model incorporating an effect-compartment, yielding a population baseline estimate of 88. Simulations demonstrated that the 0.15 mg/kg regimen achieved a sedation success rate approaching 90% in the OSA population. However, BIS simulations indicated that the 0.2 mg/kg dosage resulted in excessively deep sedation, falling below the target range of 60-80 in morbidly obese population.
Conclusion: Population pharmacodynamic models for MOAA/S and BIS were successfully developed for remimazolam. Balancing the need for adequate sedation success against the risk of excessively deep anesthesia, a bolus dose of 0.15 mg/kg may be more appropriate for the OSA population.