A Simulation Study of Propofol Effect-Site Concentration for Appropriate Sedation in Pediatric Patients Undergoing Brain MRI: Pharmacodynamic Analysis

ABSTRACT

PURPOSE: We aimed to establish the propofol effect-site concentration (Ce) for appropriate sedation by pharmacodynamic analysis and to determine the propofol Ce during occurrence of sedation-related side effects in pediatric patients undergoing brain magnetic resonance imaging (MRI). MATERIALS AND METHODS: In 50 pediatric patients scheduled for brain MRI, sedation was induced with 2.0 mg/kg propofol; additional propofol doses were 0.5–1 mg/kg. Propofol Ce was simulated by inputting the propofol administration profiles of patients into a pediatric compartmental model (Choi model). The relationship between propofol Ce and probabilities of sedation and recovery were analyzed using a sigmoidal Emax model. The simulated propofol Ce for sedation-related side effects was investigated. Population model parameters were estimated using the Nonlinear Mixed-Effects Modelling software. RESULTS: The mean values of propofol Ce₅₀ for sedation during the preparation, scanning, and recovery phases were 1.23, 0.43, and 0.39 µg/mL. The simulated propofol Ce values during oxygen desaturation (SpO₂<90%) (3 patients; 6%), hypotension (16 patients; 32%), and bradycardia (12 patients; 24%) were 3.01±0.04, 2.05±0.63, and 2.41±0.89 µg/mL, respectively. CONCLUSION: The required propofol Ce₅₀ for applying monitors during the preparation phase before the start of MRI was higher than the propofol Ce₅₀ required during the scanning phase. During low-intensity stimulation phases, such as scanning, propofol bolus dose should be strictly titrated not to exceed the propofol Ce that can lead to oxygen desaturation because of the relatively low propofol Ce (Ce₉₅, 1.43 µg/mL) required for sedation in most patients.