A pharmacodynamic analysis of factors affecting recovery from anesthesia with propofol-remifentanil target controlled infusion
Abstract
Aim: To examine individual patient’s demographic parameters and clinical variables related to return of consciousness (ROC) and the pharmacodynamic relationship between propofol effect-site concentration (Ce) and ROC from propofol-remifentanil anesthesia.
Methods: Ninety-four patients received propofol-remifentanil anesthesia using the effect-site target-controlled infusion (TCI) system. All clinical events were noted, and variables possibly related to propofol Ce at ROC were examined using linear correlation analyses. Pharmacodynamic modeling incorporating covariates was performed using NONMEM (Nonlinear Mixed Effects Modeling) VII software.
Results: The Ce values of propofol at loss of consciousness (LOC) and ROC were 4.4±1.1 μg/mL and 1.1±0.3 μg/mL, respectively. Age was negatively correlated with propofol Ce at ROC (r=−0.48, P<0.01). Including age as a covariate in Ce50 (the effect-site concentration associated with 50% probability of return of consciousness) and λ (the steepness of the concentration-versus-response relationship) significantly improved the performance of the basic model based on the likelihood ratio test, with a significant decrease in the minimum value of the objective function. The Ce50 in 25-, 50-, and 75-year-old patients was predicted to be 1.38, 1.06, and 0.74 μg/mL, respectively. The λ in 25-, 50-, and 75-year-old patients was predicted to be 12.23, 8.70, and 5.18, respectively.
Conclusion: Age significantly affects the relationship between propofol Ce and ROC, and pharmacodynamic modeling including age could lead to better predictions of ROC during emergence from propofol-remifentanil anesthesia.
Keywords:
Methods: Ninety-four patients received propofol-remifentanil anesthesia using the effect-site target-controlled infusion (TCI) system. All clinical events were noted, and variables possibly related to propofol Ce at ROC were examined using linear correlation analyses. Pharmacodynamic modeling incorporating covariates was performed using NONMEM (Nonlinear Mixed Effects Modeling) VII software.
Results: The Ce values of propofol at loss of consciousness (LOC) and ROC were 4.4±1.1 μg/mL and 1.1±0.3 μg/mL, respectively. Age was negatively correlated with propofol Ce at ROC (r=−0.48, P<0.01). Including age as a covariate in Ce50 (the effect-site concentration associated with 50% probability of return of consciousness) and λ (the steepness of the concentration-versus-response relationship) significantly improved the performance of the basic model based on the likelihood ratio test, with a significant decrease in the minimum value of the objective function. The Ce50 in 25-, 50-, and 75-year-old patients was predicted to be 1.38, 1.06, and 0.74 μg/mL, respectively. The λ in 25-, 50-, and 75-year-old patients was predicted to be 12.23, 8.70, and 5.18, respectively.
Conclusion: Age significantly affects the relationship between propofol Ce and ROC, and pharmacodynamic modeling including age could lead to better predictions of ROC during emergence from propofol-remifentanil anesthesia.