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 (C(e)) 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 C(e) at ROC were examined using linear correlation analyses. Pharmacodynamic modeling incorporating covariates was performed using NONMEM (Nonlinear Mixed Effects Modeling) VII software. RESULTS: The C(e) 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 C(e) at ROC (r=-0.48, P<0.01). Including age as a covariate in C(e50) (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 C(e50) 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 C(e) and ROC, and pharmacodynamic modeling including age could lead to better predictions of ROC during emergence from propofol-remifentanil anesthesia.