Effect-site modelling of propofol using auditory evoked potentials

Abstract

Auditory evoked potentials (AEP) were used to monitor central nervous system effects during induction and recovery from anaesthesia produced by infusion of propofol 30 mg kg-1 h-1 in 22 healthy male patients. Non-parametric and parametric modelling techniques were used successfully to calculate the parameter k(eo) which linked pharmacokinetic with pharmacodynamic aspects of drug action in only 15 of the study patients. In the non-parametric analysis, k(eo) was found to have a mean value of 0.2 (range 0.1-0.36) min-1. Estimation of k(eo) allowed calculation of the effect-site concentration (Ce50) associated with 50% of AEP effect for the population (2.08 μg ml-1 95% confidence limits 1.7-2.45). There were no significant differences between k(eo) values calculated by non-parametric and individual parametric modelling techniques. During recovery, 50% of patients demonstrated evidence of waking at an effect-site concentration of 2.28 μg ml-1.