Estimating the plasma effect-site equilibrium rate constant (K e0) of propofol by fitting time of loss and recovery of consciousness

Abstract

The present paper proposes a new approach for fitting the plasma effect-site equilibrium rate constant (Ke0) of propofol to satisfy the condition that the effect-site concentration (Ce) is equal at the time of loss of consciousness (LOC) and recovery of consciousness (ROC). Forty patients receiving intravenous anesthesia were divided into 4 groups and injected propofol 1.4, 1.6, 1.8, or 2 mg/kg at 1200 mL/h. Durations from the start of injection to LOC and to ROC were recorded. LOC and ROC were defined as an observer's assessment of alertness and sedation scale change from 3 to 2 and from 2 to 3, respectively. Software utilizing bisection method iteration algorithms was built. Then, Ke0 satisfying the CeLOC CeROC condition was estimated. The accuracy of the Ke0 estimated by our method was compared with the Diprifusor TCI Pump built-in Ke0 (0.26 min=1), and the Orchestra Workstation built-in Ke0 (1.21 min=1) in another group of 21 patients who were injected propofol 1.4 to 2 mg/kg. Our results show that the population Ke0 of propofol was 0.53=0.18 min=1. The regression equation for adjustment by dose (mg/kg) and age was Ke0=1.42-0.30±dose-0.0074=age. Only K e0 adjusted by dose and age achieved the level of accuracy required for clinical applications. We conclude that the Ke0 estimated based on clinical signs and the two-point fitting method significantly improved the ability of CeLOC to predict CeROC. However, only the Ke0 adjusted by dose and age and not a fixed Ke0 value can meet clinical requirements of accuracy. © 2013 The Pharmaceutical Society of Japan.