Estimating the Plasma Effect-Site Equilibrium Rate Constant (Ke0) of Propofol by Fitting Time of Loss and Recovery of Consciousness

The present paper proposes a new approach for fitting the plasma effect-site equilibrium rate constant (K-e0) of propofol to satisfy the condition that the effect-site concentration (C-e) 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, K-e0 satisfying the C-eLOC=C-eROC condition was estimated. The accuracy of the K-e0 estimated by our method was compared with the Diprifusor TCI Pump built-in K-e0 (0.26 min(-1)), and the Orchestra Workstation built-in K-e0 (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 K-e0 of propofol was 0.53 +/- 0.18 min(-1). The regression equation for adjustment by dose (mg/kg) and age was K-e0=1.42-0.30xdose-0.0074xage. Only K-e0 adjusted by dose and age achieved the level of accuracy required for clinical applications. We conclude that the K-e0 estimated based on clinical signs and the two-point fitting method significantly improved the ability of C-eLOC to predict C-eROC. However, only the K-e0 adjusted by dose and age and not a fixed K-e0 value can meet clinical requirements of accuracy.