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 (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 1,200 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 Ke0 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.