A novel method of deriving the effect compartment equilibrium rate constant for propofol.

Abstract

Calculation of the effect compartment concentration (Ce) in non-steady-state conditions requires the equilibrium rate constant, keo. Most studies of propofol derive the keo using EEG measurements. This study investigated an alternative method. Starting from a predicted concentration-time profile, a keo value was included so that the predicted Ce at a specific pharmacodynamic end-point was the same when using three different methods of injection. Seventy-five patients were given propofol for induction of anaesthesia. Twenty-five patients received a single bolus, 25 patients received an infusion, and 25 patients received a bolus followed by an infusion. Computer simulation was used to derive the central compartment concentration. The keo that brought about the same value for Ce at loss of the eyelash reflex using the three methods of injection was derived. Keo was found to be 0.80 min(-1). Mean (SD) Ce at loss of the eyelash reflex was 2.27 (0.69) microg ml(-1). The effect compartment equilibrium rate constant and concentration at loss of the eyelash reflex can be derived without the use of electronic central nervous system monitors.