A model of the kinetics and dynamics of induction of anaesthesia in sheep:variable estimation for thiopental and comparison with propofol

We describe a six-compartment kinetic and dynamic physiological model of in duction of anaesthesia with thiopental. The model included an accurate acco unt of initial drug distribution by representing the inter-relationships be tween initial vascular mixing, lung kinetics and cardiac output, and the us e of the brain as the target organ for anaesthesia (two-compartment submode l with slight membrane limitation). It also accounted for thiopental-induce d reductions in cerebral blood flow and cardiac output. Parameters for the model were estimated using hybrid modelling from an extensive in vivo data set collected in sheep. Simulations were used to compare the properties of the thiopental model with an analogous previously published model of propof ol. Differences in the blood:brain equilibrium half-lives of thiopental (1. 22 min) and propofol (4.32 min) contributed to significant differences in t he predicted optimal rate of bolus injection of each agent for inducing ana esthesia in sheep.