A PHYSIOLOGICAL MODEL OF INDUCTION OF ANESTHESIA WITH PROPOFOL IN SHEEP .1. STRUCTURE AND ESTIMATION OF VARIABLES

We describe a six-compartment physiological model of the kinetics and dynamics of induction of anaesthesia with propofol in sheep. It includ es a faithful description of initial bolus kinetics caused by accurate representations of the inter-relationships between initial vascular m ixing, lung kinetics and cardiac output, the use of the brain as the t arget organ for propofol anaesthesia (two-compartment sub-model with s light membrane limitation), a description of the effects of propofol-i nduced changes in cerebral blood flow and a combined description of sy stemic kinetics as two tissue pools. Variables for the model were esti mated from an extensive in vivo data set using hybrid modelling. Propo fol was characterized by rapid transit through the lungs, but a slower transit time though the brain, leading to significant delay between a rterial blood concentrations and cerebral effects.