A PHYSIOLOGICAL MODEL OF INDUCTION OF ANESTHESIA WITH PROPOFOL IN SHEEP .2. MODEL ANALYSIS AND IMPLICATIONS FOR DOSE REQUIREMENTS

The determinants of induction of anaesthesia with propofol, and their implications for dose requirements, were analysed using a physiologica l model of the process, validated previously using sheep data. The max imum depth of anaesthesia occurred 2-3 min after cessation of injectio n. Injection over 2 min minimized the induction dose. More rapid injec tion (<1 min) did not significantly hasten induction, but increased do se requirements and produced large peak arterial concentrations, poten tially risking increased hypotension. Cardiac output and cerebral bloo d flow were important determinants of the induction process. Increased cardiac output decreased the duration of anaesthesia, while increased cerebral blood flow increased the depth but not duration of anaesthes ia. The influence on dose requirements of propofol of factors such as anxiety, hyperventilation, age and co-induction with other drugs may b e interpreted in terms of their effect on cardiac output and cerebral blood flow.