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The determinants of induction of anaesthesia with propofol, and their implications for dose requirements, were analysed using a physiological model of the process, validated previously using sheep data. The maximum depth of anaesthesia occurred 2-3 min after cessation of injection. Injection over 2 min minimized the induction dose. More rapid injection (< 1 min) did not significantly hasten induction, but increased dose requirements and produced large peak arterial concentrations, potentially risking increased hypotension. Cardiac output and cerebral blood 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 anaesthesia. The influence on dose requirements of propofol of factors such as anxiety, hyperventilation, age and co-induction with other drugs may be …