THE INFLUENCE OF AGE AND ADMINISTRATION RATE ON THE BRAIN SENSITIVITYTO PROPOFOL IN RATS

Background: It is well established that the dose of propofol for induc tion of anaesthesia is influenced by patient age. This may be explaine d by differences in pharmacokinetics or pharmacodynamics. To evaluate the effect of age on propofol pharmacodynamics, the brain concentratio n of propofol at the time of an EEG end-point was used as a measure of CNS sensitivity. Methods: Ninety-five rats were assigned to 4 groups. Anaesthesia was induced by continuous propofol infusion at different rates. The dose of propofol and duration of anaesthesia were determine d from 23 up to 776 days of age. The rats were killed at 23, 287 or 77 6 days of age at the EEG end-point and samples of cerebral cortex, mid brain, cerebellum, serum and fat tissue were submitted to HPLC analysi s of propofol concentrations. Results: The induction dose of propofol varied with age and administration rate. Young animals needed a higher dose of propofol. Old animals had higher brain concentrations of prop ofol at the EEG end-point than young animals. However, propofol concen trations in serum were higher in young animals. The propofol concentra tion in the brain was influenced by the administration rate. Conclusio n: The dose of propofol for induction of anaesthesia in rats is influe nced by animal age and administration rate. Young animals need a large r induction dose than old rats, but are more sensitive as measured by the brain concentration of propofol. The larger induction dose in youn g rats when compared with adults is explained by pharmacokinetic diffe rences rather than by pharmacodynamic changes.