The rate of penetration of both opioids into the brain was rapid and not rate-limiting. Large differences in the cerebral distribution volume of meperidine and alfentanil accounted for the respective delays in their peak brain concentration relative to blood.

The time-course of propofol concentrations in the blood and brain following rapid administration of three doses were examined using a sheep preparation and regional pharmacokinetic techniques. These were compared to the timecourse of cerebral effects of propofol reported previously. There were marked differences between the time-course of propofol concentrations in arterial blood and the brain, with a close relationship between the time-course of brain concentrations and effects on depth of anaesthesia and CBF. There was evidence that the effect of propofol on cerebral blood flow altered its own rate of elution from the brain. Hysteresis between arterial propofol concentrations and cerebral effects following rapid IV administration therefore appears to have a pharmacokinetic basis, and conventional compartmental pharmacokinetic analysis using blood concentrations alone may fail to accurately predict the time-course of both brain propofol concentrations and depth of anaesthesia.

The effects of bolus administration of propofol (50 mg, 100 mg and 200 mg) on cerebral blood flow and cerebral metabolic rate for oxygen were examined in a chronically catheterized sheep preparation. Depth of anaesthesia was simultaneously measured using a withdrawal response to a noxious electrical stimulus and it was demonstrated that the 100 mg dose induced moderate sedation while the 200 mg dose induced relatively deep anaesthesia. Propofol caused transient dose-dependent decreases in cerebral blood flow, despite minimal changes in blood pressure. These were accompanied by parallel decreases in cerebral metabolic rate but no change in cerebral oxygen extraction. As cerebrovascular responses in the sheep appear similar to those in man, the parallel changes in cerebral blood flow and metabolic rate demonstrated in this study supports the suitability of propofol as a neuroanaesthetic agent.