The effect of altered cerebral blood flow on the cerebral kinetics of thiopental and propofol in sheep

Background: Thiopental and propofol are highly lipid-soluble, and their ent ry into the brain often is assumed to be limited by cerebral blood flow rat her than by a diffusion barrier. However, there is little direct experiment al evidence for this assumption. Methods: The cerebral kinetics of thiopental and propofol were examined ove r a range of cerebral blood flows using five and six chronically instrument ed sheep, respectively. Using anesthesia (2.0% halothane), three steady sta te levels of cerebral blood flow (low, medium, and high) were achieved in r andom order by altering arterial carbon dioxide tension. For each flow stat e, 250 mg thiopental or 100 mg propofol was infused intravenously over 2 mi n. To quantify cerebral kinetics, arterial and sagittal sinus blood was sam pled rapidly for 20 min from the start of the infusion, and 1.5 h was allow ed between consecutive infusions. Various models of cerebral kinetics were examined for their ability to account for the data. Results: The mean baseline cerebral blood flows for the "high" flow state w ere over threefold greater than those for the low. For the high-flow state the normalized arteriovenous concentration difference across the brain was smaller than for the low-flow state, for both drugs. The data were better d escribed by a model with partial membrane limitation than those with only f low limitation or dispersion. Conclusions: The cerebral kinetics of thiopental and propofol after bolus i njection were dependent on cerebral blood now, despite partial diffusion li mitation. Higher flows produce higher peak cerebral concentrations.