title: The effect of altered cerebral blood flow on the cerebral kinetics of thiopental and propofol in sheep.
abstract: BACKGROUND
  Thiopental and propofol are highly lipid-soluble, and their entry into the brain often is assumed to be limited by cerebral blood flow rather than by a diffusion barrier. However, there is little direct experimental evidence for this assumption.
  
  
  METHODS
  The cerebral kinetics of thiopental and propofol were examined over a range of cerebral blood flows using five and six chronically instrumented sheep, respectively. Using anesthesia (2.0% halothane), three steady state levels of cerebral blood flow (low, medium, and high) were achieved in random order by altering arterial carbon dioxide tension. For each flow state, 250 mg thiopental or 100 mg propofol was infused intravenously over 2 min. To quantify cerebral kinetics, arterial and sagittal sinus blood was sampled rapidly for 20 min from the start of the infusion, and 1.5 h was allowed 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 were 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 described by a model with partial membrane limitation than those with only flow limitation or dispersion.
  
  
  CONCLUSIONS
  The cerebral kinetics of thiopental and propofol after bolus injection were dependent on cerebral blood flow, despite partial diffusion limitation. Higher flows produce higher peak cerebral concentrations.
authors.affiliation: Department of Anaesthesia and Intensive Care, Royal Adelaide Hospital, University of Adelaide, Adelaide, Australia. rupton@health.adelaide.edu.au
authors.forename: R N
authors.initials: RN
authors.lastname: Upton
authors.forename: G L
authors.initials: GL
authors.lastname: Ludbrook
authors.forename: C
authors.initials: C
authors.lastname: Grant
authors.forename: D J
authors.initials: DJ
authors.lastname: Doolette
mesh_terms: D018686:Anesthetics, Intravenous / Q000493:pharmacokinetics*; D000818:Animals; D001783:Blood Flow Velocity / Q000502:physiology; D001825:Body Fluid Compartments; D001921:Brain / Q000098:blood supply* / Q000378:metabolism*; D002560:Cerebrovascular Circulation / Q000502:physiology*; D003198:Computer Simulation; D005260:Female; D008954:Models, Biological; D015742:Propofol / Q000097:blood / Q000493:pharmacokinetics*; D012756:Sheep; D013874:Thiopental / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D018686:Anesthetics, Intravenous; D013874:Thiopental; D015742:Propofol