title: Cardiac output is a determinant of the initial concentrations of propofol after short-infusion administration.
abstract: Indicator dilution theory predicts that the first-pass pulmonary and systemic arterial concentrations of a drug will be inversely related to the cardiac output. For high-clearance drugs, these first-pass concentrations may contribute significantly to the measured arterial concentrations, which would therefore also be inversely related to cardiac output. We examined the cardiac output dependence of the initial kinetics of propofol in two separate studies using chronically instrumented sheep in which propofol (100 mg) was infused IV over 2 min. In the first study, steady-state periods of low, medium, and high cardiac output were achieved by altering carbon dioxide tension in six halothane-anesthetized sheep. The initial area under the curve and peak value of the pulmonary artery propofol concentrations were inversely related to cardiac output (R2 = 0.57 and 0.66, respectively). For the systemic arterial concentrations, these R2 values were 0.68 and 0.71, respectively. In our second study, transient reductions in cardiac output were achieved in five conscious sheep by administering a short infusion of metaraminol concurrently with propofol. Cardiac output was lowered by 2.2 L/min, and the area under the curve to 10 min of the arterial concentrations increased to 143% of control.
  
  
  CONCLUSIONS
  The initial arterial concentrations of propofol after IV administration were shown to be inversely related to cardiac output. This implies that cardiac output may be a determinant of the induction of anesthesia with propofol.
authors.affiliation: Department of Anaesthesia and Intensive Care, Royal Adelaide Hospital, University of Adelaide, Australia, SA 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: A M
authors.initials: AM
authors.lastname: Martinez
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000493:pharmacokinetics; D000771:Anesthesia, Intravenous; D018685:Anesthetics, Inhalation; D018686:Anesthetics, Intravenous / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000818:Animals; D019540:Area Under Curve; D001921:Brain / Q000378:metabolism; D002248:Carbon Monoxide / Q000097:blood; D002302:Cardiac Output / Q000502:physiology*; D005260:Female; D006221:Halothane; D006935:Hypercapnia / Q000503:physiopathology; D016857:Hypocapnia / Q000503:physiopathology; D008680:Metaraminol / Q000493:pharmacokinetics; D015742:Propofol / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D012756:Sheep
chemical_list: D000316:Adrenergic alpha-Agonists; D018685:Anesthetics, Inhalation; D018686:Anesthetics, Intravenous; D002248:Carbon Monoxide; D008680:Metaraminol; D006221:Halothane; D015742:Propofol