title: Isoflurane alters the recirculatory pharmacokinetics of physiologic markers.
abstract: BACKGROUND
  Earlier studies have demonstrated that physiologic marker blood concentrations in the first minutes after administration, when intravenous anesthetics exert their maximum effect, are determined by both cardiac output and its distribution. Given the reported vasodilating properties of isoflurane, we studied the effects of isoflurane anesthesia on marker disposition as another paradigm of altered cardiac output and regional blood flow distribution.
  
  
  METHODS
  The dispositions of markers of intravascular space and blood flow (indocyanine green), extracellular space and free water diffusion (inulin), and total body water and tissue perfusion (antipyrine) were determined in four purpose-bred coonhounds. The dogs were studied while awake and while anesthetized with 1.7%, 2.6%, and 3.5% isoflurane (1.15, 1.7, and 2.3 minimum alveolar concentration, respectively) in a randomized order determined by a Latin square experimental design. Marker dispositions were described by recirculatory pharmacokinetic models based on very frequent early, and less frequent later, arterial blood samples. These models characterize the role of cardiac output and regional blood flow distribution on drug disposition.
  
  
  RESULTS
  Isoflurane caused a significant and dose-dependent decrease in cardiac output. Antipyrine disposition was profoundly affected by isoflurane anesthesia, during which nondistributive blood flow was maintained despite decreases in cardiac output, and the balance between fast and slow tissue volumes and blood flows was altered.
  
  
  CONCLUSIONS
  The isoflurane-induced changes in marker disposition were different than those the authors reported previously for halothane anesthesia, volume loading, or hypovolemia. These data provide further evidence that not only cardiac output but also its peripheral distribution affect early drug concentration history after rapid intravenous administration.
authors.affiliation: Department of Anesthesiology, Northwestern University Medical School, Chicago, Illinois 60611-3008, USA. mja190@nwu.edu
authors.forename: M J
authors.initials: MJ
authors.lastname: Avram
authors.forename: T C
authors.initials: TC
authors.lastname: Krejcie
authors.forename: C U
authors.initials: CU
authors.lastname: Niemann
authors.forename: C
authors.initials: C
authors.lastname: Enders-Klein
authors.forename: C A
authors.initials: CA
authors.lastname: Shanks
authors.forename: T K
authors.initials: TK
authors.lastname: Henthorn
mesh_terms: D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D000983:Antipyrine / Q000493:pharmacokinetics; D019540:Area Under Curve; D015415:Biomarkers / Q000097:blood; D002248:Carbon Monoxide / Q000097:blood; D004396:Coloring Agents / Q000493:pharmacokinetics; D004285:Dogs; D006439:Hemodynamics / Q000187:drug effects; D007208:Indocyanine Green / Q000493:pharmacokinetics; D007444:Inulin / Q000493:pharmacokinetics; D007530:Isoflurane / Q000494:pharmacology*; D008297:Male; D008723:Methohexital / Q000494:pharmacology; D012039:Regional Blood Flow; D014018:Tissue Distribution
chemical_list: D018685:Anesthetics, Inhalation; D015415:Biomarkers; D004396:Coloring Agents; D002248:Carbon Monoxide; D007444:Inulin; D007530:Isoflurane; D008723:Methohexital; D007208:Indocyanine Green; D000983:Antipyrine