Isoflurane alters the recirculatory pharmacokinetics of physiologic markers

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 outp ut and its distribution. Given the reported vasodilating properties of isof lurane, we studied the effects of isoflurane anesthesia on marker dispositi on as another paradigm of altered cardiac output and regional blood flow di stribution. 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 a nesthetized with 1.7%, 2.6%, and 3.5% isoflurane (1.15, 1.7, and 2.3 minimu m 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 car diac output, Antipyrine disposition was profoundly affected by Isoflurane a nesthesia, during which non-distributive blood flow was maintained despite decreases in cardiac output, and the balance between fast and slow tissue v olumes and blood flows was altered. Conclusions: The isoflurane-induced changes in marker disposition mere diff erent than those the authors reported previously for halothane anesthesia, volume loading, or hypovolemia, These data provide further evidence that no t only cardiac output but also its peripheral distribution affect early dru g concentration, history after rapid intravenous administration.