Cardiac output is a determinant of the initial concentrations of propofol after short-infusion administration

Indicator dilution theory predicts that the first-pass pulmonary and system ic arterial concentrations of a drug will be inversely related to the cardi ac output. For high-clearance drugs, these first-pass concentrations may co ntribute significantly to the measured arterial concentrations, which would therefore also be inversely related to cardiac output. We examined the car diac 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, me dium, and high cardiac output were achieved by altering carbon dioxide tens ion in six halothane-anesthetized sheep. The initial area under the curve a nd peak value of the pulmonary artery propofol concentrations were inversel y related to cardiac output (R-2 = 0.57 and 0.66, respectively). For the sy stemic arterial concentrations, these R-2 values were 0.68 and 0.71, respec tively. In our second study, transient reductions in cardiac output were ac hieved in five conscious sheep by administering a short infusion of metaram inol concurrently with propofol. Cardiac output was lowered by 2.2 L/min, a nd the area under the curve to 10 min of the arterial concentrations increa sed to 143% of control. Implications: The initial arterial concentrations o f propofol after TV administration were shown to be inversely related to ca rdiac output. This implies that cardiac output may be a determinant of the induction of anesthesia with propofol.