Fentanyl Phamacokinetics in Hemorrhagic Shock A Porcine Model

Background: It is common clinical practice to administer reduced doses of opioid to patients suffering from hemorrhagic shock to minimize adverse hemodynamic consequences and to prevent prolonged opioid effect. However, the scientific foundation supporting this practice is not well established. The aim of this study was to test the hypothesis that hemorrhagic shock alters both the distribution and clearance of opioids using fentanyl in a porcine isobaric hemorrhage model. Methods: Eighteen pigs were randomized to shock or control groups. The animals in the shock group were subjected to hemorrhage using an isobaric method. Pigs in both groups received fentanyl (50 pg/kg) intravenously over 5 min. Frequent arterial blood samples were obtained for radioimmunoassay. Each animal’s pharmacokinetic parameters were estimated by fitting a three-compartment model to the concentration versus time data. Nonlinear mixed-effects popu-