title: Fentanyl pharmacokinetics in hemorrhagic shock: a porcine model.
abstract: 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 microg/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 population pharmacokinetic models examining the influence of mean arterial pressure and cardiac index were also constructed. Clinical simulations using the final population model were performed.
  
  
  RESULTS
  The shock cohort reached substantially higher fentanyl concentrations. The shock group's central clearance and central- and second-compartment distribution volumes were significantly reduced. The most useful population model scaled all pharmacokinetic parameters to mean arterial pressure. The simulations illustrated that hemorrhagic shock results in higher fentanyl concentrations for any given dosage scheme.
  
  
  CONCLUSIONS
  The essential finding of the study is that fentanyl pharmacokinetics are substantially altered by hemorrhagic shock. The reduced opioid requirement commonly observed during hemorrhagic shock is at least partially attributable to pharmacokinetic mechanisms.
authors.affiliation: University of Utah School of Medicine, Salt Lake City, USA. TEGAN@anesth.med.utah.edu
authors.forename: T D
authors.initials: TD
authors.lastname: Egan
authors.forename: S
authors.initials: S
authors.lastname: Kuramkote
authors.forename: G
authors.initials: G
authors.lastname: Gong
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.forename: S W
authors.initials: SW
authors.lastname: McJames
authors.forename: P L
authors.initials: PL
authors.lastname: Bailey
mesh_terms: D000701:Analgesics, Opioid / Q000493:pharmacokinetics*; D000818:Animals; D003198:Computer Simulation; D005260:Female; D005283:Fentanyl / Q000493:pharmacokinetics*; D008102:Liver Circulation; D008297:Male; D008954:Models, Biological; D012771:Shock, Hemorrhagic / Q000378:metabolism*; D013552:Swine
chemical_list: D000701:Analgesics, Opioid; D005283:Fentanyl