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The cardiopulmonary effects and pharmacokinetics of fentanyl in the dog: The influence of isoflurane anesthesia and sedative administration during anesthetic recovery

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Title: The cardiopulmonary effects and pharmacokinetics of fentanyl in the dog: The influence of isoflurane anesthesia and sedative administration during anesthetic recovery
Author: Keating, Stephanie
Department: Department of Clinical Studies
Program: Veterinary Science
Advisor: Kerr, Carolyn
Abstract: The objectives of this study were to determine the cardiopulmonary effects and pharmacokinetics of fentanyl in dogs during isoflurane anesthesia and during anesthetic recovery with or without dexmedetomidine or acepromazine sedation. This was investigated in 7 healthy dogs using a randomized cross over study design. Dogs were given fentanyl as an initial IV loading dose (5 μg/kg) followed by an infusion (5 μg/kg/hr) for 120 minutes during isoflurane anesthesia and for 60 minutes following isoflurane discontinuation. Dogs received IV dexmedetomidine (2.5 μg/kg), acepromazine (0.05 mg/kg) or saline at the time of isoflurane discontinuation. Cardiopulmonary variables were measured and blood samples were obtained at multiple time points during the anesthetic maintenance and recovery phases. Plasma concentrations of fentanyl were measured using HPLC-MS, and subsequent population pharmacokinetic analysis was performed. During isoflurane anesthesia, fentanyl bolus administration resulted in significant changes in measured cardiopulmonary variables, however, many returned to baseline values during the maintenance of anesthesia. During anesthetic recovery, dexmedetomidine administration resulted in significant increases in PaCO2, and decreases in PvO2 and CI. Systemic arterial blood pressures were significantly lower in dogs receiving acepromazine, however CI and PvO2 were significantly higher compared to the other treatments. Analysis of fentanyl plasma concentrations showed that fentanyl pharmacokinetics best fit a 2-compartmental model, with average concentrations in the treatment groups ranging from 1.6 to 4.5 ng/mL during isoflurane anesthesia, and from 1.6 to 2.0 ng/mL during anesthetic recovery. Plasma concentrations of fentanyl were significantly higher with dexmedetomidine administration compared to the other treatments during the recovery period. Compared to the maintenance phase of anesthesia, anesthetic recovery with dexmedetomidine administration did not significantly change fentanyl pharmacokinetics, while acepromazine administration increased systemic and intercompartmental clearance, and recovery without sedation increased the central volume of distribution and systemic clearance. In conclusion, recovery from anesthesia with concurrent fentanyl administration, with or without sedation, caused clinically significant alterations in cardiopulmonary function that influenced fentanyl disposition in healthy dogs.
Date: 2013-04
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