Propofol-fentanyl interaction in Beagles - Apnea, response to mechanical ventilation, endotracheal tube, and tetanic stimulation.
The objective of this study was to characterize the propofol-fentanyl interaction in Beagles for four pharmacodynamic endpoints: apnea, response to mechanical ventilation, endotracheal tube, and tetanic stimulation. After anesthesia was induced with varying combinations of propofol and fentanyl, the pharmacodynamic endpoints were assessed in intubated dogs (n=6) using the cross-over design. Effective concentrations of propofol plasma concentration (Cp) and fentanyl Cp were assessed using additive, reduced Greco, Minto, and hierarchical interaction models. The interaction was best described as synergistic by the hierarchical model. A 1ng/mL fentanyl Cp reduced the effective propofol Cp to half or less of that without fentanyl for all endpoints. An additional increment of fentanyl Cp to 5ng/mL or higher hardly reduced effective propofol Cp for all endpoints except response to tetanic stimulation. Additionally, the effective propofol Cp in 50% dogs for response to tetanic stimulation (15% increase of heart rate) was lower than that for the other endpoints at fentanyl Cp >7ng/mL. Peripheral oxygen saturation decreased below 90% after extubation in five treatments in which fentanyl Cps were ≥5ng/mL. Propofol and fentanyl interacted synergistically. To avoid patient-ventilator dyssynchrony and hypoxemia after extubation, fentanyl Cp at 1-5ng/mL may be appropriate in intubated dogs. When a dog responds to mechanical ventilation or endotracheal tube at a high fentanyl Cp >5ng/mL under propofol anesthesia even if the dog tolerate to tetanic stimulation, it may be necessary to increase propofol Cp to eliminate the responses because an additional fentanyl may be little impact.
Laboratory of Veterinary Surgery, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.
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Iizuka
Department of Anesthesiology, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan. Electronic address: kenichi@masuinet.com.
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Masui
Center of Human Evolution Modeling Research, Primate Research Institute, Kyoto University, Inuyama, Aichi 484-8506, Japan.
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Miyabe-Nishiwaki
Faculty of Pharmacy, Keio University, 1-5-30 Shibakoen, Minato-ku, Tokyo 105-8512, Japan.
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Kanazawa
Laboratory of Veterinary Surgery, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.
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Nishimura
D000701:Analgesics, Opioid / Q000494:pharmacology*; D018686:Anesthetics, Intravenous / Q000494:pharmacology; D000818:Animals; D001049:Apnea / Q000139:chemically induced*; D004285:Dogs; D005260:Female; D005283:Fentanyl / Q000494:pharmacology*; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D007442:Intubation, Intratracheal / Q000662:veterinary*; D008297:Male; D008954:Models, Biological; D015742:Propofol / Q000494:pharmacology*; D012121:Respiration, Artificial / Q000662:veterinary*
D000701:Analgesics, Opioid; D018686:Anesthetics, Intravenous; D006993:Hypnotics and Sedatives; D005283:Fentanyl; D015742:Propofol
Dog; Drug interaction; Fentanyl; Pharmacodynamics; Propofol