Iizuka T, Masui K, Miyabe-Nishiwaki T, Kanazawa H, Nishimura R
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.
Department of Anesthesiology, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan.
Res Vet Sci. 2017 Dec;115:34-42. doi: 10.1016/j.rvsc.2017.01.021. Epub 2017 Jan 23.
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.
本研究的目的是针对四个药效学终点来描述丙泊酚 - 芬太尼在比格犬中的相互作用：呼吸暂停、对机械通气的反应、气管插管以及强直刺激。在用丙泊酚和芬太尼的不同组合诱导麻醉后，采用交叉设计对插管犬（n = 6）的药效学终点进行评估。使用相加模型、简化的格雷科模型、明托模型和分层相互作用模型评估丙泊酚血浆浓度（Cp）和芬太尼Cp的有效浓度。分层模型将这种相互作用最佳描述为协同作用。对于所有终点，1ng/mL的芬太尼Cp可将有效的丙泊酚Cp降低至无芬太尼时的一半或更低。除对强直刺激的反应外，芬太尼Cp额外增加至5ng/mL或更高对所有终点几乎不会降低有效的丙泊酚Cp。此外，在芬太尼Cp >7ng/mL时，50%的犬对强直刺激（心率增加15%）的有效丙泊酚Cp低于其他终点。在芬太尼Cp≥5ng/mL的五种处理中，拔管后外周血氧饱和度降至90%以下。丙泊酚和芬太尼存在协同相互作用。为避免插管犬拔管后出现患者 - 呼吸机不同步和低氧血症，芬太尼Cp为1 - 5ng/mL可能是合适的。当犬在丙泊酚麻醉下，芬太尼Cp >5ng/mL时对机械通气或气管插管有反应，即使犬耐受强直刺激，可能有必要增加丙泊酚Cp以消除反应，因为额外增加芬太尼可能影响不大。
