Influence of hemorrhagic shock on the pharmacokinetic and pharmacodynamic effects of inhalational anesthetics

背景：我们以前报道过，在代偿性失血性休克条件下，出血不会改变异氟醚的脑电图效果。本文研究失代偿性失血性休克和随后的液体复苏对异氟醚脑电图效应的影响。方法：用2%异氟醚麻醉12头猪。然后将吸入浓度降至0.5%并维持25分钟，然后再降至2%并维持25分钟（对照期）。然后在30分钟内取血28 ml kg- ih诱导失血性休克。30分钟稳定期后，吸入浓度变化与对照期相同。最后，用相当于取血量的羟乙基淀粉输液30分钟。30分钟稳定期后，吸入浓度再次变化，与对照期相同。在整个研究过程中记录了潮末异氟烷浓度和光谱边缘频率。药效采用s型抑制最大效应谱边频率-效应位点浓度模型进行表征。结果：失代偿性失血性休克轻微但显著地将浓度-效应关系向左移动，表明在光谱边缘频率上达到最大效应的50%所需的效应位点浓度降低了1.12倍。液体复苏逆转了因出血而延迟的异氟醚的发作，但没有逆转终末器官敏感性的增加。结论：尽管失代偿性失血性休克改变了异氟醚的脑电图效果，而不考虑液体复苏，但与几种静脉麻醉药相比，这种变化似乎很小。

Background: We have previously reported that hemorrhage does not alter the electroencephalographic effect of isoflurane under conditions of compensated hemorrhagic shock. Here, we have investigated the influence of decompensated hemorrhagic shock and subsequent fluid resuscitation on the electroencephalographic effect of isofluraneMethods: Twelve swine were anesthetized through inhalation of 2% isoflurane. The inhalational concentration was then decreased to 0.5% and maintained for 25 min, before being returned to 2% and maintained for 25 min (control period). Hemorrhagic shock was then induced by removing 28 ml kg-Iof blood over 30 min. After a 30-minute stabilization period, the inhalational concentration was varied as in the control period. Finally, fluid infusion was performed over 30 min using a volume of hydroxyethylstarch equivalent to the blood withdrawn. After a 30-minute stabilization period, the inhalational concentration was again varied as in the control period. End-tidal isoflurane concentrations and spectral edge frequency were recorded throughout the study. The pharmacodynamics were characterized using a sigmoidal inhibitory maximal effect model for spectral edge frequency versus effect-site concentration.Results: Decompensated hemorrhagic shock slightly but significantly shifted the concentration-effect relationship to the left, demonstrating a 1.12-fold decrease in the effect-site concentration required to achieve 50% of the maximal effect in the spectral edge frequency. Fluid resuscitation reversed the onset of isoflurane, which was delayed by hemorrhage, but did not reverse the increase in end-organ sensitivity.Conclusions: Although decompensated hemorrhagic shock altered the electroencephalographic effect of isoflurane regardless of fluid resuscitation, the change appeared to be minimal, in contrast to several intravenous anesthetics.