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

背景资料：我们以前曾报道过，在代偿性失血性休克条件下，出血不会改变异氟烷的脑电图效应。本文研究了失代偿性失血性休克及液体复苏对异氟醚脑电效应的影响。方法：12只猪经2%异氟醚吸入麻醉。然后将吸入浓度降至0.5%并维持25 min，然后恢复至2%并维持25 min（对照期）。然后通过在30分钟内抽取28 ml kg-1的血液诱导失血性休克。在30分钟的稳定期后，吸入浓度与对照期相同。最后，使用与抽取的血液相当的体积的羟乙基淀粉进行30分钟的液体输注。在30分钟的稳定期后，吸入浓度再次如对照期那样变化。在整个研究期间记录潮气末异氟烷浓度和光谱边缘频率。药效学的特点是使用S形抑制最大效应模型的频谱边缘频率与效应部位concentration.Results：失代偿性失血性休克轻微，但显着转移的浓度-效应关系向左，表现出1.12倍的减少效应部位浓度需要达到50%的最大效果的频谱边缘频率。液体复苏逆转了异氟烷的发病，这是延迟出血，但并没有扭转终末器官sensitivity.Conclusions的增加：虽然失代偿性失血性休克改变了异氟烷的脑电图效果，无论液体复苏，变化似乎是最小的，在几个静脉麻醉药。

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 Finally, fluid infusion was performed over 30 min using a volume of hydroxyethylstarch equivalent to the blood withdrawn.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.