Lipid emulsion facilitates reversal from volatile anesthetics in a rodent model
Lipid emulsion facilitates reversal from volatile anesthetics in a rodent model
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DOI：
10.1080/15563650.2021.2020280
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发表时间：
2022-01-03
影响因子：
3.3
通讯作者：
Mori, Takashi
中科院分区：
文献类型：
--
作者：
Hori, Kotaro;Matsuura, Tadashi;Mori, Takashi
背景脂肪乳剂输注是对抗局部麻醉药毒性的一线治疗方法，也是治疗其他药物过量的潜在方法，尤其是高亲脂性药物。考虑到挥发性麻醉药的亲脂性，我们假设脂肪乳剂可以逆转全身麻醉。方法以成年大鼠为研究对象，观察七氟醚和异氟醚停药后输注脂肪乳剂对苏醒时间的影响，并进一步评价七氟醚持续麻醉下翻正反射的恢复情况。在连续七氟烷吸入下，还研究了脂肪乳剂输注期间的脑电图。通过测量呼吸频率、PaCO 2（动脉CO2分压）、血压和心率，评价脂肪乳剂对七氟烷诱导的呼吸和血流动力学抑制的影响。使用锥形瓶体外装置评估脂肪乳剂与七氟烷和异氟烷的结合特性。结果与生理盐水输注相比，脂肪乳剂输注显著缩短了七氟烷麻醉苏醒时间（131 +/- 53 vs. 237 +/- 69 s），并恢复了连续七氟烷吸入期间的翻正反射。与行为结果一致，连续七氟烷下的脑电图显示，在开始脂肪乳剂输注后5 min，δ频段功率降低。除了逆转催眠外，脂肪乳剂还恢复了七氟烷诱导的呼吸和血流动力学抑制。在异氟烷麻醉中也观察到苏醒时间缩短（203 +/- 111 vs. 314 +/- 154 s）。为了研究脂肪乳剂输注的结合机制，体外实验显示与脂肪乳剂混合可显著降低七氟烷和异氟烷的麻醉剂浓度。结论脂肪乳剂促进挥发性麻醉药的逆转，如几个参数所示。由于脂肪乳剂可与挥发性麻醉药结合并简单地降低其作用，我们的研究结果表明，脂肪乳剂是一种潜在的有用药物，以逆转全身麻醉。
Background Lipid emulsion infusion is a first-line therapy against the toxicity of local anesthetics and is a potential treatment for other drug overdoses, especially for highly lipophilic drugs. Considering the lipophilic property of volatile anesthetics, we hypothesized that lipid emulsion could reverse general anesthesia. Methods Using adult rats, we tested the effect of lipid emulsion infusion on time to emergence after discontinuation of sevoflurane and isoflurane, and further evaluated restoration of righting reflex under continuous sevoflurane anesthesia. Electroencephalogram during lipid emulsion infusion was also investigated under continuous sevoflurane inhalation. The effect of lipid emulsion on sevoflurane-induced respiratory and hemodynamic depressions was evaluated by measuring respiratory rate, PaCO2 (arterial partial pressure of CO2), blood pressure, and heart rate. The binding property of lipid emulsion on sevoflurane and isoflurane was assessed using in vitro setting with a conical flask. Results Lipid emulsion infusion significantly decreased time to emergence from sevoflurane anesthesia (131 +/- 53 vs. 237 +/- 69 s) and restored righting reflex during continuous sevoflurane inhalation, by comparing normal saline infusion. Consistent with the behavioral findings, the electroencephalogram under continuous sevoflurane showed decreased power of the delta bands at 5 min after the initiation of lipid emulsion infusion. In addition to reversing hypnosis, lipid emulsion recovered respiratory as well as hemodynamic depressions induced by sevoflurane. Decreased time to emergence was observed also in isoflurane anesthesia (203 +/- 111 vs. 314 +/- 154 s). To investigate the binding mechanism of lipid emulsion infusion, in vitro experiments revealed significantly decreased anesthetic concentrations of sevoflurane and isoflurane by mixing with lipid emulsion. Conclusions Lipid emulsion facilitated reversal from volatile anesthetics, as shown by several parameters. As lipid emulsion could bind to volatile anesthetics and simply decrease their effects, our findings suggest that lipid emulsion is a potentially useful agent to reverse general anesthesia.