Department of Anesthesiology, Osaka City University Graduate School of Medicine, Osaka, Japan.
Department of Anesthesiology, Osaka City Juso Hospital, Osaka, Japan.
Clin Toxicol (Phila). 2022 Jun;60(6):716-724. doi: 10.1080/15563650.2021.2020280. Epub 2022 Jan 5.
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.
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, PaCO (arterial partial pressure of CO), blood pressure, and heart rate. The binding property of lipid emulsion on sevoflurane and isoflurane was assessed using setting with a conical flask.
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 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, experiments revealed significantly decreased anesthetic concentrations of sevoflurane and isoflurane by mixing with lipid emulsion.
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.
脂肪乳剂输注是对抗局部麻醉剂毒性的一线治疗方法，也是其他药物过量的潜在治疗方法，特别是对高度亲脂性药物。考虑到挥发性麻醉剂的亲脂性，我们假设脂肪乳剂可以逆转全身麻醉。
使用成年大鼠，我们测试了脂肪乳剂输注对七氟醚和异氟醚停药后苏醒时间的影响，并进一步评估了在持续七氟醚麻醉下恢复翻正反射的情况。还在持续吸入七氟醚的情况下研究了脂肪乳剂输注期间的脑电图。通过测量呼吸频率、PaCO（动脉二氧化碳分压）、血压和心率，评估了脂肪乳剂对七氟醚引起的呼吸和血液动力学抑制的影响。使用带有锥形瓶的设置评估了脂肪乳剂对七氟醚和异氟醚的结合特性。
与生理盐水输注相比，脂肪乳剂输注显著缩短了七氟醚麻醉苏醒时间（131±53 秒对 237±69 秒），并恢复了持续七氟醚吸入期间的翻正反射。与行为学发现一致，在脂肪乳剂输注开始后 5 分钟，持续七氟醚下的脑电图显示 频段的功率降低。除了逆转催眠作用外，脂肪乳剂还恢复了七氟醚引起的呼吸和血液动力学抑制。异氟醚麻醉也观察到苏醒时间缩短（203±111 秒对 314±154 秒）。为了研究脂肪乳剂输注的结合机制，实验表明混合脂肪乳剂后七氟醚和异氟醚的麻醉浓度显著降低。
几项参数表明，脂肪乳剂促进了挥发性麻醉剂的逆转。由于脂肪乳剂可以与挥发性麻醉剂结合并简单地降低其作用，我们的发现表明脂肪乳剂是一种潜在有用的逆转全身麻醉的药物。
