Methylphenidate actively induces emergence from general anesthesia.
Methylphenidate actively induces emergence from general anesthesia.
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DOI：
10.1097/aln.0b013e31822e92e5
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发表时间：
2011-10
期刊：
影响因子：
8.8
通讯作者：
Brown EN
中科院分区：
文献类型：
--
作者：
Solt K;Cotten JF;Cimenser A;Wong KF;Chemali JJ;Brown EN
虽然越来越多的证据表明，唤醒途径在大脑中发挥重要作用，从全身麻醉的出现，单胺能唤醒电路的作用还不清楚。在这项研究中，我们测试的假设，哌甲酯（多巴胺和去甲肾上腺素转运体抑制剂）诱导异氟烷麻醉苏醒。使用成年大鼠，我们测试了哌甲酯IV对异氟烷麻醉苏醒时间的影响。然后，我们进行了实验，分别测试哌甲酯诱导的觉醒变化和每分钟通气量的变化。进行了剂量反应研究，以测试在连续异氟烷麻醉期间哌甲酯诱导的翻正恢复。采用表面脑电描记法观察神经电生理变化。进行体积描记术记录和动脉血气分析，以评估哌醋甲酯诱导的呼吸功能变化。给予氟哌利多IV以测试哌醋甲酯作用的抑制。哌醋甲酯使中位苏醒时间从280秒缩短至91秒。与哌甲酯相比，未使用哌甲酯的至苏醒时间的中位差异为200 [155，331] s（中位数，[95%置信区间]）。在连续吸入异氟烷期间，哌甲酯以剂量依赖性方式诱导翻正恢复，诱导脑电功率从delta转变为theta，并诱导每分钟通气量增加。在哌甲酯（5 mg/kg IV）之前给予氟哌利多（0.5 mg/kg IV）在很大程度上抑制哌甲酯诱导的苏醒行为、脑电图变化和每分钟通气量变化。哌醋甲酯可能通过激活多巴胺能和肾上腺素能唤醒回路，通过增加唤醒和呼吸驱动主动诱导异氟烷麻醉苏醒。我们的研究结果表明，哌醋甲酯可能是临床上有用的代理，以扭转全身麻醉诱导的意识丧失和呼吸抑制在手术结束。
Although accumulating evidence suggests that arousal pathways in the brain play important roles in emergence from general anesthesia, the roles of monoaminergic arousal circuits are unclear. In this study we tested the hypothesis that methylphenidate (an inhibitor of dopamine and norepinephrine transporters) induces emergence from isoflurane anesthesia. Using adult rats we tested the effect of methylphenidate IV on time to emergence from isoflurane anesthesia. We then performed experiments to test separately for methylphenidate-induced changes in arousal and changes in minute ventilation. A dose-response study was performed to test for methylphenidate–induced restoration of righting during continuous isoflurane anesthesia. Surface electroencephalogram recordings were performed to observe neurophysiological changes. Plethysmography recordings and arterial blood gas analysis were performed to assess methylphenidate-induced changes in respiratory function. Droperidol IV was administered to test for inhibition of methylphenidate's actions. Methylphenidate decreased median time to emergence from 280 to 91 s. The median difference in time to emergence without compared to with methylphenidate was 200 [155, 331] s (median, [95% confidence interval]). During continuous inhalation of isoflurane, methylphenidate induced return of righting in a dose-dependent manner, induced a shift in electroencephalogram power from delta to theta, and induced an increase in minute ventilation. Administration of droperidol (0.5 mg/kg IV) prior to methylphenidate (5 mg/kg IV) largely inhibited methylphenidate-induced emergence behavior, electroencephalogram changes, and changes in minute ventilation. Methylphenidate actively induces emergence from isoflurane anesthesia by increasing arousal and respiratory drive, possibly through activation of dopaminergic and adrenergic arousal circuits. Our findings suggest that methylphenidate may be clinically useful as an agent to reverse general anesthetic-induced unconsciousness and respiratory depression at the end of surgery.