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麻醉剂:从作用模式到意识丧失和神经毒性。

Anesthetics: from modes of action to unconsciousness and neurotoxicity.

机构信息

Vi Riddell Pain Program, Alberta Children's Hospital Research Institute, Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.

Department of Neuroscience, Faculty of Science, University of Calgary, Calgary, Alberta, Canada.

出版信息

J Neurophysiol. 2019 Aug 1;122(2):760-787. doi: 10.1152/jn.00210.2019. Epub 2019 Jun 26.

Abstract

Modern anesthetic compounds and advanced monitoring tools have revolutionized the field of medicine, allowing for complex surgical procedures to occur safely and effectively. Faster induction times and quicker recovery periods of current anesthetic agents have also helped reduce health care costs significantly. Moreover, extensive research has allowed for a better understanding of anesthetic modes of action, thus facilitating the development of more effective and safer compounds. Notwithstanding the realization that anesthetics are a prerequisite to all surgical procedures, evidence is emerging to support the notion that exposure of the developing brain to certain anesthetics may impact future brain development and function. Whereas the data in support of this postulate from human studies is equivocal, the vast majority of animal research strongly suggests that anesthetics are indeed cytotoxic at multiple brain structure and function levels. In this review, we first highlight various modes of anesthetic action and then debate the evidence of harm from both basic science and clinical studies perspectives. We present evidence from animal and human studies vis-à-vis the possible detrimental effects of anesthetic agents on both the young developing and the elderly aging brain while discussing potential ways to mitigate these effects. We hope that this review will, on the one hand, invoke debate vis-à-vis the evidence of anesthetic harm in young children and the elderly, and on the other hand, incentivize the search for better and less toxic anesthetic compounds.

摘要

现代麻醉化合物和先进的监测工具彻底改变了医学领域,使得复杂的手术能够安全有效地进行。当前麻醉剂更快的诱导时间和更快的恢复期也显著降低了医疗保健成本。此外,广泛的研究使人们更好地了解麻醉作用模式,从而促进了更有效和更安全的化合物的开发。尽管人们已经认识到麻醉是所有手术程序的前提,但有证据表明,发育中的大脑暴露于某些麻醉剂可能会影响未来的大脑发育和功能。虽然来自人类研究的支持这一假设的数据存在争议,但绝大多数动物研究强烈表明,麻醉剂确实在多个脑结构和功能水平上具有细胞毒性。在这篇综述中,我们首先强调了各种麻醉作用模式,然后从基础科学和临床研究的角度辩论了麻醉剂造成伤害的证据。我们从动物和人类研究中提供了证据,说明麻醉剂对年轻发育中的大脑和老年大脑可能产生的有害影响,同时讨论了减轻这些影响的潜在方法。我们希望这篇综述一方面能够就麻醉对儿童和老年人的危害的证据引发争论,另一方面也能够激励人们寻找更好、毒性更小的麻醉化合物。

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