Are general anesthetics neurotoxic?

Abstract

Introduction: General anaesthesia has been used worldwide since its first public demonstration with ether in 1846. Until a little more than a decade ago, it was believed that the anaesthetic state was limited to the period of exposure. Studies in rats, pigs, and rhesus monkeys have shown that almost all general anaesthetics accelerate the apoptotic process in neurones, oligodendrocytes, and glial cells. Objective: Our aim was to analyse the relationship between general anaesthetics and their role in triggering neuroapoptosis in laboratory animals. Method: A search was carried out in PubMed and Google Scholar with the keywords "neurotoxicity" and "general anesthetics" for selecting articles published in the last five years. After having evaluated the abstracts, 77 articles were selected and read by 2 independent investigators. All authors met and discussed the most relevant aspects. Results: All general anaesthetics, when inhaled or administered intravenously, enhance neuroapoptosis, mainly during the gestational and neonatal stages in rats, pigs, and non-human primates. Neurones and oligodendrocytes that are capable of neurogenesis and synaptogenesis are the most affected. General anaesthetics commonly lead to learning and behavioural disorders, in addition to permanent memory deficit. Conclusion: The neurotoxicity of general anaesthetics affects different mammalian species and accelerates the neuroapoptotic process. This deleterious effect involves specific brain areas and occurs in developing neurones. The exceptions are the dentate gyrus and the olfactory bulb, which undergo apoptosis even in adulthood, albeit to a lesser extent.