Are anaesthetics toxic to the brain?
Are anaesthetics toxic to the brain?
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DOI：
10.1093/bja/aer122
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发表时间：
2011-07-01
影响因子：
9.8
通讯作者：
Hemmings, H. C., Jr.
中科院分区：
文献类型：
--
作者：
Hudson, A. E.;Hemmings, H. C., Jr.
一般认为麻醉剂从麻醉中苏醒后只有很小的或没有持久的影响。然而，全身麻醉剂作用于中枢神经系统中的多个离子通道、受体和细胞信号系统来产生麻醉，因此它们也具有从有益到有害的非麻醉作用也就不足为奇了。越来越多的证据迫使麻醉界质疑全麻在极端年龄时的安全性。临床前数据表明，吸入麻醉剂可以通过增加神经细胞死亡(细胞凋亡)和减少神经发生，在新生动物的关键神经发育时期产生深远而持久的影响。关于这些实验室数据对儿科人群的意义，临床数据仍然相互矛盾。在年龄的另一个极端，老年患者术后认知功能障碍(POCD)的风险增加，术后认知功能下降是公认的。其潜在的机制以及麻醉在POCD中的作用仍不清楚。实验室模型表明麻醉剂与神经退行性机制的相互作用，例如与阿尔茨海默病的发生和发展有关的机制，但它们的临床相关性仍不确定。前瞻性随机临床试验正在进行中，以解决这些发现的临床意义，但在设计、执行和解释此类试验方面存在重大挑战。在不久的将来，不太可能有明确的临床研究来免除全身麻醉剂的神经毒性，这需要临床医生在对脆弱的患者使用这些深度神经抑制药时做出谨慎的判断。
It has been assumed that anaesthetics have minimal or no persistent effects after emergence from anaesthesia. However, general anaesthetics act on multiple ion channels, receptors, and cell signalling systems in the central nervous system to produce anaesthesia, so it should come as no surprise that they also have non-anaesthetic actions that range from beneficial to detrimental. Accumulating evidence is forcing the anaesthesia community to question the safety of general anaesthesia at the extremes of age. Preclinical data suggest that inhaled anaesthetics can have profound and long-lasting effects during key neurodevelopmental periods in neonatal animals by increasing neuronal cell death (apoptosis) and reducing neurogenesis. Clinical data remain conflicting on the significance of these laboratory data to the paediatric population. At the opposite extreme in age, elderly patients are recognized to be at an increased risk of postoperative cognitive dysfunction (POCD) with a well-recognized decline in cognitive function after surgery. The underlying mechanisms and the contribution of anaesthesia in particular to POCD remain unclear. Laboratory models suggest anaesthetic interactions with neurodegenerative mechanisms, such as those linked to the onset and progression of Alzheimer's disease, but their clinical relevance remains inconclusive. Prospective randomized clinical trials are underway to address the clinical significance of these findings, but there are major challenges in designing, executing, and interpreting such trials. It is unlikely that definitive clinical studies absolving general anaesthetics of neurotoxicity will become available in the near future, requiring clinicians to use careful judgement when using these profound neurodepressants in vulnerable patients.