Bovill J G
Department of Anaesthesiology, Leiden University Medical Centre, Leiden, The Netherlands.
Handb Exp Pharmacol. 2008(182):121-42. doi: 10.1007/978-3-540-74806-9_6.
Modern anaesthesia is said to have began with the successful demonstration of ether anaesthesia by William Morton in October 1846, even though anaesthesia with nitrous oxide had been used in dentistry 2 years before. Anaesthesia with ether, nitrous oxide and chloroform (introduced in 1847) rapidly became commonplace for surgery. Of these, only nitrous oxide remains in use today. All modern volatile anaesthetics, with the exception of halothane (a fluorinated alkane), are halogenated methyl ethyl ethers. Methyl ethyl ethers are more potent, stable and better anaesthetics than diethyl ethers. They all cause myocardial depression, most markedly halothane, while isoflurane and sevoflurane cause minimal cardiovascular depression. The halogenated ethers also depress the normal respiratory response to carbon dioxide and to hypoxia. Other adverse effects include hepatic and renal damage. Hepatitis occurs most frequently with halothane, although rare cases have been reported with the other agents. Liver damage is not caused by the anaesthetics themselves, but by reactive metabolites. Type I hepatitis occurs fairly commonly and takes the form of a minor disturbance of liver enzymes, which usually resolves without treatment. Type II, thought to be immune-mediated, is rare, unpredictable and results in a severe fulminant hepatitis with a high mortality. Renal damage is rare, and was most often associated with methoxyflurane because of excessive plasma fluoride concentrations resulting from its metabolism. Methoxyflurane was withdrawn from the market because of the high incidence of nephrotoxicity. Among the contemporary anaesthetics, the highest fluoride concentrations have been reported with sevoflurane, but there are no reports of renal dysfunction associated with its use. Recently there has been a renewed interest in xenon, one of the noble gases. Xenon has many of the properties of an ideal anaesthetic. The major factor limiting its more widespread is the high cost, about 2,000 times the cost of nitrous oxide.
现代麻醉学据说始于1846年10月威廉·莫顿成功演示乙醚麻醉，尽管早在两年前一氧化二氮就已用于牙科麻醉。乙醚、一氧化二氮和氯仿（于1847年引入）麻醉迅速成为外科手术的常用方法。其中，只有一氧化二氮至今仍在使用。除氟烷（一种氟化烷烃）外，所有现代挥发性麻醉剂都是卤代甲基乙基醚。甲基乙基醚比二乙醚麻醉作用更强、更稳定，是更好的麻醉剂。它们都会引起心肌抑制，氟烷最为明显，而异氟烷和七氟烷引起的心血管抑制最小。卤代醚还会抑制对二氧化碳和低氧的正常呼吸反应。其他不良反应包括肝和肾损伤。氟烷最常引起肝炎，不过也有其他麻醉剂引起罕见病例的报道。肝损伤不是由麻醉剂本身引起的，而是由活性代谢产物导致的。I型肝炎相当常见，表现为肝酶的轻微紊乱，通常无需治疗即可恢复。II型肝炎被认为是免疫介导的，很罕见，不可预测，会导致严重的暴发性肝炎，死亡率很高。肾损伤很罕见，最常与甲氧氟烷有关，因为其代谢会导致血浆氟浓度过高。由于肾毒性发生率高，甲氧氟烷已退出市场。在当代麻醉剂中，七氟烷的氟浓度最高，但尚无与其使用相关的肾功能障碍报告。最近，人们对惰性气体之一的氙重新产生了兴趣。氙具有许多理想麻醉剂的特性。限制其更广泛应用的主要因素是成本高昂，约为一氧化二氮成本的2000倍。
