麻醉，那些医生都不知道的事儿
现在，只要是去牙医那里做点小手术，几乎都得要麻醉。麻醉，这项技术要归功于18世纪时一位叫做戴维.道尔顿天才化学家，是他发现了一氧化二氮（笑气）的神奇功效。戴维，这位雄心勃勃的年轻人，一连数月每天都吸入一氧化二氮以严格测试这种气体的性质（这孩子多亏不是一氧化碳的发现者...），在平常的时候，他会跟他的一群朋友一起“吸食”，这些人有塞缪尔泰勒律治（文艺男青年），杰姆斯.瓦特（改进蒸汽机那个）和罗伯特.骚塞（文艺男青年）。骚塞同学后来就在一封信内写到：天堂里一定充满了这美妙的气体（哥们，你high了吧...）。而这些早期的实践，为现代医学麻醉奠定了基础。然而，直到如今的现代社会，虽然麻醉在质量上和选择性上都有了巨大的飞跃，我们仍然对麻醉是如何在大脑里运作知之甚少。基于这些基本知识，近日，研究人员惊奇的发现了我们是如何失去知觉又是如何恢复知觉的。通常情况下，人们认为失去知觉和恢复知觉的原理是一样的，虽然这两者方向不同。然而，近日在公共科学图书馆协会发表的一篇论文，提出失去知觉和恢复知觉是截然不同的。
宾夕法尼亚州大学制药系的麦克斯.科尔茨的研究团队发现，相比大脑麻醉，陷入失去知觉的状态需要更多麻醉剂。因此，研究团队引入了神经迟钝的理论，用以解释这种现象：大脑自身会抵抗在清醒和昏迷之间切换。神经迟钝对于麻醉医师每日的工作来说至关重要，一方面使得病人在手术中感受不到疼痛，另一方面又能让病人在术后一段时间内苏醒过来。通过此类研究也可深入到如何脱离昏迷状态。
依据传统模型，麻醉剂通过作用在中枢神经上以达到让病人失去知觉的效果。随着时间推移，随着麻醉剂慢慢在神经系统中被分解，病人恢复知觉。如果此类假设正确，麻醉剂浓度在注射时和复苏时应当是相同的。因此，研究人员对小白鼠和果蝇进行了一系列的实验以证明此观点。他们测量了失去直接又恢复时大脑内的麻醉剂浓度，事实证明复苏阶段大脑内麻醉剂的浓度低于注入时的浓度--显示了一种延迟，或是抵抗，以回到苏醒状态。
临床人体治疗也提供了支持神经迟缓的有力证明。患有猝倒郑的纳克普斯患有严重的日间睡眠障碍并伴有突发性肌肉失调。对于普通病人只需要几分钟的麻醉复苏，这类病人可能要花上八个小时才能复苏。通常认为这类病症是由于下视丘分泌素分泌不足造成的，下视丘分泌素负责调整清醒和快速眼球运动睡眠切换。研究人员对下视丘分泌素基因异常的小白鼠进行了一系列测试。基因异常的小白鼠表现出了明显的从昏迷状态复苏的延迟现象，但是进入昏迷却没有问题，这表明下视丘分泌素只在复苏阶段发挥作用。
在关于神经迟钝的神经回路的研究仍然处在初级阶段，就已经表现出在此领域产生巨大冲击的潜力。作为一名麻醉医师，麦克斯 科尔茨博士认为神经迟钝是保持病人失去知觉的关键因素。有不多数的病人说自己在手术中依然有感觉----大搞千分之一的概率，但是如果想想每天要做麻醉的病人总数是如此之多，这就不能忽视。从另一个角度来考虑，如果病人在麻醉后的一段时间后不能清醒过来，这也十分恐怖。未来在神经迟钝的研究，将赋予麻醉师更加精准的时间控制。
最近纽约时报杂志刊登了一系列医生成功将昏迷数年的病人成功复苏的案例。这项发现源于一次偶然将安眠药用于昏迷病人以提高其睡眠质量的案例。令人惊奇的是，已经昏迷了三年的病人惊人醒了过来，并且能够认出他的母亲。基于此项发现的深入研究，又有一位已被认为是植物人的病人得到治愈。虽然效果只是暂时的，但是长期用药，病人就可以完全恢复知觉。大多数人都不了解安眠药在此过程中的工作原理，相信后续关于神经迟钝理论的研究可以完全揭示出昏迷与清醒转换的原理。
(allgewalt 译言网) What Doctors Don't Understand about Anesthesia Researchers suggest a theory of "neural inertia" to explain a puzzle about how patients emerge from unconsciousness
http://www.xqnmz.com/attachments/month_1203/1203040653612f50a3812173ee.jpg Today anesthetics are considered as routine as a trip to the dentist. They have been around at least since the 18th century when a talented chemist namedHumphry Davy discovered the mysterious effect of nitrous oxide (laughing gas). Davy, young and ambitious, set out to rigorously test the gas’s effect, inhaling nitrous oxide daily for several months. Under slightly less rigorous conditions, Davy shared the gas with a distinguished group of friends including Samuel Taylor Coleridge, James Watt, and Robert Southey—who wrote in a letter that “the atmosphere of the highest of all possible heavens must be composed of this gas.” These early trials laid the foundation for anesthesia’s emergence in medicine today. Yet in the modern era, despite tremendous advances in the quality and selectivity of anesthetics, we still have a poor understanding of how anesthetics work in the brain. Highlighting these fundamental gaps in knowledge, a group of researchers recently made a surprising discovery about how we transition out of consciousness and back. The common view holds that going under (induction) and coming back up (emergence) are the same process, albeit in different directions. However, a recent study published in the journal PLoS ONE suggests that going under is not the same as coming back up.The researchers, led by Dr. Max Kelz at the University of Pennsylvania School of Medicine, observed that less anesthetic is required to keep the brain anesthetized than to induce unconsciousness. To explain these observations, the researchers have introduced a concept they call “neural inertia,” referring to the brain’s resistance to transitions between consciousness and unconsciousness. Elucidating the mechanisms of neural inertia could be critical to the task anesthesiologists perform every day, namely preventing patients from experiencing pain or awareness during surgery and in helping those patients who exhibit delays returning to the conscious state. This line of research could also provide insights into disrupted states of consciousness like coma.
According to the common model, an anesthetic drug reaches its site of action in the central nervous system, causing the patient to become unconscious. Over time, as the anesthetic is passively eliminated from the system, the patient comes back up. If this assumption is true then concentrations of anesthetic should be the same at entrance and emergence. Researchers performed a simple experiment in mice and fruit flies to test this idea. They measured the concentration of anesthetic in the brain going under and the concentration in the brain coming back up from the anesthetized state. They found that the concentration of anesthetic at emergence was lower than the concentration entering the anesthetized state —indicating a delay in, or resistance to, returning to the waking state. Clinical observations in humans also provide evidence for neural inertia. Narcolepsy with cataplexy is a sleep disorder marked by intense daytime sleepiness coupled with sudden losses of muscle tone. These patients can take as long as eight hours to emerge from general anesthesia, whereas the typical patient emerges in minutes. Their disorder is known to be caused by reduced amounts of a protein called hypocretin, which helps regulate wakefulness and REM sleep. In another experiment, the researchers tested mice with mutations in a hypocretin gene causing sleep disturbances similar to humans with narcolepsy. The mutant mice did indeed show a significant delay in emerging from unconsciousness, but no difference entering into the anesthetized state, indicating that only emergence is dependent on the hypocretin system.
Research efforts are just beginning to illuminate the neural circuits underlying neural inertia, but they have the potential to make a significant impact on the field. As an anesthesiologist, Dr. Kelz sees a key function of neural inertia, namely keeping the patient unconscious. A small percentage of patients report experiencing awareness during surgery—estimates are low (around 1 in 1000 cases), but significant if you consider the number of patients who undergo general anesthesia every day. On the other end of the spectrum, patients with certain neurological conditions may not wake up for an extended period after general anesthesia. Future investigations of the circuits involved in neural inertia may give the anesthesiologist more control over anesthesia at the bedside. A recent article in the New York Times Magazine described a series of astonishing cases in which doctors successfully woke some patients from coma after years of unresponsiveness. The discovery came accidentally when a coma patient was given an insomnia drug to improve sleep quality. To everyone’s surprise, the patient woke up and recognized his mother after three years of unresponsiveness. Since the discovery, subsequent investigations have yielded similar effects in a subset of patients declared vegetative. While the effects are temporary, with continued use some patients have fully regained consciousness. Nobody understands exactly how the insomnia drugs work for these patients, but studies that begin to untangle the complex biology of neural inertia may help illuminate the transitions between conscious states that most of us take for granted.Are you a scientist who specializes in neuroscience, cognitive science, or psychology? And have you read a recent peer-reviewed paper that you would like to write about? Please send suggestions to Mind Matters editor Gareth Cook, a Pulitzer prize-winning journalist at the Boston Globe. He can be reached at garethideas AT gmail.com or Twitter @garethideas.
ABOUT THE AUTHOR(S)
Stephen Dougherty holds an M.Sc. in Neuroscience from McGill University and works as a freelance science writer in Boston.
http://www.scientificamerican.com/article.cfm?id=anesthesia-what-doctors-dont-understand 很有启发性的一篇文章，对做全麻很有指导意义。
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