Developing a clinical indicator of depth of anaesthesia based on auditory evoked potentials

当病人去医院做一个严重的手术时，他们通常需要全身麻醉，使他们在手术过程中进入睡眠状态，使他们感觉不到任何疼痛。然而，全身麻醉偶尔也会出现问题，患者会在手术过程中醒来。在手术中，当病人被给予肌肉松弛剂以阻止他们四处走动时，这是一个特别的问题，因为病人无法移动，也无法告诉工作人员他们醒着，即使他们可能正在经历痛苦的手术。麻醉师因此热衷于开发方法来监测人们在手术中何时醒来。一种方法是测量大脑对声音的反应，这通常使用通过耳机播放的点击声。追溯到20世纪80年代的研究表明，当你入睡时，大脑对声音的反应会发生变化。然而，大脑的反应非常小（大约百万分之一伏特）。因此，在经常有许多电干扰源的手术室中，很难准确地测量如此小的信号。这意味着测量的结果可能是不可靠的，因此使用现有的技术，可能很难判断病人是醒着还是睡着。在南安普顿大学，我们一直在寻找新的数学技术来更好地测量这种来自大脑的小信号，称为听觉诱发电位。我们一直在寻找改变刺激声音的方法，以最有效的方式唤起大脑的反应。我们已经研究了以不规则的方式呈现刺激的方法，使我们能够非常快速地呈现刺激。这很重要，因为我们可以快速记录许多相似的信号，并通过将它们平均在一起，获得更好的质量测量。我们用来快速呈现声音的特殊序列被称为最大长度序列。我们也改变了声音从点击到一个快速的频率扫描称为啾啾。这些唧唧声比咔哒声在大脑中产生更大的反应。它们被认为能同时刺激听觉系统中的许多神经细胞。将这两种技术结合在一起，我们发现我们可以在正常听力的受试者中多次提高对大脑小信号的测量。我们已经开始研究这种新技术，在少数接受手术的病人身上测量大脑对声音的反应，我们已经看到了麻醉后发生的变化。然而，我们在麻醉中发现的变化模式与早期研究中发现的不同。这可能是因为我们更准确地测量了反应。然而，到目前为止，我们只测试了一小部分受试者，我们不知道测量大脑反应的新技术是否比旧技术更可靠。这个研究项目将在更多的实验对象身上测试这项技术，看看我们是否真的可以正确地识别操作中的意识，并验证我们在早期研究中发现的大脑对麻醉剂的反应变化模式。它还将把测量大脑对声音反应的新技术与一种已经在许多研究项目中使用的旧的现有方法进行比较。我们还想进一步改进数学技术，以可靠地提取小信号，并对大脑信号进行分类，以便医生能够清楚地指出患者的状态（清醒或睡眠）。如果这项新技术被证明是非常可靠的，它可能会成为一种标准的方法来监测人们是否在手术中醒来。

When patients go for a serious operation in a hospital they often need a general anaesthetic which puts them to sleep during the operation and stops them feeling any pain. However there are occasionally problems with the general anaesthetic and patients wake up in the middle of the operation. This is particularly a problem in operations when patients are given muscle relaxants to stop them from moving around, as the patients are unable to move and tell the staff they are awake, even though they may be undergoing painful surgery. Anaesthetists are therefore keen to develop ways to monitor when people wake up in operations. One way to do this is to this is to measure the response of the brain to sound, This often uses click sounds which are played through headphones. Research dating back to the 1980s has shown that the response of the brain to sound changes as you fall asleep. However, the response of the brain is very small (about a millionth of a volt). It is therefore hard to measure such a small signal accurately in an operating theatre where there are often many sources of electrical interference. This means that the result of the measurement can be unreliable and so using the existing technique, it might be difficult to tell if a patient is awake or asleep.At the University of Southampton, we have been looking at new mathematical techniques to better measure this small signal from the brain, called an auditory evoked potential. We have specifically been looking at ways to change the stimulating sound to evoke a response from the brain in the most efficient manner. We have investigated ways of presenting the stimulus in an irregular way that allows us to present the stimulus very fast. This is important as we can record lots of similar signals quickly and by averaging them together, obtain a better quality measurement. The special sequences we use to present the sounds quickly are known as maximum length sequences. We have also changed the sounds from a click to a fast frequency sweep called a chirp. These chirps have been shown to produce a larger response from the brain than a click. They are thought to stimulate lots of nerve cells in the auditory system to fire at the same time. Putting the two techniques together, we have found that we can improve the measurement of the small signal from the brain many times in normal hearing subjects.We have started to investigate this new technique for measuring the response of the brain to sound in a small number of patients undergoing operations and we have seen changes that occur with anaesthesia. However, the pattern of changes we found with anaesthetic differs from that found in earlier studies. This might be because we have measured the response more accurately. However we have only tested a small number of subjects so far and we do not know if the new technique for measuring the brain response is more reliable than the old one. This research project will test the technique on a larger number of subjects to see if we really can identify awareness in operations correctly and also to verify the pattern of changes in the response of the brain with anaesthetics that we found in our earlier study. It will also compare the new technique for measuring the brain response to sound to an older existing method that has been used in a number of research projects. We also want to further improve the mathematical techniques to extract the small signal reliably and to categorise the brain signals so that the patient state (awake or asleep) can be clearly indicated to doctors. If the new technique is found to be very reliable, it might become a standard way to monitor if people wake up in operations.