Concepts and correlations relevant to general anaesthesia.

General anaesthesia has become so safe since its introduction just over 150 years ago that the risk associated with it has become almost immeasurably small: less than one death solely attributable to anaesthesia occurs per 200 000 procedures. This progress has been achieved in the absence of generally accepted hypotheses for the mechanisms of general anaesthesia. Does it matter whether mechanisms of anaesthesia are understood? Providing more anaesthetic than is necessary is best avoided, as are the side-effects of anaesthetic procedures, but how little anaesthetic is suf®cient? Patients are anxious that they might not wake up from anaesthesia but they are also very concerned that they may wake up during the surgical procedure. Awareness during general anaesthesia has become much more of a problem with the introduction of new (such as total intravenous) anaesthesia techniques. How can clinical outcome from different anaesthesia procedures (perioperative awareness, postoperative pain, emesis or recovery from surgery) be compared unless there are ways to quantitatively establish that these different procedures were identical in the level of anaesthesia they provided? There is a lack of devices that can monitor the level, or `depth', of anaesthesia adequate for surgery. However, before an anaesthesia monitor can be constructed it must be clear what anaesthesia-related quantity the monitor should measure. This requires an understanding of the mechanisms of anaesthesia. Concepts and correlations that are relevant to the study of mechanisms of anaesthesia will be discussed ®rst. A number of concepts mentioned in this review were discussed by Overton more than a hundred years ago, some of which unfortunately seem to have been forgotten. In order not to re-invent the wheel, Overton's book 39 is still a book worth reading. However, we have made substantial progress in understanding and in experimental technology and have appreciated that the topic of general anaesthesia is much more complex than Overton could have been aware of. Subsequent reviews will present new scienti®c insights resulting from and in connection with the Sixth International Conference on Molecular and Basic Mechanisms of Anaesthesia (MAC2001), while the ®nal review summarizes these ®ndings on targets and mechanisms of anaesthetic actions and evaluates their implications for theories of anaesthesia. Concepts addressed at the conference and in these reviews have been brought together here in this ®rst review. They may also help young researchers entering this ®eld to be less naõ Ève about the ®eld than we were when we ®rst entered it.