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• W2077029495 abstract "What should we properly monitor, when we monitor the brain for ‘anaesthesia’? Any answer is likely to depend on what we mean by ‘anaesthesia’. The article by Escallier et al. in this issue of Anaesthesia is an important review of the status of processed EEG (pEEG) monitoring in anaesthesia 1. Central to the role of pEEG (or any other type) of ‘depth of anaesthesia’ monitors is their putative ability to detect when a paralysed patient is suitably anaesthetised or not; apparently a simple binary decision-making process. Yet, this article contains a profound sentence whose implications, if widely accepted, are likely to change our entire view of ‘anaesthesia’, for reasons I will explain in this editorial. The apparently innocuous sentence is: “There is a growing consensus that intra-operative awareness is a spectrum of brain states” [my emphasis]. The following questions immediately come to mind: what is the basis for this new consensus? What does this consensus imply for mechanisms of anaesthesia? And what does it imply for monitoring of the anaesthetic state? Traditionally, anaesthesia has been regarded as an all-or-nothing, binary phenomenon. This view was most clearly proposed by Prys-Roberts when he wrote: “There cannot be degrees of anaesthesia nor for that matter can there be variable depths of anaesthesia” 2, a statement that was unsupported by other references but a sentiment that became nevertheless widely repeated in standard texts 3. Superficially, this makes sense: either you are anaesthetised or you are not. Once you are anaesthetised, it is difficult to conceive then how you can be ‘more’ anaesthetised. It is not (to borrow Sleigh's phrase 4) as if ‘the patient is a submarine’! Yet, things are never really so simple and this traditional view is now challenged in several ways. Assuming that anaesthetic drugs act at protein channel receptor targets, we know that dose-response pharmacology is not binary or all-or-nothing. Rather, the drug-dose-response relationship is characteristically continuous, described by relatively simple models in which the drug effect is non-linearly proportional to drug concentration, up to some maximum receptor effect. At some concentration of drug lower than this maximum, the active drug-receptor combination reaches a threshold that triggers the intended response (in this case, ‘anaesthesia’). If there were no variability in individual organism sensitivity or receptor state, then all animals of a species would become anaesthetised at exactly the same anaesthetic concentration. We know that this is not true: at a given clinically relevant concentration, there will always be some proportion of animals not anaesthetised (this proportion dependent upon the steepness of the population ‘dose-response’ relationship for the drug) 5. In this way, Dilger has elegantly summarised how continuous dose-response relationships at molecular level can translate into near (but not quite) binary relationships at population level 6 (Fig. 1). Figure 1 also raises another question. Even if anaesthesia is attained at the threshold concentration (in this example of Fig. 1, ~1 arbitrary dose unit), but further drug is administered to the organism, the panel on the left indicates that there is continued drug-receptor binding and a greater effect at the receptor. In other words, from the perspective of the receptor, maximal effect has yet not been reached and the drug must presumably be achieving something. What is an anaesthetic drug doing to the brain, if given in a concentration greater than that required to achieve anaesthesia? Let us return to this question later. A binary view of anaesthesia implies that, just as ‘being anaesthetised’ is regarded as a singular brain state, then being ‘not anaesthetised’ is also a singular (opposite) state. Accidental awareness during anaesthesia is one situation in which anaesthesia is intended, but fails, and the patient is ‘not anaesthetised’. The full results are awaited of the 5th National Audit Project (NAP5) of the Association of Anaesthetists of Great Britain & Ireland and of the Royal College of Anaesthetists 7: this will present detailed reports of what patients experienced and the manner in which they were ‘not anaesthetised’. However, the results of the NAP5 Baseline Survey 8, 9 already clearly indicate that, instead of being a singular state, there is in fact a spectrum of experiences when ‘not anaesthetised’, with the majority being apparently neutral and only a third involving pain or distress. I have argued elsewhere that the brain state of a patient undergoing the isolated forearm technique, who responds both spontaneously to the surgery and to the verbal command to move their forearm (i.e. likely to be fully awake) cannot be the same as that of a patient who responds only to the command (who, I have proposed, is in a state of ‘dysanaesthesia’ 10-14). These two patients are ‘not anaesthetised’ in very different ways, and the latter appears an acceptable state for surgery to continue. Shafer and Stanski have argued that anaesthetic depth can be regarded as the probability of separately attaining several different endpoints relevant to anaesthesia 15. Sleigh has alluded to the analogy of anaesthesia's being the process of switching off a set of switches that are related to different functions such as ‘pain’, ‘memory’, ‘autonomic response’, etc 4. This idea is not necessarily new, since Hopkin in the 1960s used a similar analogy of anaesthesia's being the switching off of different lights: the challenge he proposed was to work out ‘which stayed flashing and which were off’ during clinical anaesthesia 16. Thus all these authors challenge the view that anaesthesia is binary, and there is indeed an emerging consensus that anaesthesia as a spectrum of brain states. A single brain state is characterised by its own, singular pattern of neuronal activity (the ‘neural signature’), which can be identified by electrophysiology or brain imaging technologies 17, 18. However, if as discussed above, several different brain states are compatible with ‘anaesthesia’ (including some that involve degrees of awareness), then it follows that all anaesthetic drugs do not necessarily produce the same pattern of neuronal activity, but potentially induce their own, distinct patterns. In other words, the drugs used to achieve the distinct brain states compatible with anaesthesia must be acting by different fundamental mechanisms. Table 1 shows the crude spectrum of channel activities for a range of agents. Although it is generally the case that the GABA-A receptor is activated by all agents and generally the case that the nACh receptor is inhibited, other candidate receptors show a very heterogenous activity profile across the agents. It may be tempting to conclude, therefore, that this indicates that these other receptors are not really candidate receptors at all for general anaesthesia. However, this conclusion is only valid if we are restricting ourselves to considering a unitary mechanism of action. If we broaden our horizons and accept the possibility (as implied by Escallier et al.'s statement 1) that there are several distinct forms of anaesthesia, then immediately it becomes clear that Table 1 is illustrating the different ways that each agent can induce anaesthesia via its own unique spectrum of receptor activities. Thus, the anaesthesia induced by etomidate cannot be an identical brain state to the anaesthesia induced by propofol or thiopental, etc. Furthermore, given the gaps in knowledge displayed within Table 1, it is conceivable that even each volatile agent is subtly unique in its actions (e.g. isoflurane vs sevoflurane). Moreover, the coupling of intravenous induction with volatile maintenance (with supplementary nitrous oxide) may result in some interesting interactions, some of which may even be potentially antagonistic at certain receptors, each resulting in their own unique anaesthetic state. I asked earlier: what does additional anaesthetic dosing do after the state of anaesthesia has been achieved? The information discussed above helps address this question, at least in part. Additional dosing increases the degree or type of loss of brain function. Thus if, say, propofol acting on a GABA-A receptor achieves the threshold drug-receptor concentration to produce the endpoint of loss of consciousness or loss of response to verbal stimulation, then additional propofol might produce loss of response to a different endpoint of, say, nociceptive stimulus 18. Or, at higher doses, propofol interacts with nACh receptors in the brain, where at conventional doses it is only weakly active (Table 1), and hence at high dose produces a wider loss of function of those activities mediated by these receptors (e.g. interference of sleep or of learning and memory) 27. Thus, dosing produces quantitative effects related to a single receptor, as well as qualitative effects related to activation of multiple receptors 28. This all makes our approach to unconsciousness resemble more closely our approach to other physiological systems, such as the cardiovascular, respiratory or renal. We readily accept that the cardiovascular system is composed of several more basic elements such as blood pressure, cardiac output, cardiac filling/venous return, etc, each of which requires its own separate measurement. In turn, we acknowledge that antihypertensives, for example, are not a single class of drug, but work in unique ways on one or more of these fundamental elements of the cardiovascular system (e.g. cardiac output or peripheral resistance, etc) to produce the common effect of ‘lower blood pressure’. It is not sufficiently informative to say that a drug has reduced the blood pressure; in anaesthesia and critical care we need to know the mechanism(s) by which it has done so 29. We view bronchodilators in the respiratory system, or diuretics in the kidney, in similar ways. Table 1 suggests that ‘anaesthetics’ may be a very crude term for a group of drugs that produce a superficially similar neurophysiological state, but that (like the antihypertensives) have highly specific actions 29. The implications of this train of logic for monitoring the brain state are important. A brain monitor that yields as its output a single numerical value to reflect the state of the system is, at best, only providing a general estimate about the probability of the system (its ‘capacity’) to generate consciousness 30, 31. It is not telling us which specific elemental functions contributing to consciousness are lost and which are retained. A single number is therefore of little or no use if, in fact, there are several different brain states induced by anaesthetic drugs, and if anaesthesia can be achieved with a spectrum of brain states, in some of which the capacity for consciousness is retained. Even high-quality studies simply grasp for correlations between EEG/brain activity signatures with the moment of loss of/return to consciousness, and they often only study single agents, in the absence of surgery 32. While correlations are indeed discovered by such experimental paradigms, it remains unclear if these really do signify sufficient loss of brain functions as to allow surgery to proceed acceptably, or if the same signatures pertain with different agents or mixtures of agents. Other methodologies indicate that brain responses are highly agent-specific 33, 34. Recent work using functional magnetic resonance imaging (fMRI) has suggested that with very slow propofol induction, a state is reached where the thalamocortical region of the brain becomes an ‘island’ of activity, apparently separated from sensory input, and that this is associated with loss of this region's response to auditory and nociceptive inputs 18. However, other parts of the brain retained their response to these stimuli. The suggestion was that, perhaps akin to the state of dysanaesthesia 10, these subjects were technically aware of the sensory stimulation but disinclined to be interested in it. It is not known if the same fMRI results are seen with other agents, or if this brain state is compatible with surgery. The fact that many pEEG monitors such as the bispectral index (BIS) yield a different value when patients appear equally well anaesthetised with some agents (e.g. propofol) vs others (e.g. ketamine or xenon) has been argued to show that the monitors are very poor at detecting the state of ‘anaesthesia’ 35. However, this interpretation is valid only if it is assumed there is a single brain state for anaesthesia. If, in fact, there are multiple brain states compatible with anaesthesia, then these results are telling us that the monitors are possibly very good at detecting some of these states (e.g. those achieved by propofol) but very poor at detecting others (e.g. those achieved by ketamine). If the technology only accommodates a single monitor to detect just the one brain function, then it follows that multiple monitors, where each focuses on a separate brain function, are more likely to be beneficial than just one. This is then akin to all other body systems, such as the cardiovascular, where we readily accept the need for separate monitors to provide information about the electrical activity of the heart, the blood pressure, cardiac output, etc. Sleigh reaches a broadly similar conclusion, focusing on the need for separate monitors calibrated for specific endpoints such as memory loss, nociceptive arousal systems, inflammatory responses, etc 4. The anaesthetic literature is surprisingly sparse on the properties of the ‘ideal’ depth of anaesthesia monitor(s), although Avidan and colleagues have cogently approached the problem, focusing on EEG-based monitoring 36, 37. Whyte and Booker suggested some ideal properties in an educational publication 38, as did Gelb in unpublished material accessible on the internet 39. Table 2 summarises these proposals, with the last column indicating what might be considered ideal, based on the discussions in this article. Each anaesthetic agent appears to act via its own unique spectrum of affinity/efficacy for different channel receptors 19. The resulting effect is not just related to effect of dose on one receptor system, but also to the spectrum of receptors on which the agents act at a given dose. Since these receptors are unevenly distributed in different parts of the brain, this suggests that each agent acts on its own unique set of brain regions 28. And since brain function is localised by region, this suggests in turn that each anaesthetic drug may induce anaesthesia by its own unique mechanism involving different, specific brain functions. These conclusions are in contrast to the previous, widely-held view that there must a singular, binary mechanism by which all anaesthetics induce anaesthesia. Furthermore, there is an emerging consensus that accidental awareness during anaesthesia is also a spectrum of brain states, some of which are in fact broadly acceptable to patients (even though they involve a degree of awareness of surroundings, which may be surprising or unanticipated at the time) 10. In this way, the train of logic arising from Escallier et al.'s innocuous statement has led us to a redefinition of ‘anaesthesia’. In a highly restricted sense, anaesthesia is purely the brain state of complete mental oblivion with no sensory-perceptual experience, thoughts or recall of events. In a pragmatic sense, however, ‘anaesthesia’ is any drug-induced mental state that makes surgery acceptable at the time, and later, whether or not that includes some awareness and recall of events. In one (extreme) sense, this concept is not new to us: a technique employing regional anaesthesia (spinal or epidural) with light sedation is an entirely acceptable form of ‘anaesthesia’ wherein the patient is likely to be aware of events but unconcerned by them. The new notion presented here is that a rather similar state might arise, unanticipated, where the original intention was to induce complete mental oblivion. This wider meaning and use of the word ‘anaesthesia’ might also yield strategic benefits for the specialty as a whole. First, it can act as an important driver for research, directed to linking the outputs of pEEG and other monitors to specific brain functions. Second, it can aid positive public engagement. Because hitherto, the professional and public understanding of what ‘anaesthesia’ is has been the narrow one, the involvement of an ‘anaesthetist’ in patient care has been assumed to imply that the input will solely be to induce a state of complete mental oblivion, and little else 40, 41. Indeed, anecdotally there can be surprise and even disappointment that mental oblivion is not always the proposed solution to the presenting clinical problem. By redefining ‘anaesthesia’ to mean the more subtle manipulation of sensory-perceptual modalities to create a range of possible acceptable mental states for surgery, this might in turn broaden the public view of anaesthetists’ skills and knowledge in contributing to patient care 41. JJP is Clinical Lead of NAP5; the views expressed here are his own and not those of NAP5, the Royal College of Anaesthetists or the Association of Anaesthetists of Great Birtain and Ireland. No funding or other competing interests declared." @default.
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• W2077029495 date "2014-06-06" @default.
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• W2077029495 title "Monitoring (un)consciousness: the implications of a new definition of ‘anaesthesia’" @default.
• W2077029495 cites W127395960 @default.
• W2077029495 cites W1559156040 @default.
• W2077029495 cites W1584639503 @default.
• W2077029495 cites W1909386929 @default.
• W2077029495 cites W193442710 @default.
• W2077029495 cites W1963914175 @default.
• W2077029495 cites W1967229443 @default.
• W2077029495 cites W1969958069 @default.
• W2077029495 cites W1973723804 @default.
• W2077029495 cites W1987575276 @default.
• W2077029495 cites W1992733054 @default.
• W2077029495 cites W2002996884 @default.
• W2077029495 cites W2008092439 @default.
• W2077029495 cites W2008440727 @default.
• W2077029495 cites W2017718631 @default.
• W2077029495 cites W2025312180 @default.
• W2077029495 cites W2039882662 @default.
• W2077029495 cites W2043833974 @default.
• W2077029495 cites W2045221743 @default.
• W2077029495 cites W2045823870 @default.
• W2077029495 cites W2062804217 @default.
• W2077029495 cites W2071646875 @default.
• W2077029495 cites W2080512618 @default.
• W2077029495 cites W2140750662 @default.
• W2077029495 cites W2141824226 @default.
• W2077029495 cites W2154228706 @default.
• W2077029495 cites W2157618404 @default.
• W2077029495 cites W2157969621 @default.
• W2077029495 cites W2207635412 @default.
• W2077029495 cites W4230923095 @default.
• W2077029495 cites W4238006064 @default.
• W2077029495 cites W4239287070 @default.
• W2077029495 cites W4244075422 @default.
• W2077029495 cites W4250638933 @default.
• W2077029495 cites W58383299 @default.
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