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• W2994383417 abstract "Consider a thought experiment. A scientist takes a cricket, cuts off one leg at a time, and with each cruel amputation asks the cricket to jump. Lo and behold, with the severance of each jointed leg, the distance jumped by the cricket is decreased. Finally, with detachment of the last leg, the cricket jumps no more. The scientist reasonably concludes that a cricket with no legs cannot hear. Now let us conduct a second thought experiment. A clinical researcher determines that a patient is inadequately anaesthetised by asking the patient to lift an arm high in the air, which the patient does. The researcher then administers increments of rocuronium, and with each dose the elevation of the patient's arm decreases. After the sixth increment of rocuronium, the arm remains immobile despite the request to lift it high, and the researcher reasonably concludes that the patient is now unconscious. In this issue of Anaesthesia, Le Guen et al. report the results of their intriguing double-blind, randomised crossover study, the aim of which was to determine whether, under an adequate and stable intravenous anaesthetic level, reversal of neuromuscular blockade by sugammadex is associated with clinical signs of awakening and large increases of the bispectral index 1. Of the 59 enrolled patients, 51 were included in the final analysis. Surprisingly, the investigators found that sugammadex reversal of neuromuscular blockade was often associated with clinical signs of awakening (14 patients) and substantial (≥ 20 point) elevations of bispectral index readings (22 patients), despite attempted maintenance of general anaesthesia with target-controlled propofol and remifentanil infusions 1. These findings are provocative since there is no known biological mechanism by which sugammadex could directly cause arousal from propofol anaesthesia. This is in contrast to physostigmine, which crosses the blood–brain barrier, and, through central cholinesterase inhibition, increases acetylcholine, which activates central cholinergic muscarinic transmission, thereby theoretically promoting arousal from propofol anaesthesia 2. Also the findings of Le Guen et al. are in conflict with a previous study that showed no evidence of clinical arousal or increase in bispectral index readings at the end of surgery when sugammadex was administered to patients receiving propofol and remifentanil 3. However, there has been one well-documented case report of clinical and electro-encephalographic signs of arousal with sugammadex, while a patient was still receiving i.v. anaesthetic agents following surgery 4. The afferentation theory in relation to general anaesthesia proposes that decreased input to the brain results in decreased activation of sensory brain regions, in turn promoting hypnosis 5. This theory has been applied to neuromuscular blockade 5, 6. The thesis is that during general anaesthesia, administration of neuromuscular blocking agents results in decreased muscle spindle activity, thereby decreasing input from the muscles to the brain, in turn resulting in deeper hypnotic component of general anaesthesia 7. This hypothesis laid the theoretical foundation for the ‘Liverpool technique’. The notion was that by administering a non-depolarising neuromuscular blocking agent in addition to a combination of nitrous oxide and an opioid analgesic, an adequate hypnotic depth of anaesthesia could be achieved without (much) use of barbiturate or ether. Thomas Cecil Gray popularised the use of neuromuscular blocking agents as essential components of general anaesthesia in Liverpool in the late 1940s 8. The underlying principle of the new technique was ‘minimal narcotisation with adequate curarisation’ 8. There are several major problems with the afferentation theory. First, it has been clearly demonstrated during general anaesthesia that sensory stimuli still reach and activate the cortex 9; however, this is probably not associated with conscious experience or awareness, or at least with both consciousness and memory consolidation (awareness with recall). Second, innovative research by Schuller et al. showed that administering either succinylcholine or rocuronium to awake volunteers did not appear to lead to blunting of conscious experience or memory consolidation 10. Third, we have no foolproof method to confirm unconsciousness when neuromuscular blocking drugs are administered. Fourth, we know that people with locked-in syndrome, including the impressive writer Jean-Dominique Bauby, and people with profound motor neuron disease, including the prize winning physicist Professor Stephen Hawking, can be fully consciousness and cognitively impressive. Le Guen et al. provide compelling examples of a linkage between sensory deprivation and sleepiness 1. However, muscle paralysis cannot be equated with sensory deprivation, and it is hard to argue that a patient whose breastbone is being cleaved with an electrical saw is experiencing sensory deprivation. And fifth, traumatic intra-operative awareness almost invariably occurs when patients receive neuromuscular blocking agents in the setting of insufficient hypnotic depth 11. The study by Le Guen et al. is predicated on the notion that we can determine an “adequate and stable anaesthetic level” 1. We cannot. First, even with stable anaesthetic drug concentrations and in the absence of noxious stimuli, we have discovered that general anaesthesia is a dynamic, not a stable state 12. Second, as mentioned previously, in the presence of neuromuscular blockade we cannot currently reliably know that a patient is actually anaesthetised 13. Indeed, responsiveness to commands has even been demonstrated during intended general anaesthesia with electro-encephalographic persistent alpha spindles phase amplitude coupled with delta waves 13, which is an electro-encephalogram pattern suggested to be indicative of general anaesthesia. With propofol, which was used in an attempt to maintain stable anaesthesia in this study, inter-patient pharmacokinetic and pharmacodynamic variability 14 is much more marked than with volatile agents. Therefore, the notion that anaesthesia was stable in this study is rendered all the more controversial. Furthermore, we now have ample evidence that a bispectral reading between 40 and 60 is no guarantee of an adequate or stable ‘level’ of anaesthesia 10. A bispectral index reading does not have direct neurophysiological meaning, and at best it provides a crude approximation of hypnotic depth. Although no patients were found on questioning in the recovery area to have experienced ‘explicit awareness’, all we really know is that at very early postoperative time of questioning there was no evidence of explicit recall. Awareness without recall could have occurred, and delayed explicit recall could also have occurred; questioning in the recovery area is unreliable 15, since recovery of cognition is often only partial at this time. The take-home message from Le Guen et al. is “it is necessary (with total intravenous anaesthesia) to maintain sedation until complete muscular function recovery to avoid potential awareness during this period” 1, since administration of suggamadex might lead to sudden arousal. An alternative interpretation is that this innovative study revealed that even when we believe that patients who have received neuromuscular blocking drugs are adequately anaesthetised with propofol and remifentanil, administration of sugammadex often reveals that they are in fact conscious, despite BIS readings between 40 and 60 and apparently adequate anaesthetic concentrations. Therefore, if we truly wish to minimise the risk of intra-operative awareness with recall, we must continue to limit our administration of neuromuscular blocking drugs, although we now have a reliable reversal agent in sugammadex. However, it is always important to keep an open mind in science. Perhaps sugammadex does in fact reverse hypnosis as well as neuromuscular blockade. After all, a cricket's ears are located on its front legs 16. No competing interests declared." @default.
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• W2994383417 title "A cricket with no legs cannot hear" @default.
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