Masui. The Japanese journal of anesthesiology
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Recent advancement in functional brain imaging techniques has revealed much of the global effects of general anesthetics on the human brain. General anesthetics preferentially suppress specific brain areas including the parietal association cortex and the thalamus, part of which appears to mirror the default mode network. ⋯ Midazolam-induced loss of consciousness is associated with remarkable suppression of cortico-cortical propagation of evoked currents. Overall, those results prompt us to hypothesize that general anesthetics induce loss of consciousness by disrupting the integrative properties of the cerebral cortex.
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Recently, almost all kinds of general anesthetics currently used in human clinical anesthesia, have been shown to exert neurodegenerative effects such as apoptosis of neuronal cells during the rapid synaptogenesis of immature mammalian brains, and later neurocognitive impairment. There are several drugs or strategies to reduce this phenomenon such as alpha(2) agonist, xenon, melatonin, lithium, hypothermia and erythropoietin, but their safety and efficacy should be investigated much further. ⋯ Larger-sized prospective randomized studies in human such as SAFEKIDS (http://www.iars.org/safekids/) to ascertain if current clinical practice of general anesthesia impairs neurocognitive development of human neonates and infants, are expected. They will also clarify what kind of anesthetics and anesthetic strategies may be the risk factors of neurocognitive impairment in human neonates and infants.
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Although general anesthetics were first used more than 160 years ago, their mechanisms have remained mysterious. During the past decade, significant progress in our understanding of general anesthetic action at the cellular and network system levels has been made. Our recent work demonstrates (a) that intravenous anesthetics, but not volatile agents, enhance the discharge of GABA from presynaptic terminals, (b) that intravenous anesthetics produce frequency-dependent modification (FDM) of anesthesia, and (c) that FDM is responsible for the unsuccessful immobilization or hypnosis during intravenous anesthesia. In addition, we review the development of hypothesis for anesthetic action, non-specific versus specific action, cutoff phenomenon in n-alcohols, and anesthesiological approach to consciousness.
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It is widely known that electroencephalogram (EEG) shows dramatic changes with increase of the concentration of anesthetic. It is considered that volatile anesthetics (i. e. isoflurane, sevoflurane), barbiturates, propofol show anesthetic effect by potentiating GABAA receptor. Changing patterns of EEG by these anesthetics are quite similar. ⋯ However this is not always the required condition for adequate anesthesia, because alpha power never becomes larger in some patients even when the anesthetic level was judged as adequate by concentration dependent changing patterns of EEG. As EEG changes in relation to the concentration of anesthetic, it seems to be correlated with the level of consciousness. But EEG patterns during anesthesia are mainly determined by the condition of thalamic neurons, and it would merely indicate the level of hypnosis indirectly.
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We showed the effect sites of anesthetics in the central nervous system (CNS) network. The thalamus is a key factor for loss of consciousness during natural sleep and anesthesia. Although the linkages among neurons within the CNS network in natural sleep are complicated, but sophisticated, the sleep mechanism has been gradually unraveled. ⋯ Recent literatures have shown that the effects of anesthetics are specific rather than global in the brain. It is interesting to note that thalamic injection of anti-potassium channel materials restored consciousness during inhalation anesthesia, and that the sedative components of certain intravenous anesthesia may share the same pathway as natural sleep. To explore the sensitivity and susceptibility loci for anesthetics in the thalamocortical neurons as well as arousal and sleep nuclei within CNS network may be an important task for future study.