Sleep science in anesthesiology
KeywordsSleep Anesthesia Sleep disturbance Mechanism of general anesthesia
The discipline of sleep science offers two merits to anesthesiology: a basic aspect and a clinical aspect. The basic aspect’s merit is that sleep science provides knowledge that can be useful to elucidate the mechanism by which general anesthesia works, especially concerning the loss of consciousness. On the other hand, the clinical aspect’s merit is that knowledge of sleep science may provide answers to solving postoperative sleep disturbance, which is widely recognized as one of the established factors that exacerbates problems associated with the postoperative course.
Anesthesia-induced amnesia is a distinct state from physiological sleep, especially considering that general anesthesia has the potential to be harmful. If we develop a method of anesthesia that results in a state of amnesia similar to physiological sleep, it may be beneficial to patients.
Anesthesia and sleep: from the viewpoint of basic medicine
There are a number of general anesthetics including gaseous, inhaled, and intravenous anesthetics. All of these anesthetics have distinct physical and chemical properties. Therefore, general anesthesia includes various agents that induce a reversible state of altered consciousness that satisfies the following conditions: loss of consciousness, analgesia, muscle relaxation, and the suppression of autonomic nervous reflexes.
The strategy for basic research on anesthesiology is divided into the macro-to-micro hierarchy. We have yet to discover a uniform theory that is able to explain all anesthesia-induced phenomena across the entire hierarchy. At the micro level, many studies investigated how anesthetics affect the dynamics of the consciousness-related quantum , molecules, classical neurotransmitters, and modifiers. Recently, the trend has been to clarify how general anesthetics affect consciousness-related neuronal network systems [2, 3].
On the other hand, there are also a number of excellent studies that investigated the mechanism of general anesthesia by identifying common points between sleep and anesthesia. For example, a revolutionary study by Nelson et al. discovered that GABAergic anesthetics, dexmedetomidine as well as GABA agonist itself, all induced a similar neuronal activity pattern, known as c-fos expression, in the so-called endogenous sleep circuit regardless of whether the animal was anesthetized or sleeping .
Currently, we have two theories for the mechanism by which general anesthesia works. The first, the so-called bottom-up paradigm, explains that general anesthetics act on various nuclei in the brain responsible for sleep states and awakening from those states, resulting in a loss of consciousness. The top-down paradigm, on the other hand, argues that modulation of signal transmission of neural networks between the cerebral cortex and the thalamus causes loss of consciousness. The issue of which of these paradigms is superior is still under investigation [3, 5, 6, 7]. Both theories agree that the disconnection of information transfer in the central nervous system is one of the essential mechanisms of general anesthesia-induced loss of consciousness. In contrast, only Akeju and Brown  propose that general anesthesia is neurophysiologically distinct from sleep, because the changes in EEG patterns are anesthetic agent dependent and some agents produce different EEG patterns from sleep.
Anesthesia studies that utilize sleep science have revealed that the process of induction and emergence from anesthesia is not a simple mirror of the unitary mechanism. Previous studies have established that physiological sleep is an active process rather than a passive process such as a suppression of wakefulness. For example, orexin, an endogenous wakefulness-promoting substance, also facilitates the emergence from anesthesia, but not the delayed induction of anesthesia [2, 9, 10, 11]. Another endogenous wakefulness-promoting substance, neuropeptide S, also facilitates the emergence from anesthesia, but not induction . These results may confirm a theory that explains the process of anesthesia-induced loss of consciousness and emergence as not being a simple mirror of the unitary mechanism and, moreover, that these processes are diverse depending on the anesthetic agent. For example, in rats as well as humans, propofol and dexmedetomidine produce a calm induction of anesthesia and emergence. Conversely, anesthesia and emergence are relatively unstable with ketamine. Indeed, rats maintain a state of wakefulness for several hours without any sleep-like behavior after emergence from ketamine anesthesia .
Anesthesia and sleep: from the clinical aspect
Sleep disorders after general anesthesia are harmful.
Do general anesthetics replace sleep?
In general, the term general anesthesia does not distinguish between pharmacologically different phenomena.
Sleep shares some common mechanisms with general anesthesia-induced loss of consciousness.
Studies on sleep may elucidate the mechanism concerning how general anesthesia induces loss of consciousness.
The process of anesthesia-induced loss of consciousness and emergence is not a simple mirror of the unitary mechanism.
- 5.Sleep disorders following general anesthesia are harmful.
Suppressed immunity results in infection and the exacerbation of cancer.
REM sleep disorder leads to an imbalance of autonomic nervous activity, resulting in a wide range of serious disorders in the respiratory and circulatory systems such as ischemic cerebrovascular disease, heart disease, and bronchial asthma.
Higher brain functions are also impaired. As a result, memory and cognitive impairment may occur. Patients who have cognitive impairment after surgery have a high mortality rate within 1 year.
- 6.Do general anesthetics replace sleep?
Inhalation anesthetics cannot be an alternative.
GABA receptor agonists (propofol) and α2 adrenergic receptor agonists (dexmedetomidine) may partially serve to complement sleep.
Anesthesiology is a field that is interdisciplinary. As part of a cross-disciplinary approach, incorporating sleep science research into anesthesiology will contribute to developing the knowledge base of anesthesiology.
This article was supported by funds from the Ministry of Education, Culture, Sports, Science and Technology of Japan (Grants-in-aid for scientific research: 26462327 and 18K08807).
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