CLINICAL REVIEWAnesthesia and sleep
Introduction
In humans and animals, induction of general anesthesia produces a state of reduced responsiveness often described by anesthetists and patients as ‘sleep’.1 While sleep and anesthesia have similar behavioral characteristics, however, distinct behavioral and physiological differences clearly distinguish the two states2 (Table 1). Unlike sleep for example, general anesthesia does not occur spontaneously, is not reversible with external stimuli, and is characterized by an electroencephalographic (EEG) pattern devoid of distinct stages and of the cycling between stages typical of naturally occurring sleep. Moreover, sleep is regulated both homeostatically and via circadian cues, and can be disturbed by environmental factors. In contrast, the duration and depth of general anesthesia is governed primarily by agent dose and duration of administration.
Nevertheless, behavioral similarities between anesthesia and naturally occurring sleep have hinted at underlying neurophysiological similarities between the states. Recent work focusing on anesthetic effects at specific molecular receptors and on specific brain nuclei have identified changes in brain activity with anesthetic administration that bear a striking resemblance to those that occur during sleep.3 In addition, some receptor-based effects of general anesthetics appear to occur at the tuberomammillary nucleus (TMN), a known sleep regulatory center in the brain.4 Taken together, these findings raise the possibility that some characteristics of general anesthesia may be produced in part by effects of anesthetics on neuronal networks normally involved in generating or maintaining naturally occurring sleep.
The possibility that anesthesia and sleep may share common neurophysiological elements has been supported by behavioral studies in animals indicating that both states may produce similar effects. Work in rats suggests that during prolonged anesthesia, sleep need does not accrue, and that recovery from sleep deprivation can occur during anesthesia.5., 6. Moreover, both circadian rhythmicity and sleep deprivation clearly alter anesthetic action,7., 8. indicating a link between factors known to regulate sleep and anesthesia.
Little is known about how the anesthetized state might modulate the mechanisms governing sleep homeostasis. Anesthetics may act either directly, by reversing the buildup of sleep ‘debt’ in the brain, or indirectly by preventing normal wake-associated processes from doing the same. Nevertheless, understanding the effect of sleep on anesthetic action may help physicians predict and manage the variability in anesthetic and sedative action produced by sleep homeostatic control. Treatment of longstanding sleep deprivation in patients with sleep apnea, for example, may prevent exaggerated responses to postoperative pain and sedative administration. In the Intensive Care Unit (ICU), where natural sleep is difficult to obtain, administration of anesthesia may substitute for sleep, and prevent detrimental physiological consequences of sleep deprivation. This article will briefly review current knowledge regarding anesthetic mechanisms, present an overview of current work on physiological and pharmacological interactions between anesthesia and sleep, examine behavioral correlates of those interactions, and identify potential clinical and research implications of relationships between anesthesia and sleep.
Section snippets
Anesthesia: clinical definition
Although the first clinical demonstration of general anesthesia occurred in 1846,9 the specific mechanisms by which anesthetic administration causes unconsciousness remains unknown today. Because clinical characteristics of anesthesia are agent specific, no uniform physiological definition of anesthesia or anesthetic action exists. The anesthetic ketamine, for example, generally produces tachycardia and hypertension on induction whereas opposite effects occur with the anesthetic propofol.10
Sleep: clinical definition
Sleep can be defined as a reversible behavioral state of perceptual disengagement from, and unresponsiveness to the environment.30 Unlike anesthesia, however, which can vary with type of anesthetic, normal sleep possesses clearly defined behavioral and physiological endpoints. Two distinct physiological states have been defined within sleep, for example: non-rapid eye movement or NREM sleep, and rapid-eye-movement, or REM sleep. In humans, NREM sleep has been further subdivided into four stages
Anesthesia and sleep: clinical interactions
Speculation on the relationship between drug-induced unconsciousness and sleep has existed since the time of Shakespeare. In Romeo and Juliet (IV, i), an anesthetic is given to Juliet whose effects are described as: “And in this borrow'd likeness of shrunk death/Thou shalt continue two and forty hours/and then awaken as from a pleasant sleep”. Today, effects of modern anesthetics on subsequent sleep behavior are known for some but not all anesthetics. In humans, isoflurane anesthesia alone
Research issues
Similarities between naturally occurring sleep and the anesthetized state raise significant obstacles with respect to investigating possible effects of anesthesia on sleep homeostasis. While sleep is described primarily by its behavioral and EEG appearance, the anesthetized state itself can have a similar behavioral appearance. Anesthesia also produces its own EEG signature during administration, potentially obfuscating that produced by naturally occurring sleep. As a result, it is
Conclusions
The possibility that behavioral similarities between general anesthesia and naturally occurring sleep also represent physiological similarities has tantalized researchers in both fields for years. Recent insights into the neurophysiological characteristics of both states have begun to identify a mechanistic basis for such similarities, increasing our understanding of both states and shedding new light on interactions between sleep deprivation and anesthetic action.
Current research into
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Cited by (84)
Sleep and anesthesia
2023, Encyclopedia of Sleep and Circadian Rhythms: Volume 1-6, Second EditionProgress in modelling of brain dynamics during anaesthesia and the role of sleep-wake circuitry
2021, Biochemical PharmacologyCitation Excerpt :Interestingly, delta power also increases during anaesthesia in a dose-dependent manner [48,49] up until a certain point where a plateau is achieved and burst suppression (see Section 2.3) emerges, followed by an isoelectric EEG [6,40]. In addition, the NREM homeostatic sleep pressure is reduced with anaesthetic-induced unconsciousness in a similar way to that found in physiological sleep [33,50]. In sleep, these oscillations travel throughout the cortex [51–53] and are associated with clearing metabolic by-products from the brain [54,55].
Neurobiological Parallels, Overlaps, and Divergences of Sleep and Anesthesia
2019, Handbook of Behavioral NeuroscienceCitation Excerpt :If this is, indeed, the case, understanding the differences in the pharmacological and physiological actions of different anesthetics may offer insight into both endogenous sleep homeostatic processes and the functional relevance of NREM and REM states. It has long been held that anesthesia is not a suitable surrogate for the cyclic alternations of state that are observed in natural sleep, due to the unitary, NREM-like brain activity observed under most anesthetics (Adapa, 2017; Lydic & Baghdoyan, 2005; Tung & Mendelson, 2004). However, spontaneous and cyclic alternations between an activated state of cortical desynchronization and hippocampal theta (~ 4 Hz) and a deactivated state of synchronous large-amplitude, slow oscillations in the cortex and hippocampus have been observed under urethane anesthesia in both rats and mice (Clement et al., 2008; Pagliardini, Gosgnach, & Dickson, 2013).