Introduction:
In response to pain, general anesthetics cause a reversible condition that includes specific behavioral and physiological traits such as unconsciousness, amnesia, analgesia, and immobility with corresponding autonomic, cardiovascular, respiratory, and thermoregulatory system stability. According to Meyer and Overton, anesthetics disrupt the lipid bilayer of neuronal cell membranes. The electroencephalogram (EEG) shows distinct patterns during general anesthesia, the most common of which is a progressive increase in low-frequency, high-amplitude activity as the level of general anesthesia increases.
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Humans spend roughly one-third of their lives sleeping. Sleep, a state of reduced alertness actively generated by nuclei in the hypothalamus, brain stem, and forebrain, is critical for health maintenance.
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At approximately 90-minute intervals, normal human sleep cycles between two states: rapid-eye-movement (REM) sleep and non-REM sleep.
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Rapid eye movements, dreaming, irregular respiration, and heart rate, penile and clitoral erection, and airway and low-level skeletal muscle tone are all symptoms of REM sleep in which the cerebral cortex is active and is more similar to an awake state. During REM sleep, the EEG shows active high-frequency, low-amplitude rhythms.
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Non-REM sleep has three distinct EEG stages (N1-N3) from lighter to deep sleep, characterized by higher amplitude, lower-frequency rhythms, waxing and waning muscle tone, decreased body temperature, and decreased heart rate.
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There has been growing attention in the last few years to understanding how anesthetic drugs interact with neural pathways of sleep to produce unconsciousness.
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Sleep is a useful metaphor for anesthesiologists to utilize when explaining general anesthesia to patients because the two share the behavioral trait of reversible unconsciousness.
What Is the Correlation between Anesthesia and Sleep States?
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Although the reversible loss of consciousness is common for both, the depth of unconsciousness varies greatly.
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Responding to loud verbal or strong tactile stimulation, as well as the ability to maintain or restore a patent airway with sufficient spontaneous ventilation, remain intact during natural sleep.
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Natural sleep is comparable to current sedation in terms of lack of responsiveness and respiratory patency, according to the American Society of Anesthesiologists. Whereas in the case of general anesthesia, behavioral unresponsiveness, even to painful stimuli.
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Homeostatic mechanisms (the pressure to sleep that increases with prolonged wakefulness) and circadian rhythms are the two main mechanisms that influence the timing and duration of sleep.
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Molecular studies have shown that Sevoflurane, Dexmedetomidine, and Propofol could inhibit the expression of key circadian clock genes. However, these effects were more pronounced when anesthetics were given during the active phase (dark phase for rodents) rather than the inactive phase (light phase for rodents).
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Overall, sleep debt is not typically considered when clinicians administer anesthetics for surgery; ongoing research can improve postoperative care by investigating postoperative sleep disturbances.
The Table Shows the Comparison of Natural Sleep and General Anesthesia.
What Are the Electroencephalogram Findings in General Anesthesia and Sleep?
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The frontal electroencephalogram (EEG) demonstrates certain similarities and significant state and drug-specific variations during regular rest and anesthetic intervention.
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Once rest begins, frontal slow (1 Hertz) and delta (1-4 Hz) oscillations increase, with frontal areas synchronizing earlier than other cortical areas.
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Human NREM sleep is divided into three stages, further differentiated by EEG features like sleep spindles in the range of 12 to 16 Hz high and k-complexes.
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The most noticeable EEG aspect shared by natural sleep and general anesthesia is the presence of significant high amplitude and slow delta oscillations.
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Slow-delta oscillations can be induced by anesthetics such as Dexmedetomidine, Propofol, and ether. They are partly caused by a loss of excitatory inputs from the brainstem arousal nuclei to the cortex.
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Dexmedetomidine, a selective alpha2-adrenergic receptor agonist, generates EEG results similar to NREM sleep.
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Spindles, common in NREM stage 2, can also be seen in the frontal EEG during Dexmedetomidine sedation, with a peak power of around 13 Hz. Higher doses of anesthesia cause deeper drowsiness, spindles subside, and delta oscillations that slowly dominate the EEG, identical to NREM stage 3 sleep.
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Volatile anesthetics (Halothane and Isoflurane) produce a strong EEG theta rhythm (5 to 9 Hz) identical to REM sleep. GABAergic (gamma-aminobutyric acid) agents such as Barbiturates, Alphaxalone, and Propofol cause EEG slow waves (4 Hz) and spindles (single, 1 s oscillatory events in the 11-16 Hz range), indicating thalamocortical circuitry recruitment.
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Propofol produces larger amplitude slow oscillations than Dexmedetomidine, indicating more extended periods of neuronal silence and enhanced disconnection from the environment.
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When Propofol is given, there is an anteriorization of alpha power from the occipital cortex to the frontal cortex, which is reversed when the patient regains consciousness. Propofol causes continuous alpha oscillations (8-12 Hz) and improves functional connectivity between the anterior and posterior cingulate cortices.
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Propofol produces burst suppression at very high doses, a pattern of intermittent bursts of activity accompanied by electrical silence, which is not observed during natural sleep.
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Receptors like gamma-aminobutyric acid type -A and glutamate, and K(2P) channels are modulated by ether anesthetics such as Isoflurane and Sevoflurane to produce neuronal inhibition. Sevoflurane increases slow-delta and alpha oscillations.
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The latter are concentrated in the frontal cortex and have a peak frequency of around 10 Hz during sleep. Sevoflurane at higher doses causes increased theta (4-8 Hz) oscillations, which are not seen with Propofol anesthesia. Ether anesthetics, like Propofol, produce burst suppression at very high doses.
Conclusion:
General anesthetics are a wide and varied group of drugs that seem to cause unconsciousness by targeting a wide range of neural circuits in the cortical and subcortical regions. Each anesthetic tends to produce unique cortical EEG signatures that vary with doses, implying that multiple levels of neural circuits significantly contribute to unconsciousness. A new genetic technique for tracking, targeting, and stimulating specific neural populations has recently enabled the targeting of specific behavior-associated brain loci, including "anesthesia-activated neurons" (AANs) in the hypothalamic supraoptic nucleus. A wide range of anesthetic agents activated these AAN neurons, and these emerging techniques could advance our understanding of neural circuitry and the underlying complex processes. Understanding the neural circuitry underlying general anesthesia and sleep will lead to better techniques for controlling arousal states in the operating room.
