The Differences Between General Anesthesia, Sleep and Coma

In movies, before starting surgery, doctors' typical line is to ask anesthesiologists to 'put the patient to sleep', but actually, general anesthesia has nothing to do with sleep, being much closer to a state of coma.

Luckily, a new review article appearing in the December 30 issue of New England Journal of Medicine (NEJM), presents anesthesia's similarities with and differences from sleep and coma.

When undergoing a surgical procedure, patients are under general anesthesia, because it is the usual procedure used in hospitals and medical facilities worldwide.

But even if this is such a popular method, not much is known about the actual effects of the anesthetic drugs of the brain and the body.

So this review gathers, for the first time, information from several disciplines, neuroscience and sleep medicine included, to better understand the biological mechanisms that underlie general anesthesia.

The lead author of the paper is Emery Brown, MD, PhD, of the Massachusetts General Hospital (MGH) Department of Anesthesia, Critical Care and Pain Medicine, who is also the Warren M. Zapol Professor of Anesthesia at Harvard Medical School and also professor in the Department of Brain and Cognitive Sciences at Massachusetts Institute of Technology and in the Harvard-MIT Division of Health Sciences and Technology.

Along with his co-authors, Ralph Lydic, PhD, a sleep expert from the University of Michigan, and Nicholas Schiff, MD, an expert in coma from Weill Cornell Medical College, Brown gives the definitions of these three terms (anesthesia, sleep and coma), before comparing the physical signs and electroencephalogram (EEG) patterns of general anesthesia to those of sleep.

Between going to sleep and general anesthesia, there are significant differences, and only the deepest stages of sleep are similar to the lightest phases of anesthesia caused by some types of agents.

Most people know that sleep has several phases, part of normal sleep cycles, but when it comes to anesthesia, the patient is taken and kept in the most appropriate phase for the procedure, which is actually more similar to a state of coma.

Brown explains that “people have hesitated to compare general anesthesia to coma because the term sounds so harsh, but it really has to be that profound or how could you operate on someone?

“The key difference is this is a coma that is controlled by the anesthesiologist and from which patients will quickly and safely recover.”

The authors also describe the case of a brain-injured patient in a minimally conscious state who managed to recover some functions thanks to the sleep-inducing drug zolpidem (Ambien).

Schiff previously analyzed this case, and saw that the patient had a common occurrence called paradoxical excitation, that can be seen in some patients in the first stage of general anesthesia that move around or vocalize.

The scientists said that zolpidem suppresses the activity of a brain structure called the globus pallidus, that normally inhibits the thalamus (a key neural control center), so the activity of the thalamus is actually stimulated.

Their hypothesis is that paradoxical excitation is caused by a similar mechanism.

“Anesthesiologists know how to safely maintain their patients in the states of general anesthesia, but most are not familiar with the neural circuit mechanisms that allow them to carry out their life-sustaining work,” explains Brown.

The authors presented the way that different anesthetic agents act on different brain circuits, and pointed out some information that seemed contradictory, like some drugs (ketamine) that activate rather than suppress neural activity, causing hallucinations at lower doses.

Ketamine blocks receptors for the excitatory transmitter glutamate, but this blockage actually stimulates activity, since ketamine affects certain inhibitory neurons.

So the brain is actually hyperactive and this generates unconsciousness, just like in an overcharged circuit, or in a state of unconsciousness caused by a seizure.

It also seems that recent reports suggest the use of ketamine for treating depression, since very low doses of the drug have managed to quickly reduce symptoms in chronically depressed patients who were not responding to traditional antidepressants.

Today, the drug is being prescribed to patients that start taking a new antidepressant (to avoid suicide risks) and it looks like its effects are comparable to those of electroconvulsive therapy.

Brown says that “the information we are presenting in this article – which includes new diagrams and tables that don't appear in any anesthesiology textbook – is essential to our ability to further understanding of general anesthesia, and this is the first of several major reports that we anticipate publishing in the coming year.”

“We think this is, conceptually, a very fresh look at phenomena we and others have noticed and studied in sleep, coma and use of general anesthesia,” Schiff adds.

“By reframing these phenomena in the context of common circuit mechanisms, we can make each of these states understandable and predictable.”

“A key point of this article is to lay out a conceptual framework for understanding general anesthesia by discussing its relation to sleep and coma, something that has not been done in this way before,” explains Brown.

This report was supported by the National Institutes of Health Director's Pioneer Award to Brown, other NIH grants, the MGH and University of Michigan Departments of Anesthesia and the James S. McDonnell Foundation.

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