New research is shedding light on the effects of general anesthesia on the brain and the body.

In the United States, nearly 60,000 patients receive general anesthesia for surgery every day. It causes specific patterns of activity in the brain, which can be viewed on an electroencephalogram (EEG). The most common pattern is a gradual rise in low-frequency, high-amplitude activity as the level of anesthesia deepens.

Emery Brown, MD, of Massachusetts General Hospital believes, “How anesthetic drugs induce and maintain the behavioral states of general anesthesia is an important question in medicine and neuroscience.”

His team investigated general anesthesia versus sleep and coma. They carried out a review of anesthesia studies from a range of areas, including neuroscience and sleep medicine.

“It may sound nitpicky, but we need to speak precisely about what this state is,” Brown says. “This paper is an attempt to start at square one and get clear definitions in place.”

He explained, “We started by stating the specific physiological states that comprise general anesthesia, specifically unconsciousness, amnesia, lack of pain perception and lack of movement, and then we looked at how they are comparable to and different from sleep and coma.”

The team compared the physical signs and EEG patterns of these states. They found significant differences, with only the deepest stages of sleep being similar to the lightest stages of anesthesia. General anesthesia essentially is a “reversible coma.”

“While natural sleep normally cycles through predictable phases, general anesthesia involves the patient being taken to and maintained at the phase most appropriate to the procedure,” they report in the New England Journal of Medicine.

“The phases of general anesthesia at which surgery is performed are most similar to states of coma.”

Brown says, “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 recover quickly and safely.”

“This information is essential to our ability to further understanding of general anesthesia.”

“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,” adds co-author Nicholas Schiff, MD.

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

In their research the team were surprised to find that some drugs, including ketamine, actually activate rather than suppress brain activity. This is why ketamine can trigger hallucinations at low doses. But at higher doses the excess brain activity leads to unconsciousness by creating disorganized patterns and “blocking any coherent signal,” similar to the experience of seizure-induced unconsciousness.

Low doses of ketamine may even be of help for people with depression, according to Brown. It acts quickly and could help “bridge the gap” between different types of antidepressant. He believes that the drug’s effects are comparable to electroconvulsive therapy.

Another surprising finding is that the sleep-inducing drug zolpidem (Ambien) may help minimally conscious brain-injured patients to recover some functions. This paradox is due to a common phenomenon in which patients in the first stage of anesthesia may move around or vocalize, due to stimulation of the thalamus.

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

“Anesthesia hasn’t been attacked as seriously as other questions in neuroscience,” he adds. “Why shouldn’t we be doing the same thing for questions of general anesthesia?”

Andreas Loepke, MD, at the University of Cincinnati College of Medicine, agrees. “Anesthetics are very powerful medications with a very narrow safety margin, as evidenced by the unfortunate events surrounding Michael Jackson’s death,” he says.

“These medications carry potent side effects, such as respiratory depression, loss of protective airway reflexes, blood-pressure instability, as well as nausea and vomiting.”

He concludes that a better understanding of how general anesthesia works at the cellular and molecular level could aid the development of anesthestic drugs that lack those side effects.