General anesthesia ‘puts brain into a state of reversible coma, not sleep’

LONDON - Three neuroscientists have claimed that the brain under general anesthesia isn’t “asleep” as surgery patients are often told - it is placed into a state that is a reversible coma.

This insight and others reported in their review article could eventually lead to new approaches to general anesthesia and improved diagnosis and treatment for sleep abnormalities and emergence from coma.

The study was led by Dr. Nicholas D. Schiff, a professor of neurology and neuroscience at Weill Cornell Medical College and a neurologist at NewYork-Presbyterian Hospital/Weill Cornell Medical Center. Co-authors of the study are Dr. Emery Brown of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard Medical School, and Dr. Ralph Lydic from the University of Michigan.

The researchers explain that a fully anesthetized brain is much closer to the deeply unconscious low-brain activity seen in coma patients, than to a person asleep. Essentially, general anesthesia is a coma that is drug-induced, and, as a consequence, reversible. The states operate on different time scales — general anesthesia in minutes to hours, and recovery from coma in hours to months to years, if ever. The study of emergence from general anesthesia and recovery from coma could help to better understand how both processes occur.

One critically important circuit the authors describe involves specific brain areas. One major player is the cortex, which is made up of layers of neural tissue at the outer edge of the brain, and another is the thalamus, a ball of neural tissue at the center of the brain. These areas are connected to each other through nerve cell axons, which act like information highways, passing signals. The cortex and the thalamus “talk” to each other in different ways over a 24-hour cycle.

Also part of the circuit is the basal ganglia, within the front of the brain, which is used to control certain actions. It does this in part by setting up two feedback loops. One is a negative feedback release on behavior, and that part of the circuit is always active when overall brain activity is reduced, Dr. Schiff says. For example, it works to stop a sleeping person from physically acting out their dreams.

The second feedback loop, however, releases the brake imposed by the first feedback loop, the researchers say. Certain drugs, such as the sleep aid zolpidem (Ambien), and propofol, a powerful general anesthetic with similar pharmacologic properties, can trigger that loop to function, producing what is known as “paradoxical excitation.”

This phenomenon described in transitions observed in the early stages of general anesthesia appears to be common across all three states, because the drugs are triggering this same feedback loop, the authors explained..

Eventually the brake is switched back on in these three states — giving way to sedation and deeper sleep, or in the case of the severely brain patient, the return to a state of diminished responsiveness.

There is another phenomenon that results from this circuit, the authors said.

“Emergence delirium is the flip side,” said Brown.

“For example, when bringing a person out of general anesthesia, the brain is woken up enough to be active, but it is not coherent or organized, which can explain the slower recovery time we see in some patients.”

It is these two areas — losing consciousness and returning to consciousness — that the researchers believe they might be able to target to provide better therapies for sleep, emergence from coma, and general anesthesia with fewer side effects.

The neuroscientists have published an extensive review of general anesthesia, sleep and coma in the New England Journal of Medicine. (ANI)