Going Under

Since 1846, when a Boston dentist named William Morton gave the first public demonstration of general anesthesia using ether, scientists and doctors have tried to figure out what happens in the brain of an anesthetized patient.

Emery Brown, an MIT neuroscientist and an anesthesiologist at Massachusetts General Hospital, wants to approach the question more rigorously than anyone has done before. Writing in the New England Journal of Medicine, he and two colleagues recently laid out a new neuro­scientific framework for studying general anesthesia by relating it to what is already known about sleep and coma.

Such an approach could help researchers discover new ways to induce anesthesia and improve our understanding of brain problems such as drug addiction, epilepsy, and Parkinson’s disease, says Brown, who is a professor in the Department of Brain and Cognitive Sciences and the Harvard-MIT Division of Health Sciences and Technology. “Anesthesia hasn’t been attacked as seriously as other questions in neuroscience, such as how the visual system works,” he says.

In the United States, 60,000 people undergo general anesthesia every day. Though doctors sometimes tell their patients they will be “going to sleep,” that is not accurate, says Brown. “This may sound nitpicky, but we need to speak precisely about what this state is,” he says.

In the NEJM paper, the researchers define general anesthesia as a “drug-induced, reversible condition that includes specific behavioral and physiological traits”—unconsciousness, amnesia, pain numbing, and inability to move. Body functions such as respiration, circulation, and temperature regulation remain stable.

Using EEG (electroencephalography) readings, which reveal electrical activity in the brain, Brown and his colleagues showed that even the deepest sleep is not as deep as the lightest general anesthesia. The sleeping brain cycles through three stages of non-REM (rapid eye movement) sleep, alternating with REM sleep. Each stage has a distinctive EEG pattern, yet none of those resembles the EEG of a brain under general anesthesia. In fact, general-anesthesia EEG patterns are most similar to those of a comatose brain.

The researchers define coma as a state of “profound unresponsiveness,” and sleep as a state of “decreased arousal.” General anesthesia, Brown says, is essentially a “reversible coma.”

Though general anesthesia is seen as routine, it does hold some risk. Side effects can include blood pressure instability, respiratory depression, and nausea. One in 250,000 healthy recipients suffers complications that prove fatal.

A better understanding of how general anesthesia works at the molecular, cellular, and neural levels could help researchers develop anesthestic drugs that are safer, says Brown.