Even to seasoned anesthesiologist Dr. Emery N. Brown, the transition was remarkable.
The patient followed Brown’s finger with his eyes as it traced a pattern in the air. He responded to instructions. A few seconds later, he was out like a light, limp as a rag doll. His brain waves went from active spikes to barely perceptible blips. “While the changes from moment to moment are subtle, the result of general anesthesia is an extremely profound effect on the whole brain,” Brown said. “I’m really beginning to appreciate how profound it is.”
Even though general anesthesia has been used for 162 years, no one knows exactly how it works. Brown, professor of Computational Neuroscience and Health Sciences and Technology in the Department of Brain and Cognitive Sciences (BCS) and the Harvard-MIT Division of Health Sciences and Technology (HST), wants to find out so he can change general anesthesia from a blunt, one-size-fits-all instrument into a focused, personalized tool.
More than 100,000 people receive general anesthesia daily in the U.S. for surgery. Most receive a cocktail of six to eight drugs and inhalants — including derivatives of the same ethers used on wounded Civil War soldiers — to ensure that they will be unconscious, pain-free, physiologically stable, and immobile in the operating room. And they won’t recall what happened while they were under.
While highly effective, general anesthesia isn’t without risk. “Blood, lungs, brain, it goes everywhere,” said Brown, who is a professor of anesthesia at Harvard Medical School and Massachusetts General Hospital (MGH), a research partner of HST. “It dilates blood vessels and depresses the heart. A well-trained athlete can tolerate stress like that, but it’s not the same thing for a 78-year-old woman having a hip repaired.”
In addition, patients of all ages report varying degrees of “postoperative cognitive dysfunction” — wooziness, trouble concentrating, sometimes nausea and weakness — three days or longer after surgery. Brown would like to have such precise control that he could flip a figurative switch in a patient’s brain before surgery, achieve all the good effects while avoiding the bad ones, and flip it off afterward.
To that end, Brown, who is among 12 scientists nationwide to receive prestigious Pioneer Awards of $2.5 million from the National Institutes of Health last year, is conducting a series of groundbreaking experiments.
He uses functional magnetic resonance imaging (fMRI) and electroencephalograms (EEGs) to see brain blood flow and electrical activity in patients in the process of going under. While fMRI feedback changes slowly over time, EEGs are instantaneous. “If you do both at the same time, you get the best of both worlds,” he said.
In addition, Brown is looking at EEGs of patients who had undergone carotid artery surgery at Mass General. Because of the nature of the surgery, these patients’ brain activity was closely monitored, providing hundreds of hours of data for Brown to mine.
BEFORE AND AFTER
One of Brown’s biggest challenges in monitoring subjects both before and after anesthesia takes effect was overcome with the help of a generous group of patients who had had their voice boxes removed. It’s uncomfortable to have a breathing tube inserted while still conscious, but it doesn’t bother an individual without a larynx. Brown said he is grateful to these volunteers for the boost they have given his clinical research.
As part of the ambitious scope of the work, which includes interdisciplinary collaborations with investigators at BCS, HST, MGH and Boston University, Brown uses neurophysiological recordings of how the nervous system functions, as well as microdialysis, a cutting-edge technique that monitors the chemistry of extracellular space in living tissue, and mathematical modeling. The long-term goal is to establish a neurophysiological definition of anesthesia and to develop better neurophysiologically based methods for measuring the depth of general anesthesia in the human body.
His results so far are promising. “The one thing that is really interesting is that general anesthesia is not about the brain shutting down,” he said. “It’s about altering brain activity to achieve the desired behavioral and physiological state.”
Brown hopes to determine “which places in the brain we could shut down to provide these effects. Slow down traffic, so to speak, with a drug designed to block off some routes in a targeted way.” If the science and engineering work, the result could be a new, safer, and more effective way to achieve the effects of general anesthesia.