Tracking brain activity patterns may lead to better dosing and control of anesthesia.
Putting people to sleep with anesthesia during surgery works most of the time. But in rare cases — about 1 in every 10,000 operations — patients don’t quite drop off completely, and remain just conscious enough to feel pain and be aware of their operation but unable to communicate their agony.
Patients who become aware during surgery usually cannot scream or move because they are paralyzed by drugs and restrained to prevent potentially dangerous movements during delicate procedures. Monitoring heart rate and blood pressure can alert anesthesiologists to pain in the vast majority of cases, but these indirect measures don’t always capture the return of awareness.
But the latest research, published in the Proceedings of the National Academy of Sciences, suggests that keeping more rigorous track of how a patient loses consciousness could alleviate some of these unusual cases. Physicians have known since the 1930s that monitoring electrical signals on the scalp with electrodes (EEG) can offer a window on the workings of the brain. And many operating rooms currently utilize devices that are intended to combine EEG signals and produce a single reading that provides a consciousness level in order to ensure that patients are fully under the influence of anesthesia. Unfortunately, these monitors are not calibrated well enough to different anesthetics and other variables to detect signals of consciousness any better than indirect measures like blood pressure.
So to develop a clearer EEG signal, Brown and his colleagues studied 10 adults who were slowly, over the course of around two hours, given increasing doses of the anesthetic propofol until they lost consciousness. Then, the anesthesia was removed, equally gradually. This slow dosing allowed the scientists to see signals of changes in consciousness and unconsciousness that are much harder to detect when anesthesia is given quickly, as is done in surgery.
“There are highly structured oscillations in EEG scalp [measurements] that correspond to different states of consciousness during the loss and recovery of consciousness induced by the anesthetic drug propofol,” explains Patrick Purdon, lead author of the study and an instructor of anesthesia at Harvard Medical School.
The results provide a visible reading of the gradual drop-off in brain activity as it falls into a state of unconsciousness, and may help anesthesiologists to get a better sense of when a brain is completely under. “This will allow anesthesiologists to administer the drugs better so hopefully there will be less overdose and less adverse effects on cognition afterwards,” says Dr. Emery Brown, a co-author of the study and professor of computational neuroscience at MIT. Recent studies have shown that children and the elderly are at higher risk for delirium and cognitive problems following anesthesia; using lower doses that are still effective could help address this problem.
“This is really great,” says Dr. Nicholas Schiff, professor of neuroscience and neurology at Weill Cornell Medical College, who was not associated with the research. “If I had to guess, if you could more or less make equivalent measures available in every anesthesia suite, you’d eliminate the risk [of operative awareness] entirely.”
The researchers found that the patterns they saw nicely paralleled the results they found in an earlier study, in which they studied the brain activity of people with epilepsy who had electrodes implanted in their brains as they were anesthetized and returned to consciousness.
In that research, the authors found that unconsciousness was marked by a wave pattern with a slower amplitude than what is seen during wakefulness; this change seemed to put different parts of the brain out of sync with each other and prevent them from communicating effectively — keeping the patient deeply unconscious.
In the new study, as the drug took hold, the 10 participants were asked to identify either clicking sounds or words that were played to them, including their own names. At low doses of propofol, they stopped responding to the clicks, but remained able to identify words. This reflects the fact that the brain’s level of arousal isn’t simply related to objective factors like the loudness of a sound; instead, it’s the meaning of what you hear that the brain registers. A meaningless noise like a click isn’t enough to cut through the increasing drowsiness being caused by the drug, but an important word that may require attention can.
“Probably your name is most salient verbal stimuli you hear,” says Brown, “You can recognize it across the room in a noisy cocktail party.” He notes that when performing surgery, he makes sure to ask the patient what they prefer to be called so that the medical team can use the name most likely to arouse the person when needed. “Consciousness is a brain process,” says Schiff, “It’s not an on-off switch, it’s an emergent property of the brain.”
As the participants lost even the ability to respond to their names, the slow oscillation took over their brains. “The previous paper discovered this pattern and [its] constraint on individual neurons and the decoupling of cortical areas,” says Purdon, “This study shows that you can see that happening in EEG.”
It also found several distinct brain activity patterns that doctors could ultimately use to track the transition from consciousness to unconsciousness and back again. When someone was profoundly unconscious, signals known as alpha waves were highest in the frontal parts of the brain, while at the same time the low frequency oscillations were at their peak throughout the entire brain. However, when the patient was about to wake up, that pattern was reversed and the alpha peaks coincided with the slow oscillation troughs.
“There was a phase flip,” says Purdon, “About 15 minutes or so before you recover, you flip. It’s really cool because it gives an indication of when patients can come back, an early warning or prediction of when people can recover consciousness.”
Purdon and Brown have filed for a patent on a device to allow anesthesiologists to easily analyze EEG to measure the depth of anesthesia during operations. Purdon says, “It would give you a very clear neurophysiological target to take your patients to: if want sedation, you can go to that, if want unconsciousness, you go to that and if you want a medical coma, you can do that. It prevents both under-dosing and awareness but also prevents overdose because you don’t have to go beyond the point you need to render someone unconscious.”
More research is needed before any such device can be developed commercially, but the study suggests that it may be possible to keep better track of the mind as it goes from conscious to unconscious and back again.