Boston University Professor of Mathematics and Statistics Nancy Kopell co-authored a recent study that looked into ways to determine whether patients under general anesthesia (GA) are in fact conscious. The study, published this week in the PNAS Early Edition (www.pnas.org/cgi/doi/10.1073/pnas.1221180110) has important implications for avoiding the phenomenon of “anesthesia awareness,” in which patients remain conscious while under anesthesia.
According to the researchers, unconsciousness is a fundamental component of general anesthesia (GA), but anesthesiologists have no reliable ways to be certain that a patient is unconscious. In an effort to determine whether patients under GA were conscious, the researchers developed electroencephalography (EEG) signatures that track loss and recovery of consciousness under GA.
In the studies, conducted at Massachusetts General Hospital (MGH) by lead author Patrick L. Purdon from MGH and senior author Emery N. Brown from MGH and MIT, the researchers recorded high-density EEGs in humans during gradual induction of and emergence from unconsciousness with propofol, a commonly used anesthetic drug. To identify loss and recovery of consciousness, the researchers had their subjects execute auditory tasks (both verbal and click stimuli) at four-second intervals.
During induction, subjects were found to lose responsiveness to the less salient clicks before losing responsiveness to the more salient verbal stimuli; during emergence they recovered responsiveness to the verbal stimuli before recovering responsiveness to the clicks.
The median frequency and bandwidth of the frontal EEG power tracked the probability of response to the verbal stimuli during the transitions in consciousness. Loss of consciousness was marked simultaneously by an increase in low-frequency EEG power (<1 Hz), the loss of spatially coherent occipital alpha oscillations (8–12 Hz), and the appearance of spatially coherent frontal alpha oscillations.
These dynamics reversed with recovery of consciousness. The low-frequency phase modulated alpha amplitude in two distinct patterns. During profound unconsciousness, alpha amplitudes were maximal at low-frequency peaks, whereas during the transition into and out of unconsciousness, alpha amplitudes were maximal at low-frequency nadirs. This latter phase–amplitude relationship predicted recovery of consciousness.
“These results provide insights into the mechanisms of propofol-induced unconsciousness, establish EEG signatures of this brain state that track transitions in consciousness precisely, and suggest strategies for monitoring the brain activity of patients receiving GA,” says Kopell.
Significance
Anesthesiologists reversibly manipulate the brain function of nearly 60,000 patients each day, but brain-state monitoring is not an accepted practice in anesthesia care because markers that reliably track changes in level of consciousness under general anesthesia have yet to be identified. The co-authors of this study found specific behavioral and electrophysiological changes that mark the transition between consciousness and unconsciousness induced by propofol.
These results establish EEG signatures of brain states under general anesthesia that are readily visible in the EEG. These signatures can be used to monitor brain activity of patients receiving general anesthesia, offering more principled strategies to dose anesthetic drugs and a way to reduce the incidence of unintended awareness under general anesthesia.