Characterizing EEG Brain States During General Anesthesia in Children: Insights for Improved Brain Monitoring

Abstract

Current brain monitors in clinical anesthesia use electroencephalography (EEG) based single indices (patient state indices, PSIs) as a biomarker for level of unconsciousness. These values range from zero (isoelectric) to one-hundred (fully awake and alert). However several variables contribute to the non-precise application of these PSIs to operative patient care. One important variable that obscures the interpretation of the PSIs for depth of anesthesia monitors (DoAMs) is patient age. DoAMs are used less frequently in children because operatively safe clinical PSIs do not reliably correlate with the patient’s clinical exam. Nonetheless, reliable monitoring of brain activity remains an important issue for managing anesthetic care given increasing concerns about adverse neuro-cognitive effects following general anesthesia (GA) in vulnerable populations, including pediatric patients. However, a detailed analysis of EEG signals has not yet been performed in children under GA, and reliable standards of care for brain monitoring during GA have yet to be established. In an effort to establish a robust biomarker for loss of consciousness (LOC) under GA regardless of patient age, I investigated how sevoflurane, the most commonly used pediatric GA, affects brain function in childhood and young adulthood. Brain activity from patients aged 0 to 28 years (n = 54) was recorded using a 4-lead electroencephalogram (EEG) during routine care of patients receiving GA in this cross-sectional study. The EEG was characterized as a function of age and within 5 age groups: <1 yr old (n=4), 1–6 yr old (n=12), >6–14 yr old (n=14), >14–21 yr old (n=11), >21–28 yr old (n=13) which were determined based on developmental milestones and grouping after inspection of the data. The EEG power spectrum analysis using the multitaper method and coherence analysis were performed over a 10-minute period of stable anesthetic maintenance for each patient subgroup in 6 canonical EEG frequency bands. Results showed that when compared with the adolescent (>14–21 yr) and young adult (YA) populations (>21–28 yr), EEG power in the pediatric population (>1 yr) was much larger, between 0.1–50 Hz, with a peak in total power around 5–6 years old. However for patients >1 yr, alpha band coherence structure was similar, and a distinct spectral signature consisting of a dominant alpha and slow oscillation emerged for patients of all ages, which is similar to the spectral signature seen in adult patients under sevoflurane GA. The only population this spectral signature did not apply to was infants (<1 yr), who did not exhibit prominent power or coherence in the alpha band, since neural circuitry necessary for this dynamic develops at about 1 yr of age. The differences in EEG power and distribution of power across the canonical frequency bands at various ages helps explain why current DoAMs are inaccurate in kids. An ideal DoAM would be indicated for use in all age ranges. Since children >1yr and YAs have a reproducible, qualitatively similar EEG spectral signature under sevoflurane GA at operative levels, this may be used as a more reliable and robust biomarker for LOC. Furthermore, these similarities in the EEG spectra likely imply that similar underlying neurophysiological principles apply to the developing and developed brain to induce LOC. These EEG spectral anesthetic signature (SAS) patterns for various anesthetics have been associated with the onset of LOC in adults in behavioral studies in the Brown and Purdon labs, and may serve as an appropriate proxy for LOC in children as well. Based on these findings, a closed-loop brain activity monitor is being developed with the aim of dosing general anesthetics only until SAS patterns associated with the particular anesthetic drug in use is identified real-time. GA maintenance and emergence could similarly be moderated by the closed-loop system assuming the relationship between the anesthetics used, and the SAS is known. This could potentially greatly decrease drug use and the neurotoxic effects of GA overdosing in the future.