Person:

Lee, Johanna

BACKGROUND Few studies have systematically described relationships between clinical–behavioural signs, electroencephalographic (EEG) patterns and age during emergence from anaesthesia in young children. OBJECTIVE To identify the relationships between end-tidal sevoflurane (ETsevoflurane) concentration, age and frontal EEG spectral properties in predicting recovery of clinical–behavioural signs during emergence from sevoflurane in children 0 to 3 years of age, with and without exposure to nitrous oxide. The hypothesis was that clinical signs occur sequentially during emergence, and that for infants aged more than 3 months, changes in alpha EEG power are correlated with clinical–behavioural signs. DESIGN An observational study. SETTING A tertiary paediatric teaching hospital from December 2012 to August 2016. PATIENTS Ninety-five children aged 0 to 3 years who required surgery below the neck. OUTCOME MEASURES Time–course of, and ETsevoflurane concentrations at first gross body movement, first cough, first grimace, dysconjugate eye gaze, frontal (F7/F8) alpha EEG power (8 to 12 Hz), frontal beta EEG power (13 to 30 Hz), surgery-end. RESULTS Clinical signs of emergence followed an orderly sequence of events across all ages. Clinical signs occurred over a narrow ETsevoflurane, independent of age [movement: 0.4% (95% confidence interval (CI), 0.3 to 0.4), cough 0.3% (95% CI, 0.3 to 0.4), grimace 0.2% (95% CI, 0 to 0.3); P > 0.5 for age vs. ETsevoflurane]. Dysconjugate eye gaze was observed between ETsevoflurane 1 to 0%. In children more than 3 months old, frontal alpha EEG oscillations were present at ETsevoflurane 2.0% and disappeared at 0.5%. Movement occurred within 5 min of alpha oscillation disappearance in 99% of patients. Nitrous oxide had no effect on the time course or ETsevoflurane at which children showed body movement, grimace or cough. CONCLUSION Several clinical signs occur sequentially during emergence, and are independent of exposure to nitrous oxide. Eye position is poorly correlated with other clinical signs or ETsevoflurane. EEG spectral characteristics may aid prediction of clinical–behavioural signs in children more than 3 months.

General anesthetics induce structured brain oscillations that reflect activity in specific neural circuits and are readily visible in the electroencephalogram (EEG). In adults, frontal EEG patterns observed during propofol-induced unconsciousness consist of slow-delta oscillations (0.1-4 Hz) and frontally coherent alpha oscillations (8-13 Hz). Alpha oscillations are thought to reflect GABAergic mediation of thalamocortical dynamics, as evidenced by computational models, animal studies, and human studies. Given that the nervous system undergoes significant changes throughout childhood, it is not surprising that anesthesia-induced EEG oscillations in children have been found to differ significantly from those in adults. However, there has been limited work investigating the effects of general anesthesia on brain activity in children. The purpose of this thesis was to characterize the early changes in anesthesia-induced EEG oscillations in children and explore how these changes may reflect underlying neurodevelopmental changes. Specifically, this thesis describes work characterizing age-related changes in the EEG oscillations observed during (1) intravenous propofol general anesthesia and (2) volatile sevoflurane general anesthesia, two commonly used anesthetics in the pediatric population. In Part 1, a prospective observational study was performed to investigate age-related changes in the propofol-induced EEG in children 0-21 years of age (n=97) using multitaper spectral and coherence methods. For patients 0-21 years old receiving propofol general anesthesia, total EEG power (0.1-40 Hz) peaked at about 8 years old and subsequently declined with increasing age. For patients greater than 1 year old, the propofol-induced EEG structure was qualitatively similar regardless of age, featuring slow-delta and frontally coherent alpha oscillations. For patients under 1 year of age, however, frontal alpha oscillations were not coherent. Given the distinct changes in the anesthesia-induced EEG observed within the first year, Part 2 of this thesis aimed to better characterize the EEG in very young children. In Part 2, a prospective observational study was performed to characterize the age-related changes in the sevoflurane-induced EEG in children 0-3 years of age (n=91) using multitaper spectral and coherence methods. For patients 0-3 years old receiving sevoflurane general anesthesia, slow-delta oscillations were present throughout all ages. Alpha oscillations emerged around 4 months old, anteriorized around 7 months old, and became frontally coherent around 10 months old. These age-related changes in the general anesthesia-induced EEG likely reflect the development of the underlying neural circuits engaged by propofol and sevoflurane, possibly in inhibitory circuits and the thalamocortical connections implicated in propofol- and sevoflurane-induced unconsciousness. These anesthetic-specific and age-related signatures in the EEG may also provide a unique opportunity to noninvasively study the development of neural circuits in humans. Furthermore, by understanding how the effects of general anesthesia change during development, we may be able to use EEG monitoring to develop more effective ways of tracking and establishing appropriate brain states in pediatric patients, and in doing so, enhance anesthetic safety.