Characterizing brain dynamics during ketamine-induced dissociation and subsequent interactions with propofol using human intracranial neurophysiology.

Ketamine produces antidepressant effects in patients with treatment-resistant depression, but its usefulness is limited by its psychotropic side effects. Ketamine is thought to act via NMDA receptors and HCN1 channels to produce brain oscillations that are related to these effects. Using human intracranial recordings, we found that ketamine produces gamma oscillations in prefrontal cortex and hippocampus, structures previously implicated in ketamine's antidepressant effects, and a 3 Hz oscillation in posteromedial cortex, previously proposed as a mechanism for its dissociative effects. We analyzed oscillatory changes after subsequent propofol administration, whose GABAergic activity antagonizes ketamine's NMDA-mediated disinhibition, alongside a shared HCN1 inhibitory effect, to identify dynamics attributable to NMDA-mediated disinhibition versus HCN1 inhibition. Our results suggest that ketamine engages different neural circuits in distinct frequency-dependent patterns of activity to produce its antidepressant and dissociative sensory effects. These insights may help guide the development of brain dynamic biomarkers and novel therapeutics for depression.

A Narrative Review Illustrating the Clinical Utility of Electroencephalogram-Guided Anesthesia Care in Children.

The major therapeutic end points of general anesthesia include hypnosis, amnesia, and immobility. There is a complex relationship between general anesthesia, responsiveness, hemodynamic stability, and reaction to noxious stimuli. This complexity is compounded in pediatric anesthesia, where clinicians manage children from a wide range of ages, developmental stages, and body sizes, with their concomitant differences in physiology and pharmacology. This renders anesthetic requirements difficult to predict based solely on a child's age, body weight, and vital signs. Electroencephalogram (EEG) monitoring provides a window into children's brain states and may be useful in guiding clinical anesthesia management. However, many clinicians are unfamiliar with EEG monitoring in children. Young children's EEGs differ substantially from those of older children and adults, and there is a lack of evidence-based guidance on how and when to use the EEG for anesthesia care in children. This narrative review begins by summarizing what is known about EEG monitoring in pediatric anesthesia care. A key knowledge gap in the literature relates to a lack of practical information illustrating the utility of the EEG in clinical management. To address this gap, this narrative review illustrates how the EEG spectrogram can be used to visualize, in real time, brain responses to anesthetic drugs in relation to hemodynamic stability, surgical stimulation, and other interventions such as cardiopulmonary bypass. This review discusses anesthetic management principles in a variety of clinical scenarios, including infants, children with altered conscious levels, children with atypical neurodevelopment, children with hemodynamic instability, children undergoing total intravenous anesthesia, and those undergoing cardiopulmonary bypass. Each scenario is accompanied by practical illustrations of how the EEG can be visualized to help titrate anesthetic dosage to avoid undersedation or oversedation when patients experience hypotension or other physiological challenges, when surgical stimulation increases, and when a child's anesthetic requirements are otherwise less predictable. Overall, this review illustrates how well-established clinical management principles in children can be significantly complemented by the addition of EEG monitoring, thus enabling personalized anesthesia care to enhance patient safety and experience.

An electroencephalogram biomarker of fentanyl drug effects.

Opioid drugs influence multiple brain circuits in parallel to produce analgesia as well as side effects, including respiratory depression. At present, we do not have real-time clinical biomarkers of these brain effects. Here, we describe the results of an experiment to characterize the electroencephalographic signatures of fentanyl in humans. We find that increasing concentrations of fentanyl induce a frontal theta band (4 to 8 Hz) signature distinct from slow-delta oscillations related to sleep and sedation. We also report that respiratory depression, quantified by decline in an index of instantaneous minute ventilation, occurs at ≈1700-fold lower concentrations than those that produce sedation as measured by reaction time. The electroencephalogram biomarker we describe could facilitate real-time monitoring of opioid drug effects and enable more precise and personalized opioid administration.

Sevoflurane requirements during electroencephalogram (EEG)-guided vs standard anesthesia Care in Children: A randomized controlled trial.

STUDY OBJECTIVES: Intra-operative electroencephalographic (EEG) monitoring utilizing the spectrogram allows visualization of children's brain response during anesthesia and may complement routine cardiorespiratory monitoring to facilitate titration of anesthetic doses. We aimed to determine if EEG-guided anesthesia will result in lower sevoflurane requirements, lower incidence of burst suppression and improved emergence characteristics in children undergoing routine general anesthesia, compared to standard care. DESIGN: Randomized controlled trial. SETTING: Tertiary pediatric hospital. PATIENTS: 200 children aged 1 to 6 years, ASA 1 or 2, undergoing routine sevoflurane anesthesia for minor surgery lasting 30 to 240 min. INTERVENTIONS: Children were randomized to either EEG-guided anesthesia (EEG-G) or standard care (SC). EEG-G group had sevoflurane titrated to maintain continuous slow/delta oscillations on the raw EEG and spectrogram, aiming to avoid burst suppression and, as far as possible, maintain a patient state index (PSI) between 25 and50. SC group received standard anesthesia care and the anesthesia teams were blinded to EEG waveforms. MEASUREMENTS: The primary outcomes were the average end-tidal sevoflurane concentration during induction and maintenance of anesthesia. Secondary outcomes include incidence and duration of intra-operative burst suppression and Pediatric Anesthesia Emergence Delirium (PAED) scores. RESULTS: The EEG-G group received lower end-tidal sevoflurane concentrations during induction [4.80% vs 5.67%, -0.88% (-1.45, -0.31) p = 0.003] and maintenance of anesthesia [2.23% vs 2.38%, -0.15% (-0.25, -0.05) p = 0.005], and had a lower incidence of burst suppression [3.1% vs 10.9%, p = 0.044] compared to the SC group. PAED scores were similar between groups. Children <2 years old required higher average end-tidal sevoflurane concentrations, regardless of group. CONCLUSIONS: EEG-guided anesthesia care reduces sevoflurane requirements in children undergoing general anesthesia, possibly lowering the incidence of burst suppression, without altering emergence characteristics. EEG monitoring allows direct visualization of brain responses in real time and allows clearer appreciation of varying sevoflurane requirements in children of different ages.