Neurophysiologic Correlates of Ketamine Sedation and Anesthesia: A High-density Electroencephalography Study in Healthy Volunteers

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SCIENCE
Neurophysiologic Correlates of Ketamine Sedation and Anesthesia: A High-density Electroencephalography Study in Healthy Volunteers
Key Take-Away: 

Ketamine is a unique intravenous (IV) anesthetic which provides a wide range of pharmacological effects like sedation, catalepsy, somatic analgesia, bronchodilation, and sympathetic nervous system stimulation. The relationship of ketamine with cortical oscillations and functional connectivity has been explained efficiently in this study.

Previous studies have demonstrated inconsistent neurophysiologic effects of ketamine, although discrepant findings might relate to differences in doses studied, brain regions analyzed, coadministration of other anesthetic medications, and resolution of the electroencephalograph. 

ABSTRACT: 
Background: 

Previous studies have demonstrated inconsistent neurophysiologic effects of ketamine, although discrepant findings might relate to differences in doses studied, brain regions analyzed, coadministration of other anesthetic medications, and resolution of the electroencephalograph.

The objective of this study was to characterize the dose-dependent effects of ketamine on cortical oscillations and functional connectivity.

Methods: 

Ten healthy human volunteers were recruited for study participation.

The data were recorded using a 128-channel electroencephalograph during baseline consciousness, subanesthetic dosing (0.5 mg/kg over 40 min), anesthetic dosing (1.5 mg/kg bolus), and recovery. No other sedative or anesthetic medications were administered. Spectrograms, topomaps, and functional connectivity (weighted and directed phase lag index) were computed and analyzed.

Results: 

Frontal theta bandwidth power increased most dramatically during ketamine anesthesia (mean power ± SD, 4.25 ± 1.90 dB) compared to the baseline (0.64 ± 0.28 dB), subanesthetic (0.60 ± 0.30 dB), and recovery (0.68 ± 0.41 dB) states; P < 0.001. Gamma power also increased during ketamine anesthesia.

Weighted phase lag index demonstrated theta phase locking within anterior regions (0.2349 ± 0.1170, P < 0.001) and between anterior and posterior regions (0.2159 ± 0.1538, P < 0.01) during ketamine anesthesia. Alpha power gradually decreased with subanesthetic ketamine, and anterior-to-posterior directed connectivity was maximally reduced (0.0282 ± 0.0772) during ketamine anesthesia compared to all other states (P < 0.05).

Conclusion: 

Ketamine anesthesia correlates most clearly with distinct changes in the theta bandwidth, including increased power and functional connectivity.

Anterior-to-posterior connectivity in the alpha bandwidth becomes maximally depressed with anesthetic ketamine administration, suggesting a dose-dependent effect.

Anesthesiology
Exploratory, Ketamine, Anesthesia, 128-Channel Electroencephalograph, Weighted Phase Lag Index
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