Electroencephalographic slow wave dynamics and loss of behavioural responsiveness induced by ketamine in human volunteers. (November 2019)

• Record Type: Journal Article
• Authors: Sleigh, Jamie; Pullon, Rebecca M.; Vlisides, Phillip E.; Warnaby, Catherine E.
• Is Part Of: British journal of anaesthesia. Volume 123:Number 5(2019)
• Page Start: 592
• Page End: 600
• Publication Date: 2019-11
• Subjects: consciousness -- electroencephalography -- general anaesthesia -- ketamine -- pharmacodynamics -- pharmacokinetics -- slow wave activity; Anesthesiology -- Periodicals; Anesthesia -- Periodicals; 617.9605
• DOI: 10.1016/j.bja.2019.07.021
• Languages: English
• ISSNs: 0007-0912

Abstract

Abstract: Background: Previous work on the electroencephalographic (EEG) effects of anaesthetic doses of ketamine has identified a characteristic signature of increased high frequency (beta–gamma) and theta waves alternating with episodic slow waves. It is unclear which EEG parameter is optimal for pharmacokinetic–pharmacodynamic modelling of the hypnotic actions of ketamine, or which EEG parameter is most closely linked to loss of behavioural responsiveness. Methods: We re-analysed previously published 128-channel scalp EEG data from 15 subjects who had received a 1.5 mg kg −1 bolus i.v. dose of ketamine. We applied standard sigmoid pharmacokinetic–pharmacodynamic models to the drug-induced changes in slow wave activity, theta, and beta–gamma EEG power; and examined the morphology of the slow waves in the time domain for Fz, F3, T3, P3, and Pz average-referenced channels. Results: Hypnotic doses of ketamine i.v. induced medio-frontal EEG slow waves, and loss of behavioural response when the estimated brain concentration was 1.64 (0.17) μg ml −1 . Recovery of responsiveness occurred at 1.06 (0.21) μg.ml −1 after slow wave activity had markedly diminished. Pharmacokinetic–pharmacodynamic modelling fitted best to the slow wave activity and theta power (almost half the beta–gamma channels could not be modelled). Slow wave effect-site equilibration half-time (23 [4] s), and offset, was faster than for theta (47 [22] s). Conclusions: Changes in EEG slow wave activity after a hypnotic dose of ketamine could be fitted by a standard sigmoid dose-response model. Their onset, but not their offset, was consistently associated with loss of behavioural response in our small study group.