• Jamie Sleigh, Rebecca M Pullon, Phillip E Vlisides, and Catherine E Warnaby.
• Department of Anaesthesia, Waikato Clinical Campus, University of Auckland, Hamilton, New Zealand. Electronic address: Jamie.sleigh@waikatodhb.health.nz.
• Br J Anaesth. 2019 Nov 1; 123 (5): 592-600.

BackgroundPrevious 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.MethodsWe 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.ResultsHypnotic 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).ConclusionsChanges 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.Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.

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