• P J Colin, L N Hannivoort, D J Eleveld, K M E M Reyntjens, A R Absalom, VereeckeH E MHEMDepartment of Anesthesiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands., and StruysM M R FMMRFDepartment of Anesthesiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.Department of Anaesthesia and Peri-operative Medicine, Ghent University, Ghent, Belgium..
• Department of Anesthesiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
• Br J Anaesth. 2017 Aug 1; 119 (2): 200-210.

BackgroundDexmedetomidine, a selective α 2 -adrenoreceptor agonist, has unique characteristics, such as maintained respiratory drive and production of arousable sedation. We describe development of a pharmacokinetic-pharmacodynamic model of the sedative properties of dexmedetomidine, taking into account the effect of stimulation on its sedative properties.MethodsIn a two-period, randomized study in 18 healthy volunteers, dexmedetomidine was delivered in a step-up fashion by means of target-controlled infusion using the Dyck model. Volunteers were randomized to a session without background noise and a session with pre-recorded looped operating room background noise. Exploratory pharmacokinetic-pharmacodynamic modelling and covariate analysis were conducted in NONMEM using bispectral index (BIS) monitoring of processed EEG.ResultsWe found that both stimulation at the time of Modified Observer's Assessment of Alertness/Sedation (MOAA/S) scale scoring and the presence or absence of ambient noise had an effect on the sedative properties of dexmedetomidine. The stimuli associated with MOAA/S scoring increased the BIS of sedated volunteers because of a transient 170% increase in the effect-site concentration necessary to reach half of the maximal effect. In contrast, volunteers deprived of ambient noise were more resistant to dexmedetomidine and required, on average, 32% higher effect-site concentrations for the same effect as subjects who were exposed to background operating room noise.ConclusionsThe new pharmacokinetic-pharmacodynamic models might be used for effect-site rather than plasma concentration target-controlled infusion for dexmedetomidine in clinical practice, thereby allowing tighter control over the desired level of sedation.Clinical Trial RegistrationNCT01879865.© The Author 2017. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com

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