• 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): 211-220.

BackgroundDexmedetomidine, a selective α 2 -adrenoreceptor agonist, has unique characteristics, with little respiratory depression and rousability during sedations. We characterized the haemodynamic properties of dexmedetomidine by developing a pharmacokinetic-pharmacodynamic (PKPD) model with a focus on changes in mean arterial blood pressure (MAP) and heart rate.MethodsDexmedetomidine was delivered i.v. to 18 healthy volunteers in a step-up fashion by target-controlled infusion using the Dyck model. Exploratory PKPD modelling and covariate analysis were conducted in NONMEM.ResultsOur model adequately describes dexmedetomidine-induced hypotension, hypertension, and bradycardia, with a greater effective concentration for the hypertensive effect. Changes in MAP were best described by a double-sigmoidal E max model with hysteresis. Covariate analysis revealed no significant covariates apart from age on the baseline MAP in the population pharmacokinetic model used to develop this PKPD model. Simulations revealed good general agreement with published descriptive studies of haemodynamics after dexmedetomedine infusion.ConclusionsThe present integrated PKPD model should allow tighter control over the desired level of sedation, while limiting potential haemodynamic side-effects.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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