• L Laaksonen, M Kallioinen, J Långsjö, T Laitio, A Scheinin, J Scheinin, K Kaisti, A Maksimow, R E Kallionpää, V Rajala, J Johansson, O Kantonen, M Nyman, S Sirén, K Valli, A Revonsuo, O Solin, T Vahlberg, M Alkire, and H Scheinin.
• Turku PET Centre, University of Turku and Turku University Hospital, Turku, Finland; Department of Perioperative Services, Intensive Care and Pain Medicine, Turku University Hospital, Turku, Finland. Electronic address: ltlaak@utu.fi.
• Br J Anaesth. 2018 Jul 1; 121 (1): 281-290.

IntroductionThe highly selective α2-agonist dexmedetomidine has become a popular sedative for neurointensive care patients. However, earlier studies have raised concern that dexmedetomidine might reduce cerebral blood flow without a concomitant decrease in metabolism. Here, we compared the effects of dexmedetomidine on the regional cerebral metabolic rate of glucose (CMRglu) with three commonly used anaesthetic drugs at equi-sedative doses.MethodsOne hundred and sixty healthy male subjects were randomised to EC50 for verbal command of dexmedetomidine (1.5 ng ml-1; n=40), propofol (1.7 μg ml-1; n=40), sevoflurane (0.9% end-tidal; n=40) or S-ketamine (0.75 μg ml-1; n=20) or placebo (n=20). Anaesthetics were administered using target-controlled infusion or vapouriser with end-tidal monitoring. 18F-labelled fluorodeoxyglucose was administered 20 min after commencement of anaesthetic administration, and high-resolution positron emission tomography with arterial blood activity samples was used to quantify absolute CMRglu for whole brain and 15 brain regions.ResultsAt the time of [F18]fluorodeoxyglucose injection, 55% of dexmedetomidine, 45% of propofol, 85% of sevoflurane, 45% of S-ketamine, and 0% of placebo subjects were unresponsive. Whole brain CMRglu was 63%, 71%, 71%, and 96% of placebo in the dexmedetomidine, propofol, sevoflurane, and S-ketamine groups, respectively (P<0.001 between the groups). The lowest CMRglu was observed in nearly all brain regions with dexmedetomidine (P<0.05 compared with all other groups). With S-ketamine, CMRglu did not differ from placebo.ConclusionsAt equi-sedative doses in humans, potency in reducing CMRglu was dexmedetomidine>propofol>ketamine=placebo. These findings alleviate concerns for dexmedetomidine-induced vasoconstriction and cerebral ischaemia.Clinical Trial RegistrationNCT02624401.Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.

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