Comparative effects of dexmedetomidine, propofol, sevoflurane, and S-ketamine on regional cerebral glucose metabolism in humans: a positron emission tomography study

• Published in: British journal of anaesthesia : BJA Vol. 121; no. 1; pp. 281 - 290
• Main Authors: Laaksonen, L., Kallioinen, M., Långsjö, J., Laitio, T., Scheinin, A., Scheinin, J., Kaisti, K., Maksimow, A., Kallionpää, R.E., Rajala, V., Johansson, J., Kantonen, O., Nyman, M., Sirén, S., Valli, K., Revonsuo, A., Solin, O., Vahlberg, T., Alkire, M., Scheinin, H.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.07.2018
• Subjects: cerebral blood flow; cerebral metabolism; Consciousness and Cognitive Neuroscience; Kognitiv neurovetenskap och filosofi; positron emission tomography; sedation; target-controlled infusion; cerebral blood flow; target-controlled infusion; positron emission tomography; sedation; cerebral metabolism
• ISSN: 0007-0912; 1471-6771; 1471-6771
• DOI: 10.1016/j.bja.2018.04.008

The 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. One 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. At 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. At 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. NCT02624401.