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

Abstract

Introduction: 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 (CMR_glu) with three commonly used anaesthetic drugs at equi-sedative doses.

Methods: 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 CMR_glu for whole brain and 15 brain regions.

Results: 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 CMR_glu 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 CMR_glu was observed in nearly all brain regions with dexmedetomidine (P<0.05 compared with all other groups). With S-ketamine, CMR_glu did not differ from placebo.

Conclusions: At equi-sedative doses in humans, potency in reducing CMR_glu was dexmedetomidine>propofol>ketamine=placebo. These findings alleviate concerns for dexmedetomidine-induced vasoconstriction and cerebral ischaemia.

Clinical trial registration: NCT02624401.

Keywords: cerebral blood flow; cerebral metabolism; positron emission tomography; sedation; target-controlled infusion.