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

Br J Anaesth. 2018 Jul;121(1):281-290. doi: 10.1016/j.bja.2018.04.008. Epub 2018 May 8.


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 (CMRglu) 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 CMRglu 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 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.

Conclusions: 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.

Clinical trial registration: NCT02624401.

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

Publication types

  • Clinical Trial, Phase IV
  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Anesthetics, Dissociative*
  • Anesthetics, Inhalation*
  • Brain / diagnostic imaging
  • Brain Chemistry / drug effects*
  • Cerebrovascular Circulation / drug effects
  • Dexmedetomidine*
  • Fluorodeoxyglucose F18
  • Glucose / metabolism*
  • Humans
  • Hypnotics and Sedatives*
  • Ketamine*
  • Kinetics
  • Male
  • Positron-Emission Tomography
  • Propofol*
  • Radiopharmaceuticals
  • Sevoflurane*
  • Young Adult


  • Anesthetics, Dissociative
  • Anesthetics, Inhalation
  • Hypnotics and Sedatives
  • Radiopharmaceuticals
  • Fluorodeoxyglucose F18
  • Sevoflurane
  • Dexmedetomidine
  • Ketamine
  • Glucose
  • Propofol

Associated data