title: Effects of subanesthetic doses of ketamine on regional cerebral blood flow, oxygen consumption, and blood volume in humans.
abstract: BACKGROUND
  Animal experiments have demonstrated neuroprotection by ketamine. However, because of its propensity to increase cerebral blood flow, metabolism, and intracranial pressure, its use in neurosurgery or trauma patients has been questioned.
  
  
  METHODS
  15O-labeled water, oxygen, and carbon monoxide were used as positron emission tomography tracers to determine quantitative regional cerebral blood flow (rCBF), metabolic rate of oxygen (rCMRO2), and blood volume (rCBV), respectively, on selected regions of interest of nine healthy male volunteers at baseline and during three escalating concentrations of ketamine (targeted to 30, 100, and 300 ng/ml). In addition, voxel-based analysis for relative changes in rCBF and rCMRO2 was performed using statistical parametric mapping.
  
  
  RESULTS
  The mean +/- SD measured ketamine serum concentrations were 37 +/- 8, 132 +/- 19, and 411 +/- 71 ng/ml. Mean arterial pressure was slightly elevated (maximally by 15.3%, P < 0.001) during ketamine infusion. Ketamine increased rCBF in a concentration-dependent manner. In the region-of-interest analysis, the greatest absolute changes were detected at the highest ketamine concentration level in the anterior cingulate (38.2% increase from baseline, P < 0.001), thalamus (28.5%, P < 0.001), putamen (26.8%, P < 0.001), and frontal cortex (25.4%, P < 0.001). Voxel-based analysis revealed marked relative rCBF increases in the anterior cingulate, frontal cortex, and insula. Although absolute rCMRO2 was not changed in the region-of-interest analysis, subtle relative increases in the frontal, parietal, and occipital cortices and decreases predominantly in the cerebellum were detected in the voxel-based analysis. rCBV increased only in the frontal cortex (4%, P = 0.022).
  
  
  CONCLUSIONS
  Subanesthetic doses of ketamine induced a global increase in rCBF but no changes in rCMRO2. Consequently, the regional oxygen extraction fraction was decreased. Disturbed coupling of cerebral blood flow and metabolism is, however, considered unlikely because ketamine has been previously shown to increase cerebral glucose metabolism. Only a minor increase in rCBV was detected. Interestingly, the most profound changes in rCBF were observed in structures related to pain processing.
authors.affiliation: Turku PET Centre, University of Turku, Finland.
authors.forename: Jaakko W
authors.initials: JW
authors.lastname: Långsjö
authors.forename: Kaike K
authors.initials: KK
authors.lastname: Kaisti
authors.forename: Sargo
authors.initials: S
authors.lastname: Aalto
authors.forename: Susanna
authors.initials: S
authors.lastname: Hinkka
authors.forename: Riku
authors.initials: R
authors.lastname: Aantaa
authors.forename: Vesa
authors.initials: V
authors.lastname: Oikonen
authors.forename: Hannu
authors.initials: H
authors.lastname: Sipilä
authors.forename: Timo
authors.initials: T
authors.lastname: Kurki
authors.forename: Martti
authors.initials: M
authors.lastname: Silvanto
authors.forename: Harry
authors.initials: H
authors.lastname: Scheinin
mesh_terms: D000328:Adult; D000339:Affect / Q000187:drug effects; D000778:Anesthetics, Dissociative / Q000494:pharmacology*; D001810:Blood Volume / Q000187:drug effects*; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007649:Ketamine / Q000494:pharmacology*; D008297:Male; D010101:Oxygen Consumption / Q000187:drug effects*; D015656:Respiratory Mechanics / Q000187:drug effects; D014055:Tomography, Emission-Computed
chemical_list: D000778:Anesthetics, Dissociative; D018691:Excitatory Amino Acid Antagonists; D007649:Ketamine