Effects of subanesthetic ketamine on regional cerebral glucose metabolism in humans.
BACKGROUND
The authors have recently shown with positron emission tomography that subanesthetic doses of racemic ketamine increase cerebral blood flow but do not affect oxygen consumption significantly. In this study, the authors wanted to assess the effects of racemic ketamine on regional glucose metabolic rate (rGMR) in similar conditions to establish whether ketamine truly induces disturbed coupling between cerebral blood flow and metabolism.


METHODS
18F-labeled fluorodeoxyglucose was used as a positron emission tomography tracer to quantify rGMR on 12 brain regions of interest of nine healthy male volunteers at baseline and during a 300-ng/ml ketamine target concentration level. In addition, voxel-based analysis was performed for the relative changes in rGMR using statistical parametric mapping.


RESULTS
The mean +/- SD measured ketamine serum concentration was 326.4+/-86.3 ng/ml. The mean arterial pressure was slightly increased (maximally by 16.4%) during ketamine infusion (P < 0.001). Ketamine increased absolute rGMR significantly in most regions of interest studied. The greatest increases were detected in the thalamus (14.6+/-15.9%; P = 0.029) and in the frontal (13.6+/-13.1%; P = 0.011) and parietal cortices (13.1+/-11.2%; P = 0.007). Absolute rGMR was not decreased anywhere in the brain. The voxel-based analysis revealed relative rGMR increases in the frontal, temporal, and parietal cortices.


CONCLUSIONS
Global increases in rGMR seem to parallel ketamine-induced increases in cerebral blood flow detected in the authors' earlier study. Therefore, ketamine-induced disturbance of coupling between cerebral blood flow and metabolism is highly unlikely. The previously observed decrease in oxygen extraction fraction may be due to nonoxidative glucose metabolism during ketamine-induced increase in glutamate release.
Långsjö
Jaakko W
JW
Turku PET Centre, University of Turku, and the Department of Anesthesiology and Intensive Care, Turku University Hospital, Turku, Finland.
Salmi
Elina
E
Kaisti
Kaike K
KK
Aalto
Sargo
S
Hinkka
Susanna
S
Aantaa
Riku
R
Oikonen
Vesa
V
Viljanen
Tapio
T
Kurki
Timo
T
Silvanto
Martti
M
Scheinin
Harry
H
D000328:Adult; D000704:Analysis of Variance; D000778:Anesthetics, Dissociative / Q000008:administration & dosage*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology; D019788:Fluorodeoxyglucose F18 / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007649:Ketamine / Q000008:administration & dosage*; D008297:Male; D014055:Tomography, Emission-Computed / Q000379:methods
D000778:Anesthetics, Dissociative; D019788:Fluorodeoxyglucose F18; D007649:Ketamine; D005947:Glucose