Positron emission tomography study of regional cerebral metabolism during general anesthesia with xenon in humans.
BACKGROUND
The precise mechanism by which the gaseous anesthetic xenon exerts its effects in the human brain remains unknown. Xenon has only negligible effects on inhibitory gamma-aminobutyric acid receptors, one of the putative molecular targets for most general anesthetics. Instead, xenon has been suggested to induce anesthesia by inhibiting excitatory glutamatergic signaling. Therefore, the authors hypothesized that xenon, similar to ketamine and nitrous oxide, increases global and regional cerebral metabolism in humans.


METHODS
The regional cerebral metabolic rate of glucose (rcMRGlu) was sequentially assessed in two groups of six volunteers each, using F-fluorodeoxyglucose as tracer. In the xenon group, rcMRGlu was determined at baseline and during general anesthesia induced with propofol and maintained with 1 minimum alveolar concentration xenon. In the control group, rcMRGlu was measured using the identical study protocol but without administration of xenon. rcMRGlu was assessed after the plasma concentration of propofol had decreased to subanesthetic levels (< 1.0 microg/ml). rcMRGlu was quantified in 10 cerebral volumes of interest. In addition, voxel-wise changes in rcMRGlu were analyzed using statistical parametric mapping.


RESULTS
Xenon reduced whole-brain metabolic rate of glucose by 26 +/- 7% (from 43 +/- 5 micromol x 100 g x min to 31 +/- 3 micromol x 100 g x min; P < 0.005) and significantly decreased rcMRGlu in all volumes of interest compared with the control group receiving propofol only. Voxel-based analysis revealed metabolic depression within the orbitofrontal, frontomesial, temporomesial, occipital, dorsolateral frontal, and lateral temporal cortices and thalami. No increases in rcMRGlu were detected during xenon anesthesia.


CONCLUSIONS
Xenon induces metabolic depression in the human brain, suggesting that the inhibition of the glutamatergic system is likely to be of minor significance for the anesthetic action of xenon in vivo.
Rex
Steffen
S
Department of Anesthesiology, University Hospital, RWTH Aachen, Aachen, Germany. srex@ukaachen.de
Schaefer
Wolfgang
W
Meyer
Philipp H
PH
Rossaint
Rolf
R
Boy
Christian
C
Setani
Keyvan
K
Büll
Ulrich
U
Baumert
Jan H
JH
D000328:Adult; D000768:Anesthesia, General; D018685:Anesthetics, Inhalation / Q000627:therapeutic use*; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism*; D019788:Fluorodeoxyglucose F18; D005947:Glucose / Q000378:metabolism; D006801:Humans; D008297:Male; D049268:Positron-Emission Tomography; D014018:Tissue Distribution; D014978:Xenon / Q000627:therapeutic use*
D018685:Anesthetics, Inhalation; D019788:Fluorodeoxyglucose F18; D014978:Xenon; D005947:Glucose