• Anesthesia and analgesia · Nov 2004

    Sevoflurane and propofol increase 11C-flumazenil binding to gamma-aminobutyric acidA receptors in humans.

    • Elina Salmi, Kaike K Kaisti, Liisa Metsähonkala, Vesa Oikonen, Sargo Aalto, Kjell Någren, Susanna Hinkka, Jarmo Hietala, Esa R Korpi, and Harry Scheinin.
    • Turku PET Centre, Turku University Hospital, PO Box 52, FIN-20521 Turku, Finland. elina.salmi@utu.fi
    • Anesth. Analg. 2004 Nov 1;99(5):1420-6; table of contents.

    AbstractBased on in vitro studies and animal data, most anesthetics are supposed to act via gamma-aminobutyric acid type A (GABA(A)) receptors. However, this fundamental characteristic has not been extensively investigated in humans. We studied (11)C-flumazenil binding to GABA(A) receptors during sevoflurane and propofol anesthesia in the living human brain using positron emission tomography (PET). Fourteen healthy male subjects underwent 2 60-min dynamic PET studies with (11)C-labeled flumazenil, awake and during anesthesia. Anesthesia was maintained with 2% end-tidal sevoflurane (n = 7) or propofol at a target plasma concentration of 9.0 +/- 3.0 (mean +/- sd) microg/mL (n = 7). The depth of anesthesia was measured with bispectral index (BIS). Values of regional distribution volumes (DV) of (11)C-flumazenil were calculated in several brain areas using metabolite-corrected arterial plasma curves and a two-compartment model. Separate voxel-based statistical analysis using parametric DV images was performed for detailed visualization. The average BIS index was 35 +/- 6 in the sevoflurane group and 28 +/- 8 in the propofol group (P = 0.02). Sevoflurane increased the DV of (11)C-flumazenil significantly (P < 0.05) in all brain areas studied except the pons and the white matter. In the propofol group the increases were significant (P < 0.05) in the caudatus, putamen, cerebellum, thalamus and the frontal, temporal, and parietal cortices. Furthermore, the DV increases in the frontal, occipital, parietal, and temporal cortical areas and in the putamen were statistically significantly larger in the sevoflurane than in the propofol group. Our findings support the involvement of GABA(A) receptors in the mechanism of action of both anesthetics in humans.

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