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Anesthesiology. 1997 Nov;87(5):1106-17.

Midazolam changes cerebral blood flow in discrete brain regions: an H2(15)O positron emission tomography study.

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1
Department of Anesthesiology and Critical Care Medicine, Memorial Sloan-Kettering Cancer Center and Cornell University Medical College, New York, New York 10021, USA. veselisr@mskcc.org

Abstract

BACKGROUND:

Changes in regional cerebral blood flow (rCBF) determined with H2(15)O positron emission tomographic imaging can identify neural circuits affected by centrally acting drugs.

METHODS:

Fourteen volunteers received one of two midazolam infusions adjusted according to electroencephalographic response. Low or high midazolam effects were identified using post-hoc spectral analysis of the electroencephalographic response obtained during positron emission tomographic imaging based on the absence or presence of 14-Hz spindle activity. The absolute change in global CBF was calculated, and relative changes in rCBF were determined using statistical parametric mapping with localization to standard stereotactic coordinates.

RESULTS:

The low-effect group received 7.5 +/- 1.7 mg midazolam (serum concentrations, 74 +/- 24 ng/ml), and the high-effect group received 9.7 +/- 1.3 mg midazolam (serum concentrations, 129 +/- 48 ng/ml). Midazolam decreased global CBF by 12% from 39.2 +/- 4.1 to 34.4 +/- 6.1 ml x 100 g(-1) x min(-1) (P < 0.02 at a partial pressure of carbon dioxide of 40 mmHg). The rCBF changes in the low-effect group were a subset of the high-effect group. Decreased rCBF (P < 0.001) occurred in the insula, the cingulate gyrus, multiple areas in the prefrontal cortex, the thalamus, and parietal and temporal association areas. Asymmetric changes occurred, particularly in the low-effect group, and were more significant in the left frontal cortex and thalamus and the right insula. Relative rCBF was increased in the occipital areas.

CONCLUSION:

Midazolam causes dose-related changes in rCBF in brain regions associated with the normal functioning of arousal, attention, and memory.

PMID:
9366463
[Indexed for MEDLINE]
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