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ANESTHETIC PHARMACOLOGY

Thiopental and Propofol Affect Different Regions of the Brain at Similar Pharmacologic Effects

Robert A. Veselis, MD^*,, Vladimir A. Feshchenko, PhD^*, Ruth A. Reinsel, PhD^*, Ann M. Dnistrian, PhD, Bradley Beattie, BS^||, and Timothy J. Akhurst, MBBS FRACP^,

Departments of *Anesthesiology and Critical Care Medicine, Radiology, Nuclear Medicine Service, Clinical Laboratories, Clinical Chemistry Service, and ||Neurology, Memorial Sloan-Kettering Cancer Center, New York, New York; and Weill Medical College of Cornell University, New York, New York

Address correspondence and reprint requests to Robert A. Veselis, MD, Department of Anesthesiology and Critical Care Medicine, Memorial Sloan-Kettering Cancer Center, 1275 York Ave., Box 24, New York, NY 10021. Address e-mail to veselisr{at}mskcc.org

Propofol has a greater amnesic effect than thiopental. In this study we tested whether different brain regions were affected by propofol and thiopental at similar drug effects. Changes in regional cerebral blood flow (rCBF) were identified by using SPM99 analysis of images obtained with positron emission tomography with ¹⁵O water. Ten right-handed male volunteers (age, 35 ± 10 yr; weight, 74.1 ± 7.5 kg; mean ± SD) were randomized to receive thiopental (n = 4) or propofol (n = 6) to target sedative and hypnotic concentrations with bispectral index (BIS) monitoring. Four positron emission tomography images were obtained during various tasks at baseline and with sedative and hypnotic effects. Two participants receiving propofol were unresponsive at sedative concentrations and were not included in the final analyses. Median serum concentrations were 1.2 and 2.7 µg/mL for sedative and hypnotic propofol effects, respectively. Similarly, thiopental concentrations were 4.8 and 10.6 µg/mL. BIS decreased similarly in both groups. The pattern of rCBF change was markedly different for propofol and thiopental. Propofol decreased rCBF in the anterior (right-sided during sedation) brain regions, whereas thiopental decreased rCBF primarily in the cerebellar and posterior brain regions. At similar levels of drug effect, propofol and thiopental affect different regions of the brain. These differences may help to identify the loci of action for the nonsedative effects of propofol, such as amnesia.

IMPLICATIONS: Despite very similar sedative and hypnotic effects, propofol and thiopental affect regional cerebral blood flow differently during drug effects. These differing patterns may provide clues as to how the drugs produce different behavioral effects, such as sedation and amnesia.

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