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ANESTHETIC PHARMACOLOGY

Thiopental Produces Immobility Primarily by Supraspinal Actions in Rats

Department of Anesthesia and Perioperative Care, University of California, San Francisco, California

Address correspondence and reprint requests to James M. Sonner, MD, Department of Anesthesia and Perioperative Care, S-455, University of California, San Francisco, CA 94143–0464. Address e-mail to sonnerj{at}anesthesia.ucsf.edu

The spinal cord mediates most of the immobilizing action of inhaled anesthetics. In the present study we investigated whether spinal or supraspinal sites mediate the immobilizing action of thiopental in rats. Thiopental was administered IV, intrathecally (IT), intracerebroventricularly (ICV), or simultaneously IT and ICV. Only the IV infusion produced anesthesia, defined as immobility in response to application of a tail clamp (i.e., the equivalent of minimum alveolar concentration, MAC). Consequently, the MAC-sparing effect (for isoflurane) of thiopental was used to assess the immobilizing contribution of IT and ICV infusions of thiopental. Thiopental concentrations were determined in whole brain, spinal cord, and a slice of cerebral cortex distant from the infusion sites. These concentrations were correlated with the MAC-sparing effect of the thiopental infusions in a multiple regression model. To assess the rate at which thiopental penetrates the cord, rat spinal cords were equilibrated in a bath of thiopental ex vivo and the concentration of thiopental in the cord was measured as a function of equilibration time. This was repeated in vivo with IT infusions of thiopental spanning the time of the behavioral studies. We found that IT or ICV infusion of thiopental 25 µg/min decreased isoflurane MAC <25%. The associated thiopental concentrations in the spinal cord after IT infusion, and in the whole brain after ICV infusion of 25 µg/min thiopental, exceeded by 500% and 680%, respectively, the concentrations found in the spinal cord and in the whole brain after IV infusion of thiopental in a dose that produced anesthesia in the absence of isoflurane. The percentage decrease in the MAC of isoflurane correlated primarily with the concentration of thiopental found in cerebral tissue not in contact with the cerebral ventricles. The spinal cord infusion produced an approximately 20% decrease in MAC. Ex vivo IT thiopental readily diffused into the spinal cord, with a time constant of approximately 1 h. We conclude that, unlike inhaled anesthetics, the immobilizing action of thiopental is largely supraspinal. Centers in the brain other than those near the third and fourth ventricles produce the greatest effect.

IMPLICATIONS: Thiopental produces immobility in response to noxious stimuli predominantly by actions on supraspinal sites.

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