DEXMEDETOMIDINE DECREASES THIOPENTAL DOSE REQUIREMENT AND ALTERS DISTRIBUTION PHARMACOKINETICS

Background: alpha(2)-Adrenergic agonists such as dexmedetomidine can b e used to reduce the dose requirement of intravenous and volatile anes thetics. Whereas dexmedetomidine and volatile anesthetics interact pha rmacodynamically (reduction of MAC), the mechanism of interaction betw een dexmedetomidine and intravenous anesthetics is not known. Methods: Fourteen male ASA physical status 1 patients were randomly assigned t o serve as control subjects (n = 7) or to be treated with dexmedetomid ine (n = 7; 100, 30, and 6 ng . kg(-1) . min(-1) for 10 min, 15 min, a nd thereafter, respectively). After 35 min, in all patients, thiopenta l (100 mg/min) was infused until burst suppression appeared in the raw tracing of the electroencephalogram. By using concentrations of thiop ental in plasma and the electroencephalogram as a continuous pharmacol ogic effect measure, the apparent effect site concentrations for thiop ental were estimated in both groups. Three-compartment pharmacokinetic s were calculated for thiopental. Results: Dexmedetomidine reduced the thiopental dose requirement for electroencephalographic burst suppres sion by 30%. There was no difference in estimated thiopental effect si te concentrations between dexmedetomidine and control patients, sugges ting the absence of a major pharmacodynamic interaction. Dexmedetomidi ne significantly decreased distribution volumes (V-2, V-3, and Vd(ss)) and distribution clearances (Cl-12 and Cl-13) of thiopental. Conclusi ons: The thiopental dose-sparing effect of dexmedetomidine on the elec troencephalogram is not the result of a pharmacodynamic interaction bu t rather can be explained by a dexmedetomidine-induced decrease in thi opental distribution volume and distribution clearances. Dexmedetomidi ne reduces thiopental distribution, most probably by decreasing cardia c output and regional blood flow.