Dexmedetomidine decreases thiopental dose requirement and alters distribution pharmacokinetics.
BACKGROUND
alpha 2-Adrenergic agonists such as dexmedetomidine can be used to reduce the dose requirement of intravenous and volatile anesthetics. Whereas dexmedetomidine and volatile anesthetics interact pharmacodynamically (reduction of MAC), the mechanism of interaction between dexmedetomidine and intravenous anesthetics is not known.


METHODS
Fourteen male ASA physical status 1 patients were randomly assigned to serve as control subjects (n = 7) or to be treated with dexmedetomidine (n = 7; 100, 30, and 6 ng.kg-1.min-1 for 10 min, 15 min, and thereafter, respectively). After 35 min, in all patients, thiopental (100 mg/min) was infused until burst suppression appeared in the raw tracing of the electroencephalogram. By using concentrations of thiopental in plasma and the electroencephalogram as a continuous pharmacologic effect measure, the apparent effect site concentrations for thiopental were estimated in both groups. Three-compartment pharmacokinetics were calculated for thiopental.


RESULTS
Dexmedetomidine reduced the thiopental dose requirement for electroencephalographic burst suppression by 30%. There was no difference in estimated thiopental effect site concentrations between dexmedetomidine and control patients, suggesting the absence of a major pharmacodynamic interaction. Dexmedetomidine significantly decreased distribution volumes (V2, V3, and Vdss) and distribution clearances (Cl12 and Cl13) of thiopental.


CONCLUSIONS
The thiopental dose-sparing effect of dexmedetomidine on the electroencephalogram is not the result of a pharmacodynamic interaction but rather can be explained by a dexmedetomidine-induced decrease in thiopental distribution volume and distribution clearances. Dexmedetomidine reduces thiopental distribution, most probably by decreasing cardiac output and regional blood flow.
Bührer
M
M
Institute of Anesthesiology and Intensive Care, University of Berne, Inselspital, Switzerland.
Mappes
A
A
Lauber
R
R
Stanski
D R
DR
Maitre
P O
PO
D000317:Adrenergic alpha-Antagonists / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D000328:Adult; D004334:Drug Administration Schedule; D004347:Drug Interactions; D004569:Electroencephalography / Q000187:drug effects*; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D008297:Male; D020926:Medetomidine; D008875:Middle Aged; D013874:Thiopental / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*
D000317:Adrenergic alpha-Antagonists; D007093:Imidazoles; D013874:Thiopental; D020926:Medetomidine