Bührer M, Mappes A, Lauber R, Stanski D R, Maitre P O
Institute of Anesthesiology and Intensive Care, University of Berne, Inselspital, Switzerland.
Anesthesiology. 1994 Jun;80(6):1216-27. doi: 10.1097/00000542-199406000-00008.
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.
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.
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.
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.
右美托咪定等α2肾上腺素能激动剂可用于降低静脉麻醉药和挥发性麻醉药的剂量需求。右美托咪定与挥发性麻醉药存在药效学相互作用（降低最低肺泡有效浓度），而右美托咪定与静脉麻醉药之间的相互作用机制尚不清楚。
14例美国麻醉医师协会（ASA）身体状况为1级的男性患者被随机分为对照组（n = 7）或接受右美托咪定治疗组（n = 7；分别以100、30和6 ng·kg-1·min-1的剂量持续输注10分钟、15分钟及之后）。35分钟后，所有患者均输注硫喷妥钠（100 mg/min），直至脑电图原始记录中出现爆发抑制。以血浆中硫喷妥钠浓度和脑电图作为连续的药理效应指标，估算两组患者硫喷妥钠的表观效应室浓度。计算硫喷妥钠的三室药代动力学参数。
右美托咪定使脑电图爆发抑制所需的硫喷妥钠剂量降低了30%。右美托咪定组和对照组患者估算的硫喷妥钠效应室浓度无差异，提示不存在主要的药效学相互作用。右美托咪定显著降低了硫喷妥钠的分布容积（V2、V3和稳态分布容积）和分布清除率（Cl12和Cl13）。
右美托咪定对脑电图的硫喷妥钠剂量节省效应并非药效学相互作用的结果，而是可由右美托咪定引起的硫喷妥钠分布容积和分布清除率降低来解释。右美托咪定减少硫喷妥钠的分布，很可能是通过降低心输出量和局部血流实现的。
