Wakeling H G, Zimmerman J B, Howell S, Glass P S
Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Anesthesiology. 1999 Jan;90(1):92-7. doi: 10.1097/00000542-199901000-00014.
An effect compartment has been postulated, and the ke0 has been quantified for several intravenous anesthetic drugs using electroencephalography (EEG) as the measure of effect. The authors wanted to validate that loss of responsiveness (LOR) was related to targeting an effect compartment concentration rather than a central compartment (plasma) concentration.
Twenty American Society of Anesthesiologists physical status I and II patients were randomized to receive propofol administered to a target central compartment or target effect compartment site concentration of 5.4 microg/ml propofol administered by a target-controlled infusion (TCI) using a previously validated set of pharmacokinetic parameters and a ke0 of 0.63 min(-1). Every 30 s for the first 5 min and every minute for the second 5 min the patients were asked to open their eyes. The time to LOR was measured by a blinded investigator. The authors also simulated the time to reach the desired target effect site concentration using varying ke0 values.
The median time to LOR in the group targeted to a predicted plasma propofol concentration was 3.02 min and 1.23 min in the group targeted to a predicted effect compartment propofol concentration (P < 0.05). LOR to command in both groups occurred at a predicted median effect compartment concentration of 4.55 microg/ml. Simulations demonstrated that the time predicted to LOR targeting an effect site concentration of 5.4 microg/ml is markedly altered by the value chosen for the ke0.
This study confirms the utility of the ke0 value to describe the effect compartment for propofol. The authors also illustrate the importance of selecting the correct ke0 value for the pharmacokinetic parameters used within the TCI system.
已假定存在效应室，并且使用脑电图（EEG）作为效应指标，对几种静脉麻醉药物的效应室消除速率常数（ke0）进行了量化。作者想要验证意识消失（LOR）与靶向效应室浓度而非中央室（血浆）浓度有关。
20例美国麻醉医师协会身体状况I级和II级的患者被随机分组，通过靶控输注（TCI）给予丙泊酚，使其达到目标中央室或目标效应室部位浓度5.4μg/ml，使用先前验证的一组药代动力学参数和ke0为0.63 min⁻¹。在最初5分钟内每30秒、在接下来的5分钟内每分钟要求患者睁开眼睛。由一名不知情的研究者测量意识消失的时间。作者还使用不同的ke0值模拟达到所需目标效应部位浓度的时间。
靶向预测血浆丙泊酚浓度组的意识消失中位时间为3.02分钟，靶向预测效应室丙泊酚浓度组为1.23分钟（P<0.05）。两组对指令的意识消失均发生在预测的效应室中位浓度4.55μg/ml时。模拟表明，针对ke0所选择的值，靶向效应部位浓度5.4μg/ml时预测的意识消失时间会显著改变。
本研究证实了ke0值用于描述丙泊酚效应室的实用性。作者还说明了为TCI系统中使用的药代动力学参数选择正确ke0值的重要性。
