Department of Anaesthesiology and Intensive Care Medicine, Medical University of Graz, Auenbruggerplatz 29, 8036, Graz, Austria.
Can J Anaesth. 2011 Apr;58(4):364-70. doi: 10.1007/s12630-011-9453-2. Epub 2011 Jan 25.
Variability in drug responses could result from both genetic and environmental factors. Thus, drug effect could depend on geographic location, although regional variation is not generally acknowledged as a basis for stratification. There is evidence that the pharmacokinetic set developed in a European population for the target-controlled infusion (TCI) of propofol does not apply in Chinese patients; however, we are not aware of previous studies comparing the estimated concentration-bispectral index (BIS) response of Caucasian patients in Europe with that of Chinese patients in China.
The Diprifusor™ TCI pump, incorporating the pharmacokinetic model proposed by Marsh et al., was applied to 30 Caucasian patients in Austria and 30 Chinese patients in China. The estimated plasma concentration (C(p)) of propofol for the two groups was set at 1 μg·mL(-1) and increased by 1 μg·mL(-1) every minute to gradually reach 5 μg·mL(-1) after 5 min. The BIS values were fitted against the estimated C(p) and the predicted effect-site concentration (C(e)) in a sigmoid E(max) model.
The sigmoid E(max) curves were shifted significantly to the left in the Chinese group compared with the Austrian group. After 5 min, the BIS value in the Chinese group was lower than in the Austrian group (mean ± standard deviation [SD], 47.2 ± 3.6 vs 63.6 ± 5.4, respectively; P = 0.0006). The estimated C(p) at loss of consciousness (LOC), predicted C(e) at LOC, and time to LOC, were lower in the Chinese group than in the Austrian group (3.3 ± 0.8 μg·mL(-1), 1.6 ± 0.4 μg·mL(-1), 2.8 ± 0.6 min, respectively, vs 4.6 ± 2.8 μg·mL(-1), 2.4 ± 1.5 μg·mL(-1), 3.9 ± 0.5 min, respectively; P < 0.0001).
When propofol is given using the same TCI protocol, Chinese patients in China lost consciousness faster and at a lower estimated plasma concentration than Caucasians in Austria. Larger studies are needed to map geographically appropriate TCI infusion models.
药物反应的可变性可能源于遗传和环境因素。因此，药物效应可能取决于地理位置，尽管区域差异通常不被认为是分层的基础。有证据表明，在欧洲人群中开发的用于丙泊酚靶控输注（TCI）的药代动力学模型并不适用于中国患者；然而，我们不知道之前有研究比较过欧洲白种人患者的估计浓度-脑电双频指数（BIS）反应与中国患者在中国的反应。
采用包含 Marsh 等提出的药代动力学模型的 Diprifusor™ TCI 泵，对奥地利的 30 例白种人和中国的 30 例中国人进行研究。两组的丙泊酚估计血浆浓度（C（p））设定为 1μg·mL（-1），每分钟增加 1μg·mL（-1），5 分钟后逐渐增加到 5μg·mL（-1）。BIS 值与估计的 C（p）和 sigmoid E（max）模型中的预测效应部位浓度（C（e））拟合。
与奥地利组相比，中国组的 sigmoid E（max）曲线明显向左移位。5 分钟后，中国组的 BIS 值低于奥地利组（均值±标准差[SD]，分别为 47.2±3.6 和 63.6±5.4；P=0.0006）。中国组意识丧失时的估计 C（p）、预测的 C（e）和意识丧失时间（LOC）均低于奥地利组（分别为 3.3±0.8μg·mL（-1）、1.6±0.4μg·mL（-1）和 2.8±0.6 min，以及 4.6±2.8μg·mL（-1）、2.4±1.5μg·mL（-1）和 3.9±0.5 min；P<0.0001）。
在中国使用相同的 TCI 方案给予丙泊酚时，中国患者比奥地利白种人更快地失去意识，且估计血浆浓度更低。需要进行更大规模的研究来绘制适合地理位置的 TCI 输注模型。
