Department of Anaesthesiology and Intensive Care Medicine, Medical University of Graz, Auenbruggerplatz 29, A-8036 Graz, Austria.
Br J Anaesth. 2011 Mar;106(3):331-5. doi: 10.1093/bja/aeq369. Epub 2010 Dec 23.
Variability in drug response could result from a variety of genetic and environmental factors that are often hard to define or quantify. A number of studies demonstrated regional geographic variations in potency of neuromuscular blocking agents (NMBAs). The aim of our study was to compare dose-response and time-course-of-action of cisatracurium besylate, an NMBA eliminated via the Hoffman degradation, in two countries with different life habits, diet, and ambient conditions; being Han Chinese in China and Caucasians in Bosnia.
Neuromuscular block of cisatracurium 20 µg kg(-1), followed by four incremental 10 µg kg(-1) doses, and the remainder of 100 µg kg(-1) was evaluated using the Relaxometer mechanomyograph (Groningen University, Groningen, The Netherlands). Dose-response curves were created using log-dose-probit-response transformation.
There were no significant differences in cisatracurium mean (95% confidence intervals) ED(50), ED(90), and ED(95) (effective doses for 50%, 90%, and 95% first twitch depression) in Caucasian [39.1 (35.7-42.3), 50.6 (45.5-54.3), and 54.4 (49.8-58.9) µg kg(-1)] compared with Chinese patients [39.2 (35.1-43.1), 52.4 (47.9-56.8), and 56.9 (52.8-61.9) µg kg(-1)], respectively. There were no significant differences in mean (sd) Dur(25) and Dur(0.9) (time until 25% first twitch and 0.9 train-of-four ratio recoveries) in Caucasian [47.1 (6.4) and 77.5 (9.1) min)] compared with Chinese patients [(45.9 (4.7) and 72.3 (9.1) min)], respectively.
Cisatracurium dose-response relationship and time-course-of-action were not influenced by geographic location. Thus, cisatracurium would not require dose adjustments between patients living in the two geographic locations.
药物反应的可变性可能源于多种遗传和环境因素，这些因素往往难以定义或量化。许多研究表明，神经肌肉阻滞剂（NMBAs）的效力存在区域地理差异。我们的研究目的是比较两种生活习惯、饮食和环境条件不同的国家（中国汉族人和波斯尼亚的高加索人）中顺式阿曲库铵的剂量反应和作用时间曲线。顺式阿曲库铵 20 µg kg(-1)，随后给予四个递增的 10 µg kg(-1)剂量，并用 Relaxometer 肌动描记器（荷兰格罗宁根大学）评估 100 µg kg(-1)的剩余部分。使用对数剂量-概率反应转换创建剂量反应曲线。
在高加索人[39.1（35.7-42.3）、50.6（45.5-54.3）和 54.4（49.8-58.9）µg kg(-1)]与中国人[39.2（35.1-43.1）、52.4（47.9-56.8）和 56.9（52.8-61.9）µg kg(-1)]之间，没有发现顺式阿曲库铵的平均（95%置信区间）ED(50)、ED(90)和 ED(95)（50%、90%和 95%第一强直刺激抑制的有效剂量）有显著差异。在高加索人中，没有发现平均（标准差）Dur(25)和 Dur(0.9)（达到 25%第一强直刺激和 0.9 个四串比恢复的时间）[47.1（6.4）和 77.5（9.1）分钟]与中国人[45.9（4.7）和 72.3（9.1）分钟]之间有显著差异。
顺式阿曲库铵的剂量反应关系和作用时间曲线不受地理位置的影响。因此，在这两个地理位置的患者之间，顺式阿曲库铵不需要剂量调整。
