Adamus M, Gabrhelik T, Marek O
Department of Anaesthesiology and Intensive Care Medicine, Palacký University, University Hospital and Faculty of Medicine, Olomouc, Czech Republic.
Eur J Anaesthesiol. 2008 Jul;25(7):589-95. doi: 10.1017/S026502150800402X. Epub 2008 Apr 11.
There is increasing evidence of gender differences in the pharmacokinetics and pharmacodynamics of aminosteroid neuromuscular blocking agents. Compared to males, females are more susceptible, requiring approximately 30% less rocuronium to achieve the same degree of neuromuscular block. However, little information is available whether this difference is applicable to modern benzylisoquinolines (cisatracurium).
In all, 848 patients (423 males, 425 females) undergoing general surgery under total intravenous anaesthesia with muscle relaxation, tracheal intubation and mechanical ventilation were studied. Patients were randomized to receive a single bolus dose of cisatracurium (0.1 mg kg-1, 221 males and 199 females) or rocuronium (0.6 mg kg-1, 202 males and 226 females). The onset time for 95% depression of T1, clinical duration until 25% recovery and recovery index (T1 from 25% to 75%) were determined with an NMT electromyographic module of the Datex-Ohmeda S/5 Anaesthesia Monitor. The data for male and female groups were compared with appropriate statistical tests (unpaired t-test, Mann-Whitney rank sum test and Fisher's exact test).
In both groups (cisatracurium and rocuronium), males were significantly taller (P < 0.001) and heavier (P < 0.001) than females, but the body mass index was comparable. For rocuronium, the onset time was shorter 91.7 +/- 14.3 s vs. 108.0 +/- 14.6 s (P < 0.001) and the clinical duration was increased in females 43.3 +/- 7.8 min vs. 31.3 +/- 5.5 min (P < 0.001). In the cisatracurium group, both onset times (248.9 +/- 60.7 s for males vs. 253.4 +/- 70.9 s for females) and clinical duration (42.6 +/- 6.9 min for males vs. 43.1 +/- 6.9 min for females) were similar. The recovery index was identical for males and females in both groups.
Females were more sensitive than males to a single bolus dose of rocuronium. Under the study conditions described, the onset time was shorter and the clinical duration was increased in female patients. This suggests that the routine dose of rocuronium should be reduced in females compared to males. On the contrary, we could demonstrate no gender differences in the onset time or clinical duration of cisatracurium.
越来越多的证据表明,甾体类神经肌肉阻滞剂的药代动力学和药效学存在性别差异。与男性相比,女性更敏感,达到相同程度的神经肌肉阻滞所需的罗库溴铵剂量大约少30%。然而,关于这种差异是否适用于现代苄基异喹啉类药物(顺式阿曲库铵)的信息却很少。
总共研究了848例在全静脉麻醉下接受普外科手术、使用肌肉松弛剂、气管插管和机械通气的患者(423例男性,425例女性)。患者被随机分为接受单次推注顺式阿曲库铵(0.1 mg/kg,221例男性和199例女性)或罗库溴铵(0.6 mg/kg,202例男性和226例女性)。使用Datex-Ohmeda S/5麻醉监测仪的NMT肌电图模块测定T1波幅抑制95%的起效时间、直至恢复25%的临床持续时间以及恢复指数(T1从25%恢复至75%)。对男性和女性组的数据进行了适当的统计学检验(独立样本t检验、曼-惠特尼秩和检验和费舍尔精确检验)。
在两组(顺式阿曲库铵组和罗库溴铵组)中,男性的身高(P<0.001)和体重(P<0.001)均显著高于女性,但体重指数相当。对于罗库溴铵,起效时间较短(91.7±14.3秒对108.0±14.6秒,P<0.001),女性的临床持续时间延长(43.3±7.8分钟对31.3±5.5分钟,P<0.001)。在顺式阿曲库铵组中,起效时间(男性为248.9±60.7秒,女性为253.4±70.9秒)和临床持续时间(男性为42.6±6.9分钟,女性为43.1±6.9分钟)均相似。两组中男性和女性的恢复指数相同。
女性对单次推注罗库溴铵比男性更敏感。在所述研究条件下,女性患者的起效时间较短,临床持续时间延长。这表明与男性相比,女性罗库溴铵的常规剂量应降低。相反,我们未发现顺式阿曲库铵的起效时间或临床持续时间存在性别差异。