A Comparative Study of Dose-Response and Time Course of Recovery of Atracurium and Rocuronium<?xml:namespace prefix = o ns = "urn:schemas-microsoft-com:office:office" />

廖 旭 薛富善
Liao Xu，Xue Fushan. Department of Anesthesiology，Plastic Surgery Hospital，Chinese Academy of Medical Sciences and Peking Union Medical College，Beijing，100041

ABSTRACT

Objective：To compare the characteristics of the dose-response relations and the time-course of action between atracurium and rocuronium in healthy adult patients anesthetized with N2O-O2-fentanyl-thiopental.
Methods：Sixty patients，ASA grade I，aged 18-50 years，scheduled for elective plastic surgery were studied. All the patients were randomly divided equally to either the atracurium or rocuronium group. General anesthesia was maintained with 60% nitrous oxide in oxygen，thiopentone，and fentanyl. Neuromuscular function was assessed using a accelerometer with train-of-four （TOF） stimulation at the wrist every 12 s. The percentage depression of first twitch （T1） was used as the study parameter. The dose-response relations of atracurium and rocuronium were determined by the cumulative dose-response technique.
Results：According to the dose-response curves established by least squares linear regression，the potency ratio of atracurium：rocuronium was 1:1.2. There were significant differences in the ED50，ED90，and ED95 between the two drugs. After I.V. administration of equipotent doses of both drugs （1.5′ED95），the duration of peak effect，clinical duration，and total duration were significantly different between the two drugs，but the recovery index of the two drugs were similar.
Conclusions：Atracurium and rocuronium are the low-potency nondepolarizing relaxants with intermediate duration. As compared to atracurium，the neuromuscular blocking effect of rocuronium was about 20% less potent and its duration of action was shorter.
Keywords：Atracurium，Rocuronium， Dose-response，Time-course of recovery

　　阿曲库铵和罗库溴铵均是临床广泛使用的新型中效非去极化肌肉松弛药，恢复速率快，无心血管副作用。目前仍无研究在成人比较两药的量-效关系和作用时相。本研究通过比较性观察阿曲库铵和罗库溴铵的量-效关系和恢复时相特征，旨在为临床麻醉中安全使用此两种中效非去极化肌肉松弛药提供资料。<?xml:namespace prefix = o ns = "urn:schemas-microsoft-com:office:office" />

资料和方法

　　60例ASA I级施择期整形外科手术的患者，年龄18～50岁，体重47～84kg，预计手术时间超过2h。全部患者术前各项检查及心、肺、肝、肾功能检查均正常，无神经肌肉系统疾病史。术前亦未服用对肌肉松弛药有影响的药物史。将患者随机平均分成阿曲库铵组和罗库溴铵组。

所有患者术前1h肌内注射阿托品0.01mg/kg、地西泮0.2mg/kg和哌替啶1mg/kg。静脉注射2.5%硫喷妥钠6～8mg/kg和芬太尼2～4mg/kg诱导麻醉，以2%利多卡因表面麻醉后行气管内插管。吸入3：2笑气-氧气混合气，总流量5L/min维持麻醉，必要时间断静脉注射硫喷妥钠50～100mg或芬太尼50～100mg。术中机械通气，调整潮气量和呼吸频率，维持PETCO2于4～5kPa之间。麻醉中连续监测血压、ECG、心率及SpO2。
　　麻醉平稳后，用Biometer加速度仪监测神经肌肉功能，在腕部应用TOF刺激方式刺激尺神经，超强刺激方波的波宽为0.2ms，频率为2Hz，刺激间隔为12s，以T1反应抑制作为研究指标。待T1稳定在100％10min后开始给药观察。采用累计给药方法观察阿曲库铵和罗库溴铵的量-效关系曲线，每个患者应用4个剂量，阿曲库铵组的首次剂量为50mg/kg，3个累计剂量分别为50、25、25mg/kg。 罗库溴铵组的首次剂量为100mg/kg，3个累计剂量均为50mg/kg。在前次剂量反应抑制稳定（连续三次T1反应相同）或经5min仍无T1下降时，给予下次剂量。如果第2次累计剂量后T1抑制大于90％，则不再应用第3个累计剂量。
　　曲线的绘制以药量的对数值为横坐标，以T1抑制百分比的概率值为纵坐标。用最小二乘法建立每个患者量-效关系曲线的回归方程，并用一维方差分析和q检验评估量-效关系曲线的平行性。如果平行性良好，则从中计算阿曲库铵和维库溴铵的ED50、ED90和ED95。并在此基础上建立各组全部患者的平均量-效关系。
　　应用第2或第3次累计剂量后，待T1抑制稳定，在阿曲库铵组，再给每个患者静脉注射阿曲库铵250或275mg/kg（总量400mg/kg）；在罗库溴铵组，再给每个患者静脉注射罗库溴铵400或350mg/kg(总量600mg/kg)。在T1达100％抑制患者观察两药的恢复时相，记录从给药至T1恢复至5%所需时间（高峰时间）；T1恢复至25%所需时间（临床肌肉松弛作用时间）；T1恢复至90%所需时间（体内作用时间）和T1从25%恢复至75％所需时间（恢复时间）。

　　全部数据处理采用上海科技出版社编辑的POMS统计学程序，用协方差分析比较两组患者的量-效关系曲线。用t检验比较其他数据在两组间的差别。P<0.05为有显著性差异。<?xml:namespace prefix = o ns = "urn:schemas-microsoft-com:office:office" />

结　果

　　两组病人的基本情况均无显著性差异（表1）。整个麻醉过程中患者的循环系统稳定，且体温正常。第1、2、3次累计剂量的应用时间在阿曲库铵组分别为3.8±1.2、7.5±2.1和10.2±3.3min；在罗库溴铵组分别为2.5±0.5、4.6±1.3和8.2 ±2.5min。两组间具有明显差别（P<0.05）。
　　两药量-效关系曲线的斜率无明显差别，但罗库溴铵量-效关系曲线的截距明显比阿曲库铵组低，说明阿曲库铵和罗库溴铵的量-效关系曲线相平行，但罗库溴铵的量-效关系曲线明显右移（附图），即罗库溴铵的作用强度较阿曲库铵弱。根据从量-效关系曲线得出的ED95，阿曲库铵/罗库溴铵的强度比率为1.2，两药的ED50、ED90和ED95均有明显差别。应用阿曲库铵400mg/kg或罗库溴铵600mg/kg（1.5×ED95）后，全部患者的颤搐反应达100％抑制。阿曲库铵的高峰时间、临床肌肉松弛作用时间和体内作用时间明显较罗库溴铵长，但两药的恢复时间无明显差别（表3）。

讨　论

　　本研究的目的是观察阿曲库铵和罗库溴铵量效反应和作用时相的差别。因为神经肌肉阻滞对血药浓度具有质反应的特点，所以其药效动力学适用于用对数剂量和概率反应之间的直线回归方程来描述3。本研究建立的量效关系曲线显示，根据达95％颤搐抑制所需的剂量，阿曲库铵的作用强度较罗库溴铵大约高20%。因为两药的量效关系曲线相互平行，所以此强度比率适用于所有剂量。

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