肝移植手术不同分期对罗库溴铵药效学的影响

Effects of hepatic function on pharmacodynamics of rocuronium during different stages of liver transplantation

目的观察肝移植术中罗库溴铵的药效学。方法全身麻醉下肝移植术患者30例，随机分为罗库溴铵间断组（Ⅰ组）和连续输注组（Ⅱ组）。采用TOF刺激方式，监测拇内收肌收缩反应，记录肌松效应及用药量等。结果两组年龄、体重、尿量、出血量、无肝期及手术时间的差异无统计学意义。两组肌松起效和恢复时间及用药量差异无统计学意义。Ⅰ组无肝期临床作用时间（97．9±26．1）min和新肝期肝动脉开放前第一次给药的作用时间（82．0±20．9）min，明显长于无肝前期（65．0±22．2）min。Ⅰ组和Ⅱ组无肝期及新肝期罗库溴铵的用量分别为（1．61±1．18，2．16±1．23）μg·kg^-1·min^-1和（1．44±0．53，2．01±1．24）μg·kg^-1·min^-1，显著低于无肝前期（5．07±1．01，5．68±1．75）μg·kg^-1·min^-1。术中转氨酶显著升高（P〈0．01），血尿素氮和肌酐有增高趋势，肌酐清除率有降低趋势。无肝期和新肝初期内环境变化显著。结论肝移植术中间断和连续两种给药方式，罗库溴铵的用药量和肌松恢复时间相似。无肝期肝功能缺如、新肝缺血再灌注及肝动脉化，以及肝外途径等协同作用，使得无肝期和新肝期罗库溴铵的作用时间延长，维持同等程度肌松时用药量明显低于无肝前期。

Objective To investigate the effects of hepatic function on pharmacodynamics of rocuronium during different stages of liver transplantation. Methods Thirty patients were randomly assigned into group Ⅰ（ receiving bolus of rocuronium） or group Ⅱ （ receiving continuous infusion of rocuronium） during general anesthesia. The responses of pollex adductor to train-of-four （TOF） stimulation of ulnar nerve were monitored. The time course and doses of rocuronium were recorded. Results There were no significant differences in onset time, recovery time and total close requirement of rocuronium between two groups. The clinical acting duration of rocuronium in group Ⅰ was 97.9 min ± 26.1 min in anhepatic phase and 82.0 min ± 20.9 min given before hepatic artery reperfusion of neohepatic phase, which was significantly longer than that in preanhepatic phase （ 65.0 min ± 22.2 min）. Rocuronium requirement decreased significantly in anhepatic phase （1. 61 μg·kg^-1·min^-1 ± 1. 18 μg·kg^-1·min^-1 and 2. 16 μg·kg^-1·min^-1 ± 1.23 μg·kg^-1·min^-1 in group I and group Ⅱ, respectively） and in neohepatic phase （1.44μg·kg^-1·min^-1 ± 0.53μg·kg^-1·min^-1 and 2.01μg·kg^-1·min^-1 ± 1.24μg·kg^-1·min^-1 in group Ⅰ and group Ⅱ, respectively） , compared with that in preanhepaticphase （5.07 μg·kg^-1·min^-1±1.01 μg·kg^-1·min^-1 and 5.68 μg·kg^-1·min^-1 ±1.75 μg·kg^-1·min^-1 in group Ⅰ and group Ⅱ, respectively ）. Serum aminotransferase and creatinine and urea nitrogen increased while creatinine filtration rate decreased during operation. The internal milieu changed significantly in anhepatic and neohepatic phases. Conclusion Dose requirement and paralysis recovery of rocuronium given by intermittent bolus or continuous injection are similar. Clinical acting duration of rocuronium prolonges and dose requirements decreases significantly in anhepatic and early neohepatic phases which seems to be related to the loss of hepatic function during anhepatic phase, to the reperfusion and re-arterialization of new liver, and to extra-hepatic factors.