腹部手术中慢性肝功能不全病人罗库溴铵的药效学

Pharmacodynamics of rocuronium in patients with chronic liver dysfunction

目的观察腹部手术中肝功能不全病人罗库溴铵的药效学。方法择期行开腹手术的病人26例,ASAⅠ-Ⅲ级,根据肝功能情况分为2组,Ⅰ组为门脉高压肝硬化病人(肝功能不全组)。Ⅱ组为无肝脏疾病的病人(肝功能正常组),每组13例;监测神经肌肉传导功能,静脉注射诱导剂量罗库溴铵后T1恢复至5%时,持续静脉输注罗库溴铵,初始速率为600μg·kg-1·h-1,每隔5 min以此间隔前速率的10%-20%为标准,调整输入速率,当维持T1=5%的输入速率不发生变化达到1 h以上, 则视为稳态需求量。记录起效时间(注肌松药毕至T1消失的时间)、高峰持续时间(T1由0恢复至5%的时间)、临床有效作用时间(肌松药停止持续输注后T1恢复由5%至25%的时间)和恢复指数(T1 恢复由25%至750%的时间)、持续输注总量、手术时间、瑞芬太尼、异丙酚和咪达唑仑的用量。结果与Ⅱ组比较,Ⅰ组除术前肝功能指标差异有统计学意义外(P<0.05),年龄、性别比、体重、手术时间、瑞芬太尼、异丙酚和咪达唑仑用量差异无统计学意义(P>0.05),罗库溴铵起效时间、高峰持续时间、临床有效作用时间和恢复指数延长(P<0.01)。两组罗库溴铵持续静脉输注的时间相似(P>0.05), 罗库溴铵持续输注总量、平均用量和稳态需求量减少(P<0.05或0.01)。结论罗库溴铵0.6 mg/kg 用于全麻诱导为肝功能不全和肝功能正常病人提供相似的气管插管条件,但在肝功能不全病人中其起效时间、临床作用时间和恢复时间延长,持续输注用量减少。

Objective To investigate the effect of hepatic dysfunction on pharmacodyamics of rocuronium and the dose for infusion in patients with hepatic cirrhosis. Methods Twenty-six patients undergoing elective abdominal surgery under general anesthesia were divided into 2 groups according to their liver function： group Ⅰ patients with liver dysfunction （Child class B） （n=13） and group Ⅱ patients with normal liver function （n=13）. The patients were premedicated with intramuscular phenobarbital 0.1g and scopolamine 0.3 mg. Neuro-muscular function was monitored using TOF-WATCH SX accelography （Organon, Netherlands）. The force of thumb adductionin response to TOF stimulation （2Hz, 0.2 ms duration, 60 mA） of ulna nerve was measured and recorded. Anesthesia was induced with midasolam 0.1 mg·kg^-1, remifentanfl 1.5 μg·kg^-1 and TCI of proporol （target plasma concentration 2.5 μg·ml^-1）. Rocuronium （Rocu） 0.6 mg·kg^-1 was given i.v. to facilitate intubation. The patients were mechanically ventilated PET CO2 was maintained at 33-38 mm Hg. Anesthesia was maintained with remifentanil infusion at 0.2-0.3 μg·kg^-1·min^-1 and TCI of propofol （target plasma concentration 2.5-3.0 μg·ml^-1）. The infusion rate of Rocu was adjusted to maintain T1 at 5% of control （95% N-M block）. The onset time （time from injection of Rocu to maximal paralysis）, the duration of peak effect （time for T1 from 0-5 %）, the time for T1 from 5 %-25 %, and recovery index （time for T1 from 25 %-75 %）. The duration of Rocu infusion, the total amount of Rocu infused and the dose of Rocu infused during 1 h when T1 was maintained at 5 % of control were recorded. Results The two groups were comparable with regard to age, sex, body weight, duration of operation （〉2 h） and the amount of remifentanil, propofol and midazolam administered. The onset time, duration of peak effect （ T1 from 0-5 %）, the time for T1 from 5 %-25 % and recovery index （T1 from 25 %-75 % ） were significantly longer in group Ⅰ than in group Ⅱ （P〈0.01）. There was no significant difference in Rocu infusion time between the two groups. The total dose of Rocu infused was significantly lower in group Ⅰ than in group Ⅱ （P〈0.05）. Conclusion A bolus dose of Rocu 0.6 mg·kg^-1 provides similar N-M blockade in patients with hver dysfunction and normal function. The onset time, duration of action and recovery time are prolonged and the dose of Rocu infusion is lower in patients with hepatic cirrhosis.