肝功能异常病人硬膜外注射罗哌卡因的药效学和药代动力学  

Pharmacokinetics and pharmacokinetics of epidural ropivacaine in patients with liver dysfunction

作　　者：马民玉[1] 冉菊红[1] 马君志[1] 

机构地区：[1]郑州大学第一附属医院麻醉科,450052

出　　处：《中华麻醉学杂志》2006年第5期417-420,共4页Chinese Journal of Anesthesiology

基　　金：河南省科技攻关资助项目(0211043900)

摘　　要：目的观察肝功能异常病人硬膜外注射罗哌卡因的药效学和药代动力学特性。方法择期上腹部手术病人20例,10例阻塞性黄疸伴肝功能异常病人(ASAⅢ级)为肝功能异常组(Ⅰ组), 10例肝功能未见异常病人(ASA Ⅰ或Ⅱ级)为对照组(Ⅱ组)。两组均采用硬膜外阻滞复合全身麻醉, T8．9硬膜外穿刺置管,证实在硬膜外后2 min内注入0．75％罗哌卡因(含肾上腺素5μg·ml-1)2 mg· kg-1。记录注药后30 min内感觉和运动阻滞情况,用高效液相色谱法测定注药后0-720 min罗哌卡因血浆浓度,计算其各药代动力学参数。结果硬膜外注药后30 min内,两组感觉、运动阻滞效果差异无统计学意义。两组罗哌卡因的血浆药物浓度-时间曲线均符合二房室开放模型;与Ⅱ组比较,Ⅰ组硬膜外注药后180-720min罗哌卡因血浆浓度升高,消除半衰期延长,曲线下面积增加,清除率降低,消除速率常数减小(P<0．05或0．01)。结论肝功能异常病人0．75％罗哌卡因硬膜外阻滞后30 in内的感觉和运动阻滞效果无异常,但罗哌卡因的代谢明显减慢,血药浓度升高。Objective To investigate the pharmacokinetics of epidural ropivacaine in patients with liver dysfunction. Methods Twenty patients aged 20-58 yrs weighing 45-73 kg scheduled for upper abdominal surgery under general combined with epidural anesthesia were divided into 2 groups （n = 10 each） ： group Ⅰ patients with obstructive jaundice and group Ⅱ patients with normal liver function. Epidural block was performed at ＂Is.9 interspace. 0.75% ropivacaine 2 mg·kg^-1 （containing adrenaline 5 μg·ml^-1 ） was injected into epidural space over 2 min. General anesthesia was induced at 30 min after epidural ropivacaine with y-hydroxybutyrate 60-80 mg·kg^-1, remifentanil 2 μg·kg^-1 and atracurium 0.5 mg·kg^-1 . The patients were intubated and mechanically ventilated. Anesthesia was maintained with inhalation of N2 O ： O2 （ 1 ： 1 ） and intermittent i.v. boluses of atracurium and remifentanil infusion when needed. Pinprick sensory level, onset of analgesia and degree of motor block （Bromage scale） were assessed. Blood samples were taken from central vein at 0, 10, 20, 30, 45, 60, 90, 120, 150, 180, 240, 360, 480, 720 min after epidural ropivacaine for determination of plasma concentration of ropivacaine （HPLC）.Results The two groups were comparable with respect to F/M ratio, age, body weight, duration of operation, intraoperative blood loss and amount of fluid infused. There was no significant difference in onset time and height of sensory block and degree of motor block. The plasma ropivacaine concentration was significantly higher in group Ⅰ- （patients with liver dysfunction） than in group Ⅱ during 180-720 min after epidural ropivacaine. The concentration-time curves in the two groups were fitted to two compartment open pharmacokinetic model. The t1/2β was significantly prolonged, AUC0-t was significantly increased, CL and K10 were significantly decreased in group Ⅰ- as compared with group Ⅱ . Conclusions Liver dysfunction does not affect the sensory and motor block produced b

关 键 词：酰胺类 肝功能不全 药代动力学 麻醉 硬膜外 

分 类 号：R614.42[医药卫生—麻醉学]