PLASMA-CONCENTRATIONS OF LAUDANOSINE, BUT NOT OF ATRACURIUM, ARE INCREASED DURING THE ANHEPATIC PHASE OF ORTHOTOPIC LIVER-TRANSPLANTATION IN PIGS
PLASMA-CONCENTRATIONS OF LAUDANOSINE, BUT NOT OF ATRACURIUM, ARE INCREASED DURING THE ANHEPATIC PHASE OF ORTHOTOPIC LIVER-TRANSPLANTATION IN PIGS
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DOI：
10.1097/00000542-199001000-00024
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发表时间：
1990-01-01
期刊：
影响因子：
8.8
通讯作者：
BENAKIS, A
中科院分区：
文献类型：
--
作者：
PITTET, JF;TASSONYI, E;BENAKIS, A
为了量化由于肝功能和循环缺乏而引起的阿曲库铵和劳丹诺辛血浆浓度的变化，作者研究了九只接受原位肝移植的家猪（22-25公斤）和三只未经手术的对照动物，使用阿曲库铵作为肌肉松弛剂。在2-3％异氟烷促进插管后，用异氟烷(0.5％氧气)和芬太尼(4μg.cntdot.kg-1.cntdot.hr-1)维持麻醉。控制通气以将呼气末CO2保持在35-40mmHg，体温保持在35.5-37.5℃，动脉pH保持在7.35-7.50。用神经刺激器刺激右侧坐骨神经，以 0.1 Hz 的频率、持续时间 0.2 毫秒的超最大刺激进行单次抽搐。通过力-位移传感器连续测量相应诱发的等长肌肉收缩的力。给予阿曲库铵单次静脉内推注(2mg/kg)以获得90-95%的抽搐抑制，随后5分钟后以120μg.cntdot.kg-1.cntdot.min-1的恒定速率静脉内输注阿曲库铵，在整个研究期间维持该值。每 15 分钟抽取血浆阿曲库铵和劳达诺辛浓度的血样。在对照组中，初次推注后阿曲库铵的血浆浓度保持稳定在6.5-8.0μg/ml之间；劳丹诺辛的血浆浓度在前60分钟内增加，然后保持稳定在0.69-0.74μg/ml之间直至研究结束。在接受移植的动物中，尽管肝脏排斥持续90分钟，阿曲库铵的血浆浓度仍稳定在10-12μg/ml之间。相反，在夹闭肝血管后45分钟，劳丹诺辛的血浆浓度显着增加（从0.57.+-.0.03.mu.g/ml到0.91.+-.0.02.mu.g/ml，平均值.+-.SE，P<0.05），进一步增加至峰值1.24.+-。 90分钟后为0.05μg/ml，并且在移植肝脏的循环恢复后保持在这些升高的浓度。本研究的结果表明，阿曲库铵在猪中的血浆清除率不依赖于肝功能。相反，其主要代谢物劳丹诺辛的血浆清除率强烈依赖于肝功能。
To quantify the changes in plasma concentrations of atracurium and laudanosine induced by the lack of hepatic function and circulation, the authors studied nine domestic pigs (22-25 kg) undergoing an orthotopic liver transplantation, and three control animals without surgery, using atracurium as the muscle relaxant. After intubation facilitated by isoflurane 2-3%, anesthesia was maintained with isoflurane (0.5% in oxygen) and fentanyl (4 .mu.g.cntdot.kg-1.cntdot.hr-1). Ventilation was controlled to keep end-tidal CO2 at 35-40 mmHg, body temperature maintained at 35.5-37.5.degree.C, and arterial pH at 7.35-7.50. The right sciatic nerve was stimulated with a nerve stimulator delivering a single twitch at 0.1 Hz with 0.2-ms duration, at supramaximal stimulation. The force of the corresponding evoked isometric muscle contraction was continuously measured by a force-displacement transducer. A single iv bolus of atracurium (2 mg/kg) was given to obtain a 90-95% twitch depression, followed by 5 min later by a constant-rate iv infusion of atracurium at 120 .mu.g.cntdot.kg-1.cntdot.min-1 maintained during the entire investigation. Blood samples for plasma atracurium and laudanosine concentrations were drawn every 15 min. In the control group, plasma concentrations of atracurium remained stable between 6.5-8.0 .mu.g/ml following initial bolus injection; plasma concentrations of laudanosine increased during the first 60 min, then remained stable between 0.69-0.74 .mu.g/ml up to the end of the study. In animals undergoing transplantation, plasma concentrations of atracurium remained stable between 10-12 .mu.g/ml, despite a 90-min duration of liver exclusion. In contrast, plasma concentrations of laudanosine were significantly increased 45 min after the hepatic vessels were clamped (from 0.57 .+-. 0.03 .mu.g/ml to 0.91 .+-. 0.02 .mu.g/ml, mean .+-. SE, P < 0.05), increased further to peak values of 1.24 .+-. 0.05 .mu.g/ml after 90 min, and remained at these elevated concentrations after restoration of circulation to the transplanted liver. The results of the present study demonstrate that in pigs plasma clearance of atracurium does not depend on hepatic function. In contrast, plasma clearance of its major metabolite laudanosine is strongly dependent on liver function.