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梗阻性黄疸对罗库溴铵作用时效和药物代谢的影响
鲍杨,张丽峰,宛泉龙,祝义军,史东平*
0
(上海市嘉定区中心医院麻醉科, 上海 201800
共同第一作者
*通信作者)
摘要:
目的 探讨梗阻性黄疸对罗库溴铵作用时效及药物代谢的影响,指导罗库溴铵在此类患者中合理使用,从而进一步指导肝胆手术麻醉的合理用药。方法 选择择期行全身麻醉手术的患者30例,分为梗阻性黄疸组(n=15)、对照组(n=15)。两组麻醉均采用连续硬膜外阻滞复合全身麻醉的方法。药效学研究:采用TOF-Watch SX加速度仪监测神经肌肉传导功能,记录药效学的相关指标,比较两组罗库溴铵药效学的差异。药物代谢研究:分别于单次给予罗库溴铵后30、60、90、120、180 min等时点采集血样,后用液相色谱-质谱联用的方法测定罗库溴铵血药浓度。比较、分析两组患者罗库溴铵体内代谢情况。结果 术前两组患者在年龄、体质指数、凝血酶原时间等方面差异无统计学意义,而总胆红素、直接胆红素和间接胆红素量差异有统计学意义(P<0.01)。两组患者罗库溴铵的起效时间差异无统计学意义,梗阻性黄疸组T1(4个成串刺激第一次颤搐反应)恢复到对照值(T1值的平台期) 10%、25%、50%、75%的时间、TOF比值(TOFR)70%的恢复时间以及恢复指数较对照组均延长(P<0.01)。单次给予罗库溴铵后检测30、60、90、120、180 min等时点患者罗库溴铵的血药浓度,发现60、90、120 min等时点梗阻性黄疸组罗库溴铵的血药浓度高于对照组(P<0.01或P<0.05)。结论 梗阻性黄疸可导致罗库溴铵临床有效作用时间延长和恢复时间延长,罗库溴铵的代谢较正常患者减慢;临床上此类患者使用罗库溴铵时,应该适当延长追加药物的时间,术中、术毕建议使用肌松监测仪指导合理用药及麻醉拔管。
关键词:  梗阻性黄疸  罗库溴铵  神经肌肉阻滞  血药浓度
DOI:10.3724/SP.J.1008.2014.01238
投稿时间:2014-03-23修订日期:2014-09-23
基金项目:上海市重点专科基金(ZK2012B19);上海市嘉定区科委基金(2010016).
Influence of obstructive jaundice on neuromuscular blocking effect and drug metabolism of rocuronium
BAO Yang,ZHANG Li-feng,WAN Quan-long,ZHU Yi-jun,SHI Dong-ping*
(Department of Anesthesiology, Central Hospital of Shanghai Jiading District, Shanghai 201800, China
Co-first authors.
*Corresponding authors)
Abstract:
Objective To observe the effect of obstructive jaundice on the neuromuscular blocking effect and drug metabolism of rocuronium, so as to guide proper use of rocuronium during anesthesia for patients undergoing hepatobiliary surgeries. Methods Thirty patients (with normal renal function and without muscle or nerves diseases, ASAⅠ-Ⅱ) receiving elective surgery were divided into 2 groups: obstructive jaundice group (group Ⅰ, n=15) and control group (group Ⅱ, n=15). All patients received continuous peridural anesthesia and general anesthesia. Neuromuscular blockade was evaluated with train-of-four (TOF) stimuli of the ulnsar nerve using TOF Watch SX nerve stimulators. The onset time, clinical duration of rocuronium, the time of TOFR from 0 to 70% and recovery index (T1 from 25%-75%) were observed. Liquid chromatography-tandem mass spectrometry (LC/MS/MS) was used to determine the concentration of rocuronium in the plasma at 30, 60, 90, 120, and 180 min after administration of 0. 9 mg/kg rocuronium. Results The age, body mass index, and prothrombin time were matched between the two groups. The total bilirubin, direct bilirubin and indirect bilirubin in groupⅠwere significantly higher than that in group Ⅱ(P<0.01) . The onset time was similar between the two groups; the clinical duration of rocuronium, the time of TOFR from 0 to 70%, and the recovery index (to 10%, 25%, 50%, and 75% of T1) in groupⅠwere significantly longer than those in groupⅡ(P<0.01). The plasma concentrations of rocuronium in groupⅠwere significantly higher than those in group Ⅱat 60, 90, 120 min after administration of rocuronium (P<0. 01 or P<0.05). Conclusion Obstructive jaundice may prolong the duration of rocuronium action and recovery time, and slows down the metabolism of rocuronium. So patients with obstructive jaundice should have a longer interval for drug addition. Peri- and post-operative monitoring of neuromuscular function is suggested for proper drug use and anesthesia extubation.
Key words:  obstructive jaundice  rocuronium  neuromuscular blocking effect  plasma concentration