Clinical Monitoring of the Effects of Pipecuronium<?xml:namespace prefix = o ns = "urn:schemas-microsoft-com:office:office" />

温　洪 岳　云 龙健晶
Wen Hong, Yue Yun, Long Jianjing.
Department of Anesthesiology，Beijing Chaoyang Hospital，Affliate of Capital University of Medical Science，Beijing 100020，China.

ABSTRACT

　Objective:To observe the effects of pipecuronium and its affection on the cardiovascular system.
　Methods:Thirty ASAⅠ～Ⅱ abdominal surgery patients were selected and the general anesthesia were inducted with midazolam，fentanyl，propofol and pipecuronium 0.1mg／kg for induction,and isoflurance，propofol and fentanyl were used for maintainace. The MAP，HR，SpO₂ and the degree of muscle relaxation (TOF measurement) were monitored continously during operation. The onset timing and the effects on the HR and MAP of pipecu-ronium were recorded. When T_l/T_c recovered to 25% of the control value(T_C), a bolus of pipecuronium 2 mg was given as to maintain the muscle relaxation. At the end of operation, when T_l／T_c＝20%～30％， neostigmine 2mg and atropine 0.5～1.0mg were given as to reverse the remained effect of pipecuronium，and the reverse sensitivity of pipecuronium(the timing of T_l/T_c recovered from 20%～30％ to 75％)were observed.
　Results:The onset timing of pipecuronium 0.1 mg／kg was 166.6±24.7s，the timing of T_l to 25％ recovery(clinical effectiveness timing) was 127.8±22.7min. After the administer of neostigmine, the timing of T_l/T_c to 75％ recovery in group A(n=19, who received only once pipecuronium) was 9.3±2.6min，and in group B(n=11，who received another bolus pipecuronium 2mg during operation) was 8.2±2.7min. There were no significant difference between the two groups(P＞0.05). The HR before using pipecuronium 0.1mg／kg was 78.9±11.8bpm，and were 78.9±11.8bpm，77.3±10.1bpm and 76.7±8.7bmp in 3min, 5min and 10min later respeatively there were no significant difference(P＞0.05). The MAP before using pipecuronium 0.1mg／kg was 91.7±14.9mmHg，and were 84.4±11.6mmHg, 86.9±12.9mmHg and 88.9±11.0mmHg in 3min, 5min and 10min later separatively，there were no significant difference(P＞0.05).
　Conclusions:Pipecuronium is a long-acting and powerful muscle relaxant with less affection on hemodynamics, its relaxation effect can be reversed effectively by the neostigmine. However，the efficacy of pipecuronium exists significant individual difference.
　Key words:Pipecuronium; Hemodynamics; Train of four;Neostigmine

　　哌库溴铵(pipecuronium,阿端)为长效非去极化型肌松药，效果确切，对血流动力学影响极轻，近年来已广用于临床麻醉。本文拟通过四个成串刺激（TOF）肌松监测，评估哌库溴铵的临床效应及对血流动力学的影响。
一、资料与方法
　　1、一般资料
　　选择30例ASAⅠ～Ⅱ级腹部手术病人，男17例，女13例，年龄44.7±10.7岁，体重71.1±13.4kg。入手术室后监测ECG、BP和SpO₂；连接肌肉机械收缩力型监测仪(MMG)施行TOF监测。麻醉诱导用咪唑安定2～3mg、芬太尼2～4μg／kg静脉注射，5min后继用丙泊酚1.5～2.0mg／kg静脉注射。睫毛反射消失后，在应用哌库溴铵前施行TOF，观察拇内收肌收缩反应，其T_l高度定标为对照值（T_C），计为100％；再在对侧前臂尺神经施行TOF（间隔14s）。随后静脉注射哌库溴铵0.1mg／kg，待T_l／T_c达到最大抑制时施行气管内插管。维持麻醉采用静吸复合麻醉，吸入异氟醚0.5～1.0MAC，输液泵连续注射丙泊酚5～12mg／(kg•h)和芬太尼1～2μg／(kg•h)，维持P_ETCO₂在30～40mmHg范围。根据BP、HR变化调整适宜的麻醉深度。手术进行中，当T_l／T_c恢复至25％时，追加单次哌库溴铵2mg(相当于1/4～1/3诱导剂量)以维持肌松。根据哌库溴铵的使用次数分为A、B两组。A组为仅于诱导期用过一次哌库溴铵者,共19例，年龄43.7±11.9岁，体重74.1±12.9kg。B组为除诱导期一次哌库溴铵外，术中再追加过一次者，共11例，年龄46.8±10.7岁，体重69.7±10.8kg。
　　2、肌松效应与血流动力学监测
　　①观察气管插管期的条件，采用Kring 4级评分法；②观察哌库溴铵的起效时间(从给哌库溴铵至T_l／T_c最大抑制的时间)、临床时效(T_l／T_c恢复至对照值25％的时间)；③观察给哌库溴铵后1min、5min和10min的MAP和HR。④手术结束前，当T_l／T_c恢复至20％～30％时，应用新斯的明2mg和阿托品0.5～1mg静脉注射以拮抗肌松残余作用，观察哌库溴铵对新斯的明的敏感性(以T_l／T_c＝75％作为肌松恢复的标准)，同时观察A组和B组肌张力恢复的时间。
　　3、统计分析
　　采用Excel软件，全部数据用x±s表示，用t检验，P＜0.05认为有显著性差异。
二、结果
　　1、A组哌库溴铵的起效时间为166.6±24.7s，临床时效为127.8±22.7min，气管内插管条件符合Ⅱ～Ⅳ级；使用新斯的明前的Tl／T_c值为24.7±4.2，使用新斯的明后T_l／T_c恢复至75％的时间为9.3±2.6min。B组于术中单剂注射哌库溴铵2mg后的肌颤搐由25％到最大抑制的时间为131.3±20.1s，使用新斯的明前的T_l／T_c值为24.6±3.3，使用新斯的明后的肌松恢复时间为8.2±2.7min。两组的年龄、体重、拮抗前T_l／T_c值均无显著性差异(P＞0.05)；使用新斯的明后的肌松恢复时间也无显著性差异。
　　2、使用哌库溴铵前的HR为78.9±11.8bpm；使用后3min、5min和10min的HR分别为8.9±11.8、77.3±10.1和76.7±8.7bpm，用药前后相比无显著性差异(P＞0.05)。使用哌库溴铵前的MAP为91.7±14.9mmHg，使用后3min、5min和10min的MAP分别为84.4±11.6、86.9±12.9和88.9±11.0mmHg，用药前后相比无显著性差异(P＞0.05)。

三、讨论
　　1、哌库溴铵的ED95为0.05～0.06mg／kg，于诱导期用其两倍ED95剂量即可获得适于气管插管和手术需要的肌松程度。据此，本文哌库溴铵诱导剂量采用0.1mg／kg，多数患者在2.5min左右出现满意的肌松，插管前的肌颤搐已达到最大抑制(T_l／T_c＝0～5％)，插管条件达到Ⅲ～Ⅳ级，30例中仅2例出现轻微呛咳反应。有人报导哌库溴铵0.05～0.08mg／kg即可达到插管Ⅲ～Ⅳ级条件，但起效时间稍有延长。
　　2、哌库溴铵的时效与剂量、复合用药等因素有密切关系。本文在静吸复合麻醉下，A组19例诱导期给哌库溴铵0.1mg／kg的肌颤搐25%恢复时间为2.0～2.5h；B组11例追加用药后肌颤搐达到最大抑制的时间约为20min，肌颤搐恢复至20%～30％的时间为0.8～1.2h。提示手术麻醉因素对哌库溴铵的时效可能有一定的影响，且数据的离散度较大。因此，在麻醉手术中哌库溴铵的时效可能得不到真实反映，需进一步验证。
　　3、哌库溴铵的肌松效应可被胆碱酯酶抑制剂拮抗。本文30例中，A组19例于术毕使用新斯的明2mg和阿托品0.5～1mg拮抗，肌颤搐恢复至75％的时间约为7～11min；B组11例术毕应用相同剂量新斯的明拮抗，其肌颤搐恢复至75％的时间约为6～10min，两组无显著性差异(P＞0.05)。说明不论单次还是术中追加单剂哌库溴铵，对新斯的明拮抗都敏感，一般不致延长苏醒时间。但也观察到哌库溴铵对新斯的明拮抗存在着个体差异，分析与病人血清胆碱酯酶水平存在差异可能有关，后者受到年龄、体重、体质、合并症等情况所影响。本文给新斯的明后肌颤搐恢复至75％的时间，比文献报导者稍有延长，可能与麻醉方法、手术类别、个体差异以及肌松监测仪灵敏度等因素有关。鉴于病人对哌库溴铵存在着个体差异，因此，利用床边肌松监测仪进行实时监测，可明显提高用药的安全性。
　　4、哌库溴铵对血流动力学的影响很小，应用其常规剂量不致消除迷走神经作用，也不引起组胺释放。Brinkmam等^[5]对冠脉搭桥手术病人使用不同的肌松药后检测血浆组胺水平，证明潘库溴铵和阿曲库铵可引起血浆组胺水平明显升高，而维库溴铵和哌库溴铵的组胺水平未出现影响。有人报导哌库溴铵可引起一过性血压下降，本文给哌库溴铵的心率和血压并无明显变化，用药前后比较P＞0.05。因此，本文认为哌库溴铵适用于心血管手术和血流动力学不稳定的病人，如果采用床旁肌松监测，对指导合理用药和提高用药安全性有益。 <?xml:namespace prefix = o ns = "urn:schemas-microsoft-com:office:office" />

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