罗比卡因复合舒芬太尼用于腰丛联合坐骨神经阻滞的对照

1、罗比卡因复合舒芬太尼用于腰丛联合坐骨神经阻滞的对照研究唐帅 洪溪 黄宇光 任洪智 叶铁虎 罗爱伦作者单位：100730 中国医学科学院 中国协和医科大学 北京协和医院麻醉科责任作者： 洪溪 摘要 目的 评价舒芬太尼复合罗比卡因用于下肢神经阻滞的临床效果。 方法 40例择期在腰丛联合坐骨神经阻滞下行下肢手术的病人随机分为两组：观察组（n=20）用药为含浓度为0.5ug/ml舒芬太尼的0.375%罗比卡因，对照组（n=20）用药为0.375%罗比卡因。分别记录两组阻滞成功率、感觉和运动阻滞起效时间、作用时间及其它相关临床麻醉信息。 结果 两组间阻滞成功率、感觉和运动阻滞起效时间、作用时间无统计学差

2、异。 结论 0.5ug/ml的舒芬太尼对于0.375%罗比卡因用于下肢神经阻滞的临床效果没有明显影响，包括阻滞成功率、起效时间和作用时间。阿片类药物相关的副作用则有增加的趋势。关键词 腰丛联合坐骨神经阻滞；罗比卡因；舒芬太尼A clinical study on combined lumbar plexus and sciatic nerve block with 0.375% ropivacaine adding 0.5ug/ml sufentanil in patients undergoing lower extremity surgery Tang Shuai , Hong Xi ,

3、Huang Yuguang ,Ren Hongzhi, Ye Tiehu, Luo Ailun, et al . Department of Anesthesiology, Peking Union Medical College Hospital , Chinese Academy of Medical Sciences and Peking Union Medical College ,Beijing 100730 , CHINAAbstract Objective To evaluate the clinical significance of adding 0.5ug/ml sufen

4、tanil to 0.375% ropivacaine during peripheral nerve block. Methods 40 ASA I-II patients undergoing elective lower extremity surgery under combined lumbar plexus and sciatic nerve block were randomly allocated into two groups in a double-blind fashion, group 1: 50 mL of 0.375% ropivacaine alone ( n=2

5、0), group 2: 0.375% ropivacaine plus 0.5ug/ml sufentanil (n=20). The onset time and the duration for sensory and motor block as well as anesthesia parameters were recorded. Results The mean onset time of sensory block is 12.45.9 min and 13.97.4 min respectively for lumbar plexus block, 14.27.0 min a

6、nd 14.68.6 min respectively for sciatic nerve block; The mean onset time of motor block is 10.54.2 min and 11.36.5 min respectively for lumbar plexus, 13.69.5 min and 15.47.3 min respectively for sciatic nerve block; The mean duration of sensory block is 15.24.6hr and 14.34.5hr, respectively, the me

7、an duration of motor block 16.75.3hr and 17.36.1hr. No statistical differences were found between groups. No differences regarding the incidence of oversedation, PONV, itching and haemodynamic instability were observed between two groups. Conclusion We conclude that adding sufentanil 0.5ug/ml to 0.3

8、75% ropivacaine solution did not provide clinically relevant advantages in terms of onset time, duration and quality of combined lumbar plexus and sciatic nerve block in patients undergoing elective lower extremity surgery.Key Words Peripheral nerve block; combined lumbar plexus and sciatic nerve bl

9、ock; Ropivacaine; Sufentanil腰丛和坐骨神经联合阻滞在临床上用于下肢的手术麻醉，常用药为局麻药物。局麻药中加入阿片类药物对于神经阻滞效果的影响，目前文献报道结论不一，尤其对于在下肢神经阻滞方面的研究报道还很少。罗比卡因和舒芬太尼均为较新型的药物，本研究旨在评价舒芬太尼复合罗比卡因用于下肢神经阻滞的临床效果。资料与方法一般资料 本研究经北京协和医院伦理委员会许可，每个病人均签署知情同意书。选择40名ASA III级、年龄1870岁、体重4070kg、拟择期在腰丛联合坐骨神经阻滞下行下肢手术的病人。排除标准包括：病人拒绝、妊娠、有神经肌肉疾病、药物滥用史以及穿刺部位感染。

10、将病人随机分为两组：观察组（n=20）用药为含25ug舒芬太尼(0.5ug/ml)的0.375%罗比卡因 ， 对照组（n=20）用药为0.375%罗比卡因 。手术前一天由不参与评估过程的人员利用随机表决定用药，并于手术当日配药（标号）予操作者。方法 操作前记录病人身高、体重，建立静脉输液通路，神经阻滞过程中及术中持续监测心电图、无创血压和脉搏氧饱和度以及呼吸频率。穿刺前10-15分钟静注咪达唑仑0.04mg/kg镇静后进行阻滞。当认为有必要减轻病人焦虑和不适时，分次追加咪达唑仑0.02mg/kg，禁忌给予阿片类药物。所有外周神经阻滞均由同一麻醉医师完成。使用长100mm的21G绝缘刺激针（St

11、imuplex A,B.Braun;made in Japan）并连接神经刺激器（Stimuplex-DIG, B.Braun）进行阻滞。刺激频率设为2Hz，刺激电流强度开始设为1.0mA，后渐减至约0.3mA并维持受刺激肌群轻微运动反应。诱发成功后注入实验用药腰丛30ml，坐骨神经20ml。神经阻滞方法：腰丛：病人取侧卧位，阻滞侧下肢在上并屈髋屈膝，两侧髂嵴最高点连线与棘突交点旁开5cm为穿刺点。行局麻后，以穿刺针与皮肤呈90角进针。按照上述方法确定位置后，缓慢注入实验用药30ml，每5ml回抽一次。坐骨神经：病人取侧卧位，阻滞侧下肢在上并屈髋屈膝，膝关节呈90角，健侧下肢伸直（Sims位）

12、。由髂后上棘与股骨大转子作一连线，连线的中垂线与股骨大转子和骶裂孔的连线相交，此点即为穿刺点。行局麻后，以穿刺针与皮肤呈90角进针，按照上述方法确定位置后，缓慢注入实验用药20ml，每5ml回抽一次。操作结束之后，30分钟内每2.5分钟、30分钟后每30分钟测试一次股神经（大腿前面）、隐神经（小腿内侧）和坐骨神经支配皮肤区域（足背外侧）的针刺痛觉是否消失，同时评价髋、膝、踝关节的运动情况。根据临床实际工作的需要，30分钟后无论阻滞情况如何均开始做消毒铺巾等术前准备。术后由操作者对病人进行随访，记录感觉和运动阻滞时间，并记录所有不良事件。观察项目 疼痛程度评估采用视觉模拟评分法VAS（010）。

13、在切皮前测试病人手术部位VAS评分，如大于3分，则改为异丙酚持续输注，待术毕行针刺试验若阴性，则定义为起效延迟；若阳性则定义为麻醉未起效。阻滞效果按以下标准评价：手术过程无痛为满意的神经阻滞；需改全麻的为阻滞失败。病人对麻醉技术的满意程度：满意（必要时会再次选择这种麻醉方法）；不满意（会选择其他不同的方法）。腰丛感觉阻滞起效时间定义为从腰丛注药结束至大腿前部完全无针刺感；坐骨神经感觉阻滞起效时间定义为从坐骨神经注药结束至足背外侧完全无针刺感；腰丛运动阻滞起效时间定义为腰丛注药结束至髋关节不能运动（大腿抬腿不能）；坐骨神经运动阻滞起效时间定义为从坐骨神经注药结束至踝关节不能运动（足背伸或背屈不能

14、）。感觉阻滞时程定义为从注药至患肢恢复知觉或麻木感消失的时间；运动阻滞时程定义为从注药至患肢恢复运动自如的时间。统计分析 用SPSS for Windows Version 11.5和Microsoft Excel 97进行统计学分析。计量资料以均数标准差（S）表示，应用成组t检验，计数资料应用2检验。P0.05为差异有显著意义。结 果两组病人年龄、身高、体重、性别、ASA分级、手术种类差异无显著意义。关于神经阻滞的麻醉效果的数据见表1，组间差异不显著。无论是观察组（0.375%罗比卡因加0.5ug/ml舒芬太尼）还是对照组（0.375%罗比卡因），均可以满足大部分的神经阻滞需要。无论是感觉或

15、是运动阻滞，腰丛阻滞起效延迟的发生均少于坐骨神经阻滞。观察组的坐骨神经阻滞起效延迟的病例数多于对照组，但无统计学差异。对30分钟内起效病例进行起效时间及维持时间的分析，可以看出，两组在起效时间和阻滞时程方面未见统计学差异 （表2）。观察组的并发症发生例数（16人次）较对照组（6人次）高，均符合阿片类药物的副反应表现。其中：恶心观察组2例，对照组1例，均为轻度；呕吐观察组2例重度，对照组1例中度；搔痒观察组3例轻度，对照组无；困倦观察组3例轻度、1例重度，对照组1例轻度；排尿困难观察组1例轻度、1例重度，对照组1例重度；血流动力学不稳定观察组3例，对照组1例；两组均未发生局麻药中毒，均未发生呼吸

16、抑制。对照组一例出现术后小腿前面感觉障碍，经过严密随访，术后2周时感觉障碍皮区基本稳定于胫前区，疑与手术或麻醉过程中神经损伤有关。表1 两组麻醉效果组别例数部位刺激强度（mA）（S）感觉阻滞（例）运动阻滞（例）满意度需要异丙酚（例）30内起效起效延迟未起效30内起效起效延迟未起效满意不满意观察组20腰丛0.320.03172116131915坐骨神经0.300.021451866对照组20腰丛0.330.04182017122003坐骨神经0.330.0414421244*表示P0.05表2 麻醉数据（S）组别例数感觉阻滞起效时间（分钟）运动阻滞起效时间（分钟）感觉阻滞时程（小时）运动阻滞时程

17、（小时）腰丛坐骨神经腰丛坐骨神经观察组2013.97.414.68.611.36.515.47.314.34.517.36.1对照组2012.45.914.27.010.54.213.69.515.24.616.75.3讨 论罗比卡因是一种新型的酰胺类局麻药，用于神经阻滞的麻醉和镇痛，安全性好，阻滞时程长。舒芬太尼是一种脂溶性极强的阿片类药，具有镇痛效能高和作用时间长的优点，与局麻药物合用于椎管内麻醉，可增强镇痛效果和延长镇痛时间1。但人们对将阿片类药用于外周神经阻滞时的临床效果尚缺乏一致的看法。本研究的结果显示，浓度为0.5ug/ml的舒芬太尼对0.375%罗比卡因进行腰丛和坐骨神经阻滞的起

18、效时间和作用时程均无显著影响。从理论上讲，当利用局麻药进行外周神经阻滞时，在神经周围直接应用阿片类药可以提供更好的镇痛作用2。 许多生化和电生理研究提示在大的传入神经元上存在阿片受体3，并且已经有人通过免疫组化方法,以及从功能的角度说明了该受体的存在。应用阿片受体激动剂结合这些受体可以起到镇痛作用，这可能是通过抑制动作电位的传导或引起兴奋性神经递质释放来达到的4； Fields用阿片类药的向心性转运机制来解释其外周注射后增强镇痛作用的现象3；阿片类药也可能沿着神经鞘播散到硬膜外腔或蛛网膜下腔与脊髓后角的阿片受体结合而起作用；此外，阿片类药也可能被外周血管吸收入血液循环作用于中枢阿片受体。在临床

19、研究中证明，不同的阿片类药对局麻药的阻滞效果有不同的影响；即便是同一种阿片类药，其效果也随应用部位或局麻药种类而变化。现今神经阻滞时加入局麻药中较常用的是阿片类药芬太尼和舒芬太尼以及阿片受体激动拮抗剂丁丙诺啡。Nishikawa等人在臂丛神经阻滞时在局麻药中加入小剂量芬太尼，结果阻滞成功率增加，感觉阻滞时程延长5；而Magistris等人报道在下肢神经阻滞时加入小剂量芬太尼后起效时间、阻滞质量和时程均没有变化6。 Bazin等人比较了不同阿片类药之后发现，使用利多卡因和布比卡因混合液进行臂丛神经阻滞时，按脂溶性依次增强的顺序加入吗啡、丁丙诺啡和舒芬太尼，结果发现丁丙诺啡和舒芬太尼均延长了术后镇

20、痛时间，舒芬太尼更明显7；国内亦有研究表明丁丙诺啡延长了术后镇痛时间8。而Bouaziz等人在臂丛阻滞时加入舒芬太尼，起效速度、感觉运动阻滞时程没有变化，副作用却有增多的趋势9。由此可见，局麻药中加入阿片类药后，神经阻滞的临床特性如何变化尚无定论。这可能与不同的神经、不同阿片类药的药理学特性、阿片类药与不同局麻药之间的相互作用、甚至不同研究者之间的方法和观察指标的差异等等许多因素有关。本研究将罗比卡因的浓度降低至0.375%，意在增加局麻药的安全性和减少其阻滞时间来突出阿片类药的作用，并加入较大剂量舒芬太尼(0.5ug/ml)，但仍未得到阳性结果，这与Magistris等人的结果一致。外周神经

21、阻滞和椎管内麻醉有区别，椎管内给药时阿片类药更容易扩散入中枢神经系统阻滞其中的阿片受体，而外周神经给药时阿片类药被包裹于局部，不易扩散入中枢神经系统。这可以用来解释为什么硬膜外应用阿片类药会明显延长镇痛时间而外周神经应用却并不明显。 如此大剂量的舒芬太尼若直接入血，必然会产生镇静、呼吸抑制等阿片类药入血的征象，但外周神经给药后，药物被包裹并缓慢吸收，血药浓度持续在较低水平，故神经周围注射此剂量的舒芬太尼是安全的。样本量可能对研究结果有影响，但因为至今尚无下肢神经阻滞加入阿片类药的阳性结果，故无法计算所需样本量，因此我们选择了国内外文献常用的样本量。本研究结果显示，0.5ug/ml的舒芬太尼对于

22、0.375%罗比卡因用于下肢神经阻滞的临床效果没有明显影响，包括阻滞成功率、起效时间和作用时间。阿片类药物相关的副作用则有增加的趋势。阿片类药对外周神经的作用机制仍不明确，在临床中的应用尚需要进一步研究，这可能还需要做一些动物试验或离体试验。参考文献1 Polley, Linda S. MD; Columb, Malachy O. FRCA; Wagner, Deborah S. PharmD; Naughton, Norah N. MD. Dose-dependent Reduction of the Minimum Local Analgesic Concentration of Bupi

23、vacaine by Sufentanil for Epidural Analgesia in Labor. Anesthesiology,1998,89:626-632.2 Stein C.The control of pain in peripheral tissue by opioids.New Engl J Med,1995,332:1685-1690.3 Fields HL,Emcen PC,Leigh BK et al.Multiple opiate receptor sites on primary afferent fibres. Nature,1980,284:351-353

24、.4 Stein C.Peripheral mechanisms of opioid analgesia.Anesth Analg,1993,76:182-191.5 Nishikawa K, Kanaya N,et al. Fentanyl improves analgesia but prolongs the onset of axillary brachial plexus block by peripheral mechanism. Anesth Analg,2000,91(2):384-387.6 Magistris L, Casati A,et al. Combined sciat

25、ic-femoral nerve block with 0.75% ropivacaine: effects of adding a systemically inactive dose of fentanyl. Eur J Anaesthesiol,2000,17(6):348-353.7 Bazin JE, Massoni C, Bruelle P,et al. The addition of opioids to local anaesthetics in brachial plexus block: the comparative effects of morphine, bupren

26、orphine and sufentanil. Anaesthesia. 1997,52(9):858-862.8 徐文庆,等.丁丙诺啡加入局麻药用于臂丛神经阻滞的术后镇痛作用.临床麻醉学杂志,2005,21:753-754.9 Bouaziz H, Kinirons BP, et al. Sufentanil does not prolong the duration of analgesia in a mepivacaine brachial plexus block: a dose response study. Anesth Analg,2000,90(2):383-387.Sufen

27、tanil does not enhance the efficacy of ropivacaine in combined lumbar plexus and sciatic block: A controlled, randomized clinical trialShuai Tang, M.D; Xi Hong, M.D; Yuguang Huang, M.D; Hongzhi Ren, M.D; Tiehu Ye, M.D; Ailun Luo,M.D;Summary To date, the efficacy of the combination of opioids and loc

28、al anesthetics in peripheral nerve block is not conclusive yet. In this study, the onset time, duration as well as quality of lumbar plexus and sciatic nerve blockade were evaluated using sufentanil and ropivacaine combination compared with plain ropivacaine. 40 patients scheduled for lower extremit

29、y surgery under combined lumbar plexus and sciatic nerve block were randomly allocated into two groups. 50ml of 0.375% ropivacaine with 0.5ug/ml sufentanil (trial group) and 0.375% plain ropivacaine (control group) were administered when the location of lumbar plexus and sciatic nerve were confirmed

30、 by a nerve stimulator. Onset and duration of sensory and motor block were investigated. Opioid-related side effects were recorded. Quality of anesthesia in terms of success rate of block, patients satisfaction were reviewed after surgery. The addition of sufentanil to ropivacaine did not facilitate

31、 the onset of the block, nor the duration of analgesia. For lumbar plexus block, the mean onset time of sensory block was 13.97.4 min (trial group) vs. 12.45.9 min (contral group) respectively, 11.36.5 min vs.10.54.2 min respectively for motor block. For sciatic nerve block, the onset time of sensor

32、y block was 14.68.6 min vs. 14.27.0 min respectively, 15.47.3 min vs. 13.69.5 min respectively for motor block. The mean duration of sensory block is 14.34.5hr(trial group) vs 15.24.6hr(contral group) respectively, the mean duration of motor block 17.36.1hr vs. 16.75.3hr respectively. Opioid-related

33、 side effects were similar between groups, as well as the success rate of the block and patients satisfaction. We concluded that, during combined lumbar plexus and sciatic nerve block, adding sufentanil 0.5ug/ml to 0.375% ropivacaine solution did not provide clinically relevant advantages in terms o

34、f onset time, duration and quality of anesthesia for patients undergoing elective lower extremity surgery.Key words: lumbar plexus and sciatic nerve block; sufentanil; ropivacaine; 1. Introduction The perineural use of opioids develops rapidly. Most investigations are focusing on the effect of opioi

35、ds in epidural anesthesia. It seems that sufentanil has been proved to be effective in promoting the anesthesia and analgesia effect of local anesthetics in epidural anesthesia1. But the results of opioids in peripheral nerve block are quite different. Some biochemical and electrophysiological studi

36、es have shown the presence of opioid receptors in major afferent neurons2,3, which was confirmed via immunohistochemical technique as well as from the point of function. Opioid agonist might take analgesia action by binding with these receptors, that was probably achieved because of inhibition of ac

37、tion potential or the release of excitatory neurotransmitters4; Fields et al2 attributed this potentiation of analgesia after injection of opioids to mechanism of concentric transportation; in addition, opioids might also propagate along the neural sheath to epidural or subarachnoid cavity, then bin

38、d with the opioid receptors located in dorsal horn of spinal cord; finally, opioids could be absorbed into peripheral blood vessels and transported through circulation to the central opioid receptors. Consequently, the adding of opioids to local anesthetic solution for peripheral nerve block should

39、present better analgesic effect theoretically5,6. Nishikawa et al7 reported greater success rate of brachial plexus block when adding fentanyl to lidocaine, with longer duration of block. Bazin et al 8 compared different opioids combined with lidocaine and bupivacaine in peripheral nerve block, and

40、found that the more lipophilic the opioid is, the longer the duration of pain reliefs after the operation.However, there are still quite a few clinical studies showing no difference considering the onset time and duration when adding opioids to local anesthetics, with increasing tendency of side eff

41、ects9. Magistris et al10 reported no change in terms of onset time, duration and quality of peripheral block on lower extremities adding small dosage of opioids. Their negative result might partly be explained with different pharmacokinetics between long-acting ropivacaine and short-acting fentanyl.

42、 Acturally this is a dilemma, it is difficult to have any inclination. So we carried out this randomized, controlled trial to compare the efficacy of plain ropivacaine with ropivacaine plus sufentanil in combined lumbar plexus and sciatic nerve block for patients undergoing elective lower extremity

43、operations.2. MethodsAfter institutional ethics approval and written informed consent, 40 patients of ASA III scheduled for elective lower extremity surgery under combined lumbar plexus and sciatic block were enrolled in this study. Patients with following conditions were excluded: patient refusal,

44、pregnancy, neuromuscular disease, drug abuse, coagulopathy and infection of local injection site. Patients were randomly allocated into two groups, the group 1(trial group, n=20) received 0.375% ropivacaine HCL(0.75%NAROPIN manufactured by Astrazeneca, Sweden) with 0.5ug/ml sufentanil citrate(Manufa

45、ctured by Impfstoffwerk Dessau-Tornau GmbH, Germany) in the solution; group 2(control group, n=20) received 0.375% plain ropivacaine HCL(0.75%NAROPIN manufactured by Astrazeneca, Sweden). The solvent is 0.9%NaCl. Allocation of patients and preparation of drug solutions were done before surgery by a

46、staff who did not participate in either anesthesia nor evaluation process. The patients height, body weight were recorded and IV route was established before anesthesia. ECG, non-invasive blood pressure and SpO2 were monitored during anesthesia and operation. Patients were sedated with midazolam 0.0

47、4mg/kg 10-15min before the block was started, and repeat dose of 0.02mg/kg each time if necessary. Systemic use of opioid was prohibited.All lumbar plexus and sciatic block were performed by the same staff anesthetist who was blind to the patients group or the drug used. A 100mm 21-gauge insulated n

48、eedle was connected with a peripheral nerve stimulator (Stimuplex-DIG, Braun; Melsugen, Germany), which was used to identify the lumbar plexus and sciatic nerve. The stimulation frequency was 2Hz, the stimulation current was initially set at 1.0mA, then was decreased gradually to less than 0.5mA whe

49、n slight muscle twitch was still present, which was identified as appropriate position of the needle. The amount of study solution applied into lumbar plexus and sciatic block was 30ml and 20ml respectively.2.1. techniquesLumbar plexus: patients were put in lateral position with block side up, hip a

50、nd knee bent. Draw a line along the spinal process and another line along the bilateral highest point of iliac crests, the block site was made 4-5cm lateral to the intersection point of the two lines. After local skin infiltration with local anesthesia, the needle connected with stimulator using 1.0

51、mA was inserted perpendicular to the skin and redirected until the twitch of quadriceps muscle of thigh was elicited. The current was turned down slowly to approximately 0.5mA and keep the twitch still present, then drug solution was injected slowly and negative aspiration was made every 5ml for blo

52、od. Patients with evidence of epidural spread, demonstrated by contralateral hip-flexor weakness before or after surgery, were recorded.Sciatic nerve: after lumbar plexus injection, patients were still in lateral position, but the lower leg was straightened and upper knee joint was bent in 90angle (

53、Sims position). sciatic nerve blocks were performed according to the classic Labat approach: a line was drawn from the posterior superior iliac spine to the midpoint of the great trochanter. A perpendicular line was drawn bisecting this line which extended 5cm caudally, and a second line was drawn f

54、rom the great trochanter to the sacral hiatus. The intersection of this latter line with the perpendicular one indicated the point of needle entry. The stimulating needle was inserted and redirected eliciting flexion or extension of the foot. The current was turned down from 1.0mA to 0.5mA with the

55、muscle twitch still present, and the solution was injected slowly and aspirated every 5ml to avoid misplacing to the blood vessel.Sensory and motor blocks on the operated limb were evaluated every 2.5min within first 30min, and every 30min later. Pinprick test were made at anterior part of the thigh

56、 for lumbar plexus, lateral part of dorsal foot for sciatic nerve, respectively. While motor block was evaluated by asking the patient to flex the leg at the hip(represents the motor function of lumbar plexus) and to plantar flex or dorsiflex the foot(represents the motor funtion of sciatic nerve)11

57、 . Patients were followed up after the operation regarding the duration of the block and all adverse events. 2.2. Outcome measuresVisual Analogue Scale (VAS, 0-10) was applied to describe pain intensity by patients. If VAS was more than 3 during surgical area before incision, propofol infusion was t

58、hen offered. By the end of operation, pinprick test was done when patients woke up, it was described as delayed onset of the block if patients felt no pain, failed if pain persisted by that time. Quality of the block was described as: satisfactory (surgical procedure without pain) ; failed (general anesthesia was needed). Patients were asked to give their comment after operation: satisfactory (would choose the same