Effect of Epidural Verapamil Instead of Fentanyl on the PCEA after Abdominal Surgery.<?xml:namespace prefix = o ns = "urn:schemas-microsoft-com:office:office" />

高建东 Gao Jiandong,岳云 Yue Yun,张雅慧 Zhang Yahui, et al.
Department of Anesthesiology, Beijing Red Cross Chaoyang Hospital, Affiliated of Capital University of Medical Science，Beijing 100020, China.

ABSTRACT

Objecitve：To investigate the possible role and side effects of the calcium channel blocker verapamil in post-operative PCEA.
　Methods：Seventy five post-operative patients (ASA Ⅰ～Ⅱ) scheduled for abdominal surgery were assigned to three groups randomly according to the different PCEA formula. Group 1:the prescription of PCEA was 0.0625%bupivacaine and fentanyl 5 μg/ml; Group 2:the prescription of PCEA was 0.0625%bupivacaine and fentanyl 2.5μg/ml and verapamil 2.5mg,dissolved in normal saline 10ml;Group 3:the priscription of PCEA was 0.0625%bupivacaine and verapamil 5 mg,dissolved in normal saline 10ml. In group1 and group 2 the administration of PCEA were in same way as immediately after operation and 10hours operation respectively.The PCEA model loading dose 4ml/h, basal infusion 1ml/h, PCA dose 4.5ml/h, lockout time 45min. Pain VAS values and PCA medication dosages and the side effects were assessed at 4h,10h,16h,24h after the operatrion in each group.
　Results：①PCA medication dosage of 24h were not significantly different among the three groups;②pain VAS values at 4h, 10h, 16h, 24h were not different among the three groups;③ side effects were not significantly different among the three groups.
　Conclusion：Suitable dosage verapamil combined with local anesthetics can be safey applied to the post-operative PCEA after abdominal surgery, and can strengthen or substitute the analgesic effect of epidural fentanyl. Possibly the calcium channel blocker plays the role in the passway of physiological pain on the spinal cord level by interfering with normal sensory processing and by preventing the establishment of central sensitization.
　Key words：Verapamil; PCEA; Fentanyl

阿片类药是应用最广和最有效的术后镇痛药，但存在嗜睡、呼吸抑制、恶心、排尿困难、便秘等不良反应，且长期应用容易产生耐药、成瘾和停药戒断综合征^[1]；从其疗效看，对慢性疼痛及神经损害性疼痛的效果较差^[2]。钙通道阻滞剂在脊髓水平上对生理性疼痛起着阻断作用，可能与干扰中枢正常感觉形成以及阻止中枢敏感化确立等作用有关^[3]。本文将维拉帕米用于腹部手术后硬膜外腔病人自控镇痛（PCEA），探索其是否能减少或甚至取代麻醉性镇痛药的效果，报道如下。

资料与方法<?xml:namespace prefix = o ns = "urn:schemas-microsoft-com:office:office" />

一、研究对象 
　　选择75例ASAⅠ～Ⅱ级择期腹部手术病人，无心血管系疾病及肝功能障碍，均在2%利多卡因硬膜外麻醉下手术。手术后根据PCEA配方的不同，随机分为三组，每组25例。Ⅰ组PCEA用0.0625%布比卡因+芬太尼5μg/ml，不用维拉帕米。Ⅱ组PCEA用0.625%布比卡因+芬太尼2.5μg/ml+维拉帕米2.5mg(溶于0.9%盐水10ml)。Ⅲ组PCEA用0.0625%布比卡因+维拉帕米5mg(用法同Ⅱ组)。Ⅱ组和Ⅲ组均分别于术毕和术后10h经硬膜外导管单次缓慢注入。
二、镇痛方法 
　　术毕用百特AP-Ⅱ电脑镇痛泵，均用负荷剂量+持续剂量+PCA即LCP给药模式。负荷剂量4ml，持续剂量1ml/h，PCA一次4.5ml，锁定时间45min。记录各组术后4h、10h、16h、24h的镇痛评分,采用视觉模拟标定法(VAS)评定镇痛分级、PCA用量及副作用发生情况。
三、统计学方法 
　　所得数据用±s或例数表示，t或χ²检验，P＜0.05为显著性差异。

结　果

一、三组病人性别、年龄、体重、麻醉时间、围术期生命体征无显著性差异，手术后PCA用量无显著性差异，见表1。
二、疼痛评分无统计学差异，见表2。
三、副作用无统计学差异，见表3。

讨　论

伤害性刺激可引起神经递质释放，这种神经递质释放被神经原突触末端膜电压依赖型钙离子介导的活化作用所连接。阻断钙离子内流，也就阻断了疼痛刺激，产生镇痛效应。外周组织损伤驱使外周敏感性和中枢敏感化的形成。外周敏感性可降低传入伤害感受器的外周末端阈值；中枢敏感化的形成依赖于脊髓神经元兴奋性的增强^[4]。研究表明这在脊髓背角的伤害性感受传递过程中与兴奋性氨基酸和神经肽有关^[5、6]。兴奋性氨基酸的活性被NMDA受体和非NMDA受体所介导；NMDA受体活化作用可致钙离子内流，由此开始一系列中枢敏感化过程，例如发条效应^[7]。中枢敏感化不仅可被氯胺酮或氢溴酸右美沙芬等NMDA拮抗剂所阻断^[8]，也可被钙离子通道阻滞剂通过阻止钙离子内流而达到同样作用。因此，我们推论硬膜外注入适量维拉帕米可以提高麻醉效果和减少麻醉药的消耗。据此，本研究的设计思路是降低芬太尼用量，而同时增加维拉帕米用量，以观察用于术后镇痛的效果及副作用。结果三组病人24h的PCA用量、镇痛评分、副作用并无统计学差异。据报道，钙通道阻滞剂维拉帕米可加强甚至取代芬太尼的镇痛作用，认为钙通道阻滞剂对生理性疼痛在脊髓水平上起着重要的作用，可能的机制是干扰正常感觉的形成，以及阻止中枢敏感化的产生。本研究第Ⅱ组用芬太尼，第Ⅲ组完全不用芬太尼而代之以维拉帕米，组间的芬太尼用量有很大的差别，但二组间的疼痛评分无显著性差异，据此我们认为硬膜外腔加入维拉帕米可以减少或不用芬太尼。因此，适量的维拉帕米与局麻药合用，可以安全应用于硬膜外腔PCEA术后镇痛，可考虑不用芬太尼。

参　考　文　献 <?xml:namespace prefix = o ns = "urn:schemas-microsoft-com:office:office" />

1.  梁建业。新型超短效镇痛药-remifentanil。国外医学麻醉学与复苏分册 1998；19:201.
2.  胡宁莉，等。慢性疼痛的药理学。国外医学麻醉与复苏分册 1998；19：218.〖ZK〗
3.  Huhn Choe, et al. Epidural verapamil reduces analgesic consumption after lower abdominal surgery. Anesth Analg 1998；86:786～90.
4.  Woolf CJ, Chong Ms. Pre-emptive analgesia: treating postoperative pain by preventing the establishment of central sensitization. Anesth Analg 1993；77:362～79.
5.  Besson JM, Chaouch A. Peripheral and spinal mechanism of nociception. Physiol Rev 1987；67:67～186.
6.  Dickenson AH. Spinal cord pharmacology of pain. Br J Anaesth 1995；75:193～200.
7.  Pockett S. Spinal cord synaptic plasticity and chronic pain. Anesth Analg 1995；80:173～9.
8.  卢玉平，等。氯胺酮的作用机制和非麻醉临床应用。国外医学麻醉与复苏分册 1998；19：222.