局部使用bupivacaine 於微創開心手術病人術後疼痛影響因子評估

Factors influencing the pain-relieving effect of bupivacaine local infusion in the wound after minimally invasive cardiac surgery

林子鏞(Tzu-Yung Lin)

指導教授 ： 謝建興

元智大學/工程學院/機械工程學系/博士(2009年)

https://doi.org/10.6838/YZU.2009.00083

摘要

病患接受心臟手術，術後常會造成接踵而來的疼痛，而開心手術中正胸及側胸的傷口切開，胸骨、肋骨、肋膜及肋骨脊椎關節的斷裂均會造成此種疼痛。局部傷口浸潤局部麻醉劑是一有效又簡單的方法。此種方法曾經被測試在髂骨手術、心臟手術後胸骨傷口、肺部手術後側胸傷口以及子宮切除傷口。此一研究主要目的是測試及評估病患接受微創開心手術後側胸傷口對於局部傷口浸潤局部麻醉劑的反應，希望能找到使用bupivacaine局部麻醉劑於傷口浸潤對於疼痛的影響因素，包括藥物濃度、浸潤的速度以及浸潤的位置。除了急性疼痛外，我們也試著評估是否使用局部麻醉劑會對慢性疼痛有所影響，以及探討bupivacaine於不停跳開心手術病人術後發炎因子的變化。
病人接受微創開心的冠狀動脈繞道手術或瓣膜手術是我們研究的對象。病人隨機分為兩組並評估術後疼痛。實驗組病人其側胸傷口接受0.15% bupivacaine以2mL/hr的速度浸潤，並同時接受靜脈注射病患自控式止痛；控制組病人僅使用靜脈注射病患自控式止痛而側胸傷口是以生理食鹽水於傷口浸潤。我們以Verbal analog pain scores評估疼痛指數。兩組各有19個病人接受此雙盲試驗，並得到使用局部靜脈注射病患自控式止痛加上bupivacaine局部傷口浸潤劑的使用，不論是1天、3天以及90天均比單獨使用靜脈注射病患自控式止痛的病人有較低的疼痛指數。我們又測試了0.375%以及0.5%的bupivacaine；並以2mL/hr及5mL/hr的速度測試濃度及速率的影響。這些病人在統計資料及手術前後無統計上的差異。接著我們收集了0.375% bupivacaine 2mL/hr 的10個病人血清並利用高效液相分析儀分析，發現24hr到48hr有上升的趨勢。最後我們利用ELISA的方式去檢驗使用0.375% bupivacaine的病人並分析血清中IL-8、IL-10的數量，0.375% bupivacaine組的IL-8趨勢相較於生理時鹽水組是比較高的。
未來我們希望能找到合適濃度及速率的局部麻醉劑並使用於開心手術病人來緩解他們的疼痛；同時可以比較與其他替代藥物或操作的止痛效果。同時，抗發炎及抗菌效果，也是我們的研究範圍。我們試著建構動物實驗模型並利用連續局部麻醉劑浸潤的方式於未來的實驗；如果此模型被證明有效，我們不只可以推廣局部傷口浸潤於開心手術病人術後止痛，並且可能可以用於預防開心手術後感染的併發症。

關鍵字

微創開心手術, 病患自控止痛, 硬脊膜外止痛, 局部麻醉藥, 疼痛

並列摘要

Patients undergoing cardiac surgery often dread the upcoming pain after surgery. The pain associated with cardiac surgery requiring sternotomy or thoracotomy originates from skin incisions, fractured sternum or ribs, parietal pleura and costoverterbral joint injury. Infusion of local anesthetics in the wound is a simple and safe method of pain control. It has been tested in various site and proved to be effective in iliac crest harvest site, sternotomy of cardiac surgery, thoracotomy after lung surgery, and hysterectomy. The main purposes of this study were to assess the effect of local wound infusion of local anesthetics on pain control in the thoracotomy wound of patients undergoing minimally invasive cardiac surgery, to disclose the factors determining the pain-controlling effect of bupivacaine wound infusion, including the concentration of bupivacaine, infusion rate, and location of infusion. Besides of acute pain, we also investigate if different duration or timing of local anesthetics administration would modify the pattern of chronic wound pain, and to investigate the effect of bupivacaine local infusion at sternotomy after off-pump coronary bypass grafting surgery on postoperative inflammatory cytokine surge.
Patients who underwent coronary artery bypass grafting or cardiac valvular procedures via a minimally invasive thoracotomy were studied. Patients were enrolled and randomly allocated to two groups with different modalities of postoperative analgesia. In the first part, the thoracotomy wound infusion group received 0.15% bupivacaine infused continuously at 2 mL/h through a catheter embedded in the wound, as well as intravenous patient-controlled analgesia. The control group had patient-controlled analgesia alone with a sham thoracotomy wound infusion of normal saline. Verbal analog pain scores (0–10 points) and recovery profiles were investigated. There were 19 patients in each group for complete data analysis. In this controlled double-blind study, thoracotomy wound infusion and patient-controlled analgesia was superior to patient-controlled analgesia alone in reducing pain at 1, 3, and 90 days after minimally invasive cardiac surgery. Second, we used 0.375% and 0.5% of bupivacaine or 2 mL/hr and 5 mL/hr to the patients to assess the effect of concentration and rate. Among these patients, there was no significant difference in both demographic data and perioperative characteristics. Third, we collected ten patients’ data and analyzed bupivacaine concentration in plasma by HPLC. All of them had 0.375% bupivacaine infused at 2ml/hour after operation. There was an increased trend from 24 to 48 hours after the operation. Forth, we also evaluate the inflammatory reaction by analyzed IL-8 and IL-10 concentration in plasma via ELISA. These patients were divided into two groups: 0.375% bupivacaine infused at 5ml/hour and normal saline. Individual variance was caused significant difference among time points. However, the trend of bupivacaine group was higher than saline group in IL-8, but the IL-10 was similar.
In the future, we want to find out the optimal concentration and infusion rate of local anesthetics wound infiltration in cardiac surgery and compare the pain relief effect of other alternative procedures or drugs. Besides, the anti-inflammation and antimicrobial effect was also noted in the in-vitro study, we try to construct an animal model and using the continuous infusion of local anesthetics methods in this model which may be helpful in this study. If this animal model is proved effective, maybe we can promote the continuous local anesthetics infiltration methods in cardiac surgery not only in pain relief, but also in the prevention of wound infection which was a major complication of cardiac surgery.

並列關鍵字

minimal invasive cardiac surgery, Patient-controlled analgesia, local anesthetics

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