2013-08-012024-05-14https://scholars.lib.ntu.edu.tw/handle/123456789/657908摘要：背景： 低溫療法是目前在急救科學很重要的議題。 我們先前的研究發現體外心肺復甦術 (ECMO assisted cardiopulmonary resuscitation, ECPR) 和傳統的急救方式比較起來預後較好。而使用葉克膜的病人若要調控體溫並不困難，只要調整體外加溫器的溫度即可達到目標溫度。 然而目前並沒有關於低溫療法應用於 ECPR 的病人的分組對照研究。 去年，我們建立了 ECPR 的低溫動物實驗模組，並觀察小腸的微循環 我們發現在ECPR 低溫療法的豬有較差的存活率和較差的小腸的微循環。今年更有臨床觀察顯示微循環較差的病患有較差的 ROSC後存活率， 而在小兔動物時驗則有低溫增加腦部微循環的報告。 縱合上述低溫對腦部的影響將是 ECPR後要不要低溫的重要考量， 而是否介由增加微循環改善預後將是重要治療方針。 在低溫的體外循環人體經驗及動物實驗中增加二氧化碳濃度有提高腦部血氧及體循環阻力下降的效果。 所以我們擬定此為期兩年的動物實驗計畫，觀察 ECPR 後有無低溫治療是否對腦部微循環有影響並且研究增加二氧化碳濃度是否改善腦部及身體的微循環及預後。 第一年我們將比較 ECPR 急救後低體溫和正常體溫的腦部微循環，希望可以解答是否低體溫可以改善腦部微循環。 第二年我們將嘗試以增加二氧化碳濃度到氧合器用在 ECPR 急救後的動物，來比較不同溫度及二氧化碳濃度在此種急救後的低灌流症候群是否能改善微循環。 方法： 本實驗採用的動物模組是 20-25 公斤的豬。 以電擊方式造成心室顫動心臟停止。ECMO-CPR 開始運作後把動物分成兩組： 對照組是體溫正常組 (n=5) ，體溫控制在 38 ℃ 維持六小時。 實驗組是低溫組(n=5)，體溫控制在 32 ℃ 維持四小時，然後在兩小時內回溫到 38 ℃。 如此使用六小時的 ECMO 後，把 ECMO 關掉並移除管路， 等待動物恢復並記錄結果。 實驗室檢查：我們每三十分鐘抽動脈血液做血液動脈氣體分析和乳酸值， 而血球計數 (CBC)、肝腎功能 (GOT GPT BUN CRE)、心肌酵素 (CK CKMB troponin I) ，則是在實驗開始時抽一基本值，心跳停止後六小時 和隔日會再抽血做檢驗。 微循環檢查： 我們會在實驗動物腦部開一小傷口，做大腦皮質顯微鏡檢觀察。我們用 OPS (Microscan ) 來觀察並記錄微循環，接著我們用軟體分析微血流 收集這些微循環資料的時間點，將在心跳停止前，啟用葉克膜 30 分鐘後，移除葉克膜前及移除後三十分鐘，我們將比較低體溫和正常體溫的兩組動物。第二年，正常體溫組動物將接受二氧化碳濃度（４０mmHg 及６０mmHg) 低體溫組動物將接受二氧化碳濃度(alpha-stat, pH-stat, 及增加到 60mmHg)，不同溫度及二氧化碳濃度在此種急救後的低灌流症候群的腦部及體循環效果。<br> Abstract: Hypothermic therapy is an important issue in resuscitation medicine. Currently, many doctors believed that hypothermia should be routinely performed in patients with returned spontaneous circulation (ROSC). ECMO assisted cardiopulmonary resuscitation (ECPR) was associated with improved outcome in patients with prolonged resuscitation. Hypothermia could be easily induced by adjust the temperature control system in ECMO. However, the evidence of benefit on hypothermia in ECPR patients is still lacking. Microcirculation dysfunction can contribute to cellular hypoxia even when global oxygen delivery is preserved. Since the improvement of microcirculation is one of the major target in post-resuscitation phase, we got the grant to study on microcirculation in animal model of ECMO-CPR with or without hypothermia. (100-2314-B-002-099-MY2) We found that the hypothermia group was associated with poorer outcome. The early survival rate of northermia group (37 °C) was 100% ( 5/5); one dead next day; three(60%) had normal appearance. In the hypothermia group (32 °C), the early survival was 80% (4/5), but three dead next day, only one(20%) normal appearance. The microcirculation of intestine is decreased in the hypothermia group. This finding implies adding hypothermia to our ECMO-resuscitation pig model did not further improve outcome. We hypothesis that the benefit of hypothermia in previous human reports might only resulted in the brain protection; instead of perfusion to other organs. In animal study and human observation, stepwise increase in arterial carbon dioxide tension was associated with a decrease in systemic vascular resistance and an increase in systemic blood flow and oxygen delivery. Cerebral oxygen saturation was also increased. We want to see if adding CO2 into the oxygenator, which could be easily performed, could benefit to the brain flow and systemic microcirculation. For the further study, we want to clarify: 1. The effect of hypothermia in cerebral blood flow in the ECMO-resuscitation pig model. 2. Could the result of ECMO-resuscitation improved by intervention on microcirculation. Material and method. Pigs, 20 to 25 kg, will be anesthetized with monitor equipment. The arrest model is performed by induced ventricular fibrillation, after a 15 minutes of no flow phase, ECMO will be performed. In the normothermia group(n=5), the temperature was controlled at 38°C, and maintained for 6 hours. In the hypothermia group(n=5), the temperature was cooled to 32°C, and maintained for 4 hours, and then rewarm to 38 °C in 2 hours. In addition to the hemodynamic monitoring and intestine microcirculation analysis, we will use the cerebral blood flow measurement, microcirculation analysis of the cerebral cortex, and metabolite of brain to clarify the effect of hypothermia. For the effect of CO2 administration: In the normothermia group with hyper CO2 group (n=5), the temperature was controlled at 38°C, and the target arterial PaCO2 will be 60mmHg. In the hypothermia group with alpha-stat cooling (n=5), pH-stat cooling (n=5) and hyperCO2 group(n=5). This will by adding CO2 mixture into the oxygenator gas.心肺復甦術葉克膜低體溫cardiopulmonary resuscitationECMOhypothermia