研究背景 心脏骤停(cardiac arrest，CA)是心血管疾病主要的死亡原因。1960年，美国Kouwenhoven WB和Safar等提出了心肺复苏的概念，时间过去了半个世纪，尽管在治疗上已经有很大的进步，但其抢救成功率仍然很低。如何提高心肺复苏的成功率，仍是全世界共同关心的热门课题。 心脏骤停死亡的常见原因包括：初始复苏困难，复苏后出现的神经功能无法恢复、多器官功能衰竭、再次发生心脏骤停以及充血性心力衰竭等。 初始复苏困难：随着心肺复苏时间的延长，胸廓弹性下降，心搏量进一步下降，冠状动脉灌流量及氧供逐步降低，而且，随着心肺复苏的进行，心肌缺血时间延长，导致其反应性逐渐下降，最终失去对各种治疗措施的反应性。 复苏后心功能不全：复苏后心功能不全是导致心脏骤停患者最终死亡的重要原因，超过半数死于复苏后心功能不全，表现为明显的低血压及休克，再发心脏骤停等。 复苏后脑损害：心脏骤停患者常因早期短暂性脑组织完全缺血(无血流状态)，心肺复苏过程中的不完全缺血(低血流或/和微血流状态)导致脑损害，脑功能恢复困难。 ECMO作为一项新的生命支持技术，其原理是经导管将静脉血引到体外，在血泵的驱动下，经过膜式氧合器氧合，再输回患者体内。其中离心泵产生循环动力，替代了心脏的工作，血液的转流减轻了心脏负荷、增加了脏器的灌注；膜式氧合器替代了肺的工作，提高了血液的氧合，全身氧供和血流动力学处在相对稳定的状态，使心肺得到充分的休息，并获得一定时间来完成功能上的改善和病理上的修复，帮助患者度过危险期，改善预后。 理论上，ECMO可以应用于心肺复苏患者的救治。由于心脏骤停是非确定性事件，发生的原因、时间、地点、救助条件等极不确定，加之有效的救治时间非常有限，RCMO的建立需要一定的时间及技术条件。ECMO能否起到稳定循环，提高血液氧合，减少或减轻复苏后综合症发生的目的？能否真正减轻脑损伤，改善脑复苏的效果？在临床上有无可行性，如何进行实施？等等诸多问题，使得BCMO未能在心肺复苏中得到广泛应用。 为证实ECMO在心肺复苏中的作用，本课题分动物实验和临床研究两部分就BCMO对心肺复苏后的呼吸循环稳定性及脑氧和能量代谢进行了相关研究，并对ECMO在心脏骤停中的临床救治路径进行了探讨，旨在为体外膜肺氧合在心肺脑复苏中的应用提供理论和临床依据。 第一部分 体外膜肺氧合对心肺复苏猪的影响 目的 建立猪心脏骤停模型，对心脏骤停猪进行心肺复苏，比较常规心肺复苏(CPR组)和体外膜肺氧合(ECMO组)两组猪的血流动力学和血气分析指标，同时对S100B进行测定，并计算脑氧代谢指标，了解心肺复苏后的呼吸循环稳定性及脑氧和能量代谢与脑损伤情况，探讨体外膜肺氧合对它们的影响，为体外膜肺氧合在心肺复苏中的应用提供理论依据。 材料与方法 1.实验动物：藏族小型猪12只。 2.实验方法 2.1 实验分组：随机分为常规心肺复苏组(CPR组)和体外膜肺氧合组(ECMO组)，每组动物各6只(n=6)。 2.2 动物手术：麻醉后，气管切开备用；右颈内动脉置入导管，右颈内静脉置入漂浮导管监测血流动力学指标；颈外静脉置入室颤诱导电极至心心室；右股动静脉置入动静脉导管，并行ECMO管道预充。 2.3 动物实验：通过诱颤电极诱发室颤，室颤8min后开始胸外心脏按压及人工呼吸(30:2，FiO₂:21%)，持续复苏5min后ECMO组在CPR组基础上进行ECMO治疗。 2.4 观察指标：监测心脏骤停前，心脏骤停8min，复苏后5min、复苏后15min、复苏后30min，复苏后1 h，复苏后2 h，复苏后3 h，复苏后4 h两组猪的血流动力学及血气分析等指标，测定S100B，并计算脑氧和能量代谢。 3.统计学方法：统计数据以x±s表示，两组间比较采用成组t检验，组内比较采用配对t检验，以SPSS10.0统计软件进行统计，P＜0.05为差异有显著性意义。 结果 1.ECMO组心肺复苏后实验猪循环情况良好，MAP渐趋平稳并接近基础值，同时维持较高的冠脉灌注压。 2.PaO₂在ECMO治疗后各时间点ECMO组均较CPR组高(P＜0.01)，PaCO₂在ECMO治疗后各时间点ECMO组均较CPR组低(P＜0.05)。 3.ECMO组的颈静脉球部血氧饱和度(S〓O2)在ECMO治疗后各时间点明显高于CPR 组(P＜0.05)。 4.ECMO组CMR〓/CMR〓在ECMO治疗后各时间点明显高于CPR组(P＜0.05)。 5.ECMO组S100B在ECMO治疗后各时间点明显较CPR组低(P＜0.05)。 结论 1.ECMO能维持较高的冠脉灌注压，有利于自主循环的恢复。 2.ECMO能维持较高的PaO₂和较低的PaCO₂，从而保证全身各重要脏器对氧的基本需求，并减轻呼吸性酸中毒。 3.ECMO维持了神经元线粒体的结构和功能的完整性。 4.ECMO组正常高值的S〓O₂提示ECMO组心肺复苏时脑氧供需相对平衡，同时也提示可能较好的预后。 5.ECMO可能通过增加脑的血供和氧供，使颅内的葡萄糖和氧增加，CMR〓/CMR〓升高，改善脑氧代谢和脑能量代谢，从而有可能减轻脑损伤。 6.ECMO组心肺复苏过程中S100B蛋白维持在较低水平，说明ECMO时，脑损伤和血脑屏障受损程度相对较轻。 第二部分 体外膜肺氧合在心肺复苏中的临床应用研究 目的 对心肺复苏患者进行体外膜肺氧合，比较体外膜肺氧合前后血流动力学和血气分析指标，并对患者的脑功能恢复情况进行评测，对体外膜肺氧合在心肺复苏中的效果进行分析，提出ECMO在心脏骤停中的临床救治路径，为体外膜肺氧合在心肺复苏中的应用提供临床依据。 材料与方法 1.病例资料：2002年6月-2008年3月符合标准的心脏骤停患者20例。 2.治疗方法：紧急建立ECMO进行呼吸循环支持，并对原发病进行治疗。 3.观察指标：监测ECMO治疗前、ECMO治疗后10min、1h、6h、12h、24h患者的血流动力学及血气分析指标；同时采用格拉斯哥昏迷评分和神经功能缺损评分对复苏早期患者的神经功能和神经性后遗症情况进行了评测。 4.统计学方法：统计数据以x±s表示，治疗前后两样本间比较采用配对t检验，采用SPSS10.0统计软件进行统计，以P＜0.05为差异有显著性意义。 结果 1.一般情况：本组20例，ECMO辅助支持治疗最短5 h，最长106 h，平均21 h。行ECMO前心脏按压时间最短15 min，最长50 min。18例顺利停机，其中14例撤除ECMO后经原发病治疗康复出院，6例完全康复，没有后遗症，能记忆发病前的情况；4例有部分记忆障碍，无躯体后遗症；2例有精神障碍，2例有肢体偏瘫。4例ECMO撤机后死亡，其中2例撤机后24小时内死于循环衰竭，2例24小时后死于多器官功能衰竭。2例不能顺利脱机者ECMO辅助期间由于循环功能恶化，最终死于多器官功能衰竭。 2.血流动力学：平均动脉压在ECMO治疗后10min比ECMO治疗前明显升高(P＜0.01)，ECMO治疗后1 h比ECMO治疗后10min有所升高(P＜0.05)；CVP在ECMO治疗后10min比ECMO治疗前，ECMO治疗后1 h比ECMO治疗后10 min有所降低(P＜0.05) ； ECMO治疗后1 h比ECMO治疗后10 min心率增加；ECMO治疗1 h后MAP、HR、CVP趋于平稳。 3.血气分析指标：ECMO治疗后低氧血症均迅速改善，ECMO治疗后10min， PaO₂与SaO₂较ECMO前明显升高，动脉血乳酸含量明显降低；ECMO治疗1 h后 PH、PaO₂、SaO₂、LA趋于平稳。 4.格拉斯哥昏迷评分：患者复苏后GCS评分逐渐增高，复苏后第7d格拉斯哥昏迷评分达12.3±1.5，与复苏即刻比较差异有非常显著性意义(p＜0.01)，说明ECMO能改善脑复苏早期患者的神经功能状况。 5.神经功能缺损评分：患者在复苏后第10、20、30d其神经功能缺损评分逐渐降低，复苏后第30d降低至13.1±1.7，说明ECMO治疗可减少脑复苏后神经性后遗症的发生。 结论 1.ECMO可维持MAP，CVP等血流动力学指标基本稳定； 2.ECMO可以有效的改善低氧血症，迅速提高氧分压； 3.ECMO可改善患者的神经功能，减轻神经性后遗症； 4.完善的操作程序和规范以及专业化队伍，是快速建立ECMO，提高抢救成功率的重要条件。 关键词：体外膜肺氧合；心肺复苏术；心脏骤停；血流动力学；氧代谢

 Background Cardiac arrest (CA) is the leading cause of death in developed countries. The concept of cardiopulmonary resuscitation (CPR) was put forward by American Scientists Safer etc. in 1960. During the last half-century, the technology of CPR has been improved a lot, however, the achievement ratio of rescue is still quite low. Therefore, how to improve the achievement ratio of the technology of CPR is still a hot topic concerned by people around the world. The common causes of death from CA include difficult initial resuscitation, irrecoverable nerve function after resuscitation, multiple organ dysfunction syndrome, one more cardiac arrest, congestive heart failure and etc. Difficult initial resuscitation: With the prolongation of CPR, the elasticity of thoracic cage decreases and cardiac output drops more. Moreover, the increasing myocardial ischemia time will cause the reactivity decrease gradually, and in the end all the various measures will become ineffective at all. Post-resuscitation myocardial dysfunction: Post-resuscitation myocardial dysfunction is an important cause of the death from CA. Over a half of CA patients died of post-resuscitation myocardial dysfunction. The symptoms are obviously low blood pressure, shock, cardiac arrest again and etc. Post-resuscitation brain injury: Transient ischemic attack in the initial stage (no blood flow condition) and incomplete cerebral ischemia during the CPR stage (low blood flow or/and micro-blood flow condition) often cause brain injure and hard to improve the brain function. As a new life support technique, extracorporeal membrane oxygenation (ECMO) is an extracorporeal technique of providing both cardiac and respiratory support oxygen to patients. Through cannulae placed in large blood vessels, venous blood drains into the ECMO circuit. The ECMO machine continuously pumps blood from the patient through a "membrane oxygenator" that imitates the gas exchange process of the lungs, i.e. it removes carbon dioxide and adds oxygen. Oxygenated blood is then returned to the patient. The circulating force produced by the centrifugal pump takes the place of the heart, then the blood (low reduces the load of the heart, increases perfusion of organs at the same time. The membrane oxygenator functions as the lung to improve blood oxygenization. Consequently, oxygen supply and the hemodynamics remains relatively stable. In this way, the heart and lung can get sufficient rest and have the time to get functional improvement or even recovery. Theoretically, ECMO can be applied in treat CPR patients. However, due to the uncertainty of CA (that is, factors such as the cause, time, place, medical treatment condition and etc. are quite uncertain), limited effective treatment time, as well as time and technique requirements when establishing ECMO, the clinical application of ECMO remains questionable. Can ECMO really stabilize the circulatory, improve blood oxygenization, and reduce the chance of having post-resuscitation syndrome or mitigate post-resuscitation syndrome? Can ECMO really mitigate brain injury to improve brain function? Is ECMO feasible in clinical application and how to perform? These questions make ECMO not widely used in CPR currently To verify the effect of ECMO in CPR, this study has investigated its effect on the stability of respiratory and circulatory and the effect on cerebral oxygen metabolism and energy metabolism as well. It also has discussed clinical pathway of ECMO in cardiac arrest cases. The study aims to provide theoretical and clinical bases for the clinical application of extracorporeal membrane oxygenation in CPR. Part Ⅰ The effects of Extracorporeal Membrane Oxygenation on Porcine of Cardiopulmonary Resuscitation Objective Perform cardiopulmonary resuscitation on the pig model of cardiac arrest that has been developed. However, two groups are adopted, of which, one is Group CPR with traditional CPR way, the other is Group ECMO. Then, the variables of the hemodynamics and blood-gas analysis of the two groups are compared. Meanwhile, S100B is measured and then cerebral oxygen metabolism is calculated. Therefore, find out the situation of the stability of respiratory and circulatory, cerebral oxygen and energy metabolism, and brain injury. Discuss the influence of ECMO on them, and aim to provide theoretical basis for its clinical application in cardiopulmonary cerebral resuscitation (CPCR). Materials and Methods 1.Laboratory animals: 12 Tibetan miniature pigs 2.Methods 2.1 12 animals were randomly assigned to either CPR with the ECMO (n=6) or to standard CPR (n=6). 2.2 Surgical Preparations: After anaesthesia, perform tracheostomy for subsequent use. Cannula is placed in the right internal carotid artery and Swan-Ganz catheter is placed in the right internal jugular vein to monitor the parameter of hemodynamics. An electrode is placed in external jugular vein which connects the right ventricle to induce ventricular fibrillation. Cannulae are placed in right femoral artery and vein, and prime the ECMO circuit. 2.3 Experiment: Induce ventricular fibrillation through the electrode. 8 minutes later, apply external chest compression and artificial respiration (30:2, FiO₂: 21%). 5 minutes after continuous CPR, two groups are randomly selected, of which, one is Group CPR with traditional cardiopulmonary resuscitation, and the other is Group ECMO. that is. besides the application of CPR. the technique of ECMO is also applied. 2.4 Variables: Monitor the variables of hemodynamics and blood-gas analysis at the points of before the cardiac arrest, 8 min after cardiac arrest, 5 min after CPR, 15 min after CPR, 1 hr after CPR, 2 hr after CPR, 3 hr after CPR, 4 hr after CPR. S100B is measured and cerebral oxygen and energy metabolism are calculated. 3.Statistical method: All variables were given as mean±sem.Statistical analysis was performed with an t-test by using SPSS 10.0 software package. Statistical significance was considered at P＜0.05. Results 1.The laboratory pigs of the ECMO Group has good circulation. The MAP gradually became stable and close to the basic value, and the perfusion pressure was also maintained at a quite high level. 2.At each time point, the PaO₂ of the ECMO is higher than that of CPR (P＜0.01), while the PaCO₂ of the ECMO is lower than that of CPR (P＜0.05). 3.At each time point, the S〓O₂ of the ECMO is higher than that of CPR (P＜0.05) obviously. 4.At each time point, the CMR〓/CMR〓 of the ECMO is higher than that of CPR (P＜0.05) obviously. 5.At each time point, the S100B is lower than that of CPR (P＜0.05) obviously. Conclusions 1.ECMO can maintain sufficient coronary perfusion pressure and also help recovery of autonomous cardiac rhythm and spontaneous circulation. Therefore, the time of restoration of spontaneous circulation is shortened. 2.ECMO can maintain PaO₂ at a high level and PaCO₂ at a low level, so as to ensure the oxygen supply for the important organs and mitigate symptoms of respiratory acidosis. 3.ECMO maintains the structural and functional integrality of neuronal mitochondria. 4.The S〓O₂ of Group ECMO indicates the balance between oxygen demand and supply during cardiopulmonary resuscitation and good prognosis. 5.ECMO may enhance encephalic dextrose and oxygen by means of increasing cerebral blood supply and oxygen supply, and then improve cerebral oxygen metabolism and cerebral energy metabolism. Thus, the brain injury may be reduced. 6.The S100B of Group ECMO was maintained at a low level, which indicates that the brain injury and the injury of blood-brain barrier was relatively light during CPR. Part Ⅱ Clinical study of Extracorporeal Membrane Oxygenation for Cardiopulmonary resuscitation Objective To investigate the clinical application of ECMO. Compare the variables of hemodynamics and blood-gas analysis before and after providing ECMO to CPR patients. Observe the brain functional recovery. And meanwhile, discuss the effect of ECMO in CPR and put forward clinical pathway of ECMO in the Cardiac arrest cases. Thus, to provide theoretical basis for its clinical application in cardiopulmonary cerebral resuscitation (CTCR). Materials and Methods 1.Case data: 20 cases of cardiac arrest patients from June 2002 to March 2008 complying with the standard. 2.Treatment: Establish ECMO to provide respiratory and circulatory support, and treat the primary disease at the same time. Variables: Monitor the variables of hemodynamics and blood-gas analysis at the points of before ECMO, 10min, 1h, 6h, 12h, 24h after ECMO. The questionnaires of glasgow coma scale (CCS). neurological functional insufficiency(NFI) were employed to evaluate the nervous functional status and nervous sequelae , and at the same time , the effects of ECMO were observed. 3.Statistical method: All variables were given as mean±sem.Statistical analysis was performed with an t-test by using SPSS10.0 software package. Statistical significance was considered at P＜0.05. Results 1.Clinical results: Of the 20 cases, 14 patients got well enough to leave hospital after treatment of primary disease, among whom 6 were completely cured without sequelae and can remember the things happened before they fallen ill, 4 had memory disorders with no hemiplegy, 2 had mental disorders, and 2 had hemiplegy. 4 patients died of circulation failure after removing ECMO. 2 patients died of multiple organ failure because of the worsen circulation during the treatment of ECMO. 2.The variables of hemodynamics: 10 minutes after ECMO treatment, mean arterial pressure rose with significantly (P＜0.01) and one hour later, it even got higher (P＜0.05). On the other hand, CVP dropped 10 minutes after ECMO and lower one hour later (P＜0.05). The heart rate (HR) rose one hour after ECMO compared with that of 10 minutes after ECMO (P＜0.05). One hour after ECMO. the variables of MAP. HR, CVP became stable. 3.The variables of blood-gas analysis: After ECMO, the low oxygen saturation condition improved rapidly. 10 minutes after ECMO, the arterial partial pressure of oxygen (PaO₂) and oxygen saturation (SpO₂) improved apparently, while concentration of lactic acid of arterial blood decreased significantly (P＜0.01). One hour after ECMO, the variables of PH, PaO₂, SpO₂ and LA became stable. 4.Glasgow Coma Scale (GCS): The CCS score increased gradually after CPR. On the 7d. the GCS score was 12.3±1.5, which is signifantly different from that shortly after CPR (P＜0.01). It shows that ECMO can improve the nerve function of cerebral resuscitation patients at the early period. 5.Neurological functional insufficiency (NFI): The NFI scores on the 10d, 20d, 30d decreased gradually, that of 30d was 13.1±1.7, which shows that ECMO can reduce the chance of getting neurological sequelae after cerebral resuscitation. Conclusions 1.The technique of ECMO can increase mean arterial pressure and coronary arterial pressure, keep hemodynamics stable, and thus assure the blood supply of important organs. 2.Through a "membrane oxygenator", ECMO adds oxygen to venous blood and at the same time removes carbon dioxide. Then, cerebral oxygen and cerebral energy metabolism are ameliorated. Accordingly, brain injury is mitigated. 3.LCMO contributes to keep organ functions, then prevent from post-resuscitation syndrome, thus mitigate reperfusion injury of heart and central nervous system. The neurological functional status and quality of life in patients after CPR were improved partly by ECMO. 4.Integrated ECMO system and operating procedures, as well as professional team are important conditions for ECMO in clinical application. Key words: Cardiopulmonary cerebral resuscitation; Cardiac arrest; Extracorporeal membrane oxygenation; hemodynamics; oxygen metabolism