CLots and Oxygen in Va-ExtracorpoReal membrane oxygenation (CLOVER) study

Va-体外真实膜氧合 (CLOVER) 研究中的 CLots 和氧气

• 批准号: 10370823
• 负责人: Sung-Min Cho
• 金额: $ 17.35万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-01-21 至 2026-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10370823
• 关键词: Acute; Acute Brain Injuries; Address; Adult; Anticoagulation; Automobile Driving; Award; Biometry; Blood; Blood Cells; Blood Platelets; Blood coagulation; Blood gas; Brain; Brain Injuries; Brain hemorrhage; COVID-19; Cannulations; Cardiac Surgery procedures; Cardiopulmonary Resuscitation; Caring; Cerebral Emboli; Cerebrovascular Circulation; Cerebrum; Clinical Investigator; Clinical Trials; Clinical Trials Design; Coagulation Process; Collaborations; Complication; Critical Care; Critical Illness; Data; Data Science; Devices; Echocardiography; Exposure to; Extracorporeal Membrane Oxygenation; Frequencies; Funding; Future; Goals; Grant; Guidelines; Heart Arrest; Heart failure; Hospitals; Hour; Hyperoxia; Hypoxic-Ischemic Brain Injury; Injury; Interdisciplinary Study; Intervention; Ischemic Stroke; Knowledge; Lead; Life; Mechanics; Mentors; Methodology; Methods; Monitor; Morbidity - disease rate; Nervous System Trauma; Neurologic; Neurological outcome; Neurology; Outcome; Oxygen; Oxygen Therapy Care; Oxygenators; Partial Pressure; Patients; Perfusion; Physiology; Production; Prospective Studies; Protocols documentation; Pump; Refractory; Reperfusion Injury; Reperfusion Therapy; Research; Respiratory Failure; Risk; Risk Factors; Running; Savings; Scientist; Severities; Shock; Side; Signal Transduction; Stroke; Testing; Thrombophilia; Thrombosis; Thrombus; Tissues; Training; Transcranial Doppler Ultrasonography; Trauma; United States; United States National Institutes of Health; World Health Organization; base; blood damage; career; career development; experience; improved; interest; ischemic injury; left ventricular assist device; mechanical circulatory support; modifiable risk; mortality; multidisciplinary; neurophysiology; novel; novel coronavirus; oxygen toxicity; pandemic coronavirus; patient oriented; prevent; prospective; respiratory; restoration

ABSTRACT/SUMMARY Venoarterial Extracorporeal Membrane Oxygenation (VA-ECMO) is a life-saving intervention for patients with refractory cardiac failure, and the frequency of its use continues to increase in the United States. However, during ECMO, exposure of blood to the non-biological material in the ECMO circuit and to trauma from the pump or oxygenator initiates the coagulation cascade. Consequently, patients become vulnerable to stroke and require systemic anticoagulation. VA-ECMO carries a risk of arterial circuit thrombosis as well as microemboli from platelet aggregates or damaged blood cells, which is hypothesized to cause acute ischemic stroke in patients on ECMO support. In addition, as VA-ECMO immediately restores perfusion to brain, routine administration of high-percentage oxygen for the first hours after ECMO cannulation is hypothesized to cause acute brain injury and worsening of injured brain with reperfusion injury. This neurologic injury early after ECMO cannulation provides an opportunity for intervention strategy when the relation between acute brain injury and these modifiable risk factors, ECMO circuit clots, and hyperoxia, is established. For many years, I have had a strong interest in the effects of arterial-sided thrombosis and hyperoxia on acute brain injury and neurologic outcome. Additionally, I have extensive research experience in brain injury and neurologic outcome in adult patients with mechanical circulatory support devices. I am the director of adult ECMO research at Johns Hopkins Hospital and am involved with studies that have helped to define the association between left ventricular assist devices and neurologic injury. My interest in mechanical circulatory support devices has led me to address key knowledge and practice gaps in VA-ECMO, the concomitant acute brain injury, and its impact on neurologic outcome. The proposed research addresses two important “modifiable” factors—blood clots and hyperoxia—in adult VA-ECMO patients and their relation to neurologic outcome. I propose to investigate whether arterial-sided ECMO-generated clots are associated with acute ischemic stroke (Aim 1) and the effects of hyperoxia within 24 hours of ECMO cannulation on neurologic outcome at hospital discharge (Aim 2). Should ECMO-generated clots and hyperoxia prove to carry a substantial risk for acute brain injury and unfavorable neurologic outcome, I will propose clinical trials to target these modifiable factors by strategies such as using conservative oxygen therapy after ECMO cannulation and changing anticoagulation approaches to reduce cerebral emboli. This grant will equip me with the content, methodological expertise, and multidisciplinary collaboration required to be successful as an independent NIH-funded, patient-oriented clinician-scientist in collaboration with cardiac surgery, critical care, and neurology. This award will also provide critically novel discoveries that may likely impact care related to arterial-sided ECMO-generated clots and hyperoxia in these vulnerable adult patients with critical illness.

摘要/摘要 venoarterial体外膜氧合（VA-ECMO）是对患者的生命干预措施 在美国，难治性心力衰竭及其使用的频率持续增加。但是，期间 ECMO，血液暴露于ECMO电路中的非生物材料，并从泵或 氧合启动凝血级联。因此，患者容易中风，需要 全身抗凝。 VA-ECMO具有动脉回路血栓形成的风险以及来自 血小板聚集体或受损的血细胞，假设患者会引起急性缺血性中风 关于ECMO的支持。此外，由于VA-ECMO立即恢复了对大脑的灌注，因此常规给药 假设ECMO插管后的最初几个小时高度氧气引起急性脑损伤 并担心因再灌注损伤而受伤的大脑。 ECMO插管后早期这种神经损伤 当急性脑损伤与这些关系之间的关系时，提供了干预策略的机会 建立了可修改的危险因素，ECMO电路云和高氧。 多年以来，我一直对人工制品和高氧对急性的人工制品的影响产生了浓厚的兴趣 脑损伤和神经系统损伤。此外，我在脑损伤和 具有机械电路支持装置的成年患者的神经系统结果。我是成人ECMO的主任 约翰·霍普金斯医院的研究，并参与了有助于定义协会的研究 在左心室辅助装置和神经系统损伤之间。我对机械电路支持的兴趣 设备使我解决了伴随急性大脑VA-ECMO中的关键知识和练习空白 伤害及其对神经系统结果的影响。拟议的研究涉及两个重要的“可修改” 成年VA-ECMO患者及其与神经系统结局的关系的因素 - 血栓和高氧。我 提议研究伪造或侧面生成的布与急性缺血性中风有关 （AIM 1）以及在ECMO插管后24小时内高氧对医院神经系统结局的影响 放电（AIM 2）。生成生成的布料和高氧是否应该证明具有急性大脑的巨大风险 损伤和不利的神经系统结局，我将提出临床试验，以通过 诸如ECMO插管后使用保守的氧疗法和抗凝改变之后的策略 减少脑栓的方法。这笔赠款将使我掌握内容，方法论专业知识和 多学科合作必须作为独立的NIH资助，面向患者的独立合作 临床科学家与心脏手术，重症监护和神经病学合作。该奖项也将提供 至关重要的发现可能会影响与动脉侧生成的布料相关的护理 这些脆弱的成年患者的高氧。