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/总结 静脉动脉外膜肺氧合（VA-ECMO）是一种挽救生命的干预措施， 难治性心力衰竭，其使用频率在美国持续增加。但在 ECMO、血液暴露于ECMO回路中的非生物材料以及泵造成的创伤，或 氧合器启动凝血级联。因此，患者变得容易中风， 全身抗凝。VA-ECMO具有动脉回路血栓形成的风险，以及来自 血小板聚集或受损的血细胞，这被假设为导致患者急性缺血性卒中 体外膜肺氧合支持此外，由于VA-ECMO立即恢复脑灌注，因此常规给予 假设ECMO插管后最初几个小时的高百分比氧气会导致急性脑损伤 和再灌注损伤的受损脑的恶化。ECMO插管后早期的神经损伤 提供了一个机会，干预策略时，急性脑损伤与这些 确定了可改变的风险因素、ECMO回路血栓和高氧。 多年来，我一直对动脉侧血栓形成和高氧对急性心肌梗死的影响有着浓厚的兴趣。 脑损伤和神经学结果。此外，我在脑损伤方面有丰富的研究经验， 使用机械循环支持装置的成人患者的神经学结局。我是成人体外膜肺氧合主任 约翰霍普金斯医院的研究，我参与了有助于确定这种关联的研究 左心室辅助装置和神经损伤之间的联系我对机械循环支持的兴趣 设备使我能够解决VA-ECMO中的关键知识和实践差距，伴随急性脑损伤， 损伤及其对神经学结果的影响。拟议的研究解决了两个重要的“修改” 成人VA-ECMO患者的凝血因子和高氧及其与神经功能结局的关系。我 拟研究动脉侧ECMO生成的凝块是否与急性缺血性卒中相关 (Aim 1）以及ECMO插管24小时内高氧对医院神经系统结局的影响 放电（目标2）。ECMO产生的血凝块和高氧应该被证明对急性脑损伤有很大的风险吗 损伤和不利的神经系统结果，我将建议临床试验，以针对这些可改变的因素， ECMO插管后保守氧疗、抗凝治疗等策略 减少脑栓塞的方法。这笔赠款将装备我的内容，方法的专业知识， 作为一个独立的NIH资助的，以病人为导向的， 与心脏外科、重症监护和神经病学合作的临床医生-科学家。该奖项还将提供 可能影响与动脉侧ECMO生成的凝块相关的护理的关键新发现， 高氧在这些脆弱的成年危重病患者。