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

基本信息

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
项目类别：
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

项目摘要

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/总结静脉动脉体外膜氧合 (VA-ECMO) 是一种挽救生命的干预措施然而，在美国，其使用频率持续增加。 ECMO，血液暴露于 ECMO 回路中的非生物材料以及泵或泵造成的创伤氧合器启动经过测试的凝血级联，患者容易中风并需要治疗。全身抗凝治疗存在动脉回路血栓形成以及微栓塞的风险。血小板聚集或受损的血细胞被重新捕获导致患者急性缺血性中风此外，由于 VA-ECMO 可以立即恢复大脑灌注，因此需要常规给药。 ECMO 插管后最初几个小时内的高浓度氧气被清除，导致急性脑损伤 ECMO 插管后早期的神经损伤会因再灌注损伤而恶化。当急性脑损伤与这些疾病之间的关系时，为干预策略提供了机会确定了可改变的危险因素、ECMO 回路血栓和高氧血症。多年来，我一直对动脉侧血栓形成和高氧对急性发作的影响非常感兴趣。此外，我在脑损伤和神经系统结果方面拥有丰富的研究经验。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该协会的研究我对机械循环支持的兴趣。设备帮助我解决了 VA-ECMO（伴随的急性大脑）的关键知识和实践差距损伤及其对神经系统结果的影响拟议的研究解决了两个重要的“可改变的”问题。成人 VA-ECMO 患者的血栓和高氧因素及其与神经系统结果的关系 I。提议调查动脉侧 ECMO 生成的血栓是否与急性缺血性中风相关（目标 1）以及 ECMO 插管 24 小时内高氧对医院神经系统结局的影响 ECMO 产生的血栓和高氧是否会带来急性脑损伤的重大风险？损伤和不利的神经系统结果，我将提出临床试验来针对这些可改变的因素策略，例如 ECMO 插管后使用保守氧疗和改变抗凝治疗减少脑栓塞的方法这笔赠款将为我提供内容、方法学专业知识和作为一个由 NIH 资助、以患者为中心的独立机构，需要多学科合作才能取得成功该奖项还将提供与心脏外科、重症监护和神经病学合作的临床医生科学家。至关重要的新发现可能会影响与动脉侧 ECMO 生成的血栓相关的护理这些脆弱的成年危重患者出现高氧血症。