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

摘要/摘要 静脉动脉体外膜氧合(VA-ECMO)是一种挽救患者生命的干预措施 顽固性心力衰竭，其使用频率在美国持续增加。然而，在 ECMO，血液暴露于ECMO回路中的非生物材料以及泵或 氧合器启动凝固级联反应。因此，患者变得容易中风，并需要 全身抗凝。Va-ECMO存在动脉回路血栓形成的风险，以及 血小板聚集或血细胞受损，被认为是导致患者急性缺血性中风的原因 关于ECMO支持。此外，由于VA-ECMO立即恢复脑灌注，常规给药 ECMO插管后头几个小时的高比例氧气被认为会导致急性脑损伤 再灌流损伤后脑损伤加重。ECMO插管后早期的神经损伤 为干预策略提供了机会，当急性脑损伤与这些 可改变的危险因素ECMO电路血栓和高氧血症已确定。 多年来，我一直对动脉侧血栓形成和高氧对急性脑出血的影响产生浓厚的兴趣。 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年患者的神经学结果。我是成人ECMO的主管 我在约翰·霍普金斯医院从事研究，并参与了帮助定义这种联系的研究 左心室辅助装置和神经损伤之间的关系。我对机械循环支持的兴趣 设备让我解决了VA-ECMO的关键知识和实践差距，VA-ECMO是伴随而来的急性大脑 损伤及其对神经学结果的影响。拟议的研究涉及两个重要的“可修改的” 成人VA-ECMO患者的因素--血块和高氧血症--及其与神经系统预后的关系。我 建议研究动脉侧ECMO生成的血栓是否与急性缺血性卒中有关 (目标1)和ECMO插管后24小时内高氧对医院神经预后的影响 排放(目标2)。ECMO产生的血栓和高氧血症是否会证明对急性脑部有实质性风险 损伤和不利的神经结局，我将提出临床试验来针对这些可修改的因素，通过 ECMO置管后保守氧疗及更换抗凝等策略 减少脑血栓的方法。这笔赠款将为我提供内容、方法和专业知识 作为一家由美国国立卫生研究院资助、以患者为导向的独立机构，多学科协作需要取得成功 临床医生--与心脏外科、重症监护和神经病学合作的科学家。该奖项还将提供 关键的新发现，可能会影响与动脉侧ECMO生成的血栓和 这些患有危重疾病的脆弱的成年患者的高氧血症。

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.