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.

PROJECT NARRATIVE … Adult patients with heart and lung failure are sometimes supported with temporary mechanical support called extracorporeal membrane oxygenation (ECMO) and its use has increased dramatically in the United States over the last 10 years. Although ECMO is a life-saving intervention for patients, a potential complication is acute brain injury. We will examine whether ECMO causes the production of blood clots that lodge in the brain and cause stroke and whether too much oxygen may contribute to injury in this proposal and understanding these risks may enable us to suggest changes to treatment that can be tested in future studies.