DELTA ECMO ABI study (Assessing Acute Brain Injury after Rapid Reduction of PaCO2 upon ECMO Cannulation using Portable MRI and Biomarkers)

PROJECT SUMMARY/ABSTRACT … Extracorporeal Membrane Oxygenation (ECMO) is a life-saving therapy for people with severe heart and lung failure, and its use as therapeutic support continues to increase in the United States. However, acute brain injury (ABI) commonly occurs during this intervention, often leading to considerable disability or even death. Currently,

we lack a solid understanding of why ABI occurs during ECMO, although previous research has implicated the potential impacts of carbon dioxide (CO2) regulation on cerebral physiology. For example, we do not have a good understanding of the sequelae resulting from the rapid physiologic changes that accompany ECMO support in

the first 24 hours of treatment, when refractory cardiopulmonary failure in these patients is being rapidly reversed. These patients frequently experience severe acidosis and hypercapnia prior to cannulation, which is rapidly reversed upon ECMO initiation by adjusting sweep gas flow across the oxygenator membrane. The proposed

research aims to address this evidence gap, by improving our understanding of the early physiologic changes that impact outcomes after ECMO initiation. We hypothesize that the acute △PaCO2, which often accompanies the initiation of ECMO with its rapid correction of PaCO2, causes cerebral vasoconstriction

resulting in a substantial decrease in cerebral oxygen delivery and ABI. The rationale for our hypothesis is that CO2 is a potent cerebral vasodilator and prolonged hypercapnia can impair cerebral autoregulation. Our preliminary data provide convincing evidence that △PaCO2 represents a major mechanism for ABI in ECMO

patients, leading to poor long-term neurological and psychiatric outcomes. Our data also show that bedside detection of ABI is feasible using readily available low-field portable brain MRI and brain injury plasma biomarkers. Our proposed research, the DELTA ECMO ABI study (Assessing Acute Brain Injury after Rapid Reduction of

PaCO2 upon ECMO Cannulation using Portable MRI and Biomarkers) uses an innovative neuroimaging system and plasma biomarkers to test our central hypothesis that higher peri-cannulation △PaCO2 is associated with ABI, leading to poor long-term neuropsychiatric outcomes. We will prospectively enroll ECMO patients and

collect multiple arterial blood gas samples (every 4 hours) 24 hours pre- and post-cannulation. ABI will be diagnosed by early low-field portable brain MRI at 24 and 72 hours along with the assessment of elevated plasma biomarker levels and cerebral autoregulation. We will investigate whether the magnitude of peri-cannulation

ΔPaCO2 is associated with cerebral perfusion autoregulatory dysfunction and ABI (Aim 1); and whether the presence of ABI is associated with worse 6-month neuropsychiatric outcomes (Aim 2). Our proposed research is a high-reward project that holds significant potential to change clinical practice, by investigating an innovative

hypothesis utilizing a unique approach. Our research can significantly advance the understanding of ECMO- associated ABI, setting the stage for the development of future approaches aimed at mitigating ABI as a complication of ECMO therapy.