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.
