The candidate, Melania M. Bembea, is on faculty at the Johns Hopkins University, in the Department of Anesthesiology and Critical Care Medicine. Her goal is to become an independent clinician scientist focused on applying rigorous research design to quality improvement in the pediatric intensive care unit, with an emphasis on evaluating complications and outcomes associated with the use of extracorporeal life support technologies in critically-ill newborns. To realize this goal, she is on course to complete the PhD track of the Johns Hopkins Graduate Training Program in Clinical Investigation, and she will receive structured mentoring by senior investigators for the conduct of supervised, innovative research.
The specific aims and related hypotheses of the proposed research are: [Aim 1. Determine if periods of lost cerebrovascular auto regulation during ECMO in neonates are correlated with periods of elevations in plasma biomarkers for brain injury (e.g. GFAP). Hypothesis: Periods of loss of cerebrovascular auto regulation occur frequently during ECMO in infants, and these periods expose the brain to ischemia which leads to the release of protein biomarkers into the systemic circulation.
Aim 2. Determine if periods of loss of auto regulation and release of protein biomarkers for brain injury into the systemic circulatio during ECMO are correlated with conventional neuroimaging markers for injury including cranial ultrasound and magnetic resonance imaging (MRI). Hypothesis: The length and severity of periods of loss of cerebrovascular auto regulation and the release of protein biomarkers from brain injury into the systemic circulation will correlate with elevations in neuroimaging markers for injury and will occur before changes in neuroimaging.
Aim 3. Determine if elevated plasma brain injury biomarker concentrations and loss of auto regulation during ECMO as well as neuroimaging markers of brain injury are independent predictors of survival and neurologic outcomes at hospital discharge, and at 6 months and 1 year post-ECMO. Hypothesis: Elevations in brain injury biomarkers and periods of loss of cerebrovascular auto regulation as well as neuroimaging markers for brain injury (head ultrasound and MRI) will predict later neurological disability, but changes in biomarkers and auto regulation will provide an earlier correlate of injury.] Completion of the proposed research will significantly advance our knowledge of how best to monitor for and diagnose impending or incident brain injury during ECMO and plan for neuroprotective interventions in future trials [(e.g., targeting blood pressure to a level above an individual's lower cerebral blod flow auto regulatory threshold during ECMO vs. standard blood pressure management)]. These projects and the career development plan described will build a foundation for a successful career as an independent investigator.

Public Health Relevance

Extracorporeal membrane oxygenation (ECMO) is a life-saving technique by which critically-ill patients with refractory heart and lung failure are being salvaged in the intensive care unit. However, ECMO is fraught with complications, the most feared one being brain injury such as brain hemorrhage or ischemia. This proposal seeks to use non-invasive methods of real-time monitoring for brain injury risk factors (e.g., altered cerebrovascular auto regulation) and for incident brain injury during ECMO (e.g., by measuring plasma brain injury biomarkers serially), in an effort to develop new preventive strategies or, when injury already happened, to implement neuroprotective interventions earlier than what is possible with today's clinical care capabilities.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Mentored Patient-Oriented Research Career Development Award (K23)
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Mcneil, Dawn E
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Johns Hopkins University
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Bembea, Melania M; Valentine, Stacey L; Bateman, Scot T et al. (2018) The Pediatric Critical Care Transfusion and Anemia Expertise Initiative Consensus Conference Methodology. Pediatr Crit Care Med 19:S93-S97
Bembea, Melania M; Cheifetz, Ira M; Fortenberry, James D et al. (2018) Recommendations on the Indications for RBC Transfusion for the Critically Ill Child Receiving Support From Extracorporeal Membrane Oxygenation, Ventricular Assist, and Renal Replacement Therapy Devices From the Pediatric Critical Care Transfusion and Anem Pediatr Crit Care Med 19:S157-S162
Conrad, Steven A; Broman, L Mikael; Taccone, Fabio S et al. (2018) The Extracorporeal Life Support Organization Maastricht Treaty for Nomenclature in Extracorporeal Life Support. A Position Paper of the Extracorporeal Life Support Organization. Am J Respir Crit Care Med 198:447-451
Boyle, Katharine; Felling, Ryan; Yiu, Alvin et al. (2018) Neurologic Outcomes After Extracorporeal Membrane Oxygenation: A Systematic Review. Pediatr Crit Care Med 19:760-766
Valentine, Stacey L; Bembea, Melania M; Muszynski, Jennifer A et al. (2018) Consensus Recommendations for RBC Transfusion Practice in Critically Ill Children From the Pediatric Critical Care Transfusion and Anemia Expertise Initiative. Pediatr Crit Care Med 19:884-898
Lasa, Javier J; Jain, Parag; Raymond, Tia T et al. (2018) Extracorporeal Cardiopulmonary Resuscitation in the Pediatric Cardiac Population: In Search of a Standard of Care. Pediatr Crit Care Med 19:125-130
Barbaro, Ryan P; Paden, Matthew L; Guner, Yigit S et al. (2017) Pediatric Extracorporeal Life Support Organization Registry International Report 2016. ASAIO J 63:456-463
Walker, Tracie C; Bembea, Melania M (2017) Stuck at the Abstract: Where Is the Article? Pediatr Crit Care Med 18:813-814
Caprarola, Sherrill D; Kudchadkar, Sapna R; Bembea, Melania M (2017) Neurologic Outcomes Following Care in the Pediatric Intensive Care Unit. Curr Treat Options Pediatr 3:193-207
Goswami, Dheeraj; Bembea, Melania M (2016) Extracorporeal Membrane Oxygenation: Insult to Acute Kidney Injury. Pediatr Crit Care Med 17:1186-1187

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