Novel methods for brain injury detection and outcome prediction in pediatric ECMO

儿科 ECMO 脑损伤检测和结果预测的新方法

• 批准号: 8650927
• 负责人: Melania Maria Bembea
• 金额: $ 18.98万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-07-01 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8650927
• 关键词: Acute; Anesthesiology; Anticoagulation; Biological Assay; Biological Markers; Blood Circulation; Blood Pressure; Brain; Brain Injuries; Brain Ischemia; Brain hemorrhage; Cannulations; Cardiopulmonary; Cardiopulmonary Bypass; Cephalic; Cerebrum; Childhood; Clinical Research; Clinical Trials; Commit; Critical Care; Critical Illness; Detection; Development; Development Plans; Diagnosis; Diagnostic; Doctor of Philosophy; Early Intervention; Environment; Extracorporeal Membrane Oxygenation; Faculty; Failure; Foundations; Fright; Funding; Future; Glial Fibrillary Acidic Protein; Goals; Head; Heart; Homeostasis; Hospitalization; Hospitals; Incidence; Individual; Infant; Injury; Institutes; Institution; Intensive Care Units; Intervention; Ischemia; Knowledge; Lead; Length; Life; Lung; Magnetic Resonance Imaging; Measures; Medical; Medicine; Mentors; Methods; Modality; Monitor; Near-Infrared Spectroscopy; Neck; Neonatal Brain Injury; Neurologic; Neurological outcome; Newborn Infant; Outcome; Patients; Pediatric Intensive Care Units; Perioperative; Physicians; Plasma; Prevention strategy; Prospective Studies; Proteins; Quality of life; Refractory; Regulation; Reporting; Research; Research Design; Research Personnel; Risk Factors; Scientist; Severities; Stroke; Structure; Techniques; Technology; Testing; Therapeutic; Therapeutic Intervention; Time; Training; Training Programs; Ultrasonography; Universities; Validation; Work; career; career development; cerebrovascular; clinical care; critically ill newborn; disability; high risk; innovation; long term hospitalization; member; mortality; neonate; neuroimaging; novel; post intervention; public health relevance; research and development

DESCRIPTION (provided by applicant): 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.

描述（由申请人提供）：候选人 Melania M. Bembea 是约翰·霍普金斯大学麻醉学和重症监护医学系的教员。她的目标是成为一名独立的临床科学家，专注于应用严格的研究设计来提高儿科重症监护病房的质量，重点是评估与危重新生儿使用体外生命支持技术相关的并发症和结果。为了实现这一目标，她即将完成博士学位 她将参加约翰·霍普金斯大学临床研究研究生培训计划，她将接受高级研究人员的结构化指导，以进行受监督的创新研究。拟议研究的具体目标和相关假设是： [目标 1. 确定新生儿 ECMO 期间脑血管自动调节丧失的时期是否与脑损伤血浆生物标志物（例如 GFAP）升高的时期相关。 假设：婴儿 ECMO 期间经常发生脑血管自动调节丧失的时期，这些时期使大脑暴露于缺血，导致蛋白质生物标志物释放到体循环中。目标 2. 确定 ECMO 期间自动调节丧失和脑损伤蛋白质生物标志物释放到体循环中的时期是否与传统的损伤神经影像标志物（包括颅脑超声和磁共振成像 (MRI)）相关。假设：脑血管自动调节丧失时期的长度和严重程度以及脑损伤导致的蛋白质生物标志物释放到体循环中将与损伤的神经影像标志物的升高相关，并且发生在神经影像学变化之前。目标 3. 确定 ECMO 期间血浆脑损伤生物标志物浓度升高和自动调节丧失以及脑损伤的神经影像学标志物是否是出院时以及 ECMO 后 6 个月和 1 年生存和神经系统结果的独立预测因素。假设：脑损伤生物标志物的升高和脑血管自动调节丧失的时期以及脑损伤的神经影像学标志物（头部超声和 MRI）将预测以后的神经功能障碍，但生物标志物和自动调节的变化将提供早期损伤的相关性。] 完成拟议的研究将显着提高我们对如何在 ECMO 期间最好地监测和诊断即将发生或发生的脑损伤并制定计划的了解。 未来试验中的神经保护干预措施[（例如，与标准血压管理相比，在 ECMO 期间将血压目标控制在个体较低的脑血流自动调节阈值以上）]。这些项目和所描述的职业发展计划将为独立调查员的成功职业生涯奠定基础。