Neonatal Hypoxic Ischemic Encephalopathy: Potential of Innovative NIRS to Optimize Hypothermia

新生儿缺氧缺血性脑病：创新 NIRS 优化低温的潜力

• 批准号: 10446683
• 负责人: Patricia Ellen Grant
• 金额: $ 60.14万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-06-01 至 2027-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10446683
• 关键词: Achievement; Affect; Blood Pressure; Brain; Cerebrovascular Circulation; Cerebrum; Clinical; Cognitive; Cognitive deficits; Consensus; Custom; Data; Devices; Diffuse; Electroencephalography; Ensure; Evolution; Frequencies; Funding; Future; Goals; Grant; Guidelines; Health; Homeostasis; Hour; Hypoxia; Hypoxic-Ischemic Brain Injury; Impairment; Infant; Infant Development; Infrastructure; Injury; Investigation; Lead; Live Birth; Magnetic Resonance Imaging; Measurement; Measures; Mediating; Medical; Metabolic; Metabolism; Monitor; Morbidity - disease rate; Neonatal; Neonatal Intensive Care Units; Neuronal Injury; Neurons; Outcome; Oxygen; Perinatal mortality demographics; Risk; Secondary to; Severities; Spectrum Analysis; System; Technology; Therapeutic; Time; Ventilator; adverse outcome; cerebral hemodynamics; cloud based; design; flexibility; hemodynamics; improved; improved outcome; innovation; mortality; natural hypothermia; neonatal encephalopathy; neonatal hypoxic-ischemic brain injury; neonatal outcome; neonate; neurovascular coupling; novel; outcome prediction; prevent; prototype; secondary analysis; success; tissue oxygenation; treatment guidelines; treatment optimization; trend; Achievement; Affect; Blood Pressure; Brain; Cerebrovascular Circulation; Cerebrum; Clinical; Cognitive; Cognitive deficits; Consensus; Custom; Data; Devices; Diffuse; Electroencephalography; Ensure; Evolution; Frequencies; Funding; Future; Goals; Grant; Guidelines; Health; Homeostasis; Hour; Hypoxia; Hypoxic-Ischemic Brain Injury; Impairment; Infant; Infant Development; Infrastructure; Injury; Investigation; Lead; Live Birth; Magnetic Resonance Imaging; Measurement; Measures; Mediating; Medical; Metabolic; Metabolism; Monitor; Morbidity - disease rate; Neonatal; Neonatal Intensive Care Units; Neuronal Injury; Neurons; Outcome; Oxygen; Perinatal mortality demographics; Risk; Secondary to; Severities; Spectrum Analysis; System; Technology; Therapeutic; Time; Ventilator; adverse outcome; cerebral hemodynamics; cloud based; design; flexibility; hemodynamics; improved; improved outcome; innovation; mortality; natural hypothermia; neonatal encephalopathy; neonatal hypoxic-ischemic brain injury; neonatal outcome; neonate; neurovascular coupling; novel; outcome prediction; prevent; prototype; secondary analysis; success; tissue oxygenation; treatment guidelines; treatment optimization; trend

PROJECT SUMMARY/ABSTRACT Hypoxic ischemic encephalopathy (HIE), a major cause of perinatal mortality and long-term morbidity, affects 1- 5/1000 live births. Hypoxic ischemic insults (HII) lead to HIE through a cascade of neuronal injury that continues for hours to days. Therapeutic hypothermia (TH) proved that brain injury from HII can be avoided, revolutionizing treatment of HIE. Despite TH success, additional improvements are urgently needed as up to 63% of infants still die or have long term cognitive deficits. Also, guidelines for treatment are highly subjective, with no consensus on when to treat mild HIE. Our first premise is that adverse outcomes are due to ongoing neuronal injury after HII. As neurons are the primary consumer of oxygen, measures of cerebral oxygen metabolism (CMRO2) would provide a potential means to monitor neuronal health and the evolution of injury. Our second premise is that hemodynamic instability contributes to adverse outcomes through secondary neuronal injury. Secondary injury may be preventable with bedside measures of cerebral blood flow (CBF) to ensure the brain’s metabolic needs are met. In fact, direct CBF measures enable assessment of cerebral autoregulation (CA) and neurovascular coupling (NVC), which reflect hemodynamic stability. Bedside measures of CMRO2 and CBF could enable treatment optimization to prevent secondary injury and inform decisions on who to treat. In R01HD076258, our major achievement was performing >500 Frequency-Domain NIRS and Diffuse Correlation Spectroscopy (FDNIRS- DCS) measurements in >100 neonates with HIE, demonstrating that routine direct bedside measurement of CBF and CMRO2 are possible. Our major finding is that CMRO2 in the days after TH was the only early predictor of outcome, with higher CMRO2 strongly associated (r=0.62, P=0.002) with better 18-month cognitive scores of Bayley Scales of Infant Development 3rd edition (BSID-3). Our renewal goal is to perform early, continuous bedside monitoring of CMRO2 and CBF, demonstrating their potential as vital signs with three aims: Aim 1: Extend current infrastructure to enable continuous, real-time bedside monitoring of neonatal CBF and CMRO2 at 100Hz, integrated with data from other clinical monitors. Aim 2: In neonates with HIE, determine evolution of CMRO2, CA and NVC during TH and their association with post-TH CMRO2; validate that post-TH CMRO2 predicts 2-year outcome. Aim 3: In controls and neonates at risk for HIE but not meeting criteria for TH, determine CMRO2, CA and NVC during the first 24 hours; determine if day 1 CMRO2 predicts 2-year outcome. In the first grant, we demonstrated that bedside measures of CBF and CMRO2 are feasible and discovered that CMRO2 after TH predicts of outcome. In this renewal, we propose to turn CMRO2 and CBF into early, continuous, real-time, bedside vital signs. Our goal is to determine if there is evidence of neuronal injury (decreased CMRO2) mediated by cerebral hemodynamic instability (impaired CA and NVC). If successful, CMRO2 and CBF monitoring may improve neonatal outcomes by enabling medical optimization of hemodynamic stability during TH as well as to screen for neonates at risk for HIE who may benefit from TH.

项目摘要/摘要 低氧缺血性脑病（HIE）是围产期死亡率和长期发病率的主要原因，影响1- 5/1000活产。缺氧性缺血性损伤（HII）导致通过一系列神经元损伤继续进行HIE 几个小时到几天。治疗性体温过低（Th）证明了HII的脑损伤可以避免，革命性 治疗Hie。尽管取得了成功，但迫切需要进一步的改进，因为仍有63％的婴儿仍需 死亡或长期认知缺陷。同样，治疗指南是高度主观的，没有共识 关于何时治疗温和的hie。我们的第一个前提是，不良后果是由于持续的神经元损伤 嗨。由于神经元是氧气的主要消费者，因此脑氧代谢（CMRO2）的度量将 提供了监测神经元健康和损伤进化的潜在手段。我们的第二个前提是 血液动力学不稳定通过继发性神经元损伤导致不良结果。继发伤害 可以通过大脑血流（CBF）的床边测量来预防，以确保大脑的代谢需求 被满足。实际上，直接CBF测量值可以评估脑自动调节（CA）和神经血管 耦合（NVC），反映了血液动力学稳定性。 CMRO2和CBF的床边量度可以启用 治疗优化，以防止继发性伤害并告知关于谁治疗的决定。在R01HD076258中，我们的 重大成就是进行> 500个频域NIR和弥漫性相关光谱（FDNIRS- DCS）测量> 100个新生儿，并证明了常规的直接床边测量CBF 和cmro2是可能的。我们的主要发现是，CMRO2在TH之后的日子是唯一的早期预测指标 结果，较高的CMRO2密切相关（r = 0.62，p = 0.002），具有更好的18个月认知评分 贝利婴儿发展第三版（BSID-3）。我们的更新目标是提早执行 CMRO2和CBF的床头监控，表明其作为生命体征的潜力具有三个目标：AIM 1： 扩展当前基础设施以实现新生儿CBF和CMRO2的连续实时床边监测 在100Hz，与其他临床监测器的数据集成在一起。目标2：在带有HIE的新生儿中，确定 TH期间的CMRO2，CA和NVC及其与TH后CMRO2的关联；验证cmro2之后 预测2年的结果。目标3：在有风险的控制和新生儿中，但不符合TH的标准， 在最初的24小时内确定CMRO2，CA和NVC；确定第1天CMRO2是否预测2年结果。在 第一个赠款，我们证明了CBF和CMRO2的床边措施是可行的，并发现 CMRO2在预测结果后。在此续约中，我们建议将CMRO2和CBF变成早期，继续，继续 实时，床边生命体征。我们的目标是确定是否存在神经元损伤的证据（CMRO2降低） 由脑血动力学不稳定性（CA和NVC受损）介导。如果成功，CMRO2和CBF 监测可以通过实现对血液动力学稳定性的医学优化在期间的医学优化来改善新生儿结果 以及筛选可能从TH中受益的Hie风险的新生儿。