Investigation of Cerebral Hemodynamics and Oxygenation Relationships Under Sedation in Children: ICHOR USC

儿童镇静状态下脑血流动力学和氧合关系的调查：ICHOR USC

• 批准号: 10687918
• 负责人: Matthew Borzage
• 金额: $ 18.52万
• 依托单位: CHILDREN'S HOSPITAL OF LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-10 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10687918
• 关键词: 1 year old; 8 year old; Acute; Address; Adult; Aerobic; Affect; Age; Anesthesia procedures; Anesthetics; Animals; Apoptosis; Blood flow; Brain; Brain Hypoxia; Brain Hypoxia-Ischemia; Brain Injuries; Calcium; Cell physiology; Cerebrovascular Circulation; Cerebrum; Characteristics; Chemicals; Child; Childhood; Clinical; Cognitive; Cohort Studies; Coupled; Coupling; Critical Care; Dendrites; Diagnosis; Diagnostic; Disease; Enrollment; Equipoise; Exhibits; Exposure to; Future; Goals; Hypoxia; Image; Impairment; Individual Differences; Infant; Injury; Investigation; Ion Channel; Knowledge; Learning; Link; Liquid substance; MRI Scans; Magnetic Resonance Imaging; Measurement; Measures; Mediating; Medical; Metabolic; Metabolism; National Heart, Lung, and Blood Institute; Neurons; Neurotoxins; Outcome; Oxygen; Patient Care; Patients; Pharmaceutical Preparations; Pilot Projects; Propofol; Provider; Randomized; Regulation; Reporting; Research; Research Design; Research Project Grants; Risk; Scanning; Sedation procedure; Techniques; Testing; Translational Research; Traumatic Brain Injury; adverse outcome; axon injury; behavioral outcome; brain metabolism; career; cerebral hemodynamics; cerebral oxygenation; clinical practice; cognitive performance; cohort; cytotoxic; design; hemodynamics; image processing; improved; metabolomics; neonatal hypoxic-ischemic brain injury; neural; neurite growth; neurodevelopment; neuroimaging; neurotoxicity; pediatric patients; potential biomarker; predictive marker; preference; prevent; response; sedative; sevoflurane; skills; treatment response; 1 year old; 8 year old; Acute; Address; Adult; Aerobic; Affect; Age; Anesthesia procedures; Anesthetics; Animals; Apoptosis; Blood flow; Brain; Brain Hypoxia; Brain Hypoxia-Ischemia; Brain Injuries; Calcium; Cell physiology; Cerebrovascular Circulation; Cerebrum; Characteristics; Chemicals; Child; Childhood; Clinical; Cognitive; Cohort Studies; Coupled; Coupling; Critical Care; Dendrites; Diagnosis; Diagnostic; Disease; Enrollment; Equipoise; Exhibits; Exposure to; Future; Goals; Hypoxia; Image; Impairment; Individual Differences; Infant; Injury; Investigation; Ion Channel; Knowledge; Learning; Link; Liquid substance; MRI Scans; Magnetic Resonance Imaging; Measurement; Measures; Mediating; Medical; Metabolic; Metabolism; National Heart, Lung, and Blood Institute; Neurons; Neurotoxins; Outcome; Oxygen; Patient Care; Patients; Pharmaceutical Preparations; Pilot Projects; Propofol; Provider; Randomized; Regulation; Reporting; Research; Research Design; Research Project Grants; Risk; Scanning; Sedation procedure; Techniques; Testing; Translational Research; Traumatic Brain Injury; adverse outcome; axon injury; behavioral outcome; brain metabolism; career; cerebral hemodynamics; cerebral oxygenation; clinical practice; cognitive performance; cohort; cytotoxic; design; hemodynamics; image processing; improved; metabolomics; neonatal hypoxic-ischemic brain injury; neural; neurite growth; neurodevelopment; neuroimaging; neurotoxicity; pediatric patients; potential biomarker; predictive marker; preference; prevent; response; sedative; sevoflurane; skills; treatment response

Project Summary The broad objective of this research is to use neuroimaging to understand the hemodynamic responses to anesthesia and sedation. Anesthesia and sedation, commonly used in pediatric patients, cause profound and rapid changes in cerebral blood flow and metabolism. Under normal conditions in adults, these changes are tightly coupled to one another to protect the brain from hypoxia and ischemia. However, the extent to which flow and metabolism are coupled during anesthesia and sedation in pediatric patients is unknown. The aims of this project are (1) to quantify the hemodynamic and metabolic responses to anesthesia in infants, and (2) to compare those responses during the administration of specific anesthetics in infants with differing disease states that may make them more vulnerable to the uncoupling of flow from metabolism. If our hypotheses are borne out and infants are particularly vulnerable to this uncoupling, our findings will lead to future studies to assess hemodynamic responses as potential biomarkers that predict and mediate adverse outcomes in infants exposed to anesthesia. Therefore, this project is relevant to the NHLBI's strategic objective to identify factors that account for individual differences in pathobiology and treatment response. This project requires an opportunity for making simultaneous flow and metabolism measurements in anesthetized infants. Clinical MR imaging provides this opportunity. Therefore, we will enroll into a Naturalistic Cohort Study 120 infants younger than 1 year of age who require a clinical MRI scan, half receiving anesthesia and half not. Enrolled infants will be imaged with MRI sequences that measure cerebral blood flow and metabolism. In addition, we will enroll 30 additional infants of the same age into a Pilot Randomized Comparator Trial (RCT), in which the infants will be randomized to receive either propofol or sevoflurane anesthesia. Randomization will dramatically reduce potential confounding of diseases and anesthetic agents present in the naturalistic study. Learning to design RCTs (Goal 1) is addressed with didactics and a practicum to advance my translational research skills. This project requires my learning how anesthetics and sedatives alter hemodynamics and fluid dynamics (Goal 2) and how the known and putative mechanisms of neurotoxicity and flow-metabolism uncoupling affect the developing brain (Goal 3). This project and my research career will help infants who require anesthesia or sedation. It creates a paradigm in which the hemodynamic response to anesthesia can be explored safely in pediatric critical care patients. It requires the combination of MRI and image processing know-how - skills that I already have - with a deeper understanding of the pathophysiological consequences of altered hemodynamic responses to anesthesia in infants. It also requires that I develop an improved ability to design research projects that fit within a rigorous and narrow clinical opportunity - skills that I will gain with this K25 support.

项目摘要 这项研究的广泛目的是使用神经影像来了解血液动力学反应 麻醉和镇静。通常用于小儿患者的麻醉和镇静 大脑血流和代谢的深刻变化。在正常条件下 成年人，这些变化彼此紧密耦合，以保护大脑免受缺氧和 缺血。但是，在麻醉期间流动和新陈代谢的程度 小儿患者的镇静剂尚不清楚。该项目的目的是（1）量化 对婴儿麻醉的血液动力学和代谢反应，（2）比较这些反应 在疾病状态不同的婴儿的特定麻醉剂中，可能 使它们更容易受到新陈代谢流动的脱偶联的影响。如果我们的假设是存在的 外出和婴儿特别容易造成这种解偶联，我们的发现将导致未来 评估血液动力学反应作为预测和介导不良的潜在生物标志物的研究 暴露于麻醉的婴儿的结局。因此，该项目与NHLBI的 战略目标，以识别因病原体学的个体差异的因素和 治疗反应。 该项目需要一个机会，以同时进行流动和代谢测量 麻醉婴儿。临床MR成像提供了这个机会。因此，我们将注册 一项自然主义的研究研究120名需要临床MRI扫描的婴儿小于1岁的婴儿， 一半接受麻醉，一半没有接受。注册婴儿将与MRI序列成像 测量脑血流和代谢。此外，我们还将注册30个婴儿 试点随机比较试验（RCT）的同一年龄，婴儿将是 随机接受丙泊酚或七氟尿液麻醉。随机化将急剧 减少自然主义研究中存在的疾病和麻醉剂的潜在混杂。 学习设计RCT（目标1）的说法和实践来促进我的 翻译研究技能。这个项目需要我学习麻醉和镇静剂 改变血液动力学和液体动力学（目标2）以及如何使用已知和推定的机制 神经毒性和流动代谢的解偶联会影响发育中的大脑（目标3）。这个项目和 我的研究生涯将帮助需要麻醉或镇静的婴儿。它创建了一个范式 可以在小儿重症监护中安全探索对麻醉的血液动力学反应 患者。它需要MRI和图像处理专有技术的组合 - 我已经已经 具有 - 更深入地了解改变血液动力学的病理生理后果 对婴儿麻醉的反应。它还要求我发展出改进的设计能力 研究项目适合严格而狭窄的临床机会 - 我会的技能 通过此K25支持获得。