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: 10216102
• 负责人: Matthew Borzage
• 金额: $ 18.58万
• 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/10216102
• 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; Lead; 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; neurite growth; neurodevelopment; neuroimaging; neurotoxicity; pediatric patients; potential biomarker; predictive marker; preference; prevent; relating to nervous system; 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.

项目概要 这项研究的主要目标是利用神经影像学来了解血流动力学反应 达到麻醉和镇静的目的。儿科患者常用的麻醉和镇静会导致 脑血流量和新陈代谢发生深刻而快速的变化。在正常条件下 成年人，这些变化彼此紧密相连，以保护大脑免受缺氧和 缺血。然而，麻醉期间流量和代谢的耦合程度 儿童患者的镇静作用尚不清楚。该项目的目标是 (1) 量化 婴儿对麻醉的血流动力学和代谢反应，以及 (2) 比较这些反应 在对患有不同疾病状态的婴儿使用特定麻醉剂期间，可能会 使它们更容易受到新陈代谢流动脱钩的影响。如果我们的假设成立 婴儿特别容易受到这种脱钩的影响，我们的研究结果将导致未来 评估血流动力学反应作为预测和介导不良反应的潜在生物标志物的研究 暴露于麻醉的婴儿的结果。因此，该项目与 NHLBI 相关 战略目标是确定导致病理学个体差异的因素 治疗反应。 该项目需要有机会同时进行流量和代谢测量 麻醉婴儿。临床磁共振成像提供了这个机会。因此，我们将报名参加 自然队列研究 120 名 1 岁以下的婴儿需要进行临床 MRI 扫描， 一半接受麻醉，一半不接受麻醉。登记的婴儿将接受 MRI 序列成像， 测量脑血流量和新陈代谢。此外，我们还将额外招收30名婴儿 将相同年龄的婴儿纳入试点随机比较试验（RCT），其中婴儿将 随机接受异丙酚或七氟烷麻醉。随机化将显着 减少自然研究中存在的疾病和麻醉剂的潜在混淆。 学习设计 RCT（目标 1）通过教学和实践来提高我的水平 转化研究技能。这个项目需要我学习麻醉剂和镇静剂 改变血流动力学和流体动力学（目标 2）以及已知和推定的机制如何 神经毒性和流动代谢解偶联影响发育中的大脑（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。它创造了一个范式 可以在儿科重症监护中安全地探索麻醉的血流动力学反应 患者。它需要结合 MRI 和图像处理专业知识 - 我已经具备的技能 - 对血流动力学改变的病理生理学后果有更深入的了解 婴儿对麻醉的反应。它还要求我提高设计能力 适合严格且狭窄的临床机会的研究项目 - 我将掌握的技能 通过 K25 支持获得收益。