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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

基本信息

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
项目类别：
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

项目摘要

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主要目标是使用神经成像来了解血液动力学反应。麻醉和镇静。麻醉和镇静，通常用于儿科患者，导致脑血流和代谢发生深刻而迅速的变化。在正常情况下成年人，这些变化是紧密耦合在一起的，以保护大脑免受缺氧和缺血症。然而，麻醉期间血流和新陈代谢耦合的程度儿科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)比较这些反应在给有不同疾病状态的婴儿使用特定麻醉药期间，可能使它们更容易受到新陈代谢中的流动分离的影响。如果我们的假设成立 Out和婴儿特别容易受到这种脱钩的影响，我们的发现将导致未来评估血流动力学反应作为预测和调节不良反应的潜在生物标志物的研究暴露在麻醉下的婴儿的结局。因此，这个项目与NHLBI的战略目标：确定在病理生物学和生物医学上的个体差异治疗反应。这个项目需要一个机会进行同时流动和代谢测量在被麻醉的婴儿。临床磁共振成像提供了这个机会。因此，我们将报名参加一项自然主义队列研究对120名1岁以下需要进行临床核磁共振扫描的婴儿进行了研究，一半接受麻醉，另一半不接受麻醉。登记的婴儿将通过MRI序列进行成像，测量脑血流和新陈代谢。此外，我们将额外招收30名婴儿进入试验性随机对照试验(RCT)，在该试验中，婴儿将随机接受异丙酚或七氟醚麻醉。随机化将极大地减少自然主义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)是通过教学和实践来推进我的翻译研究技能。这个项目需要我学习麻醉剂和镇静剂是如何改变血流动力学和流体动力学(目标2)以及已知的和假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。它创建了一个范例，在儿科重症监护中可以安全地探讨麻醉对血流动力学的反应病人。它需要MRI和图像处理技术的结合，我已经对血流动力学改变的病理生理后果有了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符合严格而狭隘的临床机会的研究项目--我会通过此K25支持获得收益。