Pulmonary Hypertension-Associated Pediatric Cardiac Arrest

肺动脉高压相关的小儿心脏骤停

基本信息

批准号：
9977346
负责人：
Ryan William Morgan
金额：
$ 15.94万
依托单位：
CHILDREN'S HOSP OF PHILADELPHIA
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-04-01 至 2025-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/9977346
关键词：
Accounting Acidosis Address Adult Affect American Heart Association Automobile Driving Award Blinded Blood Circulation Blood flow Carbon Dioxide Cardiac Output Cardiopulmonary Resuscitation Characteristics Chest Child Childhood Clinical Clinical Data Clinical Research Clinical Trials Cohort Studies Consensus Coronary Data Development Plans Diastolic blood pressure Disease Dose Echocardiography Environment Epidemiology Epinephrine Evaluable Disease Event Family suidae Foundations Functional disorder Funding Goals Guidelines Heart Arrest Hospitalized Child Hospitals Hour Hypertension Hypoxemia Infrastructure Intensive Care Units International Intervention Studies Intervention Trial Knowledge Laboratories Lead Life Lung Mechanics Mentors Modeling Outcome Patients Pediatric Hospitals Pediatric Intensive Care Units Pennsylvania Pharmaceutical Preparations Philadelphia Physiological Physiological Processes Physiology Prevalence Process Prospective Studies Pulmonary Hypertension Pulmonary Vascular Resistance Pulmonary artery structure Randomized Recommendation Records Reporting Research Research Personnel Resolution Resuscitation Science Scientist Shock Survival Rate System Systemic blood pressure Techniques Therapeutic Time Titrations Universities Vasoconstrictor Agents Vasodilator Agents base career career development clinical efficacy clinical investigation coronary perfusion design experience hemodynamics hypertension treatment improved improved outcome indexing inhaled nitric oxide insight patient oriented patient response pre-clinical pressure primary outcome professor prospective response secondary outcome skills survival outcome therapy design

项目摘要

Project Abstract Of the thousands of children with cardiac arrests annually, more than half do not survive. In hospitalized children, cardiac arrest results from the progression of many disease processes. Targeting these processes through physiology-directed cardiopulmonary resuscitation (CPR) is a promising means of personalizing resuscitation to improve survival outcomes. One particularly challenging physiologic process in children with cardiac arrest is pulmonary hypertension (PH). Based on preliminary data, it appears that by limiting pulmonary blood flow during CPR, PH impedes cardiac output and leads to lower systemic blood pressures, values of which are correlated with survival outcomes. Despite consensus opinion that PH- associated pediatric cardiac arrest is tied to worse outcomes and the American Heart Association and International Liaison Committee on Resuscitation identifying it as a significant knowledge gap, there is a paucity of high-quality data on the topic. Our preliminary clinical data indicates that PH is present in 18-35% of children prior to cardiac arrest. Moreover, PH physiology may be present in far more patients during cardiac arrest due to the detrimental effects of acidosis and hypoxemia on the pulmonary vasculature. Therefore, we performed a randomized and blinded trial of inhaled nitric oxide (iNO), a pulmonary vasodilator, during CPR in a swine model of PH-associated cardiac arrest and demonstrated higher blood pressures and improved rates of survival with iNO. Thus, there is a readily available potential therapeutic for this serious problem, but dedicated clinical study is necessary. The scientific objectives of this application are to delineate the epidemiology of PH-associated pediatric in-hospital cardiac arrest and to quantify the physiologic effects of PH and of iNO treatment during CPR. Two prospective observational cohort studies will be performed. The first will utilize the infrastructure of an ongoing R01-funded prospective cardiac arrest trial to report on survival from PH-associated cardiac arrest and the association of PH with intra-arrest hemodynamics. The second will take place in a single center with extensive, high-fidelity physiology data-capturing systems to better define the physiologic effects of iNO therapy during CPR. The successful completion of these studies will form the foundation of our knowledge on this understudied problem and inform the design of prospective clinical trials to treat it. The candidate, Dr. Ryan Morgan, is a pediatric intensivist and Assistant Professor at the Children's Hospital of Philadelphia and University of Pennsylvania. His goal is to become an independent, patient-oriented investigator studying pediatric cardiac arrest and the tailoring of resuscitation therapies to patient-specific physiology. Through the proposed studies, the parallel career development plan, a team of dedicated and experienced mentors and advisors, and a world-class environment for resuscitation science at the Children's Hospital of Philadelphia and University of Pennsylvania, this award will facilitate the candidate's successful transition to independence.

项目摘要每年有数千名心脏骤停的儿童，其中一半以上无法存活。在住院儿童的心脏骤停是许多疾病过程进展的结果。针对这些通过生理学指导的心肺复苏 (CPR) 过程是一种很有前景的方法个性化复苏以改善生存结果。一种特别具有挑战性的生理过程小儿心脏骤停就是肺动脉高压（PH）。根据初步数据看来，通过 CPR 期间限制肺血流量，PH 会阻碍心输出量并导致全身血流量降低压力，其值与生存结果相关。尽管共识认为希盟- 相关的小儿心脏骤停与更糟糕的结果有关，美国心脏协会和国际复苏联络委员会认为这是一个重大的知识差距，缺乏有关该主题的高质量数据。我们的初步临床数据表明 PH 存在于 18-35% 的人中心脏骤停之前的儿童。此外，更多的心脏病患者可能会出现 PH 生理学变化。由于酸中毒和低氧血症对肺血管系统的有害影响而停止。因此，我们在心肺复苏期间进行了吸入一氧化氮 (iNO)（一种肺血管扩张剂）的随机盲法试验在与 PH 相关的心脏骤停的猪模型中，表现出较高的血压和改善的心率 iNO 的生存率。因此，对于这个严重的问题有一种现成的潜在治疗方法，但是专门的临床研究是必要的。本申请的科学目标是描述 PH 相关儿科的流行病学院内心脏骤停，并量化心肺复苏期间 PH 和 iNO 治疗的生理效应。二将进行前瞻性观察队列研究。第一个将利用基础设施正在进行的 R01 资助的前瞻性心脏骤停试验，报告 PH 相关心脏骤停的生存情况以及 PH 与逮捕期间血流动力学的关系。第二次将在一个中心举行广泛的高保真生理学数据采集系统，以更好地定义 iNO 的生理效应心肺复苏期间的治疗。这些研究的成功完成将为我们的知识奠定基础这个尚未得到充分研究的问题，并为治疗该问题的前瞻性临床试验的设计提供信息。候选人，博士。瑞安·摩根 (Ryan Morgan) 是费城儿童医院的儿科重症监护医师兼助理教授宾夕法尼亚大学。他的目标是成为一名独立的、以患者为中心的研究人员小儿心脏骤停以及根据患者特定生理情况定制复苏治疗。通过拟议的研究、并行的职业发展计划、一支敬业且经验丰富的导师团队以及顾问以及费城儿童医院世界一流的复苏科学环境对于宾夕法尼亚大学来说，这一奖项将有助于候选人成功过渡到独立。