Pulmonary Hypertension-Associated Pediatric Cardiac Arrest

肺动脉高压相关的小儿心脏骤停

• 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
• 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

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 每年有成千上万的心脏骤停儿童中，有超过一半的儿童无法生存。在 住院儿童，心脏骤停的结果是许多疾病过程的进展。针对这些 通过生理学指导的心肺复苏（CPR）的过程是一种有希望的手段 个性化复苏以改善生存结果。一个特别具有挑战性的生理过程 心脏骤停的儿童是肺动脉高压（pH）。基于初步数据，看来 限制CPR期间肺血流，pH会阻碍心脏输出，并导致较低的全身血液 压力，其值与生存结果相关。尽管有共识， 相关的儿科心脏骤停与美国心脏协会的结果和美国心脏协会和 国际复苏联络委员会将其确定为重要的知识差距，有一个 关于该主题的高质量数据的差异。我们的初步临床数据表明，pH值为18-35％ 心脏骤停之前的孩子。此外，在心脏中可能存在pH生理学 由于酸中毒和低氧血症对肺脉管系统的有害影响而停滞。因此，我们 在CPR期间，进行了肺血管扩张剂的吸入一氧化氮（INO）的随机和盲试验 在猪相关心脏骤停的猪模型中，表现出更高的血压和提高的速率 与Ino生存。因此，对于这个严重问题，有一种可用的潜在治疗方法，但是 专门的临床研究是必要的。 该应用的科学目标是描述pH相关儿科的流行病学 院内心脏骤停并量化CPR期间pH和INO治疗的生理作用。二 将进行前瞻性观察队列研究。第一个将利用 正在进行的R01资助的前瞻性心脏骤停审判报告有关pH相关心脏骤停生存的报告 以及pH的关联与暂停性血流动力学的关联。第二个将在一个中心与 广泛的高保真生理学数据捕获系统，以更好地定义INO的生理效应 CPR期间的治疗。这些研究的成功完成将构成我们知识的基础 这个研究了问题，并告知了前瞻性临床试验的设计。候选人，博士 瑞安·摩根 宾夕法尼亚大学。他的目标是成为一个独立的，以患者为导向的研究者 儿科心脏骤停和针对患者特异性生理的复苏疗法的剪裁。通过 拟议的研究，平行的职业发展计划，由敬业和经验丰富的导师组成的团队以及 顾问，以及费城儿童医院的复苏科学环境 宾夕法尼亚大学，该奖项将促进候选人的成功过渡到独立。