Pulmonary Hypertension-Associated Pediatric Cardiac Arrest

项目摘要 在每年数以千计的心脏骤停儿童中，超过一半的人无法存活。在……里面 在住院的儿童中，心脏骤停是许多疾病过程进展的结果。瞄准这些人 通过生理导向心肺复苏(CPR)的过程是一种很有前途的方法 个性化复苏以改善生存结果。其中一个特别具有挑战性的生理过程是 心脏骤停的儿童是肺动脉高压(PH)。根据初步数据，似乎通过 在心肺复苏期间限制肺血流，PH会阻碍心输出量并导致全身血液减少 压力，其值与生存结果相关。尽管普遍认为PH值- 相关的儿科心脏骤停与更差的结果有关，美国心脏协会和 复苏问题国际联络委员会认为这是一个重大的知识差距， 缺乏关于这一主题的高质量数据。我们的初步临床数据表明，在18%-35%的人中存在PH 心脏骤停前的儿童。此外，在心脏手术期间，可能有更多的患者存在PH生理学。 由于酸中毒和低氧血症对肺血管系统的有害影响而导致的停搏。因此，我们 在心肺复苏期间进行了一项吸入一氧化氮(INO)的随机、盲法试验 在一种与PH相关的心脏骤停的猪模型中，显示出更高的血压和改善的比率 与ino一起生存的机会。因此，对于这个严重的问题，有一个现成的潜在治疗方法，但 有必要进行专门的临床研究。 这项应用的科学目标是描述与PH相关的儿科疾病的流行病学。 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。第一个项目将利用 正在进行的由R01资助的心脏骤停前瞻性试验报告PH相关心脏骤停的存活率 PH与术中血流动力学的关系。第二次将在一个中心举行， 广泛、高保真的生理数据采集系统，以更好地定义iNO的生理效应 心肺复苏术中的治疗。这些研究的成功完成将为我们了解 这一未被充分研究的问题为设计治疗它的前瞻性临床试验提供了信息。这位候选人是Dr。 瑞安·摩根是费城儿童医院的儿科重症医生和助理教授， 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 儿科心脏骤停和针对患者特定生理学的复苏治疗。通过 拟议的研究、平行的职业发展计划、一支敬业和经验丰富的导师团队以及 顾问，以及费城儿童医院世界级的复苏科学环境 宾夕法尼亚大学的这一奖项将有助于候选人成功过渡到独立。

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.