Pulmonary Hypertension-Associated Pediatric Cardiac Arrest

项目摘要 每年有数千名儿童心脏骤停，其中一半以上无法存活。在 对于住院的儿童来说，心脏骤停是由许多疾病过程的进展引起的。靶向这些 通过生理学指导的心肺复苏（CPR）过程是一种很有前途的方法， 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， 儿童心脏骤停是肺动脉高压（PH）。根据初步数据， 在CPR期间限制肺血流量，PH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- 相关的儿科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， 缺乏关于这一专题的高质量数据。我们的初步临床数据表明，PH存在于18-35%的 心脏骤停前的儿童。此外，PH生理学可能存在于更多的患者中， 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呼吸骤停。所以我们 进行了一项随机和盲法试验，在心肺复苏术期间吸入一氧化氮（iNO），一种肺血管扩张剂， 在PH相关心脏骤停的猪模型中， iNO的生存。因此，有一种现成的潜在治疗这个严重的问题，但 需要专门的临床研究。 本申请的科学目的是描述PH相关儿科疾病的流行病学， 在医院心脏骤停和量化的PH和iNO治疗在CPR过程中的生理效应。两 将进行前瞻性观察性队列研究。第一个将利用一个 正在进行的R 01资助的前瞻性心脏骤停试验，以报告PH相关心脏骤停的生存率 以及PH与停搏时血流动力学的关系。第二次将在一个中心举行， 广泛的高保真生理数据采集系统，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形成我们的知识的基础， 这一未充分研究的问题，并通知前瞻性临床试验的设计，以治疗它。 Ryan Morgan是费城儿童医院的儿科重症监护医师和助理教授， 宾夕法尼亚大学.他的目标是成为一名独立的，以病人为导向的研究者， 儿科心脏骤停和根据患者的具体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，一个专门和经验丰富的导师团队， 顾问，以及费城儿童医院的世界级复苏科学环境， 宾夕法尼亚大学，这个奖项将促进候选人的成功过渡到独立。

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.