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.
Pediatric cardiac arrest affects thousands of children each year, and pulmonary hypertension among children with cardiac arrest is an understudied problem that is likely associated with worse survival outcomes. The objectives of this research are to define the epidemiology of pulmonary hypertension-associated cardiac arrest and to quantify its physiologic effects as well as the physiologic impact of a potential therapeutic, inhaled nitric oxide. These studies will form the foundation of our collective knowledge on this topic and will potentially lead to prospective clinical trials to improve outcomes from pediatric cardiac arrest.