Corticosteroid Therapy in Neonates Undergoing Cardiopulmonary Bypass

描述（由申请人提供）：本申请提出了一项使用糖皮质激素改善心脏手术后新生儿临床病程的随机双盲安慰剂对照试验。体外循环（CPB）是心脏外科手术的关键，但CPB引起的病理生理过程对术后恢复起着重要作用。用于改善这些CPB诱导过程的类糖皮质激素给药的用途、剂量和时间表变化很大，没有明确的数据提供指导。本研究的主要目的是比较术中甲泼尼龙与安慰剂对新生儿CPB后复合发病率-死亡率结局的影响。次要终点包括：强心剂需求、低心输出量综合征的发生率、液体平衡、ICU住院参数、炎症分子水平、神经发育结果和安全参数。这项研究将集中于新生儿，因为他们的体外循环后临床过程通常更严重，而高水平的严重程度本身为确定特定治疗的积极作用提供了基础。最后，被确定为有益的疗法在该脆弱人群中具有最大的获益潜力。该方案的一个独特方面是使用新型多路复用技术，该技术允许从一毫升或更少的全血样品中分析广泛的细胞因子、基质金属蛋白酶和微核糖核酸。这项研究的结果应该清楚地定义类固醇的临床效用，并帮助确定任何观察到的效果的机制。根据复杂先天性心脏病的频率、低心输出量的发生率和ICU护理的每日费用，估计术后发病率的降低每年可使美国的总医疗支出减少数亿美元。 公共卫生相关性：虽然心肺转流（心肺机）是心脏手术的必要组成部分，但它并非没有后果。心脏搭桥术引发了一种强有力的炎症反应，继发于身体对心肺机异常环境的识别。这种炎症反应可能导致心脏手术后心脏、肺和肾功能不良。这反过来会导致呼吸机（呼吸机）上的时间更长，需要更高剂量的心脏药物，在重症监护室停留更长时间，甚至死亡。这在不到一个月的婴儿中尤其如此 由于他们的大小和器官的不成熟，他们的年龄。对心肺转流术后炎症反应的认识导致了许多旨在减少炎症反应的干预措施。没有治疗被认为是标准的护理;然而，类固醇治疗已被应用最多，尽管不清楚的证据的好处。这项研究旨在确定类固醇是否能改善接受心脏手术的婴儿的预后。

DESCRIPTION (provided by applicant): This application proposes a randomized double-blind placebo controlled trial of the use of glucocorticoids to improve the clinical course of neonates following cardiac surgery. Cardiopulmonary bypass (CPB) is critical to cardiac surgery, but the pathophysiologic processes engendered by CPB play an important role in post- operative recovery. The use, doses and schedule of glucortocoid administration to ameliorate these CPB induced processes is highly variable and without clear data to provide direction. The Primary Aim of this study is to compare the effects of intraoperative methypredisolone to placebo on a composite morbidity-mortality outcome following neonatal CPB. Secondary Endpoints include: inotropic requirements, incidence of low cardiac output syndrome, fluid balance, ICU stay parameters, levels of inflammatory molecules, neuro-developmental outcomes, and safety parameters. The study will focus on neonates because their post-CPB clinical course is typically more severe, and that high level of severity itself provides a substrate for identifying the positie effects of a particular therapy. Finally, a therapy identified as beneficial has the greatest potential for benefit in this vulnerable population. A unique aspect of the protocol is the use of novel multiplexer technology which allows analysis of a broad array of cytokines, matrix metalloproteinases and microribonucleic acids from a sample of one milliliter or less of whole blood. The results of this study should clearly define the clinical utility of steroids and help determine the mechanisms for any observed effect. Based on the frequency of complex congenital heart defects, the incidence of the low cardiac output, and the daily costs of ICU care, a reduction in postoperative morbidity can be estimated to decrease total healthcare expenditures in the US by hundreds of millions of dollars annually. PUBLIC HEALTH RELEVANCE: Although cardiopulmonary bypass (heart-lung machine) is a necessary component of heart surgery, it is not without consequences. Cardiopulmonary bypass initiates a potent inflammatory response secondary to the body's recognition of the abnormal environment of the heart-lung machine. This inflammatory response may lead to poor heart, lung and kidney function after the heart surgery. This is turn can lead to longer times on the ventilator (breathing machine), the need for higher doses of heart medications, a longer stay in the intensive care unit and even death. This is particularly true in infants less than one month of age due to their size and the immaturity of their organs. The appreciation of the post-cardiopulmonary bypass inflammatory response has resulted in a number of interventions directed at its reduction. No therapy has been recognized as the standard of care; however steroid therapy has been applied most often despite unclear evidence of a benefit. This study aims to determine if steroids improve the outcomes of babies undergoing heart surgery.