Corticosteroid Therapy in Neonates Undergoing Cardiopulmonary Bypass

项目总结/摘要 本申请提出了一项使用糖皮质激素的随机双盲安慰剂对照试验， 改善心脏手术后新生儿的临床病程。心脏搭桥术（CPB）对于 心脏手术，但由CPB产生的病理生理过程中发挥重要作用， 手术恢复糖皮质激素给药的用途、剂量和时间表，以改善这些CPB 诱导过程是高度可变的，没有明确的数据提供方向。本研究的主要目的 比较术中甲基强的松龙与安慰剂对复合发病率-死亡率的影响， 新生儿CPB后的结局。次要终点包括：正性肌力要求，低 心输出量综合征，液体平衡，ICU住院参数，炎症分子水平，神经- 发育结果和安全性参数。该研究将重点关注新生儿，因为他们的CPB后 临床过程通常更严重，高水平的严重性本身提供了识别的基础。 某种疗法的积极效果最后，被确定为有益的疗法具有最大的潜力， 来帮助这些弱势群体该协议的一个独特之处是使用了一种新颖的多路复用器 该技术允许分析广泛的细胞因子、基质金属蛋白酶和微核糖核酸 从一毫升或更少的全血样品中提取的酸。这项研究的结果应明确界定 类固醇的临床效用，并帮助确定任何观察到的效果的机制。基于频率 复杂先天性心脏病的发生率、低心排血量的发生率以及ICU护理的日常费用， 据估计，术后发病率的降低可降低美国的总医疗费用， 每年花费数亿美元。

Project Summary/Abstract 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-mortalitiy 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 positive 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 a 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.