Corticosteroid Therapy in Neonates Undergoing Cardiopulmonary Bypass

项目摘要/摘要 本申请提出了一项随机、双盲、安慰剂对照试验，使用糖皮质激素治疗 改善新生儿心脏手术后的临床病程。体外循环(CPB)对 心脏手术，但CPB引起的病理生理过程在心脏手术后发挥重要作用 手术恢复。糖皮质激素在改善体外循环中的应用、剂量和时间安排 诱导过程是高度多变的，没有明确的数据来提供方向。这项研究的主要目的 比较术中甲基强的松龙和安慰剂对综合发病率和死亡率的影响 新生儿体外循环转归。次要终点包括：肌力要求、低发生率 心输出量综合征，液体平衡，ICU住院参数，炎症分子水平，神经- 发育结果和安全参数。这项研究将集中在新生儿身上，因为他们在体外循环后 临床病程通常更严重，且最高严重程度本身提供了识别 一种特殊疗法的积极效果。最后，被确认为有益的疗法具有最大的潜力。 在这些脆弱的人群中受益。该协议的一个独特方面是使用了一种新型的多路复用器 一种可以分析多种细胞因子、基质金属蛋白酶和微核的技术 一毫升或更少的全血样本中的酸。这项研究的结果应该清楚地界定 类固醇的临床效用，并有助于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、低心输出量的发生率以及ICU护理的日常费用， 据估计，术后发病率的降低将使美国的总医疗费用减少 每年数以亿计的美元。

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.