Corticosteroid Therapy in Neonates Undergoing Cardiopulmonary Bypass

描述（由申请人提供）：本申请提出一项随机双盲安慰剂对照试验，使用糖皮质激素改善新生儿心脏手术后的临床病程。体外循环（CPB）是心脏外科手术的关键，而体外循环引起的病理生理过程在术后恢复中起着重要作用。糖皮质激素用于改善CPB诱导的这些过程的使用、剂量和时间表是高度可变的，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基泼地龙与安慰剂对新生儿CPB后综合发病率-死亡率的影响。次要终点包括：肌力需求、低心输出量综合征发生率、体液平衡、ICU住院参数、炎症分子水平、神经发育结局和安全性参数。这项研究将重点放在新生儿身上，因为他们在cpb后的临床过程通常更严重，而这种高水平的严重程度本身为确定特定治疗的积极效果提供了基础。最后，一种被确定为有益的治疗方法在这一弱势群体中具有最大的获益潜力。该方案的一个独特方面是使用新颖的多路复用器技术，该技术允许从一毫升或更少的全血样本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应用，并有助于确定任何观察到的效果的机制。根据复杂先天性心脏缺陷的频率、低心输出量的发生率和ICU护理的日常费用，术后发病率的降低可以估计为美国每年减少数亿美元的医疗保健总支出。

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.