Intravenous Magnesium for Sickle Cell Vasoocclusive Crisis

描述(由申请人提供)：每年有超过18,000名儿童因镰状细胞疾病继发血管闭塞危象而住院，住院天数为75,000天。这些住院的绝大多数是因为疼痛危象，使疼痛成为患有镰状细胞病的儿童最重要的疾病之一。在过去的三十年里，对这些疼痛危机的急性治疗几乎没有改变，主要依靠静脉输液、阿片类药物和非类固醇药物。最近，人们对一氧化氮在疼痛危机发病机制中的作用有了更多的认识，正在研究吸入一氧化氮作为一种可能的治疗方法。我们最近测试了一种替代方法，静脉注射镁，它通过内皮依赖的一氧化氮机制产生血管扩张，并直接作用于潜在的血管平滑肌。镁的安全性、易管理性和低成本使其作为镰刀细胞疗法的潜力特别令人兴奋。在这项应用中，我们利用儿科急救应用研究网络，在儿科急救医学和儿科镰状细胞中心之间建立了一个四中心合作，通过一项双盲、随机、安慰剂对照试验来测试这种新疗法，评估在镰状细胞疼痛危机的标准治疗中添加静脉镁的影响。主要临床结果是儿童镰状细胞疼痛危象住院时间的减少，次要临床结果是衡量住院期间静脉注射镁对阿片类止痛药使用的影响。除了临床结果，我们还将通过测量溶血、一氧化氮途径代谢产物以及细胞损伤和炎症的标记物来了解镰状细胞危象的病理生理学。在这项研究的结论中，我们有可能使用一种低成本、低风险的治疗方法来改善镰状细胞病儿童的护理。 与公共卫生相关：仅在美国，每年就有超过18,000名儿童因镰状细胞疾病继发血管闭塞性疼痛发作而住院，住院天数为75,000天；这些儿童中绝大多数是非洲裔美国人。通过这项应用，我们的目标是减少儿童在这些危机中经历的痛苦，从而缩短住院时间，降低与护理患有这种痛苦疾病的儿童相关的成本。

DESCRIPTION (provided by applicant): There are over 18,000 hospitalizations and 75,000 hospitalization days annually for children suffering vaso-occlusive crises secondary to sickle cell disease. The vast majority of these hospitalizations are for pain crisis, making pain one of the most significant morbidities for children with sickle cell disease. The acute treatment for these pain crises has changed little over the past three decades, mainly relying on intravenous fluids, opioids and non-steroidals. More recently, there has been a greater recognition of the role that nitric oxide plays in the pathogenesis of pain crises, and inhaled nitric oxide is being studied as a possible treatment. We have recently tested an alternative approach, intravenous magnesium, that produces vaso- dilation through both endothelium-dependent nitric oxide mechanisms, as well as direct action on the underlying vascular smooth muscle. The safety profile, ease of administration, and low cost of magnesium make its potential as a sickle cell therapy particularly exciting. In this application, we utilize the Pediatric Emergency Care Applied Research Network to develop a four-center collaboration between pediatric emergency medicine and pediatric sickle cell centers to test this novel therapy through a double-blind, randomized, placebo controlled trial assessing the impact of the addition of intravenous magnesium to standard therapy for sickle cell pain crisis. The primary clinical outcome is the decrease in length of hospital stay for pediatric sickle cell pain crisis, with a secondary clinical outcome measuring the effect of intravenous magnesium on the use of opioid pain medication during the hospitalization. In addition to the clinical outcomes, we will gain valuable insight into the pathophysiology of sickle cell crisis through the measurement of hemolysis, nitric oxide pathway metabolites, and markers of cellular injury and inflammation. At the conclusion of this study, we have the potential to improve the care of children with sickle cell disease using a low cost, low risk treatment. PUBLIC HEALTH RELEVANCE: In the United States alone, there are over 18,000 hospitalizations and 75,000 hospitalization days annually for children suffering vasoocclusive pain episodes secondary to sickle cell disease; the vast majority of these children are African-American. With this application, we aim to decrease the pain children experience with these crises, thus shortening hospitalizations and decreasing the cost associated with caring for children with this painful disease.