Intravenous Magnesium for Sickle Cell Vasoocclusive Crisis

静脉注射镁治疗镰状细胞血管闭塞危机

• 批准号: 8059606
• 负责人: David C Brousseau
• 金额: $ 54.63万
• 依托单位: MEDICAL COLLEGE OF WISCONSIN
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-04-09 至 2014-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8059606
• 关键词: 18 year old; Absence of pain sensation; Accident and Emergency department; Acute; Acute Pain; Adverse event; African American; Analgesics; Applied Research; Asthma; Attenuated; Blinded; Calcium; Cell Therapy; Cells; Child; Child Care; Childhood; Clinic; Clinical; Collaborations; Disease; Dose; Double-Blind Method; Emergency Care; Emergency Medicine; Endothelial Cells; Endothelium; Enrollment; Esthesia; Event; Functional disorder; Hemoglobin; Hemolysis; Hospitalization; Hospitals; Hour; Hypotension; IV Fluid; Individual; Inflammation; Inflammatory; Inflammatory Response; Infusion procedures; Injury; Inpatients; Institution; Interferon Type II; Interleukin-6; Intervention; Intravenous; Length of Stay; Lipopolysaccharides; Magnesium; Magnesium Deficiency; Magnesium Sulfate; Measurement; Measures; Monitor; Morbidity - disease rate; Nitric Oxide; Nitric Oxide Pathway; Nitrites; Opioid; Outcome; Outcome Measure; Pain; Pathogenesis; Patients; Pharmaceutical Preparations; Physicians; Placebo Control; Placebos; Plasma; Play; Production; Randomized; Research; Reticulocyte count; Risk; Role; Safety; Secondary to; Selectins; Sickle Cell; Sickle Cell Anemia; Study Subject; TNF gene; Telephone; Testing; Thalassemia; United States; Vascular Cell Adhesion Molecule-1; Vascular Smooth Muscle; Vasodilation; Vasodilator Agents; cell injury; cost; cytokine; double-blind placebo controlled trial; effective intervention; experience; follow-up; improved; in vivo; inhaled nitric oxide; innovation; insight; intervention effect; novel; novel strategies; public health relevance; randomized placebo controlled trial; response; sickle cell crisis; translational study; vaso-occlusive pain

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.

描述（由申请人提供）：每年有超过 18,000 名患有镰状细胞病继发血管闭塞危象的儿童住院治疗，住院天数超过 75,000 个。绝大多数住院治疗都是因为疼痛危机，这使得疼痛成为镰状细胞病儿童最重要的发病率之一。这些疼痛危机的紧急治疗在过去三十年中几乎没有变化，主要依靠静脉输液、阿片类药物和非类固醇药物。最近，人们更加认识到一氧化氮在疼痛危机发病机制中所起的作用，并且正在研究吸入一氧化氮作为一种可能的治疗方法。我们最近测试了另一种方法，即静脉注射镁，它通过内皮依赖性一氧化氮机制以及对底层血管平滑肌的直接作用产生血管舒张作用。镁的安全性、易于管理和低成本使其作为镰状细胞疗法的潜力特别令人兴奋。在此应用中，我们利用儿科急诊护理应用研究网络在儿科急诊医学和儿科镰状细胞中心之间建立四中心合作，通过双盲、随机、安慰剂对照试验来测试这种新型疗法，评估该疗法的影响在镰状细胞性疼痛危象的标准疗法中添加静脉注射镁。主要临床结果是减少小儿镰状细胞性疼痛危象住院时间，次要临床结果测量静脉注射镁对住院期间阿片类止痛药使用的影响。除了临床结果外，我们还将通过测量溶血、一氧化氮途径代谢物以及细胞损伤和炎症标志物，获得对镰状细胞危象病理生理学的宝贵见解。这项研究的结论是，我们有潜力通过低成本、低风险的治疗来改善镰状细胞病儿童的护理。 公共卫生相关性：仅在美国，每年就有超过 18,000 名儿童因镰状细胞病继发血管闭塞性疼痛而住院治疗，住院天数超过 75,000 个；这些儿童绝大多数是非裔美国人。通过此应用程序，我们的目标是减少儿童在这些危机中经历的痛苦，从而缩短住院时间并降低与照顾患有这种痛苦疾病的儿童相关的费用。