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: 7758174
• 负责人: David C Brousseau
• 金额: $ 43.15万
• 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/7758174
• 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; In Vitro; 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; Telephone; Testing; Thalassemia; United States; 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例住院治疗和75，000个住院日用于患有继发于镰状细胞病的血管闭塞性危象的儿童。绝大多数住院治疗是因为疼痛危象，使疼痛成为镰状细胞病儿童最重要的发病原因之一。在过去的三十年里，这些疼痛危机的急性治疗几乎没有变化，主要依靠静脉输液，阿片类药物和非类固醇药物。最近，人们越来越认识到一氧化氮在疼痛危象发病机制中的作用，并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，通过内皮依赖性一氧化氮机制以及对基础血管平滑肌的直接作用产生血管扩张。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。在本申请中，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开展四中心合作，通过双盲、随机、安慰剂对照试验测试这种新疗法，评估在标准疗法中加入静脉镁对镰状细胞疼痛危象的影响。主要临床结局是儿科镰状细胞疼痛危象的住院时间缩短，次要临床结局测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的标志物来获得对镰状细胞危象的病理生理学的有价值的见解。在这项研究的结论中，我们有可能使用低成本，低风险的治疗来改善镰状细胞病儿童的护理。 公共卫生关系：仅在美国，每年就有超过18，000例因镰状细胞病继发血管闭塞性疼痛发作的儿童住院治疗和75，000个住院日;这些儿童中绝大多数是非洲裔美国人。通过这一应用，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，降低与照顾患有这种痛苦疾病的儿童相关的成本。