Intravenous Magnesium: Prompt Use for Asthma in Children Treated in the Emergency Department (IMPACT-ED)

项目总结摘要 哮喘是儿童最常见的慢性病，也是住院和医疗保健的主要原因。 孩子们的开销。大多数因哮喘住院的儿童首先接受呼吸治疗和类固醇 根据国家指南，急诊科(ED)的药品。一种额外的药物， 静脉注射硫酸镁(IVMG)，可能有助于重病儿童避免住院。全国性哮喘 指南建议将静脉注射镁用于重症儿童，但注意到缺乏一致的证据来支持这一点 推荐。只有大约四分之一因哮喘住院的儿童在急诊室接受静脉注射镁。估计数 更广泛地使用IVMG对住院的潜在影响的研究受到先前试验规模较小的限制，但 增加使用量可能每年避免18,000次住院，直接节省成本65美元 此外，每年还能节省大量因缺课和家长工作而产生的间接成本。 有关IVMG的几个主要问题仍然存在。首先，它在早期ED治疗中没有经过测试，当产生影响 入院治疗将是最棒的。其次，低血压的临床影响是低使用率的驱动因素。 没有在以前的试验或临床数据库中表现出特征。第三，没有试验比较不同的静脉注射镁剂量或 测量血清镁水平以优化剂量，因此最有效的剂量尚不清楚。 所有先前对哮喘儿童进行的IVMG试验都是小规模的。一项大型随机、安慰剂对照临床试验 可以回答静脉注射镁是否可以减少住院的静脉注射镁试验对一些人来说可能是具有挑战性的 理由。首先，招募足够快的患者以在ED治疗的早期给予IVMG是具有挑战性的。第二, 了解静脉注射镁后的血压变化对于为更大规模的试验计划安全监测至关重要。第三, 几乎没有药理学信息被收集来指导要测试的IVMG的剂量。我们必须进行 一项小型试点临床试验，以测试我们的程序并收集必要的信息来计划大型试验。 儿科急救应用研究网络(PECARN)是一个由儿童急救中心组成的网络，它具有 对病情危重的儿童进行了类似的研究。我们在这个项目中的目标是： 1.论证将患有严重急性哮喘的儿童纳入急诊科的可行性 安慰剂、低剂量静脉注射镁或高剂量静脉注射镁的多中心随机对照试验。 2.论证及时向入选患者提供研究药物的可行性 以标准化方案评估血压和相关不良事件。 3.对之前构建的PK模型进行外部验证，并开发了PK/PD组合模型 静脉注射镁(总镁和电离镁)的血药浓度及其相关性 哮喘儿童的安全性和呼吸窘迫的测量。 在三个地点完成这项试点试验后，我们将计划对患有 在更多的地点招募更多的严重急性哮喘儿童，以了解静脉注射镁是否可以减少住院。

PROJECT SUMMARY ABSTRACT Asthma is the most common chronic illness of childhood and a leading cause of hospitalization and healthcare costs for children. Most children hospitalized for asthma first receive breathing treatments and steroid medicines in an emergency department (ED) according to national guidelines. An additional medicine, intravenous magnesium sulfate (IVMg), may help severely sick children avoid hospitalization. National asthma guidelines recommend IVMg for severely sick children, but note a lack of consistent evidence to support this recommendation. Only about one in four children hospitalized for asthma received IVMg in the ED. Estimates of the potential effects of broader use of IVMg on hospitalization are limited by the small size of prior trials, but increased use could potentially avoid 18,000 hospitalizations each year, producing direct cost savings of $65 million yearly in addition to saving significant indirect costs of missed school and parental work. A few major questions remain about IVMg. First, it has not been tested early in ED treatment, when the impact on hospitalization would be greatest. Second, the clinical impact of hypotension, a driver of low utilization, is not characterized in prior trials or clinical databases. Third, no trials have compared different IVMg doses or measured serum magnesium levels to optimize dosing, so the most effective dose is unknown. All prior trials of IVMg in children with asthma have been small. A large randomized, placebo-controlled clinical trial of IVMg that could answer whether IVMg can reduce hospitalization might be challenging for a few reasons. First, enrolling patients fast enough to give IVMg early in ED treatment is challenging. Second, understanding blood pressure changes after IVMg is essential to plan safety monitoring for a larger trial. Third, little pharmacologic information has been gathered to guide the doses of IVMg to be tested. We must conduct a small pilot clinical trial to test our procedures and gather necessary information to plan the large trial. The Pediatric Emergency Care Applied Research Network (PECARN) is a network of children’s EDs that has conducted similar research involving acutely ill children. Our goals in this project are to: 1. Demonstrate the feasibility of enrolling children in the ED with severe acute asthma in a multicenter, randomized, controlled trial of placebo, low-dose IVMg, or high-dose IVMg. 2. Demonstrate the feasibility of timely delivery of study medication to enrolled patients and assessment of blood pressure and associated adverse events in a standardized protocol. 3. Externally validate a previously constructed PK model and develop a combined PK/PD model for IVMg using magnesium (total and ionized) serum concentrations and their correlation with measures of safety and respiratory distress in children with asthma. After completing this pilot trial in three sites, we will plan a multi-center randomized trial of IVMg in children with severe acute asthma at more sites to enroll enough children to know if IVMg can reduce hospitalization.