Effect of randomization to neuromuscular blockade on physical functional impairment and recovery in ARDS

神经肌肉阻滞随机化对 ARDS 患者身体功能损伤和恢复的影响

• 批准号: 10249878
• 负责人: Catherine Lee Hough
• 金额: $ 24.27万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-12-15 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10249878
• 关键词: Effect; randomization; neuromuscular; blockade; physical

Project Summary/Abstract Background: The acute respiratory distress syndrome (ARDS) continues to be a major health problem, affecting nearly 200,000 people in the United States each year. Mortality is high (up to 40%), and nearly all survivors develop muscle loss and weakness during critical illness, termed ICU-acquired neuromuscular dysfunction. This neuromuscular dysfunction is associated with poor outcomes including: increased hospital mortality, delayed liberation from mechanical ventilation, prolonged hospitalization, impaired post-discharge functional activity, and continued risk of death among survivors of critical illness. Medications used during critical illness are frequently implicated in the cause of ICUAW, but data are inconclusive. For example, neuromuscular blocking agents (NMB) work directly on the neuromuscular junction and prevent muscle depolarization in response to nerve excitation. As a result, NMBAs can cause functional denervation and ultimately: neuropathy, myopathy, deconditioning, and prolonged neuromuscular weakness. However, NMB may also improve mortality in ARDS by reducing ventilator induced lung injury. Despite much debate about these risks and benefits, a randomized trial in ARDS patients is required to understand the effect of NMB on mortality, neuromuscular function, and recovery. The NHLBI PETAL Network will be conducting a randomized trial of NMB in ARDS, which provides a unique opportunity to study the effect of NMB on ICU-acquired neuromuscular dysfunction and recovery. Proposal and hypothesis: We propose to conduct an ancillary study at five of the PETAL network centers that will leverage the network infrastructure, complement the conduct of the clinical trial, and most importantly enhance the understanding of the utility of NMB for critically ill patients. We hypothesize that randomization to NMB will increase ICU-acquired neuromuscular dysfunction, leading to an increase in neuromyopathy early in critical illness, to impaired muscle strength and function at hospital discharge, and to reduced long term physical recovery. Specific Aims: Our specific aims are to determine the effect of randomization to NMB on development of neuromyopathy early in ARDS, on weakness at hospital discharge, and on physical functional recovery and healthcare utilization at 6 and 12 months after ARDS. We will conduct these aims by performing rigorous, standardized assessments of physical function using electrophysiology, ultrasound, hands-on strength and functional assessments, detailed questionnaires, and in-person follow-up after hospital discharge. We will use state-of-the art techniques for cohort retention and data analysis. With these results, we will definitively determine the acute and post-hospital effects of NMB on physical function. This knowledge is crucial for providing highest quality critical care that is focused not only on survival, but also the quality of survivorship.

项目摘要/摘要 背景：急性呼吸窘迫综合征（ARDS）仍然是一个主要的健康问题， 每年在美国影响近200,000人。死亡率很高（高达40％），几乎全部 幸存者在危重疾病期间会出现肌肉丧失和无力，称为ICU获得的神经肌肉 功能障碍。这种神经肌肉功能障碍与不良预后有关，包括：增加医院 死亡率，从机械通气中解放延迟，住院时间长，病后损害 功能活动，以及重症疾病幸存者的持续死亡风险。在期间使用的药物 重症疾病经常与ICUAW的原因有关，但数据尚无定论。例如， 神经肌肉阻断剂（NMB）直接在神经肌肉连接处起作用并防止肌肉 响应神经激发的去极化。结果，NMBA可以引起功能神经，并 最终：神经病，肌病，解剖和长时间的神经肌肉无力。但是，NMB 还可以通过减少呼吸机诱导的肺损伤来提高ARDS的死亡率。尽管有很多关于 这些风险和益处，需要在ARDS患者中进行随机试验才能了解NMB对 死亡率，神经肌肉功能和恢复。 NHLBI花瓣网络将进行随机 NMB在ARDS中的试验提供了一个独特的机会来研究NMB对ICU获得的影响 神经肌肉功能障碍和恢复。 提案和假设：我们建议在五个花瓣网络中心进行一项辅助研究，以 将利用网络基础架构，补充临床试验的行为，最重要的是 增强对重症患者NMB效用的理解。我们假设将随机分配给 NMB将增加ICU获得的神经肌肉功能障碍，从而导致神经瘤的增加 重症疾病，以损害出院时的肌肉力量和功能，并减少长期 物理恢复。 具体目的：我们的具体目的是确定随机分配到NMB对开发的影响 神经瘤早期的神经疗法，出院时无力的无力以及身体功能恢复和 ARDS后6和12个月的医疗保健利用。我们将通过执行严格的， 使用电生理学，超声，动手强度和 出院后的功能评估，详细的问卷和面对面的随访。我们将使用 用于队列保留和数据分析的最新技术。通过这些结果，我们将确定 确定NMB对身体机能的急性和院后作用。这些知识对 提供最高质量的重症监护，这不仅侧重于生存，而且还集中在生存质量上。