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

基本信息

批准号：
9080061
负责人：
Catherine Lee Hough
金额：
$ 77.65万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-08-16 至 2020-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9080061
关键词：
Acute Adult Respiratory Distress Syndrome Adverse effects Affect Ancillary Study Architecture Belief Benefits and Risks Biology Caring Cessation of life Charge Clinical Cohort Studies Complement Conduct Clinical Trials Critical Care Critical Illness Data Data Analyses Denervation Development Dual-Energy X-Ray Absorptiometry Electrophysiology (science)Enrollment Epidemiology Equilibrium Evaluation Expenditure Functional disorder Future Goals Guidelines Health Hospital Mortality Hospitalization Hospitals Human Induction of neuromuscular blockade Inflammation Injury Institution Intensive Care Units Knowledge Lead Mechanical ventilation Medical Medicine Muscle Muscle Weakness Muscle function Muscular Atrophy Myopathy National Heart, Lung, and Blood Institute Nerve Network Infrastructure Neural Conduction Neuromuscular Blocking Agents Neuromuscular Junction Neuropathy Outcome Outcome Assessment Patient Care Patient-Focused Outcomes Patients Persons Pharmaceutical Preparations Phenotype Physical Function Physical Performance Questionnaires Randomized Recovery Recovery of Function Research Research Infrastructure Respiratory Failure Risk Rosa Science Staging Surveys Survivors Techniques Testing Time Ultrasonography United States Ventilator-induced lung injury Work cohort deconditioning design disability evidence base follow-up functional disability health care service utilization improved improved outcome indium arsenide innovation insight mortality muscle strength neuromuscular neuromuscular function prevent primary outcome prospective public health relevance randomized trial response screening survivorship tool

项目摘要

DESCRIPTION (provided by applicant): 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.

描述（由适用提供）：急性呼吸窘迫综合征（ARDS）仍然是一个重大的健康问题，每年影响美国近20万人。死亡率很高（高达40％），几乎所有幸存者在危重疾病期间都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的结局有关：医院死亡率增加，机械通气延迟的解放，延长的住院时间，减损后入院功能活动受损以及在重症疾病期间使用的重症疾病中使用的持续死亡风险持续存在于ICUAW原因中，但数据却是不存在的。例如，神经肌肉阻断剂（NMB）直接在神经肌肉结上起作用，并防止肌肉沉积对神经兴奋。结果，NMBA会导致功能神经，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。尽管关于这些风险和益处有很多争议，但需要在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的影响。 NHLBI Petal网络将在ARDS中进行NMB的随机试验，该试验提供了一个独特的机会来研究NMB对ICU获得的神经肌肉功能障碍和恢复的影响。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，该研究将利用网络基础设施，完成临床试验的进行，最重要的是增强了对重症患者NMB效用的理解。我们假设与NMB的随机化将增加ICU获得的神经肌肉功能障碍，从而导致危重疾病早期神经肌病的增加，从而损害医院出院时肌肉力量和功能，并减少长期身体恢复。具体目的：我们的具体目的是确定NMB对NMB的随机化对ARDS早期神经瘤发展的影响，对医院出院时的无力以及ARDS后6和12个月的身体功能恢复和医疗保健利用的影响。我们将通过使用电生理学，超声，动手强度和功能评估，详细的问卷以及出院后的亲自随访，对身体机能进行严格的标准化评估来实现这些目标。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。这些知识对于提供不仅关注生存的最高质量重症监护至关重要，而且还集中在生存质量上。