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

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， 每年影响美国近20万人。死亡率很高(高达40%)，而且几乎所有 幸存者在危重疾病期间出现肌肉丧失和虚弱，称为重症监护病房获得性神经肌肉 功能障碍。这种神经肌肉功能障碍与不良预后有关，包括：医院增加 死亡率、延迟脱离机械通气、长时间住院、出院后受损 危重疾病幸存者的功能活动和持续的死亡风险。在此期间使用的药物 危重疾病经常与ICUAW的原因有关，但数据并不确定。例如, 神经肌肉阻滞剂(NMB)直接作用于神经肌肉接头，防止肌肉 神经兴奋时的去极化反应。因此，NMBAS可导致功能性去神经和 最终：神经病、肌病、去条件化和长期神经肌肉无力。然而，NMB 还可能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 这些风险和好处，需要在ARDS患者中进行随机试验，以了解NMB对 死亡率、神经肌肉功能和康复。NHLBI Petal Network将进行随机化的 NMB在ARDS中的试验，这为研究NMB对ICU获得性疾病的影响提供了一个独特的机会 神经肌肉功能障碍和康复。 建议和假设：我们建议在五个花瓣网络中心进行一项辅助研究 将利用网络基础设施，补充临床试验的进行，最重要的是 提高对NMB在危重病人中应用的认识。我们假设随机化是为了 NMB会增加ICU获得性神经肌肉功能障碍，导致早期神经肌病的增加 危重疾病，出院时肌肉力量和功能受损，长期病程缩短 身体恢复。 具体目标：我们的具体目标是确定随机化对NMB的影响 ARDS早期神经肌病，出院时虚弱，身体功能恢复和 ARDS后6个月和12个月的医疗保健利用率。我们将通过严格、 使用电生理学、超声波、动手力量和 出院后的功能评估、详细的问卷调查和面对面的随访。我们将使用 最先进的队列保留和数据分析技术。有了这些结果，我们肯定会 确定NMB的急性和住院后对身体功能的影响。这方面的知识对于 提供最高质量的危重护理，不仅关注生存，而且关注生存质量。

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.