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

 描述(申请人提供)：急性呼吸窘迫综合征(ARDS)仍然是一个主要的健康问题，每年在美国有近20万人受到影响。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相关，包括：住院死亡率增加，机械通气延迟，住院时间延长，出院后功能活动受损，危重疾病幸存者死亡风险持续存在，危重疾病期间使用的药物经常与ICUAW的原因有关，但数据尚不确定。例如，神经肌肉阻滞剂(NMB)直接作用于神经肌肉接头，防止肌肉因神经兴奋而去极化。因此，NMBAS可导致功能性失神经，最终导致神经病、肌病、去条件反射和长期的神经肌肉无力。然而，NMB也可能通过减少呼吸机诱导的肺损伤而提高ARDS的死亡率。尽管对这些风险和益处有很多争论，但需要在ARDS患者中进行随机试验，以了解NMB对死亡率、神经肌肉功能和恢复的影响。NHLBI Petal Network将进行一项NMB治疗ARDS的随机试验，这为研究NMB对ICU获得性神经肌肉功能障碍和康复的影响提供了一个独特的机会。建议和假设：我们建议在五个Petal网络中心进行一项辅助研究，该研究将利用网络基础设施，补充临床试验的进行，最重要的是加强对NMB对危重患者效用的理解。我们假设，随机服用NMB将增加ICU获得性神经肌肉功能障碍，导致危重疾病早期神经肌病的增加，出院时肌肉力量和功能受损，并降低长期身体恢复。具体目标：我们的具体目标是确定随机使用NMB对ARDS早期神经肌病的发展、出院时的虚弱以及ARDS后6个月和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、超声波、实际力量和功能评估、详细的问卷调查以及出院后的面对面跟进，对身体功能进行严格、标准化的评估，以实现这些目标。我们将使用最先进的技术进行队列保留和数据分析。根据这些结果，我们将明确地确定NMB对身体功能的急性和医院后影响。这些知识对于提供不仅关注生存而且关注生存质量的最高质量的危重护理至关重要。

 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.