ICU-ACQUIRED NEUROMUSCULAR DYSFUNCTION AND OUTCOMES IN ACUTE LUNG INJURY

描述(由申请人提供)： 急性呼吸窘迫综合征/急性肺损伤(ALI)的幸存者通常会出现严重且持续的神经肌肉无力和身体功能受损，但对这一重要并发症的病因、治疗和预防知之甚少。在重症监护病房(ICU)获得的神经肌肉功能障碍是常见的，但在ALI患者中尚未得到系统的研究，其与虚弱和身体功能的关系也没有得到严格的评估。我们的总体目标是改善ICU幸存者的身体功能，通过这项研究，我们将对ICU获得性神经肌肉功能障碍进行相关和严格的临床调查。假设和具体目标。我们假设，ICU获得性神经肌肉功能障碍在ALI患者中很常见，受到ICU营养和药物干预的影响，并与短期和长期的身体功能损害有关。我们的目标是：(1)确定ICU获得性神经肌肉功能障碍在ALI中的发生率；(2)研究ARDS网络随机试验干预与这种功能障碍的发生之间的关系；(3)评估ICU获得性神经肌肉功能障碍与短期和长期神经肌肉无力和身体功能的相关性。研究设计与方法。我们提出了一项前瞻性纵向队列研究，对象是在4个研究地点参加ARDS网络随机试验的270名患者。我们将通过在研究开始时和此后每周在ICU进行电生理学评估来确定ICU获得性神经肌肉功能障碍。发病率将根据ICU中任何时候检测到的患有ICU获得性神经肌肉功能障碍(肌病和/或神经病)的受试者的比例来衡量。我们将通过比较研究第7天随机治疗组之间的功能障碍发生率来调查ARDS网络干预的效果。我们将通过出院前以及ALI发病后6个月和12个月的标准化临床评估，评估神经肌肉功能障碍与短期和长期虚弱和身体功能的关系。意义重大。这项研究解决了关于ALI患者ICU获得性神经肌肉功能障碍的流行病学、实验性治疗的效果和长期后果的科学知识中的三个关键空白。这项研究的数据对于建立改善ALI幸存者通常经历的严重短期和长期后遗症所需的知识基础至关重要。公共卫生相关性：由于重症监护病房(ICU)的患者经常有急性肌肉和神经功能障碍，出院后持续虚弱和生活质量受损，迫切需要新的研究来了解这些短期和长期的疾病。我们将研究参加国家心肺血液研究所资助的临床试验的急性肺损伤(ALI)患者的ICU获得性神经肌肉功能障碍。在研究ICU获得性神经肌肉功能障碍方面，我们的目标是：(1)在ALI试验中系统地测量其发生率；(2)评估试验中测试的治疗方法是否影响其发生率；以及(3)调查其与长期身体功能的关系。

DESCRIPTION (provided by applicant): Survivors of acute respiratory distress syndrome/acute lung injury ("ALI") commonly experience significant and persistent neuromuscular weakness and impaired physical function, but little is known about the etiology, treatment and prevention of this important complication. Neuromuscular dysfunction acquired in the intensive care unit (ICU) is common, but has not been systematically studied in ALI patients, and its association with weakness and physical function has not been rigorously evaluated. Our overall goal is to improve ICU survivors' physical function, and through this research, we will conduct relevant and rigorous clinical investigations of ICU-acquired neuromuscular dysfunction. Hypotheses and specific aims. We hypothesize that ICU-acquired neuromuscular dysfunction is common in ALI patients, affected by ICU nutritional and pharmacologic interventions, and associated with short- and long-term impairment of physical function. Our aims are: (1) to determine the incidence of ICU- acquired neuromuscular dysfunction in ALI; (2) to investigate the relationship between ARDS Network randomized trial interventions and development of this dysfunction, and (3) to assess the association of ICU- acquired neuromuscular dysfunction with short- and long-term neuromuscular weakness and physical function. Study design and methods. We propose a prospective longitudinal cohort study of 270 patients enrolled in ARDS Network randomized trials at 4 study sites. We will identify ICU-acquired neuromuscular dysfunction using electrophysiologic assessments performed at study entry and weekly thereafter while in the ICU. Incidence will be measured as the proportion of subjects with ICU-acquired neuromuscular dysfunction (myopathic and/or neuropathic) detected at any time in the ICU. We will investigate the effect of ARDS Network interventions by comparing the incidence of dysfunction at study day 7 between randomized treatment groups. We will assess the association of neuromuscular dysfunction with short- and long-term weakness and physical function via standardized clinical evaluations before hospital discharge and at 6 and 12 months after ALI onset. Significance. This research addresses three critical gaps in scientific knowledge regarding the epidemiology, effect of experimental therapies, and long-term consequences of ICU-acquired neuromuscular dysfunction in ALI patients. Data from this study are essential to build the foundation of knowledge necessary to improve the serious short- and long-term sequelae commonly experienced by ALI survivors. PUBLIC HEALTH RELEVANCE: Since patients in the intensive care unit (ICU) frequently have acute muscle and nerve dysfunction, and persistent weakness and impaired quality of life after hospital discharge, new research is urgently required to understand these short and long-term morbidities. We will study ICU-acquired neuromuscular dysfunction in a subset of patients with acute lung injury (ALI) who are enrolled in National Heart Lung and Blood Institute-funded clinical trials. In studying ICU-acquired neuromuscular dysfunction, our aims are: (1) to systematically measure its incidence within the ALI trials; (2) to evaluate if the treatments tested in the trials affect its incidence; and (3) to investigate its association with longer-term physical function.