The Diagnosis and Treatment of Critical Illness Polyneuromyopathy in Patients wit

描述（由申请人提供）：急性呼吸衰竭是一种异质性疾病，每年有超过30万美国人需要进入重症监护室接受侵入性机械辅助治疗。虽然急性呼吸衰竭是一种肺部疾病，但幸存的患者出院后并不受呼吸系统症状的限制。相反，持续的神经肌肉无力是对他们的生活质量和日常功能产生不利影响的主要障碍。这些幸存者的虚弱与危重病多发性神经肌病（CIPNM）的发展有关。在这些患者中准确诊断CIPNM的能力是困难的，并且经常被延迟。目前，还没有可用的诊断筛查测试可以准确识别那些将发展为CIPNM的急性呼吸衰竭患者。早期和侵入性较低的重症患者，最终将发展CIPNM的识别可能会提高特定的药物治疗，营养支持，或强化物理治疗的疗效。我们已经确定了神经传导研究的变化，早在三天后提交到医院的危重患者。在随后的7天内，基线振幅的进行性降低预示着CIPNM的发展。在本提案的第一部分，我们将前瞻性地确定是否可以使用简单的神经传导研究的变化作为一种有效的诊断工具，为急性呼吸衰竭患者的CIPNM的发展。目前，每年估计有110，000名急性呼吸衰竭幸存者发展为CIPNM，没有治疗方法。根据我们对物理治疗师和重症监护医生的全国调查结果，从急性呼吸衰竭中恢复的神经肌肉无力患者的物理治疗的使用和类型因医院类型和患者的初步诊断而显着不同。在本提案的第二部分，我们计划进行一项随机、安慰剂对照的临床试验，以确定为期四周的强化物理治疗计划对发生CIPNM的急性呼吸衰竭患者子集的有效性。本试验将确定目前以非循证方式对美国急性呼吸衰竭患者进行的物理治疗方案的疗效。如果成功，我们的研究将确定一种诊断CIPNM患者的新方法，并为急性呼吸衰竭幸存者强化物理治疗的大型多中心临床试验铺平道路。公共卫生相关性：急性呼吸衰竭是一种异质性疾病，每年有超过300，000的美国人需要进入重症监护室接受侵入性机械通气支持。虽然急性呼吸衰竭是一种肺部疾病，但住院后存活的患者出院后并不受呼吸系统症状的限制。相反，持续的神经肌肉无力是主要的疾病，对他们的生活质量和日常功能产生不利影响。在本申请中，我们提出了一种新的方法来识别急性呼吸衰竭患者，将发展神经肌肉无力。此外，我们计划进行一项随机、安慰剂对照的临床试验，称为“立即行动研究”（神经肌肉无力的诊断和治疗），以确定强化物理治疗计划对从急性呼吸衰竭中恢复的神经肌肉无力患者的有效性。本试验将以非循证方式确定目前在美国对急性呼吸衰竭患者实施的物理治疗方案的疗效。

DESCRIPTION (provided by applicant): Acute respiratory failure is a heterogeneous disorder that results in more than 300,000 Americans requiring admission to an intensive care unit for invasive mechanical ventilatory support each year. Though acute respiratory failure is a pulmonary disorder, patients who survive are not limited by respiratory symptoms after discharge. Rather persistent neuromuscular weakness is the primary disorder that adversely affects their quality of life and ability to function on a daily basis. Weakness in these survivors is related to the development of critical illness polyneuromyopathy (CIPNM). The ability to accurately diagnose CIPNM in these patients is difficult and often delayed. Presently, there is no available diagnostic screening test that accurately identifies those patients with acute respiratory failure that will develop CIPNM. Earlier and less invasive identification of critically ill patients that will eventually develop CIPNM may improve the efficacy of specific medical therapies, nutritional support, or intensive physical therapy. We have identified alterations on nerve conduction studies as early as three days after presentation to the hospital in critically ill patients. A progressive decrease over the subsequent seven days in the baseline amplitude was predictive of the development of CIPNM. In the first part of this proposal, we will prospectively determine whether changes on simple nerve conduction studies can be used as an effective diagnostic tool for the development of CIPNM in patients with acute respiratory failure. Presently, there are no therapies to treat the estimated 110,000 acute respiratory failure survivors who have developed CIPNM each year. Based on the results of our national surveys of physical therapists and intensive care physicians, the utilization and types of physical therapy for patients recovering from acute respiratory failure with neuromuscular weakness varies significantly depending on the type of hospital and primary diagnosis of the patient. In the second part of this proposal, we plan to perform a randomized, placebo controlled clinical trial to determine the effectiveness of an intensive four week physical therapy program for the subset of patients with acute respiratory failure who have developed CIPNM. This trial will determine the efficacy of the physical therapy programs that is currently performed in a non-evidence based manner for patients with acute respiratory failure across the United States. If successful, our studies would identify a novel way to diagnose patients with CIPNM and pave the way for a larger multi-center clinical trial of intensive physical therapy for survivors of acute respiratory failure. PUBLIC HEALTH RELEVANCE: and Relevance Acute respiratory failure is a heterogeneous disorder that results in more than 300,000 Americans requiring admission to an intensive care unit for invasive mechanical ventilatory support each year. Though acute respiratory failure is a pulmonary disorder, patients who survive their hospitalization are not limited by respiratory symptoms after discharge. Rather persistent neuromuscular weakness is the primary disorder that adversely alters their quality of life and ability to function on a daily basis. In this application we propose to identify a novel method of identifying those patients with acute respiratory failure that will develop neuromuscular weakness. In addition, we plan to conduct a randomized, placebo-controlled clinical trial called the Do It Now study (Diagnosis and Treatment of Neuromuscular Weakness) to determine the effectiveness of an intensive physical therapy program for patients recovering from acute respiratory failure who have developed neuromuscular weakness. This trial will establish the efficacy of the physical therapy programs that is currently performed for patients with acute respiratory failure in a non-evidence based manner across the United States.