The Diagnosis and Treatment of Critical Illness Polyneuromyopathy in Patients wit

描述(申请人提供)：急性呼吸衰竭是一种异质性疾病，每年导致超过30万美国人需要住进重症监护病房进行有创性机械呼吸支持。虽然急性呼吸衰竭是一种肺部疾病，但存活下来的患者不受出院后呼吸道症状的限制。更确切地说，持续性神经肌肉无力是对他们的生活质量和日常功能能力产生不利影响的主要疾病。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，而且往往被推迟。目前，还没有可用的诊断筛查试验来准确地识别那些将发展为CIPNM的急性呼吸衰竭患者。对最终发展为CIPNM的危重患者进行早期、侵入性较小的识别，可能会提高特定药物治疗、营养支持或强化物理治疗的疗效。我们早在危重病人入院三天后就发现了神经传导研究的改变。在随后的7天内，基线波幅的逐渐降低预示着CIPNM的发展。在这项建议的第一部分，我们将前瞻性地确定单纯神经传导检查的变化是否可以作为急性呼吸衰竭患者发生CIPNM的有效诊断工具。目前，估计每年有11万名急性呼吸衰竭幸存者发展为CIPNM，目前还没有治疗方法。根据我国对物理治疗师和重症监护医生的调查结果，对于急性呼吸衰竭合并神经肌肉无力的康复患者，物理治疗的利用率和类型因医院类型和患者的主要诊断而有很大差异。在这项建议的第二部分，我们计划进行一项随机、安慰剂对照的临床试验，以确定四周强化物理治疗计划对发生CIPNM的急性呼吸衰竭患者的有效性。这项试验将确定目前在美国各地以非证据为基础的方式对急性呼吸衰竭患者进行的物理治疗计划的有效性。如果成功，我们的研究将确定一种诊断CIPNM患者的新方法，并为为急性呼吸衰竭幸存者进行强化物理治疗的更大规模的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30多万美国人需要住进重症监护病房接受侵入性机械呼吸支持。虽然急性呼吸衰竭是一种肺部疾病，但在住院期间幸存下来的患者在出院后并不受呼吸道症状的限制。更确切地说，持续性神经肌肉无力是对他们的生活质量和日常功能能力产生不利影响的主要疾病。在这项应用中，我们建议确定一种新的方法来识别那些将出现神经肌肉无力的急性呼吸衰竭患者。此外，我们计划进行一项随机、安慰剂对照的临床试验，名为Do It Now Study(神经肌肉无力的诊断和治疗)，以确定强化物理治疗计划对已出现神经肌肉无力的急性呼吸衰竭康复患者的有效性。这项试验将确定目前在美国各地以非循证方式对急性呼吸衰竭患者进行的物理治疗计划的有效性。

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.