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，每年导致超过30万美国人需要进入重症监护病房进行有创机械通气支持。虽然急性呼吸衰竭是一种肺部疾病，但存活下来的患者出院后不会受到呼吸道症状的限制。相反，持续的神经肌肉无力是对他们的生活质量和日常生活能力产生不利影响的主要疾病。这些幸存者的虚弱与重症多神经肌病（CIPNM）的发展有关。在这些患者中，准确诊断CIPNM的能力是困难的，而且经常延迟。目前，还没有可用的诊断筛选试验来准确识别那些将发展为CIPNM的急性呼吸衰竭患者。对最终发展为CIPNM的危重患者进行更早和更少侵入性的识别，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后三天就发现了神经传导研究的改变。基线振幅在随后的7天内逐渐下降，可预测CIPNM的发展。在本提案的第一部分，我们将前瞻性地确定简单神经传导的变化研究是否可以作为急性呼吸衰竭患者CIPNM发展的有效诊断工具。目前，每年约有11万名急性呼吸衰竭幸存者发展为CIPNM，尚无治疗方法。根据我们对物理治疗师和重症监护医生的全国调查结果，急性呼吸衰竭伴神经肌肉无力患者康复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有显著差异。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，以确定对发生CIPNM的急性呼吸衰竭患者进行为期四周的强化物理治疗的有效性。该试验将确定物理治疗方案的有效性，该方案目前在美国以非证据为基础的方式对急性呼吸衰竭患者进行治疗。如果成功，我们的研究将确定一种诊断CIPNM患者的新方法，并为更大规模的多中心临床试验铺平道路，为急性呼吸衰竭幸存者进行强化物理治疗。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病房接受有创机械通气支持。虽然急性呼吸衰竭是一种肺部疾病，但存活下来的患者出院后并不受呼吸道症状的限制。相反，持续的神经肌肉无力是对他们的生活质量和日常生活能力产生不利影响的主要疾病。在这个应用中，我们提出了一种新的方法来识别那些急性呼吸衰竭患者，将发展为神经肌肉无力。此外，我们计划进行一项随机、安慰剂对照的临床试验，称为Do It Now研究（神经肌肉无力的诊断和治疗），以确定强化物理治疗方案对急性呼吸衰竭患者的有效性，这些患者患有神经肌肉无力。该试验将确定物理治疗方案的有效性，该方案目前在美国以非证据为基础的方式对急性呼吸衰竭患者进行治疗。

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.