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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Nursing Research (NINR)
Type
Research Project (R01)
Project #
5R01NR011051-05
Application #
8535566
Study Section
Nursing Science: Adults and Older Adults Study Section (NSAA)
Program Officer
Mccloskey, Donna J
Project Start
2009-06-01
Project End
2014-08-31
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
5
Fiscal Year
2013
Total Cost
$437,093
Indirect Cost
$151,411
Name
University of Colorado Denver
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
041096314
City
Aurora
State
CO
Country
United States
Zip Code
80045
Kelmenson, Daniel A; Held, Natalie; Allen, Richard R et al. (2017) Outcomes of ICU Patients With a Discharge Diagnosis of Critical Illness Polyneuromyopathy: A Propensity-Matched Analysis. Crit Care Med 45:2055-2060
Neumeier, Anna; Nordon-Craft, Amy; Malone, Dan et al. (2017) Prolonged acute care and post-acute care admission and recovery of physical function in survivors of acute respiratory failure: a secondary analysis of a randomized controlled trial. Crit Care 21:190
Nordon-Craft, Amy; Malone, Dan; Schenkman, Margaret et al. (2016) Reply: Is an Earlier and More Intensive Physical Therapy Program Better? Am J Respir Crit Care Med 194:1032-1033
Kelmenson, Daniel A; Quan, Dianna; Nordon-Craft, Amy et al. (2016) Electrophysiological abnormalities can differentiate pre-hospital discharge functional status in critically ill patients with normal strength. Intensive Care Med 42:1504-5
Sottile, Peter D; Nordon-Craft, Amy; Malone, Daniel et al. (2015) Patient and family perceptions of physical therapy in the medical intensive care unit. J Crit Care 30:891-5
Sottile, Peter D; Nordon-Craft, Amy; Malone, Daniel et al. (2015) Physical Therapist Treatment of Patients in the Neurological Intensive Care Unit: Description of Practice. Phys Ther 95:1006-14
Malone, Daniel; Ridgeway, Kyle; Nordon-Craft, Amy et al. (2015) Physical Therapist Practice in the Intensive Care Unit: Results of a National Survey. Phys Ther 95:1335-44
Moss, Marc (2015) Mortality is the only relevant outcome in ARDS: yes. Intensive Care Med 41:141-3
Burnham, Ellen L; Janssen, William J; Riches, David W H et al. (2014) The fibroproliferative response in acute respiratory distress syndrome: mechanisms and clinical significance. Eur Respir J 43:276-85
Denehy, Linda; Nordon-Craft, Amy; Edbrooke, Lara et al. (2014) Outcome measures report different aspects of patient function three months following critical care. Intensive Care Med 40:1862-9

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