Vanderbilt Evidence-Based Practice Center
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Vanderbilt Evidence-based Practice Center AARC Review: Effectiveness of Pharmacologic Agents to Promote Airway Clearance in Hospitalized Patients Nila A. Sathe, MA, MLIS Jeff Andrews, MD Shanthi Krishnaswami, MBBS, MPH Cathy Ficzere, PharmD Melissa L. McPheeters, PhD, MPH Acknowledgements We the appreciate contributions of Ms. Rachel Walden, who conducted the searches for this review and assisted with screening studies. We also gratefully acknowledge the American Association for Respiratory Care (AARC) Pharmacologic Airway Clearance Clinical Practice Guidelines Committee. Their insight into scoping the literature and reviewing studies was invaluable. The committee includes: Chairperson: Shawna Strickland, PhD, RRT-NPS, RRT-ACCS, AE-C, FAARC AARC Irving, TX Members: Richard Branson, MS, RRT, FAARC University of Cincinnati College of Medicine Cincinnati, OH Gail Drescher, MA, RRT Washington Hospital Center Washington DC Carl Haas, MLS, RRT-ACCS, FAARC University Hospitals and Health Centers Ann Arbor, MI Catherine O’Malley, RRT-NPS Ann & Robert H. Lurie Children’s Hospital of Chicago Chicago, IL Bruce Rubin, MD, MEngr, MBA, FAARC Virginia Commonwealth University Richmond, VA Teresa Volsko, MHHS, RRT, FAARC Akron Children’s Hospital Dean Hess, PhD, RRT, FAARC Ex-officio Boston, MA Ray Masferrer, RRT, FAARC Ex-officio Dallas, TX Table of Contents Introduction ................................................................................................................................... 1 Methods .......................................................................................................................................... 1 Topic refinement and key questions ......................................................................................... 1 Literature search strategy .......................................................................................................... 2 Inclusion and exclusion criteria ................................................................................................ 2 Study selection .......................................................................................................................... 4 Data extraction and synthesis .................................................................................................... 4 Quality (Risk of Bias) assessment of individual studies ........................................................... 5 Strength of the body of evidence for each key question ........................................................... 5 Results ............................................................................................................................................ 6 Article selection ........................................................................................................................ 6 Sumary of results by agent ........................................................................................................ 8 Summary of results by outcome ............................................................................................. 13 Stength of the evidence ........................................................................................................... 15 Discussion ..................................................................................................................................... 16 Overview ................................................................................................................................. 16 Methodologic considerations and limitations ......................................................................... 16 Future research ........................................................................................................................ 16 Conclusions ............................................................................................................................. 16 References .................................................................................................................................... 18 List of Tables and Figures Table 1. Inclusion and exclusion criteria .............................................................................. 3 Table 2. Quality rating algorithm .......................................................................................... 5 Table 3. Overview of included studies .................................................................................. 7 Table 4. Summary of key findings of studies of acetylcysteine ......................................... 10 Table 5. Summary of key findings of studies of albuterol .................................................. 12 Table 6. Summary of key findings of studies of ipratropium bromide ............................... 12 Table 7. Summary of key findings of studies of heparin and acetylcysteine ...................... 13 Table 8. Summary of between group differences in final outcomes .................................. 15 Table 9. Number of randomized trials reporting key outcomes by quality rating .............. 15 Figure 1. Disposition of studies indentified for this review ................................................... 6 Appendices A. Search strategy B. Review forms C. Evidence tables D. Excluded studies E. Quality of the literature F. Harms Data Reported in Product Labeling G. Abbreviations and acronyms Introduction Mucus hypersecretion can be pathologic in individuals with severe respiratory disease or impaired cough. While airway cilia clear mucus continually in healthy individuals, in the presence of inflammation or infection mucus production increases, ciliary function may become impaired, and the biophysical properties of sputum may change.1, 2 Mucus hypersecretion is associated with declines in pulmonary function and quality of life, excess cough, discomfort, and exacerbation of conditions like chronic obstructive pulmonary disease (COPD).3, 4 Mucoactive agents may increase sputum expectoration or decrease hypersecretion of mucus.1, 5, 6 Mucolytic agents such as acetylcysteine alter disulphide bonds that comprise mucus proteins and may decrease mucus viscosity.1, 5, 6 Other mucolytics such as dornase alpha break down DNA polymers or networks of actin filaments that develop in purulent secretions. Expectorants may promote loosening of airway secretions. Agents such as saline may rehydrate mucus and promote cough.7 Mucoregulatory agents target chronic hypersecretion by goblet cells and submucosal glands.1, 5, 6 Agents include corticosteroids, macrolide antibiotics, and anticholinergics such as ipratropium bromide. Mucokinetic agents such as bronchodilators promote clearance by increasing action of the ciliary and may facilitate mucus transportability.1, 2, 7 Surfactants may also reduce mucus adhesiveness and increase transportability.6 The goal of the current project was to systematically review comparative studies of pharmacologic agents that respiratory therapists and other health professionals can employ to achieve mucus clearance in hospitalized or postoperative patients over the age of 12 months. The American Association for Respiratory Care (AARC) commissioned the review, and AARC committee members participated in the review process. As a collaborative effort, the AARC team and the Vanderbilt Evidence-based Practice Center (EPC) developed the key questions, inclusion and exclusion criteria and engaged in identification and review of abstracts. This team has previously reviewed the benefits and harms of non- pharmacologic airway clearance techniques in hospitalized patients.8 Methods Topic Refinement and Key Questions We drafted key questions and determined outcomes and interventions of interest via an iterative process involving team members with clinical and/or with methodologic expertise. Through conference call and email discussions, we decided to focus this review on pharmacologic airway techniques in individuals over one year of age. We addressed the following key questions: • In hospitalized, adult and pediatric patients without cystic fibrosis, does the use of pharmacologic therapies used in airway clearance improve oxygenation, reduce length of time on the ventilator, reduce readmission to hospital or ED admission, reduce length of stay in the intensive care unit (ICU), change sputum properties, reduce incidence of infection, affect quality of life, and/or improve respiratory mechanics vs. usual care? • In hospitalized adult and pediatric patients with neuromuscular disease, respiratory muscle weakness, or impaired cough, does the use of pharmacologic therapies used in airway clearance improve oxygenation, reduce length of stay in the hospital, reduce length of time on the ventilator, reduce readmission/emergency department (ED) visits, improve perceived quality of life, reduce incidence of infection, and/or change sputum properties vs. usual care? 1 • In postoperative adult and pediatric patients, does the use of pharmacologic therapies used in airway clearance improve oxygenation, reduce length of time on the ventilator, reduce length of stay in the hospital and/or ICU, reduce readmission, reduce incidence of infection, and/or change sputum properties vs. usual care? Literature Search Strategy Databases and Search Strategies A librarian employed search strategies provided in the appendix to retrieve relevant research on pharmacologic airway clearance therapies. All strategies were peer reviewed by a second librarian. Our primary literature search employed the MEDLINE® (via the PubMed interface)