Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate®

Acute respiratory distress syndrome: Investigational or ineffective pharmacotherapy in adults

Mark D Siegel, MD
Section Editor
Polly E Parsons, MD
Deputy Editor
Geraldine Finlay, MD


Therapy for patients with acute respiratory distress syndrome (ARDS) is supportive, aimed at improving gas exchange and preventing complications while the underlying condition that precipitated ARDS is addressed. Potential ARDS-specific pharmacotherapies are being evaluated, although none are currently recommended as routine therapy because patient-important effects are uncertain [1].

Investigational and ineffective medical therapies for ARDS are reviewed here. The pathogenesis of ARDS as well as mechanical ventilation strategies and supportive care for ARDS are discussed in separate reviews. (See "Acute respiratory distress syndrome: Epidemiology, pathophysiology, pathology, and etiology in adults" and "Acute respiratory distress syndrome: Supportive care and oxygenation in adults" and "Mechanical ventilation of adults in acute respiratory distress syndrome".)


Numerous trials investigate novel medical therapies and ventilatory interventions for patients with ARDS. These trials have frequent status updates and can be readily accessed at the US National Institute of Health.  


Few trials have rigorously examined strategies to prevent ARDS. Aspirin has no proven benefit and trials of inhaled glucocorticoids and beta-2 agonist combinations are awaited.

Aspirin — Preclinical and clinical observational studies of aspirin, as an antiplatelet and anti-inflammatory agent, have suggested a potential role for it in the prevention and treatment of ARDS [2-6]. However, in a randomized trial (LIPS-A) of 390 patients at risk of developing ARDS, aspirin was reported to be of no benefit in preventing ARDS [7]. Aspirin was administered at 325 mg followed by 81 mg daily for seven days following presentation to the emergency department, and compared with placebo, and had no effect on the incidence of ARDS at one week (approximately 10 percent in each group). However, the lower than expected rate of ARDS in this study suggested a more modest severity of illness than anticipated, which may have limited the ability to detect a study drug effect.


Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Mar 2017. | This topic last updated: Dec 14, 2016.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
  1. Duggal A, Ganapathy A, Ratnapalan M, Adhikari NK. Pharmacological treatments for acute respiratory distress syndrome: systematic review. Minerva Anestesiol 2015; 81:567.
  2. Looney MR, Nguyen JX, Hu Y, et al. Platelet depletion and aspirin treatment protect mice in a two-event model of transfusion-related acute lung injury. J Clin Invest 2009; 119:3450.
  3. Boyle AJ, Di Gangi S, Hamid UI, et al. Aspirin therapy in patients with acute respiratory distress syndrome (ARDS) is associated with reduced intensive care unit mortality: a prospective analysis. Crit Care 2015; 19:109.
  4. Chen W, Janz DR, Bastarache JA, et al. Prehospital aspirin use is associated with reduced risk of acute respiratory distress syndrome in critically ill patients: a propensity-adjusted analysis. Crit Care Med 2015; 43:801.
  5. Erlich JM, Talmor DS, Cartin-Ceba R, et al. Prehospitalization antiplatelet therapy is associated with a reduced incidence of acute lung injury: a population-based cohort study. Chest 2011; 139:289.
  6. Kor DJ, Erlich J, Gong MN, et al. Association of prehospitalization aspirin therapy and acute lung injury: results of a multicenter international observational study of at-risk patients. Crit Care Med 2011; 39:2393.
  7. Kor DJ, Carter RE, Park PK, et al. Effect of Aspirin on Development of ARDS in At-Risk Patients Presenting to the Emergency Department: The LIPS-A Randomized Clinical Trial. JAMA 2016; 315:2406.
  8. Dancer RC, Parekh D, Lax S, et al. Vitamin D deficiency contributes directly to the acute respiratory distress syndrome (ARDS). Thorax 2015; 70:617.
  9. Paine R 3rd, Wilcoxen SE, Morris SB, et al. Transgenic overexpression of granulocyte macrophage-colony stimulating factor in the lung prevents hyperoxic lung injury. Am J Pathol 2003; 163:2397.
  10. Baleeiro CE, Christensen PJ, Morris SB, et al. GM-CSF and the impaired pulmonary innate immune response following hyperoxic stress. Am J Physiol Lung Cell Mol Physiol 2006; 291:L1246.
  11. Matute-Bello G, Liles WC, Radella F 2nd, et al. Modulation of neutrophil apoptosis by granulocyte colony-stimulating factor and granulocyte/macrophage colony-stimulating factor during the course of acute respiratory distress syndrome. Crit Care Med 2000; 28:1.
  12. Paine R 3rd, Standiford TJ, Dechert RE, et al. A randomized trial of recombinant human granulocyte-macrophage colony stimulating factor for patients with acute lung injury. Crit Care Med 2012; 40:90.
  13. Herold S, Hoegner K, Vadász I, et al. Inhaled granulocyte/macrophage colony-stimulating factor as treatment of pneumonia-associated acute respiratory distress syndrome. Am J Respir Crit Care Med 2014; 189:609.
  14. Mac Sweeney R, McAuley DF. Mesenchymal stem cell therapy in acute lung injury: is it time for a clinical trial? Thorax 2012; 67:475.
  15. McIntyre LA, Moher D, Fergusson DA, et al. Efficacy of Mesenchymal Stromal Cell Therapy for Acute Lung Injury in Preclinical Animal Models: A Systematic Review. PLoS One 2016; 11:e0147170.
  16. Simonson OE, Mougiakakos D, Heldring N, et al. In Vivo Effects of Mesenchymal Stromal Cells in Two Patients With Severe Acute Respiratory Distress Syndrome. Stem Cells Transl Med 2015; 4:1199.
  17. Zheng G, Huang L, Tong H, et al. Treatment of acute respiratory distress syndrome with allogeneic adipose-derived mesenchymal stem cells: a randomized, placebo-controlled pilot study. Respir Res 2014; 15:39.
  18. Wilson JG, Liu KD, Zhuo H, et al. Mesenchymal stem (stromal) cells for treatment of ARDS: a phase 1 clinical trial. Lancet Respir Med 2015; 3:24.
  19. Headley AS, Tolley E, Meduri GU. Infections and the inflammatory response in acute respiratory distress syndrome. Chest 1997; 111:1306.
  20. Steinberg KP, Milberg JA, Martin TR, et al. Evolution of bronchoalveolar cell populations in the adult respiratory distress syndrome. Am J Respir Crit Care Med 1994; 150:113.
  21. Donnelly SC, Strieter RM, Reid PT, et al. The association between mortality rates and decreased concentrations of interleukin-10 and interleukin-1 receptor antagonist in the lung fluids of patients with the adult respiratory distress syndrome. Ann Intern Med 1996; 125:191.
  22. Davis WB, Wilson HE, Wall RL. Eosinophilic alveolitis in acute respiratory failure. A clinical marker for a non-infectious etiology. Chest 1986; 90:7.
  23. Tang BM, Craig JC, Eslick GD, et al. Use of corticosteroids in acute lung injury and acute respiratory distress syndrome: a systematic review and meta-analysis. Crit Care Med 2009; 37:1594.
  24. Meduri GU, Bridges L, Shih MC, et al. Prolonged glucocorticoid treatment is associated with improved ARDS outcomes: analysis of individual patients' data from four randomized trials and trial-level meta-analysis of the updated literature. Intensive Care Med 2016; 42:829.
  25. Meduri GU, Marik PE, Chrousos GP, et al. Steroid treatment in ARDS: a critical appraisal of the ARDS network trial and the recent literature. Intensive Care Med 2008; 34:61.
  26. Peter JV, John P, Graham PL, et al. Corticosteroids in the prevention and treatment of acute respiratory distress syndrome (ARDS) in adults: meta-analysis. BMJ 2008; 336:1006.
  27. Agarwal R, Nath A, Aggarwal AN, Gupta D. Do glucocorticoids decrease mortality in acute respiratory distress syndrome? A meta-analysis. Respirology 2007; 12:585.
  28. Steinberg KP, Hudson LD, Goodman RB, et al. Efficacy and safety of corticosteroids for persistent acute respiratory distress syndrome. N Engl J Med 2006; 354:1671.
  29. Meduri GU, Golden E, Freire AX, et al. Methylprednisolone infusion in early severe ARDS: results of a randomized controlled trial. Chest 2007; 131:954.
  30. Kawashima M, yatsunami J, Fukuno Y, et al. Inhibitory effects of 14-membered ring macrolide antibiotics on bleomycin-induced acute lung injury. Lung 2002; 180:73.
  31. Leiva M, Ruiz-Bravo A, Jimenez-Valera M. Effects of telithromycin in in vitro and in vivo models of lipopolysaccharide-induced airway inflammation. Chest 2008; 134:20.
  32. Randomized, placebo-controlled trial of lisofylline for early treatment of acute lung injury and acute respiratory distress syndrome. Crit Care Med 2002; 30:1.
  33. Walkey AJ, Wiener RS. Macrolide antibiotics and survival in patients with acute lung injury. Chest 2012; 141:1153.
  34. Bernard GR, Wheeler AP, Arons MM, et al. A trial of antioxidants N-acetylcysteine and procysteine in ARDS. The Antioxidant in ARDS Study Group. Chest 1997; 112:164.
  35. Jepsen S, Herlevsen P, Knudsen P, et al. Antioxidant treatment with N-acetylcysteine during adult respiratory distress syndrome: a prospective, randomized, placebo-controlled study. Crit Care Med 1992; 20:918.
  36. Andrews PJ, Avenell A, Noble DW, et al. Randomised trial of glutamine, selenium, or both, to supplement parenteral nutrition for critically ill patients. BMJ 2011; 342:d1542.
  37. Heyland D, Muscedere J, Wischmeyer PE, et al. A randomized trial of glutamine and antioxidants in critically ill patients. N Engl J Med 2013; 368:1489.
  38. Heyland D, Muscedere J, Wischmeyer PE, et al. A randomized trial of glutamine and antioxidants in critically ill patients. N Engl J Med 2013; 368:1489.
  39. Bone RC, Slotman G, Maunder R, et al. Randomized double-blind, multicenter study of prostaglandin E1 in patients with the adult respiratory distress syndrome. Prostaglandin E1 Study Group. Chest 1989; 96:114.
  40. Abraham E, Baughman R, Fletcher E, et al. Liposomal prostaglandin E1 (TLC C-53) in acute respiratory distress syndrome: a controlled, randomized, double-blind, multicenter clinical trial. TLC C-53 ARDS Study Group. Crit Care Med 1999; 27:1478.
  41. Zeiher BG, Artigas A, Vincent JL, et al. Neutrophil elastase inhibition in acute lung injury: results of the STRIVE study. Crit Care Med 2004; 32:1695.
  42. Bernard GR, Wheeler AP, Russell JA, et al. The effects of ibuprofen on the physiology and survival of patients with sepsis. The Ibuprofen in Sepsis Study Group. N Engl J Med 1997; 336:912.
  43. Liu KD, Levitt J, Zhuo H, et al. Randomized clinical trial of activated protein C for the treatment of acute lung injury. Am J Respir Crit Care Med 2008; 178:618.
  44. Ketoconazole for early treatment of acute lung injury and acute respiratory distress syndrome: a randomized controlled trial. The ARDS Network. JAMA 2000; 283:1995.
  45. Slotman GJ, Burchard KW, D'Arezzo A, Gann DS. Ketoconazole prevents acute respiratory failure in critically ill surgical patients. J Trauma 1988; 28:648.
  46. Yu M, Tomasa G. A double-blind, prospective, randomized trial of ketoconazole, a thromboxane synthetase inhibitor, in the prophylaxis of the adult respiratory distress syndrome. Crit Care Med 1993; 21:1635.
  47. Sinuff T, Cook DJ, Peterson JC, Fuller HD. Development, implementation, and evaluation of a ketoconazole practice guideline for ARDS prophylaxis. J Crit Care 1999; 14:1.
  48. Williams JG, Maier RV. Ketoconazole inhibits alveolar macrophage production of inflammatory mediators involved in acute lung injury (adult respiratory distress syndrome). Surgery 1992; 112:270.
  49. Perkins GD, McAuley DF, Thickett DR, Gao F. The beta-agonist lung injury trial (BALTI): a randomized placebo-controlled clinical trial. Am J Respir Crit Care Med 2006; 173:281.
  50. Simvastatin Effect on the Incidence of Acute Lung Injury/Adult Respiratory Distress Syndrome (ALI/ARDS) http://www.clinicaltrials.gov/ct2/show/NCT01195428 (Accessed on February 08, 2012).
  51. National Heart, Lung, and Blood Institute ARDS Clinical Trials Network, Truwit JD, Bernard GR, et al. Rosuvastatin for sepsis-associated acute respiratory distress syndrome. N Engl J Med 2014; 370:2191.
  52. McAuley DF, Laffey JG, O'Kane CM, et al. Simvastatin in the acute respiratory distress syndrome. N Engl J Med 2014; 371:1695.
  53. Weg JG, Balk RA, Tharratt RS, et al. Safety and potential efficacy of an aerosolized surfactant in human sepsis-induced adult respiratory distress syndrome. JAMA 1994; 272:1433.
  54. Spragg RG, Lewis JF, Wurst W, et al. Treatment of acute respiratory distress syndrome with recombinant surfactant protein C surfactant. Am J Respir Crit Care Med 2003; 167:1562.
  55. Anzueto A, Baughman RP, Guntupalli KK, et al. Aerosolized surfactant in adults with sepsis-induced acute respiratory distress syndrome. Exosurf Acute Respiratory Distress Syndrome Sepsis Study Group. N Engl J Med 1996; 334:1417.
  56. Spragg RG, Lewis JF, Walmrath HD, et al. Effect of recombinant surfactant protein C-based surfactant on the acute respiratory distress syndrome. N Engl J Med 2004; 351:884.
  57. Gregory TJ, Steinberg KP, Spragg R, et al. Bovine surfactant therapy for patients with acute respiratory distress syndrome. Am J Respir Crit Care Med 1997; 155:1309.
  58. Davidson WJ, Dorscheid D, Spragg R, et al. Exogenous pulmonary surfactant for the treatment of adult patients with acute respiratory distress syndrome: results of a meta-analysis. Crit Care 2006; 10:R41.
  59. Willson DF, Thomas NJ, Markovitz BP, et al. Effect of exogenous surfactant (calfactant) in pediatric acute lung injury: a randomized controlled trial. JAMA 2005; 293:470.
  60. Spragg RG, Taut FJ, Lewis JF, et al. Recombinant surfactant protein C-based surfactant for patients with severe direct lung injury. Am J Respir Crit Care Med 2011; 183:1055.
  61. Willson DF, Truwit JD, Conaway MR, et al. The Adult Calfactant in Acute Respiratory Distress Syndrome Trial. Chest 2015; 148:356.
  62. National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network, Matthay MA, Brower RG, et al. Randomized, placebo-controlled clinical trial of an aerosolized β₂-agonist for treatment of acute lung injury. Am J Respir Crit Care Med 2011; 184:561.
  63. Gao Smith F, Perkins GD, Gates S, et al. Effect of intravenous β-2 agonist treatment on clinical outcomes in acute respiratory distress syndrome (BALTI-2): a multicentre, randomised controlled trial. Lancet 2012; 379:229.
  64. Perkins GD, Gates S, Park D, et al. The beta agonist lung injury trial prevention. A randomized controlled trial. Am J Respir Crit Care Med 2014; 189:674.