Official reprint from UpToDate®
www.uptodate.com ©2016 UpToDate®

Ventilator-associated lung injury

Robert C Hyzy, MD
Section Editor
Polly E Parsons, MD
Deputy Editor
Geraldine Finlay, MD


An acute lung injury that develops during mechanical ventilation is termed ventilator-induced lung injury (VILI) if it can be proven that the mechanical ventilation caused the acute lung injury. In contrast, ventilator-associated lung injury (VALI) exists if a causative relationship cannot be proven. VALI is the appropriate term in most clinical situations because it is virtually impossible to prove causation outside of the research laboratory [1].

The pathogenesis, risk factors, incidence, prevention, clinical presentation, diagnosis, and management of VALI are discussed in this topic review. Other complications of mechanical ventilation are described separately. (See "Physiologic and pathophysiologic consequences of mechanical ventilation" and "Diagnosis, management, and prevention of pulmonary barotrauma during invasive mechanical ventilation in adults".)


Alveolar overdistension and cyclic atelectasis are the principal initiators of alveolar injury during positive pressure ventilation [2]. Severe alveolar injury results in high permeability interstitial and alveolar edema, alveolar hemorrhage, hyaline membranes, loss of functional surfactant, and alveolar collapse [1,3]. The relative importance of alveolar overdistension and cyclic atelectasis on the pathogenesis of VALI is unknown [3].

Alveolar overdistension — Lung injury due to alveolar distension is referred to as alveolar strain. It reflects the presence of an elevated transpulmonary pressure (the difference between the airway pressure and the pleural pressure) or, more broadly, the ratio between the volume of gas delivered during a tidal breath and the amount of aerated lung receiving it [4]. The following animal studies distinguish between the effect of volume and pressure on the lung. Specifically, they demonstrate that high tidal volumes cause lung injury, but high airway pressure does not:

Rats were mechanically ventilated using high pressure plus high tidal volumes, low pressure plus high tidal volumes, or high pressure plus low tidal volumes [5]. The only group that did not develop lung injury was the group ventilated with low tidal volumes (figure 1).


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: Sep 2016. | This topic last updated: Dec 23, 2015.
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 ©2016 UpToDate, Inc.
  1. International consensus conferences in intensive care medicine: Ventilator-associated Lung Injury in ARDS. This official conference report was cosponsored by the American Thoracic Society, The European Society of Intensive Care Medicine, and The Societé de Réanimation de Langue Française, and was approved by the ATS Board of Directors, July 1999. Am J Respir Crit Care Med 1999; 160:2118.
  2. Slutsky AS, Ranieri VM. Ventilator-induced lung injury. N Engl J Med 2013; 369:2126.
  3. Rouby JJ, Brochard L. Tidal recruitment and overinflation in acute respiratory distress syndrome: yin and yang. Am J Respir Crit Care Med 2007; 175:104.
  4. Caironi P, Cressoni M, Chiumello D, et al. Lung opening and closing during ventilation of acute respiratory distress syndrome. Am J Respir Crit Care Med 2010; 181:578.
  5. Dreyfuss D, Soler P, Saumon G. Mechanical ventilation-induced pulmonary edema. Interaction with previous lung alterations. Am J Respir Crit Care Med 1995; 151:1568.
  6. Hernandez LA, Peevy KJ, Moise AA, Parker JC. Chest wall restriction limits high airway pressure-induced lung injury in young rabbits. J Appl Physiol (1985) 1989; 66:2364.
  7. Gajic O, Dara SI, Mendez JL, et al. Ventilator-associated lung injury in patients without acute lung injury at the onset of mechanical ventilation. Crit Care Med 2004; 32:1817.
  8. Gattinoni L, Pesenti A. The concept of "baby lung". Intensive Care Med 2005; 31:776.
  9. Gattinoni L, Pesenti A, Avalli L, et al. Pressure-volume curve of total respiratory system in acute respiratory failure. Computed tomographic scan study. Am Rev Respir Dis 1987; 136:730.
  10. Gattinoni L, Protti A, Caironi P, Carlesso E. Ventilator-induced lung injury: the anatomical and physiological framework. Crit Care Med 2010; 38:S539.
  11. Sugiura M, McCulloch PR, Wren S, et al. Ventilator pattern influences neutrophil influx and activation in atelectasis-prone rabbit lung. J Appl Physiol (1985) 1994; 77:1355.
  12. Muscedere JG, Mullen JB, Gan K, Slutsky AS. Tidal ventilation at low airway pressures can augment lung injury. Am J Respir Crit Care Med 1994; 149:1327.
  13. Briel M, Meade M, Mercat A, et al. Higher vs lower positive end-expiratory pressure in patients with acute lung injury and acute respiratory distress syndrome: systematic review and meta-analysis. JAMA 2010; 303:865.
  14. Arcaroli JJ, Hokanson JE, Abraham E, et al. Extracellular superoxide dismutase haplotypes are associated with acute lung injury and mortality. Am J Respir Crit Care Med 2009; 179:105.
  15. Gao L, Grant A, Halder I, et al. Novel polymorphisms in the myosin light chain kinase gene confer risk for acute lung injury. Am J Respir Cell Mol Biol 2006; 34:487.
  16. Arcaroli J, Sankoff J, Liu N, et al. Association between urokinase haplotypes and outcome from infection-associated acute lung injury. Intensive Care Med 2008; 34:300.
  17. Hong SB, Huang Y, Moreno-Vinasco L, et al. Essential role of pre-B-cell colony enhancing factor in ventilator-induced lung injury. Am J Respir Crit Care Med 2008; 178:605.
  18. McClintock D, Zhuo H, Wickersham N, et al. Biomarkers of inflammation, coagulation and fibrinolysis predict mortality in acute lung injury. Crit Care 2008; 12:R41.
  19. Petrucci N, De Feo C. Lung protective ventilation strategy for the acute respiratory distress syndrome. Cochrane Database Syst Rev 2013; :CD003844.
  20. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. The Acute Respiratory Distress Syndrome Network. N Engl J Med 2000; 342:1301.
  21. Futier E, Constantin JM, Paugam-Burtz C, et al. A trial of intraoperative low-tidal-volume ventilation in abdominal surgery. N Engl J Med 2013; 369:428.
  22. Hickling KG, Henderson SJ, Jackson R. Low mortality associated with low volume pressure limited ventilation with permissive hypercapnia in severe adult respiratory distress syndrome. Intensive Care Med 1990; 16:372.
  23. Serpa Neto A, Cardoso SO, Manetta JA, et al. Association between use of lung-protective ventilation with lower tidal volumes and clinical outcomes among patients without acute respiratory distress syndrome: a meta-analysis. JAMA 2012; 308:1651.
  24. Ladha K, Vidal Melo MF, McLean DJ, et al. Intraoperative protective mechanical ventilation and risk of postoperative respiratory complications: hospital based registry study. BMJ 2015; 351:h3646.
  25. Neto AS, Simonis FD, Barbas CS, et al. Lung-Protective Ventilation With Low Tidal Volumes and the Occurrence of Pulmonary Complications in Patients Without Acute Respiratory Distress Syndrome: A Systematic Review and Individual Patient Data Analysis. Crit Care Med 2015; 43:2155.
  26. Terragni PP, Rosboch G, Tealdi A, et al. Tidal hyperinflation during low tidal volume ventilation in acute respiratory distress syndrome. Am J Respir Crit Care Med 2007; 175:160.
  27. Marcy TW, Marini JJ. Inverse ratio ventilation in ARDS. Rationale and implementation. Chest 1991; 100:494.
  28. Yoshida T, Uchiyama A, Matsuura N, et al. The comparison of spontaneous breathing and muscle paralysis in two different severities of experimental lung injury. Crit Care Med 2013; 41:536.
  29. Papazian L, Forel JM, Gacouin A, et al. Neuromuscular blockers in early acute respiratory distress syndrome. N Engl J Med 2010; 363:1107.
  30. Plötz FB, Slutsky AS, van Vught AJ, Heijnen CJ. Ventilator-induced lung injury and multiple system organ failure: a critical review of facts and hypotheses. Intensive Care Med 2004; 30:1865.
  31. National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network, Wheeler AP, Bernard GR, et al. Pulmonary-artery versus central venous catheter to guide treatment of acute lung injury. N Engl J Med 2006; 354:2213.