Introduction and definitions

In order to address the question of how mechanical ventilation damages lungs, one must first understand several commonly utilized related terms:

Ventilator-induced lung injury (VILI) is the term used to denote acute lung damage that develops during mechanical ventilation. Alveolar overdistension, lung strain, and atelectasis are the key inciting and defining features of VILI. Overdistension or lung stress reflects the presence of an elevated transpulmonary pressure—the difference between the airway pressure and the pleural pressure—at the end of inspiration. Strain is the ratio of the volume of gas delivered during a tidal breath to the amount of aerated lung receiving that breath: larger strain is matched by a higher mechanical stress on alveolar structures.1 In animal models, VILI is characterized by inflammatory cell infiltrates, hyaline membranes, alveolar hemorrhage, increased vascular permeability, pulmonary edema, loss of functional surfactant, and ultimately alveolar collapse. In patients, the clinical presentation of VILI is largely indistinguishable from ARDS. Nevertheless, ventilator strategies designed to reduce VILI have improved outcomes among patients with acute respiratory distress syndrome (ARDS) and in the perioperative setting, highlighting the clinical importance of VILI.

The “baby lung” concept explains how larger tidal volumes (V T ) worsen ARDS. In previously healthy animal lungs, very large (not used clinically) V T is necessary to cause VILI.1 However, early studies using computed tomography (CT) in supine ARDS patients2 showed heterogeneous consolidation and atelectasis in dorsal lung regions. Therefore, inspired gas is concentrated in a smaller, yet otherwise functional fraction of ventilated parenchyma in the ventral lung. This gas maldistribution causes regional overdistension and excessive strain from a clinically ‘acceptable’ V T .2 Conceptually, this is akin to delivering an “adult” V T to a “baby lung.” Later studies using metabolic imaging confirmed that tissue in the “baby lung” is inflamed in proportion to regional strain.3

Atelectrauma occurs with the repetitive, cyclic, opening and closing of airways and lung units during inspiration and expiration, respectively. The stretching or shear forces between aerated and atelectatic alveoli cause epithelial and endothelial cell injury and regional inflammation. Furthermore, air fluid levels cause epithelial shear and cell damage in the conducting small airways.4

Stress amplification occurs in areas where collapsed and ventilated airspaces are intermingled. High-resolution imaging shows that the ARDS lung is heterogeneous at a very small scale. Mechanical stress is then focally amplified at the interfaces between ventilated and nonventilated tissue,5 and in areas where lung inflation is reduced due to microscopic atelectasis.6 In these regions, large tidal changes in aeration (“unstable inflation”) were associated with worse progression of injury (in animal models) and with mortality in human ARDS.7

Barotrauma is the result of ventilating at high lung volumes, which can lead to alveolar rupture, air leaks or even pneumothoraces, pneumomediastinum and subcutaneous emphysema. The critical component remains regional lung overdistension, however, and not necessarily high airway pressure. Volutrauma refers to the concept that volume, or rather lung stretching and not airway pressures, is the determinant of injury.

Biotrauma results from the physical forces of atelectrauma, barotrauma, and volutrauma that cause the release of intracellular mediators. Cells are either directly injured by these mediators or indirectly injured through the activation of cell-signaling pathways in epithelial, endothelial, or inflammatory cells. The translocation of these mediators or bacteria from the airspaces into the systemic circulation through areas of increased alveolar-capillary permeability—as is classically seen in ARDS or which may be a result of volutrauma —may lead to multiorgan dysfunction and death.8