Modeling the time-course of ventilator-induced lung injury: what can we learn from interspecies discrepancies?

Excerpt

Alterations in lung fluid balance, increases in endothelial and epithelial permeability, and severe tissue damage have been widely described in animals following injurious mechanical ventilation and regrouped under the term ventilator-induced lung injury (VILI) [1]. The clinical relevance of VILI was highlighted by the acute respiratory distress syndrome (ARDS) Network trial that showed a 22% reduction of mortality in patients with ARDS when the mechanical stress applied to the lungs was lessened by reducing the tidal volume applied [2]. The pathophysiology of VILI is unequivocal, and several mechanical determinants of VILI have been identified to date: (1) regional overdistension caused by the application of a local stress or pressure that forces cells and tissues to assume shapes and dimensions that they do not assume during unassisted breathing [3‐5]; (2) so-called “low volume injury” associated with the cyclic recruitment–derecruitment of lung units [6], which causes abrasion of the epithelial airspace lining by interfacial forces [7]; (3) inactivation of surfactant triggered by large alveolar surface area oscillations [8]; (4) the interdependence mechanism that raises cell and tissue stress between neighboring structures with differing mechanical properties [9]. Early experimental studies demonstrated that the main determinant of VILI is lung end-inspiratory volume, associated with high transpulmonary pressures [10, 11]. Thus, the term “volutrauma” is preferred to the term “barotrauma”, since the absolute level of airway pressure per se is not injurious [10]. …