Ventilation‐Induced Lung Injury

Abstract

Mechanical ventilation (MV) is, by definition, the application of external forces to the lungs. Depending on their magnitude, these forces can cause a continuum of pathophysiological alterations ranging from the stimulation of inflammation to the disruption of cell-cell contacts and cell membranes. These side effects of MV are particularly relevant for patients with inhomogeneously injured lungs such as in acute lung injury (ALI). These patients require supraphysiological ventilation pressures to guarantee even the most modest gas exchange. In this situation, ventilation causes additional strain by overdistension of the yet non-injured region, and additional stress that forms because of the interdependence between intact and atelectatic areas. Cells are equipped with elaborate mechanotransduction machineries that respond to strain and stress by the activation of inflammation and repair mechanisms. Inflammation is the fundamental response of the host to external assaults, be they of mechanical or of microbial origin and can, if excessive, injure the parenchymal tissue leading to ALI. Here, we will discuss the forces generated by MV and how they may injure the lungs mechanically and through inflammation. We will give an overview of the mechanotransduction and how it leads to inflammation and review studies demonstrating that ventilator-induced lung injury can be prevented by blocking pathways of mechanotransduction or inflammation.

RETRACTED: Mechanical Ventilation as a Therapeutic Tool to Reduce ARDS Incidence

“…17 Although MV is a lifesaving therapy, 12 when applied inappropriately it will increase the incidence and mortality of ARDS by causing a secondary pathology known as VILI ( Fig 1 ). 18 Th e infl ammatory mediators produced by VILI can then injure distant organs, leading to the development of multiorgan dysfunction syndrome that is frequently the ultimate cause of death in patients with ARDS. 19 Since treatment of established ARDS is very diffi cult, and the only strategy demonstrated to reduce ARDS mortality involves protective MV, the question arises: Would it be possible to use the ventilator as a therapeutic device in at-risk patients to prevent ARDS in the same preemptive manner in which drugs are used to prevent other diseases?…”

Impact of mechanical ventilation on the pathophysiology of progressive acute lung injury

“…Discovery that the ventilator can damage the lungs of patients with established ARDS resulted in hundreds of studies investigating the molecular, cellular, and mechanical mechanisms of VILI (128). These efforts culminated in an article published in 2000 by the The New England Journal of Medicine (8) demonstrating that reduced tidal volume (VT) and plateau airway pressure were positively correlated with a reduction of ARDS mortality in a phase III clinical trial.…”

Characterization of blunt chest trauma in a long-term porcine model of severe multiple trauma

“…Both mechanical (e.g. cyclic stretching) and inflammatory aspects have been suggested as possible explanations4243. The relevance of mechanical ventilation has been emphasized by studies describing a significant increase of histologic damage in the very early phase (4 h) after blunt chest trauma, whereas no such histopathological changes were observed after chest trauma with spontaneous breathing2944.…”