The physical basis of ventilator-induced lung injury

Abstract

Although mechanical ventilation (MV) is a life-saving intervention for patients with acute respiratory distress syndrome (ARDS), it can aggravate or cause lung injury, known as ventilator-induced lung injury (VILI). The biophysical characteristics of heterogeneously injured ARDS lungs increase the parenchymal stress associated with breathing, which is further aggravated by MV. Cells, in particular those lining the capillaries, airways and alveoli, transform this strain into chemical signals (mechanotransduction). The interaction of reparative and injurious mechanotransductive pathways leads to VILI. Several attempts have been made to identify clinical surrogate measures of lung stress/strain (e.g., density changes in chest computed tomography, lower and upper inflection points of the pressure-volume curve, plateau pressure and inflammatory cytokine levels) that could be used to titrate MV. However, uncertainty about the topographical distribution of stress relative to that of the susceptibility of the cells and tissues to injury makes the existence of a single 'global' stress/strain injury threshold doubtful.

Figure 1. Chiumello et al. computed strain as the volume change between functional residual capacity and end-inspiration, normalized by functional residual capacity (strain = ΔV/FRC)

They were able to show that by titrating tidal volume (VT) to predicted body weight, the lungs of patients with a small FRC are exposed to much larger deformations than those of patients with relatively normal FRC. The above definition of strain ignores the independent effects of VT and positive end-expiratory pressure on lung injury. FRC: Functional residual capacity; TLC: Total lung capacity; VEE: Volume at end-expiration with positive end-expiratory pressure; VEI: Volume at end-inspiration. Data from [43].

Figure 2. Mechanical ventilation applies an additional stress to the prestressed lung and the resulting strain is transformed by cells into chemical signals

Edema, cellular stress failure and the innate immune response may act synergistically, but may also be manifestations of different injury pathways. The interaction of injurious and protective/reparative mechanotransductive pathways leads to ventilator-induced lung injury. Airway pressure and tidal volume are widely used in clinical practice as surrogate markers of lung stress/strain. Given their limitations, however, other measures, such as esophageal manometry and lung elastography, are under investigation.