Physical and biological triggers of ventilator-induced lung injury and its prevention

Abstract

Ventilator-induced lung injury is a side-effect of mechanical ventilation. Its prevention or attenuation implies knowledge of the sequence of events that lead from mechanical stress to lung inflammation and stress at rupture.A literature review was undertaken which focused on the link between the mechanical forces in the diseased lung and the resulting inflammation/rupture.The distending force of the lung is the transpulmonary pressure. This applied force, in a homogeneous lung, is shared equally by each fibre of the lung9s fibrous skeleton. In a nonhomogeneous lung, the collapsed or consolidated regions do not strain, whereas the neighbouring fibres experience excessive strain. Indeed, if the global applied force is excessive, or the fibres near the diseased regions experience excessive stress/strain, biological activation and/or mechanical rupture are observed. Excessive strain activates macrophages and epithelial cells to produce interleukin-8. This cytokine recruits neutrophils, with consequent full-blown inflammation.In order to prevent initiation of ventilator-induced lung injury, transpulmonary pressure must be kept within the physiological range. The prone position may attenuate ventilator-induced lung injury by increasing the homogeneity of transpulmonary pressure distribution. Positive end-expiratory pressure may prevent ventilator-induced lung injury by keeping open the lung, thus reducing the regional stress/strain maldistribution. If the transpulmonary pressure rather than the tidal volume per kilogram of body weight is taken into account, the contradictory results of the randomised trials dealing with different strategies of mechanical ventilation may be better understood. Eur Respir J 2003; 22: Suppl. 47, 15s-25s.

Time to generate ventilator-induced lung injury among mammals with healthy lungs: a unifying hypothesis

“…When a mechanical force is applied to a material, two phenomena occur as a reaction to the insult applied: generation of a pressure with equal intensity and opposite sign to the one actually applied, defined as ''stress'', and, if the material is deformable enough, modification of its resting shape, defined as ''strain'' [13]. If we consider the pulmonary fibrous skeleton as the material stressed during ventilation and the lung parenchyma as homogeneously inflating during inspiration, lung stress equals the pressure actually applied to the lung parenchyma, i.e.…”

“…the transpulmonary pressure, and lung strain equals the ratio between the end-inspiratory inflated volume and the lung resting volume, i.e. FRC [13]. Both lung stress and strain have been recently investigated as possible parameters to quantify the mechanical insult commencing the entire cascade of VILI, whether is deemed to be either an inflammatory or a pure mechanical process (or a combination of the two) [14,17].…”

“…the maximal transpulmonary pressure applied at end-inspiration, was estimated based upon data on the airway pressure recorded and measurements of partitioned respiratory mechanics for each species, as direct data on pleural pressures were not available [13]:…”

“…Maximal lung strain, i.e. the lung strain resulting at end-inspiration, was estimated as previously reported [13], assuming a monoalveolar lung model, thereby not taking into account possible dishomogeneities developing during inflation:…”

“…More recently, two different parameters describing the mechanical insult associated with ventilation have been proposed as actual determinants of VILI: lung stress, defined as the pressure developing within the lung fibrous skeleton, which equals the applied transpulmonary pressure [12], and lung strain, defined as the ratio between the lung volume variation (due to both V T and positive end-expiratory pressure, PEEP) and the lung resting volume [13]. In ARDS, we have recently shown that both V T expressed in relation to body weight and the airway pressure applied are ''inadequate surrogates'' for the evaluation of the actual lung stress and strain applied, due to a large variability in lung resting volume (functional residual capacity, FRC) and in chest wall mechanics [14].…”