Ventilator-induced lung injury and lung mechanics

Abstract

Mechanical ventilation applies physical stresses to the tissues of the lung and thus may give rise to ventilator-induced lung injury (VILI), particular in patients with acute respiratory distress syndrome (ARDS). The most dire consequences of VILI result from injury to the blood-gas barrier. This allows plasma-derived fluid and proteins to leak into the airspaces where they flood some alveolar regions, while interfering with the functioning of pulmonary surfactant in those regions that remain open. These effects are reflected in commensurately increased values of dynamic lung elastance (EL ), a quantity that in principle is readily measured at the bedside. Recent mathematical/computational modeling studies have shown that the way in which EL varies as a function of both time and positive end-expiratory pressure (PEEP) reflects the nature and degree of lung injury, and can even be used to infer the separate contributions of volutrauma and atelectrauma to VILI. Interrogating such models for minimally injurious regimens of mechanical ventilation that apply to a particular lung may thus lead to personalized approaches to the ventilatory management of ARDS.

Keywords: Over-distension; acute respiratory distress syndrome (ARDS); computational model; recruitment and derecruitment; surfactant function.

Conflict of interest statement

Conflicts of Interest: JH Bates is a member of the Advisory Board of and a minor shareholder in Oscillavent. BJ Smith has no conflicts of interest to declare.

Figures

Figure 1

Scanning electron micrograph of the collagen fiber network in a rat lung (A) showing the alveolar entrances (AE) and helical collagen structure characteristic of low inflation levels. The elastic fibers network (B) crisscross at the point where three alveolar entrances (*) meet and are sparse in the alveolar septa. Reproduced with permission from Toshima et al. (12).

Figure 2

Hypothetical fluid-mechanical stress (red arrows) during the reopening of a collapsed, fluid-occluded (blue) airway as the air-liquid interface moves from left to right. The stress at the airway wall is applied to the epithelial lining (green insets) causing cell death. Adapted with permission from Bilek et al. (55).

Figure 3

Scanning electron micrograph depicting an undamaged alveolar surface (right panel) and fragmented alveolar epithelium (left panel) caused by two hours of ventilation at high tidal volumes and zero end expiratory pressure. Reproduced with permission from Hamlington et al. (88).

Figure 4

The collapse or flooding of an alveolus (blue) leads to increased distension of the adjacent septa (red).

Figure 5

Permeability of the blood-gas barrier (ratio of fluorescent label in BALF versus serum) for three different sized dextran molecules following intravenous injection in mice. Control animals were not subjected to mechanical ventilation and ventilated animals received pressure-controlled ventilation with an end-inspiratory plateau pressure of 37.5 cmH2O. The ZEEP/Short group was ventilated with zero end-expiratory pressure for approximately 30 min. The ZEEP/Mid group was ventilated with zero PEEP for approximately 60 min. The PEEP3 group was ventilated with a positive end-expiratory pressure of 3 cmH2O for approximately 120 min. The ZEEP/2xH group was ventilated with zero PEEP until lung stiffness (H) had risen to twice its baseline value. Used with permission from Hamlington et al. (92).

Figure 6

Predicted lung injury cost function for an initially healthy mouse consisting of the product of volutrauma and atelectrauma. Black ‘X’ indicates in vivo experiments that produced lung injury, white circles demarcate in vivo experiments that were non-injurious. The white line describes a ‘safe region’ of ventilation. Adapted from Hamlington et al. (92).