Physiscal and biochemical basis of VILI

Stress is the applied force, and strain is the linear deformation of material. In the whole lung, the rough approximation of stress is the transpulmonary pressure, whereas the approximation of the average strain is the change in volume relative to the lung resting volume. The ratio between alveolar stress and strain is defined as lung-specific elastance (Espec), which is mathematically defined as: \u394PL = Espec 7 \u394V/V0 where \u394V is the volume variation applied to the lung (i.e., the tidal volume), and V0 is the lung resting volume (i.e., the functional residual capacity at atmospheric pressure [without any application of PEEP]). The lung-specific elastance is the transpulmonary pressure required to double the lung resting volume (i.e., the \u394PL when \u394V/V0 is equal to 1). In ARDS, lung-specific elastance is similar to normal, reinforcing the concept of the baby lung (lung is small and not stiff), and questions the use of normalizing the tidal volume to the ideal body weight. The same tidal volume per kilogram may result in completely different strain according to the size of the baby lung (the V0 of the previous equation). For example, a 70-kg man with ARDS may have, according to the severity of the lung injury, a residual baby lung equal to 60%, 40%, or 20% of his normal lung size. If the ventilator is set to deliver 10 mL/kg, the actual delivered tidal volume would generate an alveolar strain, which would result from the application, in normal lung, of a tidal volume equal to 17 mL/kg, 25 mL/kg, and 50 mL/kg, values associated with a significant lung injury in laboratory studies. Recently we attempted to quantify the relationship between stress-strain and VILI in healthy animals. We found that edema formation was a threshold phenomenon, induced by mechanical ventilation when the global strain reaches a critical value of about 2. This threshold roughly corresponds to the point where the stress-strain curve loses its linearity and starts an exponential growth, indicating that some lung regions reach their own total capacity and cannot expand any further. At this level of strain, in period of 24-48 hours the mechanical ventilation is lethal and the increased lung weight (2-3 times the baseline) is associated with a striking impairment of respiratory mechanics, gas exchange, hemodynamics, inflammation, distal organs damage and 100% mortality. This lethal strain, and associated stress, however, are rarely applied in clinical practice. To explain VILI in a diseases lung, therefore, alternative phenomena must be taken into account as the lung dishomogeneity and the presence of stress risers