Atelectrauma and PEEP Effects

The second mechanism of injury, cyclic changes in non-aerated lung, was deduced from the observation of lung injury during ventilation with low end-expiratory lung volume (EELV) or in the absence of PEEP. In this case, the mechanisms at the cellular level are less clear. Air bubbles flowing through a collapsed or fluid-filled airway might induce damage to the epithelium by VILI consists of tissue damage and a biological response resulting from the application of inappropriate mechanical forces to the lung parenchyma [42].

Parenchymal stability resulting from the interplay of respiratory parameters such as tidal volume, PEEP, or respiratory rate can explain the results of different clinical trials and experimental studies that do not fit with the classic barotraumas/volu- trauma model. A consequence of low EELV can be a heterogeneous lung where that the forces exerted on alveolar walls or septa in the interfaces between collapsed and aerated lung tissues can be amplified, leading to cell injury [43]. The application of PEEP is almost invariably associated with a decrease in VILI in different experimental models of lung injury, such as high TV ventilation or surfactant depletion [44, 45]. The focus of investigative attention regarding VILI has been on the individual tidal cycle - as defined by PEEP and tidal volume. However, it stands to reason that the number of damaging cycles delivered per unit time (closely correlated with minute ventilation, independently of mode) would accentuate the injury inflicted by the individual tidal cycle [46].

PEEP tends to reduce the number of lung units placed at high risk by critical junctional interfaces between expanding and reluctantly expanding tissues. For the same tidal volume, PEEP also elevates the mean airway pressure and with it the average tissue stress. In the absence of compensatory recruitment or reduction in tidal volume, PEEP therefore also tends to increase right ventricular afterload. Without a simultaneous reduction in driving pressure, raising PEEP will place the lung at higher risk for stretch-related injury. Tidal volume itself may not injure the ventilated lung, but rather, the causative variable relates to the ratio of the tidal volume to the capacity of the lung to accept it [47]. The transalveolar pressure and the swings of transalveolar pressure (transalveolar driving pressure) determine the damaging energy forces imparted to delicate tissue [48].

Experimental designs combining high PEEP with low TV make it impossible to clarify the contributions of each factor to the outcome. In intact lungs PEEP reduces VILI. One study showed that adding PEEP in intact rats ventilated with very high TV could reduce injury [44], and a randomized trial showed in patients without lung injury that ventilation with PEEP did not worsen outcome, but improved oxygenation and decreased the risk of ventilator-associated pneumonia [49]. The effect of TV on healthy lungs is also controversial. A classic experiment from Mascheroni and colleagues [7] demonstrated that, even in spontaneously breathing animals, chemically induced hyperventilation could trigger substantial lung damage. This work highlights the importance of tissue deformation, represented by increased transpulmonary pressures, even during negative pressure ventilation (absence of high alveolar pressure, more homogeneous inflation).

Low EELV has proved safe in both animals and patients, and this approach has sometimes been termed permissive atelectasis. In a recent study using an isolated lung model, Fanelli and colleagues [50] demonstrated that permissive atelectasis caused the same amount of lung injury as the open lung strategy and only subtle differences in apoptosis and ultrastructural changes favoring the open lung strategy. In the clinical setting, mortality rates in descriptive studies for patients managed with a low-pressure strategy are similar to those in clinical trials [51]. Taken together, these data contradict the volutrauma/atelectrauma model, suggesting that other mechanisms could be responsible for VILI.