The respective roles of high pressure and high tidal volume to promote high airway pressure pulmonary edema are unclear. Positive end-expiratory pressure (PEEP) was shown to reduce lung water content in this type of edema, but its possible effects on cellular lesions were not documented. We compared the consequences of normal tidal volume ventilation in mechanically ventilated rats at a high airway pressure (HiP-LoV) with those of high tidal volume ventilation at a high (HiP-HiV) or low (LoP-HiV) airway pressure and the effects of PEEP (10 cm H2O) on both edema and lung ultrastructure. Pulmonary edema was assessed by extravascular lung water content and microvascular permeability by the drug lung weight and the distribution space of 125I-labeled albumin. HiP-LoV rat lungs were not different from those of controls (7 cm H2O peak pressure ventilation). By contrast, the lungs from the groups submitted to high volume ventilation had significant permeability type edema. This edema was more pronounced in LoP-HiV rats. It was markedly reduced by PEEP, which, in addition, preserved the normal ultrastructural aspect of the alveolar epithelium. This was in striking contrast to the diffuse alveolar damage usually encountered in this type of edema. To our knowledge, this constitutes the first example of a protective effect of PEEP during permeability edema.

During mechanical ventilation, high end-inspiratory lung volume (whether it be because of large tidal volume (VT) and/or high levels of positive end-expiratory pressure) results in a permeability type pulmonary oedema, called ventilator-induced lung injury (VILI). Previous injury sensitises lung to mechanical ventilation.This experimental concept has recently received a resounding clinical illustration after a 22% reduction of mortality was observed in acute respiratory distress syndrome patients whose VT had been reduced. In addition, it has been suggested that repetitive opening and closing of distal units at low lung volume could induce lung injury but this notion has been challenged both conceptually and clinically after the negative results of the Acute Respiratory Distress Syndrome clinical Network Assessment of Low tidal Volume and Elevated end-expiratory volume to Obviate Lung Injury (ARDSNet ALVEOLI) study.Experimentally and clinically, involvement of inflammatory cytokines in VILI has not been unequivocally demonstrated. Cellular response to mechanical stretch has been increasingly investigated, both on the epithelial and the endothelial side. Lipid membrane trafficking has been thought to be a means by which cells respond to stress failure.Alterations in the respiratory system pressure/volume curve during ventilator-induced lung injury that include decrease in compliance and position of the upper inflection point are due to distal obstruction of airways that reduce aerated lung volume. Information from this curve could help avoid potentially harmful excessive tidal volume reduction. [3][4][5][6][7]. The purpose of this paper is to review the different situations in which VILI can occur based on animal studies and to place these results into a clinical perspective of ventilatory management of acute respiratory distress syndrome (ARDS). Evidence for ventilator-induced lung injury Ventilation of intact lungsHigh lung volume ventilator-induced lung injury. WEBB and TIERNEY [8] were the first to demonstrate that mechanical ventilation could cause pulmonary oedema in intact animals. They were able to show in rats subjected to positive airway pressure ventilation that pulmonary oedema was more severe and occurred more rapidly when the animals were ventilated with 45 cmH 2 O than with 30 cmH 2 O peak airway pressure. Animals ventilated for 1 h with 14 cmH 2 O peak airway pressure did not develop oedema. It was later confirmed that ventilation with high airway pressure produces capillary permeability alterations, nonhydrostatic pulmonary oedema and tissue damage resembling that observed during ARDS [9]. Further studies demonstrated that VILI depended mainly on lung volume and especially on the end-inspiratory volume [10]. The corresponding pressure is termed "plateau" pressure and its clinical importance has been emphasised in a Consensus Conference on mechanical ventilation [11]. The respective roles of increased airway pressure and increased lung volume on the development of VILI were clarified by...

Mechanical ventilation with high peak inspiratory pressure and large tidal volume (VT) produces permeability pulmonary edema. Whether it is mean or peak inspiratory pressure (i.e., mean or end-inspiratory volume) that is the major determinant of ventilation-induced lung injury is unsettled. Rats were ventilated with increasing tidal volumes starting from different degrees of FRC that were set by increasing end-expiratory pressure during positive-pressure ventilation. Pulmonary edema was assessed by the measurement of extravascular lung water content. The importance of permeability alterations was evaluated by measurement of dry lung weight and determination of albumin distribution space. Pulmonary edema with permeability alterations occurred regardless of the value of positive end-expiratory pressure (PEEP), provided the increase in VT was large enough. Similarly, edema occurred even during normal VT ventilation provided the increase in PEEP was large enough. Furthermore, moderate increases in VT or PEEP that were innocuous when applied alone, produced edema when combined. The effect of PEEP was not the consequence of raised airway pressure but of the increase in FRC since similar observations were made in animals ventilated with negative inspiratory pressure. However, although permeability alterations were similar, edema was less marked in animals ventilated with PEEP than in those ventilated with zero end-expiratory pressure (ZEEP) with the same end-inspiratory pressure. This "beneficial" effect of PEEP was probably the consequence of hemodynamic alterations. Indeed, infusion of dopamine to correct the drop in systemic arterial pressure that occurred during PEEP ventilation resulted in a significant increase in pulmonary edema. In conclusion, rather than VT or FRC value, the end-inspiratory volume is probably the main determinant of ventilation-induced edema. Hemodynamic status plays an important role in modulating the amount of edema during lung overinflation but does not fundamentally modify the characteristics of this edema which is consistently associated with major permeability alterations. These results may be relevant for ventilatory strategies during acute respiratory failure.