Positive end-expiratory pressure alters the severity and spatial heterogeneity of ventilator-induced lung injury: An argument for cyclical airway collapse

Abstract

Purpose

Ventilator-induced lung injury (VILI) is a recognized complication of mechanical ventilation. Although the specific mechanism by which mechanical ventilation causes lung injury remains an active area of study, both alveolar overdistension and cyclical airway collapse and recruitment have been suggested as contributing causes. We hypothesized that mechanical ventilation in the absence of positive end-expiratory pressure (PEEP) causes VILI to be more severe and regionally variable as compared with PEEP = 8 cm H₂O.

Materials and Methods

To test this hypothesis, anesthetized, supine rabbits were mechanically ventilated with an end-inspiratory pressure of 28 cm H₂O and either 0 or 8 cm H₂O PEEP for 4 hours. Regional lung injury was determined by histologic scoring.

Results

In the absence of PEEP, lung injury was regionally variable and greatest in the dorsal-caudal lung. This regional injury heterogeneity was abolished by the addition of PEEP = 8 cm H₂O.

Conclusions

These results suggest that VILI is regionally heterogeneous and spatially correlates with regions in which cyclical airway collapse and recruitment is most likely to occur.

Introduction

Lung injury and edema are well-documented consequences of mechanical ventilation with high distending pressures in multiple experimental models [1], [2], [3]; however, maintaining end-expiratory lung volume at some level above functional residual capacity (FRC) with positive end-expiratory pressure (PEEP) can attenuate ventilator-induced lung injury (VILI) in animal models [1], [2], [3], [4], [5], [6]. In contrast, with inadequate or absent PEEP, significant lung injury occurs with lower tidal volumes and distending pressures in a surfactant-depleted, isolated lung model [6]. The protective effect of PEEP has been attributed primarily to prevention of repeated airway collapse and expansion (RACE) [6], [7] and, to a lesser extent, limitation of tidal excursion and reduced cardiac output [8].

Much of the supporting evidence for the RACE hypothesis comes from the influential studies of Gattinoni and colleagues [9] who used CT scans to measure gas content of lung tissue in patients with acute respiratory distress syndrome (ARDS) to show that the dependent, dorsal-caudal lung regions can be “recruited” with the application of PEEP or prone positioning [10]. However, the correlation between gray scale and alveolar size only holds true if a uniform amount of water in each alveolus is present. Otherwise, any gradients seen might reflect differences in alveolar water content rather than alveolar size/expansion [11]. An additional line of evidence supporting the RACE hypothesis is that spatial analysis of lung injury distribution shows a dorsal-caudal bias, which is the lung region where RACE is predicted to occur [4], [12], [13].

Although improved outcomes in patients with ARDS ventilated with PEEP set above the lower inflection point of the inspiratory pressure-volume curve has been observed [14], a recent multicenter trial failed to show a survival advantage with a high-PEEP ventilation strategy [15]. The RACE hypothesis has been called into question recently, favoring the tidal movement of fluid and/or foam in the airways as an explanation for the mechanical behavior of the injured lung during mechanical ventilation [11]. In experiments using markers to measure regional lung parenchymal movement in an oleic acid–induced lung injury model, collapse of dependent lung units at FRC, increased vertical gradient of regional lung volumes at FRC, and cyclical collapse and reopening of dependent alveoli were not observed [16]. In addition, a recent report of saline lavage-induced lung injury found that high tidal volume/low PEEP ventilation resulted in lung injury in the nondependent lung regions in supine rats, suggesting atelectasis in the dependent lung zone shifts stretch-induced injury to the nondependent lung and argues against repetitive collapse and expansion as a cause of VILI [17]. The current technological limitations of available imaging modalities preclude accurate real-time imagining of all but the most peripheral alveoli, therefore, whether alveoli open and close during mechanical ventilation remains uncertain. However, it has been argued that alveoli are more likely to flood than collapse when subjected to the stresses of mechanical ventilation [11], [18].

The primary goal of this study was to test the hypothesis that lung injury because of large tidal volume ventilation is attenuated and its spatial distribution altered with the application of PEEP. We postulated that lung injury, unlike that reported in a recent study [17], would be predominant in the dorsal-caudal lung where RACE is most likely to occur and that the application of PEEP would not only reduce the severity of lung injury, which we recognize is a well-established finding but that the distribution of lung injury would be altered. That is to say, lung injury would be more homogeneously distributed compared with what occurs in the absence of PEEP. We are unaware of any previous studies that have examined the effects of PEEP on the regional distribution of VILI.