Ventilator-induced Airway Dysfunction?

John J. Marini

University of Minnesota, St. Paul, Minnesota

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Most descriptions of lung pathology in the acute respiratory distress syndrome (ARDS) emphasize the disrupted alveolar architecture, noting its defining features: proteinaceous edema, hyaline membranes, inflammation, and fibrosis (1). It is now clear that high ventilatory stresses applied to these acutely damaged lungs influence the nature, severity, and evolution of the alveolar histopathology. Similar principles may apply to the airways as well. Whereas bronchial damage incurred during ventilatory support has been well recognized to cause lasting problems for neonates (2), comparatively little attention has been directed to the airways of adult patients with ARDS. This inattention to airway damage extends to short-term experimental models of acute lung injury, where it is generally obscured by the consequences of alveolar disruption. The paper by Goldstein and colleagues appearing in this issue (pp. 958- 964) (3) is noteworthy, therefore, in that airway damage was the focus of a pneumonia model in which moderately high ventilating pressures were applied over several days. Airway damage varied from site to site, with bronchiolectasia predominating in nonaerated lobules and emphysema-like changes prevailing in aerated ones. Against the expressed expectations of the authors, edema was not commonly observed in nonbronchopneumonic regions. These interesting results, however, are entirely consistent with what is known about the magnitude and distribution of parenchymal stresses within a mechanically heterogeneous lung.

Simple geometric reasoning led Mead and colleagues (4) to estimate that parenchymal interdependence would amplify tensions at the junctions of open and collapsed lung units in nonlinear proportion to the ratio of their volumes. As the transalveolar pressure and volume of the open unit rise, tidal stresses were predicted to reach impressive values. Although helpful in averting collapse of unstable units, amplified forces can potentially inflict tissue damage when they fail to maintain lumenal patency and are repeated at the rate of 25,000-45,000 tidal cycles per day. Moreover, if collapsed units suddenly snap open and later reclose, high shearing forces may disrupt the airway epithelium, overstretch fragile microvessels, deplete surfactant, or provide a sufficient mechanical signal to initiate inflammation. On the other hand, blind channels that terminate in units that fail to open expose the delicate terminal airways to high pressures that may overdistend them. Distorted airways not only impair ventilation, but also serve as reservoirs for infection.

Computed tomographic (CT) evidence suggests an increased prevalence of closed and junctional units in dependent regions of the acutely injured lung, where compressive forces are highest (5). The tendency for ventilator-induced damage, therefore, would be expected to be greatest in the dorsal portions of the supine lunga predilection that has been confirmed experimentally (6). Because open lung units are of greatest dimension in nondependent areas, such observations emphasize that the maximum transalveolar stretching pressure is neither the only, nor perhaps even the most important, determinant of ventilator-induced lung injury (VILI). Alveolar reexpansion with reduction in the number of critical junctional interfaces may partially explain why positive end-expiratory pressure (PEEP) and prone positioning tend to protect against VILI.

In the experimental pneumonia model of Goldstein and coworkers (3), atelectasis was simultaneously opposed by prone positioning and encouraged by not using PEEP. That little edema formed in nonconsolidated areas might also be a consequence of prone positioning; in the well-perfused dorsal zones, hydrostatic pressures are lower, airways drain by gravity, and lymphatic flow is favored as the heart shifts to a dependent position. Furthermore, lung inflammation resulting from bacterial infection may behave differently from that induced by surfactant depletion or oleic acid (7).

When attempting to explain the proclivity for mechanical ventilation to inflict airway damage, it should be considered that higher transbronchial pressures must be developed to achieve a given lung volume than are needed during fully spontaneous breathing, and that tidal volume distributes unevenly. Small airways surrounded by noninflating consolidated or collapsed tissue may be subjected to high central airway pressures with relatively little opposing external counterpressure, overdistending bronchioles unprotected by supporting cartilage. Inflatable, nonconsolidated lung units, on the other hand, are not exposed to such stresses because flow dissipates some of the proximal airway pressure, and "transmission" of alveolar pressure to the local environment that surrounds the bronchial channel is likely to be greater. In these open zones, however, the delicate alveolar septae may overdistend. Precisely this distribution of histologic lesions was demonstrated in the study by Goldstein and colleagues (3).

In the clinical setting, higher pressures applied over extended periods can cause radiographic evidence of airspace coalescence as the inflamed lung remodels under the influence of heightened tissue stress. Cystic spaces may form throughout the lungs of patients with ARDS, with a greater prevalence in dependent regions (8). Tension gas cysts, which are a pathologically distinct subgroup (9), arise from extraalveolar gas that fails to decompress into the mediastinum. These tend to develop suddenly in juxtapleural regions, and presage life-threatening lung rupture or systemic gas embolism (9, 10).

Long-term structural changes in ARDS are a joint function of the nature and intensity of the inflammation, the substrate of the lung, and the remodeling forces of ventilating pressure. Although lung fibrosis is generally acknowledged to be the most frequent complication of ARDS, disability resulting from residual airway damage is not uncommon. Six months and longer after discharge from the hospital, ~ 20% of patients have functional abnormalities of airflow, and ~ 40% show impaired diffusing capacity that might, in part, reflect the lasting consequences of bronchial damage and airspace dilation (11, 12).

In reemphasizing that airspace damage may occur unnoticed at modest airway pressures, the current report defines a focus for further study and suggests an important clinical message. Moreover, it calls attention to the insights that may be gained from long-duration studies of ventilation. Considerably more must be learned regarding possible modifiers such as infection, vascular pressure, position, inspired oxygen concentration, and antiinflammatory agents. Understanding such interactions may help us to assign a portion of the blame for death and lingering disability from ARDS to correctable iatrogenic contributors, and thereby improve outcome.

	References

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