By Richard Kallet, MS, RRT, FAARC, FCCM
Director of Quality Assurance, Respiratory Care Services, San Francisco General Hospital
Mr. Kallet reports no financial relationships relevant to this field of study.
SYNOPSIS: Experimental acute respiratory distress syndrome was induced in mice to study local alveolar gas dynamics using advanced microimaging techniques. Heretofore unrecognized disturbances in alveolar ventilation will alter our understanding of alveolar mechanics and gas exchange dysfunction as well as promote the use of recruitment maneuvers.
SOURCE: Tabuchi A, et al. Acute lung injury causes asynchronous alveolar ventilation which can be corrected by individual sighs. Am J Respir Crit Care Med 2015;Oct 29 [Epub ahead of print].
Researchers induced experimental acute respiratory distress syndrome (ARDS) mimicking aspiration, transfusion reaction, and surfactant inactivation in mice and observed the short-term effects on subpleural alveolar clusters using intravital and dark field microscopy and multi-spectral O2 saturation imaging. Within 10 minutes of inducing ARDS, pendelluft motion (PM) replaced synchronous alveolar inflation/deflation. This was characterized by alveoli that slowly inflated during expiration and deflated during inspiration. This behavior occurred both dynamically as well as during imposed end-expiratory and end-inspiratory pauses. Alveoli immediately adjacent to alveoli with PM tended to show larger volume changes compared to nearby alveoli, and both continued to ventilate normally. PM resolved spontaneously in the majority of cases within 60 minutes.
The magnitude of PM reflected injury severity. PM occurred with similar frequency regardless of injury mechanism and, in general, did not adversely affect alveolar gas exchange or local O2 saturation. However, severe dysfunction occurred more commonly in acid-induced ARDS (affecting approximately 50% of alveoli) and resulted in marked gas exchange dysfunction. Recruitment maneuvers (RMs) of 30 cm H2O for 10 seconds reversed alveolar synchrony and improved gas exchange in acid-induced ARDS but had no effect on the surfactant-deficient model.
This study enriches our understanding of pulmonary micromechanics and gas exchange dysfunction in ARDS, supports the hypothesis of Otis et al regarding the existence of PM,1 and advances our understanding of how RMs stabilize alveoli and improve oxygenation. In particular, the authors provided a detailed description of heretofore unrecognized, nuanced variations in alveolar filling and emptying.
Sixty years ago, Otis et al reasoned that PM occurs between proximal alveolar units when differences develop in their respective time constants (the product of resistance and compliance) such that injured units with a relatively brief time constant (e.g., low compliance the predominant disturbance) reach equilibration faster. As a result, these “fast units” empty into nearby, relatively normal alveoli (which have higher compliance) still undergoing inflation. The Tabuchi et al study confirms the existence of PM at the alveolar level and provides more detailed insight into alveolar gas dynamics occurring throughout the ventilatory cycle as well as persisting during end-inspiratory and end-expiratory pauses.
A striking finding was the apparent progression from PM to alveolar stunning in severe ARDS induced by acid-injury. Authors described this as cessation of ventilation in alveoli that intriguingly maintained a fixed volume. However, the authors operationally defined alveolar stunning as alveolar volume change < 25% of its individual baseline. Therefore, some degree of ventilation or bidirectional gas diffusion may persist in these units. Both the cause and gas exchange implications of alveolar stunning remain speculative at best. Severe injury progressing to alveolar flooding is the most obvious explanation, save for the fact that discreet alveoli are involved without causing severe injury to neighboring alveoli. Other possible explanations are alveolar obstruction by liquid bridge formation, interstitial edema, tethering by adjacent alveoli, or some combination of these.
Whereas PM is readily apparent as a source of severe ventilation-perfusion mismatch (and hence increased dead-space ventilation when CO2 is the tracer gas), the effect of alveolar stunning on gas exchange remains less obvious. This would partly depend on the intensity of hypoxic pulmonary vasoconstriction, the strength of which is heterogeneously distributed throughout the lungs and appears to fail once local alveolar PO2 is < 50 mmHg.2 That would invite speculation of a shunt-like effect. Moreover, the corrective effect of RM in this study suggests that obstruction of alveolar units and/or pulmonary edema might explain the source of alveolar stunning.
Finally, the fact that only subpleural alveoli could be examined in this study limits its generalization to overall mechanical and gas exchange dysfunction in ARDS. The heterogeneous nature of clinical lung injury and its distribution and the effects of chest wall compliance, gravitational forces, pulmonary vascular injury, and other numerous factors make definitive pronouncements regarding the pathophysiologic mechanisms of ARDS elusive. Nonetheless, the emerging picture has become ever more fascinating.
Otis AB, et al. Mechanical factors in distribution of pulmonary ventilation. J Appl Physiol 1956;8:427-443.
Starr IR, et al. Regional hypoxic pulmonary vasoconstriction in prone pigs. J Appl Physiol 2005;99:363-370.