The anatomical and functional shunt conundrum: what do we really know about the pathophysiology of acute respiratory distress syndrome?

Correlation does not imply causation, nor does it elucidate mechanism. This axiom of empiricism seems self-evident, but when it comes to positive endexpiratory pressure (PEEP), recruitment, and acute respiratory distress syndrome (ARDS), the article by Dr. Cressoni and colleagues (1) in this issue of the Critical Care Medicine shows that we have indeed made many assumptions about causality. By manipulating PEEP levels and using various means of pulmonary recruitment, different authors have shown an improvement in alveolar-arterial gradients (2–5). A common theme in many of these interventions has been to use recruitment and PEEP to ensure the patency of unstable alveoli and provide ventilation in atelectatic areas of the lung to reduce the ventilation/perfusion mismatch that is a characteristic of ARDS. The assumption in interpreting these experiments has been that the mechanism underlying the improvement in PaO2 was a recruitment of collapsed alveoli and a reduction in atelectasis. To use the terms described in the article by Dr. Cressoni and colleagues (1), functional shunt was believed to be a reflection of anatomical shunt. Yet Dr. Cressoni and colleagues (1) demonstrate that anatomical recruitment, as shown by computed tomography scan, with changing levels of PEEP had only a weak association with functional shunt, as measured by Riley’s venous admixture. Furthermore, the improvement in arterial oxygen tension seen after increments in PEEP was not due to anatomical recruitment and its associated decrease in anatomical shunt. This is particularly interesting as there was very little lung available for anatomical recruitment in the subjects included in the study (13% 11% of the lung weight) (4). But there’s the rub; Dr. Cressoni and colleagues’ (1) work now raises even more questions about the pathophysiology of ARDS and the effects of PEEP, such as, how can the anatomical/functional shunt discrepancy be accounted for? What is the relative impact of various factors, and how can we measure them? When interpreting these findings, a few considerations are warranted. First, the ability to recruit collapsed lung units is not only variable among patients who have ARDS but is also a function of stress or strain, time, and perhaps the type of recruitment maneuver used (6, 7). For example, at the bedside, occasionally one can observe improvements in gas exchange and lung mechanics in ARDS without changes in mean airway pressures, which are not easily attributable to overall clinical improvement in other parameters. Second, it is speculative to assume that anatomical shunt equals nonaerated lung and similarly that anatomical recruitment is defined by changes in computed tomography scan density of consolidated lung after increasing airway pressures. For example, Mancini et al. (8) used inert gas measurements to investigate the relationship between ventilation and perfusion in patients who had ARDS. After implementing similar incremental changes in PEEP and ventilation strategy to those used by Dr. Cressoni and colleagues (1), Mancini et al. reported a stronger correlation between changes in intrapulmonary shunt and the amount of PEEP-induced lung recruitment (r .79) (8). As per Dr. Gattinoni and associates’ (9) recommendations in a previous article, a definitive understanding of the relationship between gas exchange and lung structure assessed by computed tomography scan will only be possible when regional lung perfusion is measured as well. Finally, a large number of the patients included in this study had ARDS due to severe pneumonia. It has long been recognized that the potential for recruitment is different in patients who have pulmonary and extrapulmonary causes of ARDS (10). It is tempting to speculate that in ARDS due to pneumonia, the correlation between functional and anatomical shunt may be markedly different from that in ARDS due to other etiologies. For example, Hanly et al. (11) demonstrated that perfusion of consolidated lungs measured using radioactive microspheres is markedly increased due to abolished hypoxic pulmonary vasoconstriction. Interestingly, hypoxic pulmonary vasoconstriction could be reinstituted by the administration of a nonsteroidal antiinflammatory, presumptively blocking prostaglandin-mediated pulmonary vasodilatation (11). As Dr. Cressoni and colleagues (1) point out in their discussion, studies of distribution of perfusion using positron emission tomography scan or angiography are clearly different in patients with pneumonia compared with other pulmonary pathology (1). These data likely will not change the way many of us practice and manage ARDS at the bedside. Indeed, as the authors themselves acknowledge, there are no data to support their approach of tailoring PEEP levels to minimize the “anatomical shunt” demonstrated by computed tomography scan. What this article does accomplish is to challenge our assumptions regarding the physiologic mechanisms underlying our management of ARDS. In so doing, Dr. Cressoni and colleagues (1) pave the way for novel conceptualizations of the pathophysiology and shunt mechanisms of ARDS. We can no longer assume that PEEP is simply “stenting” open alveoli that would collapse under lower airway pressure. As more experimental evidence emerges, we may need to reinterpret the find*See also p. 669.