Microcirculatory dysfunction and dead-space ventilation in early ARDS: a hypothesis-generating observational study

Ventilation/perfusion inequalities impair gas exchange in acute respiratory distress syndrome (ARDS). Although increased dead-space ventilation (V_D/V_T) has been described in ARDS, its mechanism is not clearly understood. We sought to evaluate the relationships between dynamic variations in V_D/V_T and extra-pulmonary microcirculatory blood flow detected at sublingual mucosa hypothesizing that an altered microcirculation, which is a generalized phenomenon during severe inflammatory conditions, could influence ventilation/perfusion mismatching manifested by increases in V_D/V_T fraction during early stages of ARDS.

Forty-two consecutive patients with early moderate and severe ARDS were included. PEEP was set targeting the best respiratory-system compliance after a PEEP-decremental recruitment maneuver. After 60 min of stabilization, hemodynamics and respiratory mechanics were recorded and blood gases collected. V_D/V_T was calculated from the CO₂ production ([Formula: see text]) and CO₂ exhaled fraction ([Formula: see text]) measurements by volumetric capnography. Sublingual microcirculatory images were simultaneously acquired using a sidestream dark-field device for an ulterior blinded semi-quantitative analysis. All measurements were repeated 24 h after.

Percentage of small vessels perfused (PPV) and microcirculatory flow index (MFI) were inverse and significantly related to V_D/V_T at baseline (Spearman's rho = - 0.76 and - 0.63, p < 0.001; R² = 0.63, and 0.48, p < 0.001, respectively) and 24 h after (Spearman's rho = - 0.71, and - 0.65; p < 0.001; R² = 0.66 and 0.60, p < 0.001, respectively). Other respiratory, macro-hemodynamic and oxygenation parameters did not correlate with V_D/V_T. Variations in PPV between baseline and 24 h were inverse and significantly related to simultaneous changes in V_D/V_T (Spearman's rho = - 0.66, p < 0.001; R² = 0.67, p < 0.001).

Increased heterogeneity of microcirculatory blood flow evaluated at sublingual mucosa seems to be related to increases in V_D/V_T, while respiratory mechanics and oxygenation parameters do not. Whether there is a cause-effect relationship between microcirculatory dysfunction and dead-space ventilation in ARDS should be addressed in future research.