PurposeSeptic shock has been associated with microvascular alterations and these in turn with the development of organ dysfunction. Despite advances in video microscopic techniques, evaluation of microcirculation at the bedside is still limited. Venous-to-arterial carbon dioxide difference (Pv-aCO2) may be increased even when venous O2 saturation (SvO2) and cardiac output look normal, which could suggests microvascular derangements. We sought to evaluate whether Pv-aCO2 can reflect the adequacy of microvascular perfusion during the early stages of resuscitation of septic shock.MethodsProspective observational study including 75 patients with septic shock in a 60-bed mixed ICU. Arterial and mixed-venous blood gases and hemodynamic variables were obtained at catheter insertion (T0) and 6 h after (T6). Using a sidestream dark-field device, we simultaneously acquired sublingual microcirculatory images for blinded semiquantitative analysis. Pv-aCO2 was defined as the difference between mixed-venous and arterial CO2 partial pressures.ResultsProgressively lower percentages of small perfused vessels (PPV), lower functional capillary density, and higher heterogeneity of microvascular blood flow were observed at higher Pv-aCO2 values at both T0 and T6. Pv-aCO2 was significantly correlated to PPV (T0: coefficient −5.35, 95 % CI −6.41 to −4.29, p < 0.001; T6: coefficient, −3.49, 95 % CI −4.43 to −2.55, p < 0.001) and changes in Pv-aCO2 between T0 and T6 were significantly related to changes in PPV (R2 = 0.42, p < 0.001). Absolute values and changes in Pv-aCO2 were not related to global hemodynamic variables. Good agreement between venous-to-arterial CO2 and PPV was maintained even after corrections for the Haldane effect.ConclusionsDuring early phases of resuscitation of septic shock, Pv-aCO2 could reflect the adequacy of microvascular blood flow.Electronic supplementary materialThe online version of this article (doi:10.1007/s00134-015-4133-2) contains supplementary material, which is available to authorized users.

Background: 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.Methods: 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 CO 2 production ( V CO 2 ) and CO 2 exhaled fraction ( F ECO 2 ) 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.Results: 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; R 2 = 0.63, and 0.48, p < 0.001, respectively) and 24 h after (Spearman's rho = − 0.71, and − 0.65; p < 0.001; R 2 = 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; R 2 = 0.67, p < 0.001). Conclusion: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.

Oxygen-derived parameters have been traditionally used to guide resuscitation during shock states. Nevertheless, normalization of venous oxygen saturation does not exclude the persistence of tissue hypoperfusion and tissue hypoxia. Combination of O 2 and CO 2-derived variables has consistently demonstrated to be related with clinical outcomes and its variations could anticipate changes in lactate and also predict fluid responsiveness in terms of oxygen consumption. Here we discuss the potential mechanisms leading to increase the venous-to-arterial CO 2 (Cv-aCO 2) to arterial-to-venous O 2 content difference (Ca-vO 2), i.e., the Cv-aCO 2 /Ca-vO 2 ratio, its potential clinical application, limitations and uncertainties. Finally, although biologically plausible, the potential applications of the Cv-aCO 2 /Ca-vO 2 ratio in the clinical practice require to be confirmed.

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