Venous Minus Arterial Carbon Dioxide Gradients in the Monitoring of Tissue Perfusion and Oxygenation: A Narrative...

According to Fick's principle, the total uptake of (or release of) a substance by tissues is the product of blood flow and the difference between the arterial and the venous concentration of the substance. Therefore, the mixed or central venous minus arterial CO₂ content difference depends on cardiac output (CO). Assuming a linear relationship between CO₂ content and partial pressure, central or mixed venous minus arterial PCO₂ differences (P_cv-aCO₂ and P_mv-aCO₂) are directly related to CO. Nevertheless, this relationship is affected by alterations in the CO₂Hb dissociation curve induced by metabolic acidosis, hemodilution, the Haldane effect, and changes in CO₂ production (VCO₂). In addition, P_cv-aCO₂ and P_mv-aCO₂ are not interchangeable. Despite these confounders, CO is a main determinant of P_cv-aCO₂. Since in a study performed in septic shock patients, P_mv-aCO₂ was correlated with changes in sublingual microcirculation but not with those in CO, it has been proposed as a monitor for microcirculation. The respiratory quotient (RQ)-RQ = VCO₂/O₂ consumption-sharply increases in anaerobic situations induced by exercise or critical reductions in O₂ transport. This results from anaerobic VCO₂ secondary to bicarbonate buffering of anaerobically generated protons. The measurement of RQ requires expired gas analysis by a metabolic cart, which is not usually available. Thus, some studies have suggested that the ratio of P_cv-aCO₂ to arterial minus central venous O₂ content (P_cv-aCO₂/C_a-cvO₂) might be a surrogate for RQ and tissue oxygenation. In this review, we analyze the physiologic determinants of P_cv-aCO₂ and P_cv-aCO₂/C_a-cvO₂ and their potential usefulness and limitations for the monitoring of critically ill patients. We discuss compelling evidence showing that they are misleading surrogates for tissue perfusion and oxygenation, mainly because they are systemic variables that fail to track regional changes. In addition, they are strongly dependent on changes in the CO₂Hb dissociation curve, regardless of changes in systemic and microvascular perfusion and oxygenation.