Pathophysiology and clinical implications of the veno-arterial PCO2 gap

Abstract

This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2021. Other selected articles can be found online at https://www.biomedcentral.com/collections/annualupdate2021 . Further information about the Annual Update in Intensive Care and Emergency Medicine is available from https://link.springer.com/bookseries/8901 .

Fig. 1

Physiology of CO₂ production and transport. In cells, CO₂ is produced (in mitochondria) as a byproduct of substrate oxidation. Under anaerobic conditions, CO₂ is generated in small amounts, as the results of HCO₃⁻ buffering of protons released by lactic acid and the hydrolysis of ATP. CO₂ diffuses into the interstitial tissues and then into capillaries, where it is transported as dissolved CO₂ in plasma (in equilibrium with the PCO₂), bound to hemoglobin as carbamino-hemoglobin (HbCO₂) in red blood cells (RBC), and as HCO₃⁻, following the reaction of CO₂ with H₂O within RBC, a reaction catalyzed by carbonic anhydrase to form HCO₃⁻ and H⁺. HCO₃⁻ exits the RBC in exchange with chloride anions (Cl⁻), whereas protons are buffered by hemoglobin, forming HbH

Fig. 2

The CO₂ dissociation curve. A curvilinear relationship exists between CO₂ partial pressure (PCO₂) and CO₂ content (CCO₂), so that PCO₂ = k × CCO₂. At low values of PCO₂, the slope of the relationship is steeper, implying a smaller increase of PCO₂ at any CCO₂ than at high values of PCO₂, where the slope of the relationship flattens. The position of the relationship is modified by various factors. A rightward and downward shift of the curve, corresponding to an increase of the k coefficient is produced by high PaO₂ (Haldane effect), elevated temperatures, high hemoglobin concentrations and metabolic acidosis. A rightward shift of the curves implies that, for a same CCO₂, the PCO₂ increases, as indicated by the points A, B and C

Fig. 3

The inverse relationship between cardiac output and the Pva-CO₂ gap. A reduction in cardiac output is associated with a progressive increase in the Pva-CO₂ gap, which becomes exponential at very low cardiac output values, because of the flat slope of the CO₂ dissociation curve in conditions of tissue hypercarbia. The relationship is displaced to the right at higher CO₂ production (VCO₂)

Fig. 4

Usefulness of the Pva-CO₂ gradient under conditions of circulatory shock. Proposed diagnostic algorithm integrating lactate, mixed (central) venous oxygen saturation (S(c)vO₂) and the Pva-CO₂ gap in patients with circulatory shock

Fig. 5

The Pva-CO₂ gradient in the absence of circulatory shock. Proposed diagnostic algorithm to interpret an elevation in the Pva-CO₂ gap in the absence of circulatory shock and with normal blood lactate. S(c)vO₂ mixed (central) venous oxygen saturation