Shedding light on venoarterial PCO2 gradient.

As an expression on Fick’s principle, the reduction in cardiac output is associated with a parallel increase in both mixed venoarterial CO2 content difference (Cmv-aCO2) and arterial-mixed venous oxygen content difference (Ca-mvO2). Nevertheless, disproportioned elevations in Cmv-aCO2 compared to those of Ca-mvO2 ensue when the anaerobic threshold is reached. This results from anaerobic CO2 production, secondary to the buffering of anaerobically generated protons by bicarbonate.

The clinical approach to venoarterial CO2 differences usually relies on partial pressure rather than content difference. Unfortunately, the attempts to track Cmv-aCO2 through mixed venoarterial PCO2 difference (Pmv-aCO2) might be misleading. The relationship between CO2 content and partial pressure is intricate. Moreover, the estimation of CO2 content from PCO2 is troublesome, and calculation algorithms frequently produce unreliable results. Since several factors can modify the dissociation of CO2 from Hb, Pmv-aCO2 can fail to reflect Cmv-aCO2 changes. For example, hemodilution induces opposite changes in Pmv-aCO2 and Cmv-aCO2. The high cardiac output that develops in such situation increases Pmv-aCO2 and reduces Cmv-aCO2 [1]. Other factors, such as metabolic acidosis and Haldane effect, can also play a major role in this relationship and have strong effects on Pmv-aCO2, regardless of cardiac output changes [2].

Another focus of confusion might reside in the actual meaning of venoarterial PCO2 difference. Differently to tissue-arterial PCO2 difference, Pmv-aCO2 primarily reflects the changes in systemic blood flow and not in microcirculatory perfusion. Physiologic research helps to understand this question. In an experimental model of endotoxemia, all the PCO2 differences—Pmv-aCO2, mesenteric venoarterial and mucosal villi-arterial—increased during the phase of hypodynamic shock [3]. After fluid resuscitation, Pmv-aCO2 and mesenteric venoarterial PCO2 difference normalized following the improvement in cardiac output and superior mesenteric artery blood flow. Tissue hypercarbia, however, remained present as an expression of villi microcirculatory hypoperfusion.

Although mixed venous and central venous gases are not interchangeable [4], central venoarterial PCO2 difference (Pvc-aCO2) has been used a surrogate for Pmv-aCO2. It might thus be a good marker of cardiac output, even more sensitive than central venous oxygen saturation [5]. Nevertheless, an observational study found that Pvc-aCO2 did not correlate with cardiac output but with sublingual microvascular perfusion [6]. It was therefore claimed by some authors that Pvc-aCO2 might reflect tissue perfusion. This speculation is supported neither by physiology [3] nor by relevant clinical studies. In septic shock, patients with a hyperdynamic profile showed lower Pvc-aCO2 than those with normal systemic hemodynamics, even though the microcirculatory alterations were similar in both groups [7]. So, the lack of correlation between cardiac output and Pvc-aCO2 found in septic patients [6] should be explained by modifications in the dissociation of CO2 from Hb. Disorders such as hemodilution and lactic acidosis are commonly present in septic shock and frequently display microvascular abnormalities. Certainly, the relationship between Pvc-aCO2 and microcirculation should not be interpreted as a causal phenomenon.

In this issue of Annals of Intensive Care, Mallat et al. [8] report that an acute reduction in arterial PCO2 from 44 to 34 mm Hg was associated with an increase of 2 mm Hg in Pvc-aCO2. The authors attributed this finding to the concomitant increase in oxygen consumption (VO2). Unfortunately, methodological issues might limit the relevance of the conclusions: First, the increase in Pcv-aCO2 not only was quantitatively minor and insignificant from a clinical point of view, but mainly stayed within the error of the method of PCO2 measurement. This is especially true when taking into account the error propagation produced during the calculation of the PCO2 difference. Furthermore, the use of central venous instead of mixed venous gases for computation of VO2 is questionable [4]. In addition, the subtle change in base excess that appeared during hyperventilation might also explain part of the change in Pcv-aCO2 [2]. Modifications in Hb levels before and after hyperventilation, which might have affected Pcv-aCO2 [1], were not reported. A comprehensive discussion about any Pcv-aCO2 change should consider all its determinants.

The effects of hypocapnia on Pvc-aCO2 have been previously reported in stable cardiac surgery patients [9]. An experimental study also showed that severe hypocapnia increased gut intramucosal-arterial PCO2 as a probable consequence of regional and tissue hypoperfusion. In contrast, systemic and regional venoarterial PCO2 gradients did not change [10]. In this way, the effects of hypocapnia on Pvc-aCO2 are uncertain.

Although the study from Mallat et al. [8] does not add new physiologic information and has major limitations, it emphasizes that Pvc-aCO2 is not a straightforward surrogate for blood flow. The messages for physiologists and practitioners should be that Pvc-aCO2 monitoring might contribute to the assessment of systemic hemodynamics but requires a comprehensive interpretation.