Use of CO₂-derived variables in critically ill patients

A fundamental objective of hemodynamic resuscitation is to reverse tissue hypoperfusion and prevent progression to multiorgan failure and death. Conventional tools such as clinical examination, lactate levels, and central or mixed venous oxygen saturation (ScvO₂ and SvO₂, respectively) have intrinsic limitations. These drawbacks can be mitigated by incorporating additional markers of tissue hypoperfusion and altered tissue metabolism, such as carbon dioxide (CO₂)-derived variables, into other multimodal macro and micro hemodynamic monitoring. Specifically, the mixed or central venous-to-arterial difference in partial pressure of CO₂ (Pv-aCO₂ or Pcv-aCO₂) reflects the adequacy of blood flow to transport CO₂ from peripheral tissues to the lungs for its elimination. Consequently, Pv-aCO₂ serves as a reliable marker for assessing the adequacy of blood flow relative to CO₂ production. Importantly, unlike SvO₂ and ScvO₂, Pv-aCO₂ remains informative even when oxygen extraction is impaired, as commonly occurs in septic conditions. However, Pv-aCO₂ and Pcv-aCO₂ in isolation are not direct markers of anaerobic metabolism, as these can also be influenced by oxygen consumption rates. Conversely, the ratio between Pv-aCO₂ (or Pcv-aCO₂) and the arteriovenous oxygen content difference may provide a more reliable indication of ongoing anaerobic metabolism. This review discusses the physiological foundations, prognostic significance, clinical implications, and potential applications of CO₂-derived parameters in patient management.