CO2-derived variables for hemodynamic management in critically ill patients

CO2-derived variables for hemodynamic management in critically ill patients

CO2 measurement carries significant physiologic and clinical information when analyzing hemodynamic status and ventilation of patients. While much focus is on O2 based data, CO2 derived parameters can provide a wealth of additional information. This is becoming more readily available as technological advances are making headways in CO2 measurements.

The classic targets clinicians follow in patients in shock have shortcomings. The central venous oxygen saturation (ScVO2) was once hailed as the ideal target to guide resuscitation of patients in shock (1). More recent data challenged its role and reduced its value, although it remains a helpful physiologic parameter to follow (2,3). A normal ScVO2 does not exclude tissue hypoperfusion and could misguide the clinician. Lactic acid is another closely monitored parameter which reflects tissue perfusion. It is also advocated for in multiple guidelines, but also has its own shortcomings: it can be elevated for reasons other than tissue perfusion such as adrenergic stimulation, increased glycolytic activity or reduced clearance from liver dysfunction (4-6). The venous-to-arterial CO2 partial pressure difference (ΔPCO2) and tissue CO2 could help alleviate some of these limitations.

According to the Fick equation, and similar to O2 metabolism, CO2 production (VCO2) is directly proportional to the cardiac output (CO) and the venous-to-arterial CO2 content difference. The CO2 content is linearly related to the partial pressure of CO2 over the general physiological range of CO2 content (7). Moreover, the mixed venous values correlate with the central venous values (8). Hence the Fick equation can be rewritten as follows: ΔPCO2 = k × VCO2/CO, where the k is a pseudo-linear coefficient supposed to be linear in physiological states.

Based on this modified Fick equation, and for patients in a steady state, ΔPCO2 is inversely proportional to CO. ΔPCO2 and its relation to the CO has been studied in a number of situations, including patients in shock on vasopressors, and found to be an appropriate target to titrate such agents (9,10).

ΔPCO2 has similar value in the operating room, where optimizing tissue perfusion and O2 delivery is essential to reduce post-operative complications. For high risk non cardiac surgical patients, ΔPCO2 can be used to reflect CO, identify patients that are not adequately resuscitated and along with ΔPCO2/C(a-v)O2 ratio predict post-operative complications (11). This might not be true with cardiac surgical patients, who have different macro and micro hemodynamic changes (12).

Tissue hypercarbia is a common observation in patients in circulatory failure. Tissue CO2 values are a reflection of the adequacy of tissue perfusion, as reduced blood flow leads to blood stagnation and failure of CO2 washout from the tissues. This stagnant hypercapnia phenomenon reflects tissue hypoperfusion, even earlier than systemic parameters (13). This is especially relevant in sepsis where the impaired microcirculation, arteriovenous shunting and reduction in capillary density culminate in heterogeneous tissue perfusion. Direct optical videoscopy permits to assess these microcirculatory changes, but is yet to reach the bedside for mainstream use. Tissue capnometry, on the other hand, might offer similar data and is becoming more readily available.

Gastric, sublingual, bladder and transcutaneous PCO2 values have been assessed in critically ill patients. The stomach is easy to access, can be used to detect gastric hypoperfusion and splanchnic ischemia. The gastric PCO2 correlates with outcomes in the critical care and operating room settings (14). The sublingual vasculature has drawn significant interest as it reflects pathologic changes seen during septic shock. Measuring sublingual CO2 offers a way to assess the microcirculation in such patients (15). Overall, the tissue CO2 gap seems to perform better than systemic parameters, paving the way to use it as a resuscitation target for septic shock.

Transcutaneous CO2 (tcPCO2) offers another non-invasive method to estimate PaCO2 with many studies establishing a good correlation between the 2 values (16). Some restrictions persist including the optimal site for tcPCO2 measurement (earlobe with its high vascularity seems to perform better than other sites), technological delays (time is needed to sensor equilibration) and a gap between PaCO2 variations and reflection in the tcPCO2 value. Nonetheless, when the appropriate conditions are met and the skin perfusion is normal, tcPCO2 reflects PcCO2. Similar to other tissues, and as was discussed in the prior section, for patients in shock, the transcutaneous CO2 gap is a good reflection of tissue perfusion and as such can be used for hemodynamic measurements.

Based on the Fick equation as it applies to O2 and CO2, the ΔPCO2/C(a-v)O2 ratio equals VCO2/VO2 and hence the respiratory quotient (RQ). While under aerobic conditions, RQ values ranges between 0.6 to less than 1, RQ changes with anaerobic metabolism. This is due to VCO2 increases to a larger extent than VO2 under anaerobic conditions. While this is of paramount importance diagnostically, it was also found to be valuable parameter to target during resuscitation (17,18).

The following review articles summarize the available literature on CO2 physiology and clinical value, as it pertains to the critical care setting as well as the operating room.




  1. Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 2001;345:1368-77. [Crossref] [PubMed]
  2. ProCESS Investigators., Yealy DM, Kellum JA, et al. A randomized trial of protocol-based care for early septic shock. N Engl J Med 2014;370:1683-93. [Crossref] [PubMed]
  3. ARISE Investigators, ANZICS Clinical Trials Group, Peake SL, et al. Goal-directed resuscitation for patients with early septic shock. N Engl J Med 2014;371:1496-506. [Crossref] [PubMed]
  4. Vary TC, Siegel JH, Nakatani T, et al. Effect of sepsis on activity of pyruvate dehydrogenase complex in skeletal muscle and liver. Am J Physiol 1986;250:E634-40. [PubMed]
  5. Pastor CM, Billiar TR, Losser MR, et al. Liver injury during sepsis. J Crit Care 1995;10:183-97. [Crossref] [PubMed]
  6. Levraut J, Ciebiera JP, Chave S, et al. Mild hyperlactatemia in stable septic patients is due to impaired lactate clearance rather than overproduction. Am J Respir Crit Care Med 1998;157:1021-6. [Crossref] [PubMed]
  7. Giovannini I, Chiarla C, Boldrini G, et al. Calculation of venoarterial CO2 concentration difference. J Appl Physiol (1985) 1993;74:959-64. [Crossref] [PubMed]
  8. Walley KR. Use of central venous oxygen saturation to guide therapy. Am J Respir Crit Care Med 2011;184:514-20. [Crossref] [PubMed]
  9. Mallat J, Benzidi Y, Salleron J, et al. Time course of central venous-to-arterial carbon dioxide tension difference in septic shock patients receiving incremental doses of dobutamine. Intensive Care Med 2014;40:404-11. [Crossref] [PubMed]
  10. Teboul JL, Mercat A, Lenique F, et al. Value of the venous-arterial PCO2 gradient to reflect the oxygen supply to demand in humans: effects of dobutamine. Crit Care Med 1998;26:1007-10. [Crossref] [PubMed]
  11. Robin E, Futier E, Pires O, et al. Central venous-to-arterial carbon dioxide difference as a prognostic tool in high-risk surgical patients. Crit Care 2015;19:227. [Crossref] [PubMed]
  12. Guinot PG, Badoux L, Bernard E, et al. Central Venous-to-Arterial Carbon Dioxide Partial Pressure Difference in Patients Undergoing Cardiac Surgery is Not Related to Postoperative Outcomes. J Cardiothorac Vasc Anesth 2017;31:1190-6. [Crossref] [PubMed]
  13. Teboul JL, Scheeren T. Understanding the Haldane effect. Intensive Care Med 2017;43:91-3. [Crossref] [PubMed]
  14. Mallat J, Vallet B. Mucosal and cutaneous capnometry for the assessment of tissue hypoperfusion. Minerva Anestesiol 2018;84:68-80. [PubMed]
  15. Ince C, Boerma EC, Cecconi M, et al. Second consensus on the assessment of sublingual microcirculation in critically ill patients: results from a task force of the European Society of Intensive Care Medicine. Intensive Care Med 2018;44:281-99. [Crossref] [PubMed]
  16. Eberhard P. The design, use, and results of transcutaneous carbon dioxide analysis: current and future directions. Anesth Analg 2007;105:S48-52. [Crossref] [PubMed]
  17. Monnet X, Julien F, Ait-Hamou N, et al. Lactate and venoarterial carbon dioxide difference/arterial-venous oxygen difference ratio, but not central venous oxygen saturation, predict increase in oxygen consumption in fluid responders. Crit Care Med 2013;41:1412-20. [Crossref] [PubMed]
  18. Mallat J, Lemyze M, Meddour M, et al. Ratios of central venous-to-arterial carbon dioxide content or tension to arteriovenous oxygen content are better markers of global anaerobic metabolism than lactate in septic shock patients. Ann Intensive Care 2016;6:10. [Crossref] [PubMed]

Boulos Nassar1,2, Jihad Mallat1

1Department of Critical Care Medicine, Critical Care Institute, Cleveland Clinic Abu Dhabi, Abu Dhabi, UAE;
2University of Iowa Hospitals and Clinics, Pulmonary and Critical Care Division, Iowa City, USA

doi: 10.21037/jtd.2019.04.94

Conflicts of Interest: The authors have no conflicts of interest to declare.

Cite this article as: Nassar B, Mallat J. CO2-derived variables for hemodynamic management in critically ill patients. J Thorac Dis 2019;11(Suppl 11):S1525-S1527. doi: 10.21037/jtd.2019.04.94