Intensive Care Medicine

, Volume 41, Issue 5, pp 936–938 | Cite as

Venous–arterial CO2 to arterial–venous O2 difference ratio as a resuscitation target in shock states?

  • Stephan M. Jakob
  • A. B. Johan Groeneveld
  • Jean-Louis Teboul
Editorial
In shock states, aerobically generated carbon dioxide (CO2) decreases together with oxygen (O2) consumption (VO2). When VO2 becomes dependent on O2 delivery (DO2), CO2 can be produced anaerobically mostly due to bicarbonate buffering of protons produced in excess secondary to the hydrolysis of adenosine triphosphate, so that VCO2 can exceed VO2. It has been estimated that anaerobic ATP compensates approximately 6 % of the accumulated O2 depth [1]. Therefore, a respiratory quotient (RQ) >1 may be interpreted as a sign of anaerobic metabolism, since it may indicate that more CO2 is produced than O2 is consumed (Fig. 1), although both are decreased. According to the Fick equation, VCO2 equals the product of cardiac output by the difference between mixed venous and arterial CO2 contents (Cmv–aCO2) whereas VO2 equals the product of cardiac output by the difference between arterial and mixed venous O2 contents (Ca–mvO2) (Fig. 1). By eliminating the cardiac output value, which is common to the numerator and denominator of the RQ (Fig. 1) and taking PCO2 as a surrogate of CO2 content, an increased ratio between mixed venous–arterial PCO2 difference and Cmv–aCO2 (Pmv–aCO2/Ca–mvO2) was shown to be a good indicator of anerobiosis assessed by hyperlactatemia [2]. However, the relationship between CO2 content and PCO2 is curvilinear rather than linear and is influenced by the degree of metabolic acidosis, the hematocrit and the O2 saturation. In this issue of ICM, Ospina-Tascon et al. [3] demonstrate that a Cmv–aCO2/Ca–mvO2 >1 predicts outcome early in septic shock, similar to increased arterial lactate concentration. Patients with both an increased Cmv–aCO2/Ca–mvO2 and lactate concentration 6 h after the study start had the highest mortality [3]. The authors propose that the Cmv–aCO2/Ca–mvO2 could become a resuscitation target [3]. The authors should be congratulated on having conducted this study and having performed the relatively complex calculations of the CO2 contents. However, before targeting to normalize the Cmv–aCO2/Ca–mvO2, several issues should be considered.
Fig. 1

In cases of shock states, tissue hypoxia results in decreased oxygen consumption (VO2) and aerobically generated carbon dioxide (CO2) production (VCO2). However, the global VCO2 decreased to a lesser extent than VO2 due to production of anaerobically generated CO2. Consequently, the VCO2 over VO2 ratio increases. Therefore, after elimination of cardiac output (present in both numerator and denominator), the difference between mixed venous and arterial CO2 contents (Cmv–aCO2) over the difference between arterial and mixed venous O2 contents (Ca–mvO2) should increase in such hypoxic conditions

  1. 1.

    Calculating VCO2 by multiplying Cmv–aCO2 with blood flow is only valid under steady-state conditions. If poorly perfused tissues regain flow, CO2 stores are washed out and calculated CO2 production is likely to be overestimated. This may have happened in patients in the study of Ospina-Tascon et al. [3] who were in the resuscitation phase of septic shock.

     
  2. 2.

    The amount of anaerobically produced CO2 is low compared to CO2 produced under aerobic conditions. It is therefore be questioned whether such small amounts can increase the VCO2 above VO2. For instance, when DO2 was stepwise reduced to 16 % of baseline values in an in situ, vascularly isolated, innervated dog limb, VO2 remained above VCO2 despite continually increasing RQ [4]. Admittedly, the hindlimb VCO2/VO2 relationship may not represent global RQ well.

     
  3. 3.

    The treatment may have influenced the findings of Ospina-Tascon et al. [3]. Patients with high lactate values at 6 h received more norepinephrine than those with normal values, despite a greater number of the former (around 50 %) being treated with vasopressin. Vasopressin may constrict the mesenteric vascular bed [5, 6]. If global blood flow is low, increasing mesenteric lactate production may not be cleared by the liver and arterial lactate may increase. Conversely, if the liver is able to metabolize the excess of lactate, systemic RQ may rise as a consequence of mesenteric dysoxia. Since the groups at study baseline (T0) and after 6 h (T6) do not represent the same population, it would be interesting to know the treatment in patients who increased versus decreased their Cmv–a CO2/Ca–mv O2 and lactate values between T0 and T6.

     
  4. 4.

    Computation of CO2 content seems to be cumbersome and subject to errors due to the number of variables included in the formula. This raises the question of its practical use in routine. More than a decade ago, Mekontso-Dessap et al. [2] proposed to calculate the Pmv–aCO2/Ca–mvO2 ratio to detect the presence of global anaerobiosis and showed that a value of Pmv–aCO2/Ca–mvO2 >1.4 can reliably predict the presence of hyperlactatemia in the general population of critically ill patients. In spite of this interesting finding, the use of this ratio did not become popular for managing critically ill patients, maybe because measurements of blood lactate concentration are easier to obtain. In addition, determination of the Pmv–aCO2/Ca–mvO2 ratio as well as the Cmv–aCO2/Ca–mvO2 ratio require combined samplings of arterial blood and mixed venous blood and thus require pulmonary artery catheterization, which is less and less performed in the intensive care unit. Central venous blood variables are becoming more popular than mixed venous blood variables. Central venous blood O2 saturation and the difference between central venous PCO2 and arterial PCO2 (Pcv–aCO2) are recommended to be used to assess the adequacy of cardiac output to the global metabolic conditions, although the quality of evidence is only moderate [7]. During sepsis, where central venous O2 content (CcvO2) and ScvO2 can be in the normal range despite global tissue hypoxia owing to low O2 extraction, it has recently been shown that hyperlactatemia and increased Pcv–aCO2/Ca–cvO2 ratio can predict the presence of VO2/DO2 dependence, whereas ScvO2 cannot [8]. This may suggest that the Pcv–aCO2/Ca–cvO2 ratio could be used as a surrogate for the Pmv–aCO2/Ca–mvO2 ratio to assess global tissue hypoxia. It must be further shown that taking central venous CO2 content instead of pressure, which would be more physiological, can be easily done at the bedside by using simple software able to avoid cumbersome calculations of CO2 content. For a routine use of these surrogates of RQ, it must also be shown that they respond to changes in global tissue oxygenation faster than blood lactate concentration. Finally, one must keep in mind that all these parameters allow the assessing of global but not regional or local tissue oxygenation, knowing that dissociation between systemic and local blood flows may exist in patients with septic shock [9].

     

In conclusion, the paper by Ospina-Tascon et al. [3] adds interesting information to metabolic consequences of septic shock in the phase when treatment is administered with the aim to improve DO2 and VO2. Whether a Cmv–aCO2/Ca–mvO2 ratio above 1 indicates anaerobic metabolism in unstable patients in septic shock and, if yes, why it can be associated with and without arterial hyperlactatemia, should be evaluated in more detail.

Notes

Conflicts of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

References

  1. 1.
    Gutierrez G (2002) A mathematical model of tissue–blood carbon dioxide exchange during hypoxia. Am J Respir Crit Care Med 169:525–533CrossRefGoogle Scholar
  2. 2.
    Mekonstso-Dessap A, Mekontso-Dessap A, Castelain V, Anguel N, Bahloul M, Schauvliege F, Richard C, Teboul JL (2002) Combination of venoarterial PCO2 difference with arteriovenous O2 content difference to detect anaerobic metabolism in patients. Intensive Care Med 28:272–277CrossRefGoogle Scholar
  3. 3.
    Ospina-Tascón GA, Umaña M, Bermúdez W, Bautista-Rincón DF, Hernandez G, Bruhn A, Granados M, Salazar B, Arango-Dávila C, De Backer D (2015) Combination of arterial lactate levels and venous-arterial CO2 to arterial–venous O2 content difference ratio as markers of resuscitation in patients with septic shock. Intensive Care Med. doi:10.1007/s00134-015-3720-6 PubMedGoogle Scholar
  4. 4.
    Vallet B, Teboul JL, Cain S, Curtis S (2000) Venoarterial CO2 difference during regional ischemic or hypoxic hypoxia. J Appl Physiol 89:1317–1321PubMedGoogle Scholar
  5. 5.
    Westphal M, Freise H, Kehrel BE, Bone HG, Van Aken H, Sielenkämper AW (2004) Arginine vasopressin compromises gut mucosal microcirculation in septic rats. Crit Care Med 32:194–200CrossRefPubMedGoogle Scholar
  6. 6.
    Hiltebrand LB, Krejci V, Jakob SM, Takala J, Sigurdsson GH (2007) Effects of vasopressin on microcirculatory blood flow in the gastrointestinal tract in anesthetized pigs in septic shock. Anesthesiology 106:1156–1167CrossRefPubMedGoogle Scholar
  7. 7.
    Cecconi M, Cecconi M, De Backer D, Antonelli M, Beale R, Bakker J, Hofer C, Jaeschke R, Mebazaa A, Pinsky MR, Teboul JL, Vincent JL, Rhodes A (2014) Consensus on circulatory shock and hemodynamic monitoring. Task force of the European Society of Intensive Care Medicine. Intensive Care Med 40:1795–1815CrossRefPubMedCentralPubMedGoogle Scholar
  8. 8.
    Monnet X, Monnet X, Julien F, Ait-Hamou N, Lequoy M, Gosset C, Jozwiak M, Persichini R, Anguel N, Richard C, Teboul JL (2013) 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 41:1412–1420CrossRefPubMedGoogle Scholar
  9. 9.
    De Backer D, Donadello K, Sakr Y, Ospina-Tascon G, Salgado D, Scolletta S, Vincent JL (2013) Microcirculatory alterations in patients with severe sepsis: impact of time of assessment and relationship with outcome. Crit Care Med 41:791–799CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg and ESICM 2015

Authors and Affiliations

  • Stephan M. Jakob
    • 1
  • A. B. Johan Groeneveld
    • 2
  • Jean-Louis Teboul
    • 3
  1. 1.Department of Intensive Care Medicine, University Hospital (Inselspital)University of BernBernSwitzerland
  2. 2.Department of Intensive Care of Erasmus Medical CenterRotterdamThe Netherlands
  3. 3.Medical Intensive Care Unit, University Hospital of BicetreParis-Sud UniversityLe Kremlin-BicêtreFrance

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