Standardized PaO2/FiO2 ratio in COVID-19: added Added value or risky assumption. Author's reply1

  • Irene Prediletto
    Affiliations
    Alma Mater Studiorum University of Bologna, Department of Clinical, Integrated and Experimental Medicine (DIMES), Bologna, Italy

    IRCCS Azienda Ospedaliero Universitaria di Bologna, University Hospital Sant'Orsola-Malpighi - Respiratory and Critical Care Unit, Bologna, Italy
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  • Stefano Nava
    Correspondence
    Corresponding Author at: IRCCS Azienda Ospedaliero Universitaria di Bologna, Sant'Orsola-Malpighi University Hospital. Alma Mater Studiorum University of Bologna, Department of Clinical, Integrated and Experimental Medicine, Bologna, Italy. Address: Via Massarenti 9, 40138 Bologna, Italy.
    Affiliations
    Alma Mater Studiorum University of Bologna, Department of Clinical, Integrated and Experimental Medicine (DIMES), Bologna, Italy

    IRCCS Azienda Ospedaliero Universitaria di Bologna, University Hospital Sant'Orsola-Malpighi - Respiratory and Critical Care Unit, Bologna, Italy
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  • Paolo Palange
    Affiliations
    Department of Public Health and Infectious Disease, Sapienza University of Rome – Italy. Pulmonology, Respiratory and Critical Care Unit, Policlinico Umberto I Hospital, Rome, Italy.
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Published:October 22, 2021DOI:https://doi.org/10.1016/j.ejim.2021.10.015

      Keywords

      Dear Editor,
      We have read with great interest the comment of Luciano Gattinoni and coworkers who carefully reviewed our paper “Standardized PaO2/FiO2 ratio in COVID-19: Added value or risky assumptions” recently published in the European Journal of Internal Medicine [
      • Gattinoni L
      • Busana M
      • Camporota L.
      Standardised PaO2/FiO2 ratio in COVID-19: Added value or risky assumptions?.
      ,
      • Prediletto I
      • D'Antoni L
      • Carbonara P
      • Daniele F
      • Dongilli R
      • Flore R
      • Pacilli AMG
      • Pisani L
      • Tomsa C
      • Vega ML
      • Ranieri VM
      • Nava S
      • Palange P
      Standardizing PaO2 for PaCO2 in P/F ratio predicts in-hospital mortality in acute respiratory failure due to COVID-19: A pilot prospective study.
      ]. We agree with most of their comments on the potential limitations of the standardized PaO2/FiO2 approach. There are, however, a few points that we would like to further discuss and clarify.
      First, we do not entirely agree on the need to systematically correct the alveolar partial pressure of oxygen (PAO2) using the respiratory quotient (RQ). This is usually measured at the mouth (respiratory exchange ratio, R, V'CO2/V'O2) and therefore it is extremely difficult, if not impossible, to measure during helmet CPAP or high oxygen flow supplementation (HOF) and, because of the contribution/changes in lung gas stores, R does not reflect changes in RQ. Thus, the correction for R is impractical not reflecting the metabolic state (RQ), and as pointed out in a previous work by Gattinoni and his group “the impact of the PaCO2/R ratio on alveolar PO2 (PAO2) is less dramatic unless extracorporeal CO2 removal is in use” [
      • Gattinoni L
      • Vassalli F
      • Romitti F.
      Benefits and risks of the P/F approach.
      ].
      Second, as pointed out by Gattinoni and coworkers, the advantage of standardized PaO2/FiO2 over PaO2/FiO2 is that standardized PaO2/FiO2, (i.e. PaO2 corrected for the PaCO2), takes in account the contribution of the respiratory effort sustained by the patient which has been demonstrated to be a predictor of poor outcome in acute respiratory failure. We would like to add that it also reflects the need to increase PAO2 to maintain an adequate arterial oxygenation (i.e. PaO2) at the cost of a left shift in arterial Hb-O2 dissociation curve due to respiratory alkalosis. This is a well-known compensation mechanism that occurs for example at high altitude where the need to preserve arterial oxygenation (i.e., increased Hb-O2 affinity at the lung due to increased pH) prevails on the diffusion of oxygen, from peripheral arterial capillaries at tissue levels. Obviously, other factors, such as body temperature, Hb levels and cardiac output should be taken in account to a have a clear picture of the O2 transport efficiency.
      Third, we do agree that standardized PaO2/FiO2 ratio should be used with caution when tracking patients over time, because of the influence of dead space of shunt fractions that may change along the illness. This, in fact, was not the aim of our study in which we tested the superiority of the standardized PaO2/FiO2 ratio versus the PaO2/FiO2 ratio in predicting the outcome failure and mortality measured at the time of admission to the Pulmonology unit. It should be pointed out, however, that also the use of the “classical” PaO2/FiO2 ratio has limitations not only as a single observation but also when it is used for tracking patients over time. In particular, the PaO2/FiO2 ratio is significantly influenced by the fraction of inspired oxygen (FiO2). Of notice when the patient is breathing FiO2≤0.6 the possible contribution of V’/Q’ mismatch and diffusion limitation from shunt cannot be ruled out. By contrast when breathing FiO2>0.6 the contribution of shunt mechanisms becomes clearer [
      • Aboab J
      • Louis B
      • Jonson B
      • Brochard L.
      Relation between PaO2/FIO2 ratio and FIO2: a mathematical description.
      ].
      In conclusion, although we do agree with Gattinoni and coworkers in their analysis on the need to consider all the variables that may influence gas exchange impairment in severe ARF, we believe that the standard PaO2/FiO2 ratio should be utilized in the prognostic evaluation of patients with COVID-19 acute respiratory failure.

      Declaration of Competing Interest

      The authors declare they have no conflict of interest.

      Acknowledgements

      We thank all the other authors of the work “Standardizing PaO2 for PaCO2 in P/F ratio predicts in-hospital mortality in acute respiratory failure due to Covid-19: A pilot prospective study”, Letizia D'Antoni, Paolo Carbonara, Federico Daniele, Roberto Dongilli, Roberto Flore, Angela Maria Grazia Pacilli, Lara Pisani, Corina Tomsa, María Laura Vega, and Vito Marco Ranieri for their contribution and their expertise throughout the study.

      References

        • Gattinoni L
        • Busana M
        • Camporota L.
        Standardised PaO2/FiO2 ratio in COVID-19: Added value or risky assumptions?.
        Eur J Intern Med. 2021; 92: 31-33https://doi.org/10.1016/j.ejim.2021.09.004
        • Prediletto I
        • D'Antoni L
        • Carbonara P
        • Daniele F
        • Dongilli R
        • Flore R
        • Pacilli AMG
        • Pisani L
        • Tomsa C
        • Vega ML
        • Ranieri VM
        • Nava S
        • Palange P
        Standardizing PaO2 for PaCO2 in P/F ratio predicts in-hospital mortality in acute respiratory failure due to COVID-19: A pilot prospective study.
        Eur J Intern Med. 2021; 92: 48-54https://doi.org/10.1016/j.ejim.2021.06.002
        • Gattinoni L
        • Vassalli F
        • Romitti F.
        Benefits and risks of the P/F approach.
        Intensive Care Med. 2018; 44: 2245-2247https://doi.org/10.1007/s00134-018-5413-4
        • Aboab J
        • Louis B
        • Jonson B
        • Brochard L.
        Relation between PaO2/FIO2 ratio and FIO2: a mathematical description.
        Applied Physiology in Intensive Care Medicine. Springer, Berlin, Heidelberg2006https://doi.org/10.1007/3-540-37363-2_11