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PaO2/FIO2 ratio: the mismeasure of oxygenation in COVID-19

Martin J. Tobin, Amal Jubran, Franco Laghi
European Respiratory Journal 2021 57: 2100274; DOI: 10.1183/13993003.00274-2021
Martin J. Tobin
Division of Pulmonary and Critical Care Medicine, Hines Veterans Affairs Hospital and Loyola University of Chicago Stritch School of Medicine, Hines, IL, USA
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Amal Jubran
Division of Pulmonary and Critical Care Medicine, Hines Veterans Affairs Hospital and Loyola University of Chicago Stritch School of Medicine, Hines, IL, USA
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Franco Laghi
Division of Pulmonary and Critical Care Medicine, Hines Veterans Affairs Hospital and Loyola University of Chicago Stritch School of Medicine, Hines, IL, USA
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Abstract

PaO2 is the most precise measurement of patient oxygenation in COVID-19, but its accuracy is corrupted when communicated as PaO2/FIO2 ratio https://bit.ly/3tNipTJ

Reply to A. Tulaimat:

We read with interest A. Tulaimat's letter concerning our recent editorial in the European Respiratory Journal [1]. A. Tulaimat makes several insightful comments on problems with criteria used for entering patients into randomised controlled trials of noninvasive ventilation. Among these, he notes that arterial-to-inspired oxygen (PaO2/FIO2) ratio varied between 170 and 400 among enrollees [2].

Low arterial oxygenation is the fundamental problem in a severely ill patient with coronavirus disease 2019 (COVID-19). PaO2 is directly related to the likelihood of dying and it also influences choice of therapy. Many hypoxaemic patients have been exposed unnecessarily to life-threatening therapy (intubation) when noninvasive modalities were likely to have been successful [3].

PaO2 is the most precise and least ambiguous measurement of patient oxygenation. In many case series of COVID-19 patients, oxygenation is reported solely in terms of PaO2/FIO2 and PaO2 is not mentioned. No organ in the body detects PaO2/FIO2, whereas several respond to miniscule changes in PaO2 (carotid bodies). PaO2/FIO2 plays no role in any biological process, whereas arterial oxygen saturation directly determines oxygen delivery to the brain and myocardium.

Rules of thumb (heuristics) are commonly employed to estimate FIO2 in patients receiving supplemental oxygen: 1 L equals 24%; 2 L equals 27% or 28%; 3 L equals 30% or 32% (depending on which formula is used). The resulting numbers are inherently untruthful. In truth, 2 L·min−1 by nasal cannula generates FIO2 anywhere between 24% and 35% [4]. More often than not, reporting PaO2/FIO2 involves taking a precise and physiologically meaningful entity (PaO2) and rendering it untruthful by combining it with a notoriously unreliable estimate of FIO2. To paraphrase Protagoras of Abdera, PaO2/FIO2 ratio is the mismeasure of all things oxygen.

Contemplating oxygenation in terms of PaO2/FIO2 fosters a focus on acute respiratory distress syndrome (ARDS), as the ratio has been included in all definitions of ARDS since first incorporated into the Murray score [5]. Making a diagnosis of ARDS is important for researchers to ensure homogeneity of patients being recruited into studies. It is not important for bedside doctors because not even one therapeutic action is decided by the diagnosis [6].

As a method for quantifying abnormal gas exchange, PaO2/FIO2 is fundamentally flawed. Modelling by West [7] and Dantzker [8] demonstrates that PaO2 has a curvilinear relationship with FIO2 that varies with degree of ventilation–perfusion inequality and shunt. In patients with ARDS and a fixed shunt, alterations in FIO2 caused PaO2/FIO2 to fluctuate unpredictably by greater than 100 mmHg [9]. In patients who fulfil all ARDS criteria, administration of 100% oxygen for 30 min caused PaO2/FIO2 to increase such that 58.5% were no longer categorised as ARDS [10]. (The other pillar of ARDS diagnosis, radiological infiltrates, is equally flawed because of poor interobserver agreement (kappa ≤0.55) [11].)

Murray et al. [5] opted for PaO2/FIO2 as an exemplar of abnormal gas exchange because it “is more easily calculated from information routinely available in patients’ charts”. Seldom did an intention of not wanting to burden others backfire so spectacularly. Thousands of authors endeavouring to report patient oxygenation have debased a pristine measurement by encasing it in a specious carapace. The PaO2/FIO2 ratio exemplifies one of the most glaring examples of Gresham's law in medicine.

A. Tulaimat notes that patients with PaO2/FIO2 400 (equivalent to PaO2 160 mmHg on FIO2 40%) were exposed to noninvasive ventilation for the purpose of conducting a randomised controlled trial [2]. This is disturbing. These patients should have had pulse oximetry checked while breathing room air, not viewed as candidates for a treatment that carries substantial risks. For PaO2/FIO2 300 (PaO2 120 mmHg on FIO2 40%), patients should be managed with noninvasive modalities and intubation not contemplated.

Consideration of FIO2 has never been part of the definition of hypoxaemia [12]. Some physicians quantify severity of hypoxaemia in litres of oxygen supplied to a patient. Judging severity of hypoxaemia in terms of “oxygen requirements” is to engage in circular reasoning, with hazardous consequences for patients [13].

It is probably too much to expect that PaO2/FIO2 be eliminated from the definition of ARDS, but authors could at least include PaO2 and not solely present PaO2/FIO2 in their articles. The reporting of PaO2/FIO2 values should come with a health warning.

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Footnotes

  • Conflict of interest: A. Jubran reports a grant from National Institute of Nursing Research (R01-NR016055) during the conduct of the study.

  • Conflict of interest: F. Laghi reports a grant from Veterans Administration Research (1 I01 RX002803-01A1) during the conduct of the study.

  • Conflict of interest: M.J. Tobin receives royalties for two books on critical care published by McGraw-Hill, Inc., New York.

  • Support statement: This work was supported by the Veterans Administration Research (grant 1 I01 RX002803-01A1) and the National Institute of Nursing Research (grant R01-NR016055). Funding information for this article has been deposited with the Crossref Funder Registry.

  • Received January 28, 2021.
  • Accepted February 1, 2021.
  • Copyright ©The authors 2021.
http://creativecommons.org/licenses/by-nc/4.0/

This version is distributed under the terms of the Creative Commons Attribution Non-Commercial Licence 4.0. For commercial reproduction rights and permissions contact permissions{at}ersnet.org

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PaO2/FIO2 ratio: the mismeasure of oxygenation in COVID-19
Martin J. Tobin, Amal Jubran, Franco Laghi
European Respiratory Journal Mar 2021, 57 (3) 2100274; DOI: 10.1183/13993003.00274-2021

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PaO2/FIO2 ratio: the mismeasure of oxygenation in COVID-19
Martin J. Tobin, Amal Jubran, Franco Laghi
European Respiratory Journal Mar 2021, 57 (3) 2100274; DOI: 10.1183/13993003.00274-2021
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