Scientific Letter
Correlation and concordance of SaO2/FiO2 and paO2/FiO2 ratios in patients with COVID-19 pneumonia who received non-invasive ventilation in two intensive care units⋆
Correlación y concordancia de los cocientes SaO2/FiO2 y paO2/FiO2 en pacientes con neumonía por COVID-19 que recibieron soporte ventilatorio no invasivo en dos unidades de cuidados intensivos
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"b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Correlación y concordancia de los cocientes SaO<span class="elsevierStyleInf">2</span>/FiO<span class="elsevierStyleInf">2</span> y paO<span class="elsevierStyleInf">2</span>/FiO<span class="elsevierStyleInf">2</span> en pacientes con neumonía por COVID-19 que recibieron soporte ventilatorio no invasivo en dos unidades de cuidados intensivos" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1003 "Ancho" => 1252 "Tamanyo" => 59893 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0205" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Analysis of the degree of concordance between paO<span class="elsevierStyleInf">2</span>/FiO<span class="elsevierStyleInf">2</span> and SaO<span class="elsevierStyleInf">2</span>/FiO<span class="elsevierStyleInf">2</span>. The degree of concordance is expressed (30% = 0.3 on Y-axis) for the mean difference of 0.11 (X-axis) (solid line), and for 95% concordance (0.95 on Y-axis) for the mean difference of 0.30 (X-axis) (dashed line).</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">The ratio of partial pressure of oxygen to fractional inspired oxygen (PaO<span class="elsevierStyleInf">2</span>/FiO<span class="elsevierStyleInf">2</span>) is the standard in acute respiratory distress syndrome (ARDS).<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> The invasiveness of arterial puncture for arterial blood gas testing along with the lack of continuous information have encouraged the use of less invasive tools such as pulse oximetry, which determines transcutaneous oxygen saturation (SaO<span class="elsevierStyleInf">2</span>). Other advantages of pulse oximetry include its easy interpretation, high sensitivity in hypoxemia situations, and availability in any setting.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,3</span></a> However, it presents several disadvantages such as <span class="elsevierStyleItalic">a)</span> the possibility of error in measuring severe hypoxemia and in the classification and severity level of ARDS; <span class="elsevierStyleItalic">b)</span> the inaccuracy in patients with shock or SaO<span class="elsevierStyleInf">2</span> > 97%.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,3</span></a> Although the SaO<span class="elsevierStyleInf">2</span>/FiO<span class="elsevierStyleInf">2</span> ratio has been proposed as a tool for the diagnosis and severity of ARDS,<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,3</span></a> guidelines on the management of ARDS question the validity of this ratio.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> In patients with COVID-19 related pneumonia, several studies have shown a good correlation between SaO<span class="elsevierStyleInf">2</span>/FiO<span class="elsevierStyleInf">2</span> and PaO<span class="elsevierStyleInf">2</span>/FiO<span class="elsevierStyleInf">2</span>.<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5,6</span></a> Based on this, SaO<span class="elsevierStyleInf">2</span>/FiO<span class="elsevierStyleInf">2</span> could estimate the severity of ARDS in patients with COVID-19 related pneumonia.</p><p id="par0010" class="elsevierStylePara elsevierViewall">However, for 2 variables to be used interchangeably, correlation and agreement analysis (along with the degree of agreement) are necessary.<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7–9</span></a> The objective of this study was to analyze the homogeneity between SaO<span class="elsevierStyleInf">2</span>/FiO<span class="elsevierStyleInf">2</span> and PaO<span class="elsevierStyleInf">2</span>/FiO<span class="elsevierStyleInf">2</span> ratios in patients with COVID-19 related pneumonia.</p><p id="par0015" class="elsevierStylePara elsevierViewall">This was a retrospective and observational study conducted in 2 intensive care units from March 2020 through August 2021. The study was approved by the Drug Research Ethics Committee (code 66/20), and informed consent was not deemed necessary due to the study’s characteristics. Patients ≥18 years old, admitted due to COVID-19 related pneumonia, and requiring non-invasive ventilation (NIV) were included. At the beginning of NIV, gasometric analysis was performed using an ABL 90 FlexPLUS analyzer (RadiometerMedicalApS, Brønshøj, Copenhagen, Denmark). SaO<span class="elsevierStyleInf">2</span> was recorded after verifying the correct pulse oximetry signal on the Philips IntelliVue MX700 monitor. The recorded FiO<span class="elsevierStyleInf">2</span> came from the NIV devices used, the tables established by the manufacturer (in Venturi masks), or calculation [21 + Flow (L/min) × 3] in reservoir masks.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> First, Spearman’s correlation was analyzed; subsequently, due to the non-normality of the variables, logarithmic transformation was performed to turn them into parametric variables. Afterwards, the mean difference (or mean bias) and its standard deviation (SD) were determined using the Student’s t-test. Additionally, agreement analysis (Bland–Altman test)<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7,9</span></a> and its degree (with Kaplan–Meier curve)<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> were analyzed for both ratios.</p><p id="par0020" class="elsevierStylePara elsevierViewall">Out of 428 patients—mostly men—aged 59 with hypertension (Table 1 of the Supplementary data), who had received conventional oxygen therapy, 398 patients with both oxygenation variables at the beginning of NIV were selected: PaO<span class="elsevierStyleInf">2</span>/FiO<span class="elsevierStyleInf">2</span> = 110 (84–141) and SaO<span class="elsevierStyleInf">2</span>/FiO<span class="elsevierStyleInf">2</span> = 147 (120–176), respectively. The correlation between both determinations showed an R = 0.744, as seen in the scatter plot (<a class="elsevierStyleCrossRef" href="#upi0010">Fig. S1</a>). The comparison using Student’s t-test of the logarithms of both variables was significant [mean difference, −0.11 ± 0.13 standard deviation (SD), (95%CI, −0.13 to −0.10), <span class="elsevierStyleItalic">P</span> = 0.0001]. The agreement analysis and the degree of agreement are shown in Figs. <a class="elsevierStyleCrossRef" href="#fig0005">1</a> and <a class="elsevierStyleCrossRef" href="#fig0010">2</a>. Like the studies published,<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5,6</span></a> a high positive correlation between both variables was found. However, the results shown in the agreement analysis (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>) question the homogeneity of both variables: first, several determinations were left outside the standard deviation margins when they should have been inside those margins; second, the mean difference of −0.11 for both determinations did not reach the value of 0 (indicating that both variables are equivalent); and third, there was a wide range between the limits of the standard deviations (0.25 to −0.47). Similarly, the degree of agreement was low (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>), with only approximately 30% (0.30 in <a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>) of the samples showed good agreement for the mean difference of 0.11 obtained previously (i.e., to achieve a 95% agreement between both determinations, there should be a difference of 0.30, which could lead to a significant discrepancy between the values of PaO<span class="elsevierStyleInf">2</span>/FiO<span class="elsevierStyleInf">2</span> and SaO<span class="elsevierStyleInf">2</span>/FiO<span class="elsevierStyleInf">2</span>).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">In conclusion, a good correlation between both parameters was seen, but the agreement and degree of agreement between both parameters were low, indicating the absence of similarity between both values. Therefore, the SaO<span class="elsevierStyleInf">2</span>/FiO<span class="elsevierStyleInf">2</span> ratio would give us an approximate idea of the patient’s oxygenation level but still far from the true degree of hypoxemia, which could raise doubts for the decision-making process regarding intubation. In light of the results obtained, this study supports the need for further analysis beyond correlation, such as agreement and the degree of agreement, to determine the degree of similarity between both variables, which as observed, were not homogeneous.</p><p id="par0030" class="elsevierStylePara elsevierViewall">The high demand for resources during the pandemic has led to the use of SaO<span class="elsevierStyleInf">2</span> for the management of ARDS. According to a proposed algorithm, a patient with SaO<span class="elsevierStyleInf">2</span> ≤ 97% (and a SaO<span class="elsevierStyleInf">2</span>/FiO<span class="elsevierStyleInf">2</span> ≤ 315 despite oxygen therapy) would be labeled as having ARDS, and therefore requiring invasive mechanical ventilation.<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3,10</span></a> A multicenter, retrospective study (n = 1028 patients with COVID-19) found a good correlation between PaO<span class="elsevierStyleInf">2</span>/FiO<span class="elsevierStyleInf">2</span> and SaO<span class="elsevierStyleInf">2</span>/FiO<span class="elsevierStyleInf">2</span> as determinants of the degree of ARDS: a PaO<span class="elsevierStyleInf">2</span>/FiO<span class="elsevierStyleInf">2</span> ≤ 200 and ≤100 would correspond to a SaO<span class="elsevierStyleInf">2</span>/FiO<span class="elsevierStyleInf">2</span> ≤ 336 and ≤178,<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> respectively. The question at stake is not the diagnosis of ARDS but whether with SaO<span class="elsevierStyleInf">2</span>/FiO<span class="elsevierStyleInf">2</span> values ≤178 (severe hypoxemia), we would consider intubating a patient, or request arterial blood gas testing to corroborate such hypoxemia.</p><p id="par0035" class="elsevierStylePara elsevierViewall">In conclusion, we could question the agreement of PaO<span class="elsevierStyleInf">2</span>/FiO<span class="elsevierStyleInf">2</span> and SaO<span class="elsevierStyleInf">2</span>/FiO<span class="elsevierStyleInf">2</span> ratios in our series of patients with COVID-19 related pneumonia, placing SaO<span class="elsevierStyleInf">2</span>/FiO<span class="elsevierStyleInf">2</span> as a parameter for respiratory evolutionary monitoring but requiring a PaO<span class="elsevierStyleInf">2</span>/FiO<span class="elsevierStyleInf">2</span> ratio to accurately determine the patient’s respiratory status.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Funding</span><p id="par0040" class="elsevierStylePara elsevierViewall">None declared.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Conflicts of interest</span><p id="par0045" class="elsevierStylePara elsevierViewall">None declared.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Funding" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Conflicts of interest" ] 2 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "apendice" => array:1 [ 0 => array:1 [ "seccion" => array:1 [ 0 => array:4 [ "apendice" => "<p id="par0055" class="elsevierStylePara elsevierViewall">The following are Supplementary data to this article:<elsevierMultimedia ident="upi0005"></elsevierMultimedia><elsevierMultimedia ident="upi0010"></elsevierMultimedia></p>" "etiqueta" => "Appendix A" "titulo" => "Supplementary data" "identificador" => "sec0020" ] ] ] ] "multimedia" => array:4 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1011 "Ancho" => 1258 "Tamanyo" => 96654 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0200" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Blant–Altman concordance analysis between paO<span class="elsevierStyleInf">2</span>/FiO<span class="elsevierStyleInf">2</span> and SaO<span class="elsevierStyleInf">2</span>/FiO<span class="elsevierStyleInf">2</span>. The figure represents the logarithm of the mean difference (Y-axis) between paO<span class="elsevierStyleInf">2</span>/FiO<span class="elsevierStyleInf">2</span> and SaO<span class="elsevierStyleInf">2</span>/FiO<span class="elsevierStyleInf">2</span> vs the average logarithm (X-axis) for these variables. Additionally, the difference has been established using the Student’s t-test with its 2 standard deviation margins (2SD) [−0.11 ± 2 (0.13)]. SD, standard deviation.</p>" ] ] 1 => array:8 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1003 "Ancho" => 1252 "Tamanyo" => 59893 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0205" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Analysis of the degree of concordance between paO<span class="elsevierStyleInf">2</span>/FiO<span class="elsevierStyleInf">2</span> and SaO<span class="elsevierStyleInf">2</span>/FiO<span class="elsevierStyleInf">2</span>. The degree of concordance is expressed (30% = 0.3 on Y-axis) for the mean difference of 0.11 (X-axis) (solid line), and for 95% concordance (0.95 on Y-axis) for the mean difference of 0.30 (X-axis) (dashed line).</p>" ] ] 2 => array:5 [ "identificador" => "upi0005" "tipo" => "MULTIMEDIAECOMPONENTE" "mostrarFloat" => false "mostrarDisplay" => true "Ecomponente" => array:2 [ "fichero" => "mmc1.doc" "ficheroTamanyo" => 44032 ] ] 3 => array:7 [ "identificador" => "upi0010" "etiqueta" => "Fig. S1" "tipo" => "MULTIMEDIAECOMPONENTE" "mostrarFloat" => false "mostrarDisplay" => true "Ecomponente" => array:2 [ "fichero" => "mmc2.zip" "ficheroTamanyo" => 164321 ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Spearman correlation (R) between SaO<span class="elsevierStyleInf">2</span>/FiO<span class="elsevierStyleInf">2</span> and paO<span class="elsevierStyleInf">2</span>/FiO<span class="elsevierStyleInf">2</span> ratios.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:10 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Acute respiratory distress syndrome: the Berlin definition" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "V.M. 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