Respiratory rate-oxygenation index on the 3<sup>rd</sup> day is the best predictor of treatment failure in COVID-19 patients

Federico Raimondi; Stefano Centanni; Fabrizio Luppi; Stefano Aliberti; Francesco Blasi; Paola Rogliani; Claudio Micheletto; Marco Contoli; Alessandro Sanduzzi Zamparelli; Marialuisa Bocchino; Paolo Busatto; Luca Novelli; Simone Pappacena; Luca Malandrino; Giorgio Lorini; Greta Carioli; Fabiano Di Marco

doi:10.4081/monaldi.2024.3033

Authors

Federico Raimondi

Respiratory Medicine Unit, ASST Papa Giovanni XXIII, Bergamo, Italy.

Stefano Centanni

Respiratory Medicine Unit, ASST Santi Paolo e Carlo, Milan; University of Milan, Italy.

Fabrizio Luppi

https://orcid.org/0000-0001-5775-5947

Department of Medicine and Surgery, University of Milan Bicocca, Milan; Respiratory Disease Unit, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy.

Stefano Aliberti

Department of Biomedical Sciences, Humanitas University, Pieve Emanuele; Respiratory Unit, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy.

Francesco Blasi

https://orcid.org/0000-0002-2285-9970

University of Milan; Respiratory Unit and Adult Cystic Fibrosis Center, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy.

Paola Rogliani

https://orcid.org/0000-0001-7801-5040

"Tor Vergata” University, Rome; Unit of Respiratory Medicine, “Tor Vergata” Hospital Foundation, Rome, Italy.

Claudio Micheletto

https://orcid.org/0000-0002-1138-3882

Respiratory Medicine Unit, University Hospital of Verona, Italy.

Marco Contoli

Department of Translational Medicine, University of Ferrara, Italy.

Alessandro Sanduzzi Zamparelli

https://orcid.org/0000-0002-0977-2643

Department of Clinical Medicine and Surgery, Section of Respiratory Diseases, University Federico II, Azienda Ospedaliera dei Colli-Monaldi Hospital, Naples, Italy.

Marialuisa Bocchino

https://orcid.org/0000-0001-5477-072X

Department of Clinical Medicine and Surgery, Section of Respiratory Diseases, University Federico II, Azienda Ospedaliera dei Colli-Monaldi Hospital, Naples, Italy.

Paolo Busatto

https://orcid.org/0000-0002-3546-9947

Pneumology, Ospedale di Lucca, Azienda USL Toscana Nord Ovest, Lucca, Italy.

Luca Novelli

lnovelli@asst-pg23.it

https://orcid.org/0000-0002-2705-248X

Respiratory Medicine Unit, ASST Papa Giovanni XXIII, Bergamo, Italy.

Simone Pappacena

https://orcid.org/0000-0003-2495-7512

Respiratory Medicine Unit, ASST Papa Giovanni XXIII, Bergamo; University of Milan, Italy.

Luca Malandrino

Respiratory Medicine Unit, ASST Papa Giovanni XXIII, Bergamo; University of Milan, Italy.

Giorgio Lorini

https://orcid.org/0000-0002-5735-7647

Respiratory Medicine Unit, ASST Papa Giovanni XXIII, Bergamo, Italy.

Greta Carioli

https://orcid.org/0000-0002-7012-707X

FROM Research Foundation, Papa Giovanni XXIII Hospital, Bergamo, Italy.

Fabiano Di Marco

Respiratory Medicine Unit, ASST Papa Giovanni XXIII, Bergamo; University of Milan, Italy.

Predictors of outcomes are essential to identifying severe COVID-19 cases and optimizing treatment and care settings. The respiratory rate-oxygenation (ROX) index, originally introduced for predicting the failure of non-invasive support in acute hypoxemic respiratory failure (AHRF), has not been extensively studied over time during hospitalization. This multicenter prospective observational study analyzed COVID-19-related AHRF patients admitted to eight Italian hospitals during the second pandemic wave. The study assessed the ROX index using receiver operator characteristic curves and areas under the curve with 95% confidence intervals to predict treatment failure, defined as endotracheal intubation (ETI) or death. A total of 227 patients (69.2% males) were enrolled, with a median arterial partial pressure of oxygen (PaO₂)/fraction of inspired oxygen (FIO₂) ratio at admission of 248 (interquartile range: 170-295). Nearly one-third (29.5%) required ETI or died during hospitalization. Those who experienced treatment failure were older (median age 70 vs. 61 years, p<0.001), more likely to be current or former smokers (8.5% vs. 6.4% and 42.4% vs. 25.5%, p=0.039), had a higher prevalence of cardiovascular diseases (74.6% vs. 46.3%, p<0.001), and had a lower PaO₂/FIO₂ ratio at presentation (median 229 vs. 254, p=0.014). Gender, body mass index, and other comorbidities showed no significant differences. In patients who failed treatment, the ROX index was higher at presentation and worsened sharply by days 3 and 4. Conversely, in patients who survived without requiring ETI, the ROX index remained stable and reduced after 5-6 days. The ROX index’s predictive ability improved notably by day 3 of hospitalization, with the best cut-off value identified at 8.53 (sensitivity 75%, specificity 68%). Kaplan-Meier curves indicated that a ROX index of 8.53 or lower on days 1, 2, or 3 was associated with a higher risk of treatment failure. Thus, a single ROX index assessment on day 3 is more informative than its variability over time, with values of 8.53 or lower predicting non-invasive respiratory support failure in hospitalized COVID-19 patients.

Dimensions

Altmetric

PlumX Metrics

Downloads

Citations

The RECOVERY Collaborative Group. Dexamethasone in hospitalized patients with Covid-19. N Engl J Med 2021;384:693-704. DOI: https://doi.org/10.1056/NEJMoa2021436

Havers FP, Pham H, Taylor CA, et al. COVID-19-associated hospitalizations among vaccinated and unvaccinated adults 18 years or older in 13 US states, january 2021 to april 2022. JAMA Intern Med 2022;182:1071-81. DOI: https://doi.org/10.1001/jamainternmed.2022.4299

Weiss P, Murdoch DR. Clinical course and mortality risk of severe COVID-19. Lancet 2020;395:1014-5. DOI: https://doi.org/10.1016/S0140-6736(20)30633-4

Wu Z, McGoogan JM. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China. JAMA 2020;323:1239-42. DOI: https://doi.org/10.1001/jama.2020.2648

Valencia CF, Lucero OD, Castro OC, et al. Comparison of ROX and HACOR scales to predict high-flow nasal cannula failure in patients with SARS-CoV-2 pneumonia. Sci Rep 2021;11:22559. DOI: https://doi.org/10.1038/s41598-021-02078-5

Oczkowski S, Ergan B, Bos L, et al. ERS clinical practice guidelines: high-flow nasal cannula in acute respiratory failure. Eur Respir J 2022;59:2101574. DOI: https://doi.org/10.1183/13993003.01574-2021

Roca O, Messika J, Caralt B, et al. Predicting success of high-flow nasal cannula in pneumonia patients with hypoxemic respiratory failure: the utility of the ROX index. J Crit Care 2016;35:200-5. DOI: https://doi.org/10.1016/j.jcrc.2016.05.022

Myers LC, Mark D, Ley B, et al. Validation of respiratory rate-oxygenation index in patients with COVID-19–related respiratory failure. Crit Care Med 2022;50:e638-42. DOI: https://doi.org/10.1097/CCM.0000000000005474

Cosentini R, Groff P, Brambilla AM, et al. SIMEU position paper on non-invasive respiratory support in COVID-19 pneumonia. Intern Emerg Med 2022;17:1175-89. DOI: https://doi.org/10.1007/s11739-021-02906-6

Suliman L, Abdelgawad T, Farrag N, et al. Validity of ROX index in prediction of risk of intubation in patients with COVID-19 pneumonia. Adv Respir Med 2020;89:1-7. DOI: https://doi.org/10.5603/ARM.a2020.0176

Rochwerg B, Brochard L, Elliott MW, et al. Official ERS/ATS clinical practice guidelines: noninvasive ventilation for acute respiratory failure. Eur Respir J 2017;50:1602426. DOI: https://doi.org/10.1183/13993003.02426-2016

Hoogenboom WS, Pham A, Anand H, et al. Clinical characteristics of the first and second COVID-19 waves in the Bronx, New York: a retrospective cohort study. Lancet Reg Health Am 2021;3:100041. DOI: https://doi.org/10.1016/j.lana.2021.100041

Grasselli G, Zangrillo A, Zanella A, et al. Baseline characteristics and outcomes of 1591 patients infected with SARS-CoV-2 admitted to ICUs of the Lombardy region, Italy. JAMA 2020;323:1574-81. DOI: https://doi.org/10.1001/jama.2020.5394

Vega ML, Dongilli R, Olaizola G, et al. COVID-19 pneumonia and ROX index: time to set a new threshold for patients admitted outside the ICU. Pulmonology 2022;28:13-7. DOI: https://doi.org/10.1016/j.pulmoe.2021.04.003

Novelli L, Raimondi F, Ghirardi A, et al. At the peak of COVID-19 age and disease severity but not comorbidities are predictors of mortality: COVID-19 burden in Bergamo, Italy. Panminerva Med 2021;63:51-61. DOI: https://doi.org/10.23736/S0031-0808.20.04063-X

Papoutsi E, Giannakoulis VG, Xourgia E, et al. Effect of timing of intubation on clinical outcomes of critically ill patients with COVID-19: a systematic review and meta-analysis of non-randomized cohort studies. Crit Care 2021;25:121. DOI: https://doi.org/10.1186/s13054-021-03540-6

Boscolo A, Pasin L, Sella N, et al. Outcomes of COVID-19 patients intubated after failure of non-invasive ventilation: a multicenter observational study. Sci Rep 2021;11:17730. DOI: https://doi.org/10.21203/rs.3.rs-400059/v1

Zaboli A, Ausserhofer D, Pfeifer N, et al. The ROX index can be a useful tool for the triage evaluation of COVID‐19 patients with dyspnoea. J Adv Nurs 2021;77:3361-9. DOI: https://doi.org/10.1111/jan.14848

Melo-Diaz LL, Kieling GA. The ROX index: “propelled” by high-flow nasal cannula therapy during the COVID-19 pandemic into greater applicability in respiratory support. Can J Respir Ther 2022;58:182-4. DOI: https://doi.org/10.29390/cjrt-2022-012

Gattinoni L, Coppola S, Cressoni M, et al. COVID-19 does not lead to a “typical” acute respiratory distress syndrome. Am J Respir Crit Care Med 2020;201:1299-300. DOI: https://doi.org/10.1164/rccm.202003-0817LE

Novelli L, Raimondi F, Ghirardi A, et al. Frequency, characteristics, and outcome of patients with COVID-19 pneumonia and ‘silent hypoxemia’ at admission: a severity-matched analysis. Panminerva Med 2022;64:442-51. DOI: https://doi.org/10.23736/S0031-0808.22.04609-2

Raimondi F, Novelli L, Marchesi G, et al. Worsening of gas exchange parameters at high FiO2 in COVID-19: misleading or informative? Multidiscip Respir Med 2021;16:759. DOI: https://doi.org/10.4081/mrm.2021.759

Colaianni-Alfonso N, Montiel GC, Castro-Sayat M, et al. ROX index to predict CPAP outcome in hypoxemic respiratory failure due to COVID-19. Intensive Care Med 2022;48:1818-9. DOI: https://doi.org/10.1007/s00134-022-06913-9

Nova A, Rezoagli E, Eronia N, et al. Role of PEEP on the prognostic performance of the ROX index in hypoxemic respiratory failure due to COVID-19: any further gain in outcome prediction? Intensive Care Med 2023;49:355-6. DOI: https://doi.org/10.1007/s00134-022-06965-x

Abroug F, Hammouda Z, Lahmar M, et al. Early variation of ROX index predicts high-flow nasal cannula outcome in awake subjects with severe hypoxemic COVID-19. Respir Care 2023;68:110-3. DOI: https://doi.org/10.4187/respcare.10125

Ethics Approval

This study was approved by the respective ethics committees involved (Comitato etico di Bergamo - n.308-20, 05/02/2021; Comitato etico della Brianza - EC approval on 02/04/2021; Comitato etico di Ferrara - n.373/2021/Oss/AOUFe, 22/04/2021; Comitato etico Ospedale Sacco Milano - n.2021/ST/091, 19/04/2021; Comitato etico di Palermo - n.3/2021, 31/03/2021; Comitato etico Policlinico Milano - n.433/2021, 23/04/2021; Comitato etico San Paolo Milano - n.965, 21/04/2021; Comitato etico di Verona - n.3171CESC, 11/03/2021).

How to Cite

Raimondi, Federico, Stefano Centanni, Fabrizio Luppi, Stefano Aliberti, Francesco Blasi, Paola Rogliani, Claudio Micheletto, et al. 2024. “Respiratory Rate-Oxygenation Index on the 3<sup>rd< sup> Day Is the Best Predictor of Treatment Failure in COVID-19 Patients”. Monaldi Archives for Chest Disease 94 (4). https://doi.org/10.4081/monaldi.2024.3033.

Download Citation

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

PAGEPress has chosen to apply the Creative Commons Attribution NonCommercial 4.0 International License (CC BY-NC 4.0) to all manuscripts to be published.

Respiratory rate-oxygenation index on the 3^rd day is the best predictor of treatment failure in COVID-19 patients