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  • High-flow nasal oxygen versus conventional oxygen therapy in patients with COVID-19 pneumonia and mild hypoxaemia: a randomised controlled trial

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Critical care
Original research
High-flow nasal oxygen versus conventional oxygen therapy in patients with COVID-19 pneumonia and mild hypoxaemia: a randomised controlled trial
  1. Claudia Crimi1,
  2. Alberto Noto2,
  3. Fabiana Madotto3,
  4. Mariachiara Ippolito4,5,
  5. Santi Nolasco6,
  6. Raffaele Campisi1,
  7. Stefano De Vuono7,
  8. Giuseppe Fiorentino8,
  9. Ioannis Pantazopoulos9,
  10. Athanasios Chalkias10,11,
  11. Alessandro Libra1,6,
  12. Alessio Mattei12,
  13. Raffaele Scala13,
  14. Enrico M Clini14,
  15. Begum Ergan15,
  16. Manel Lujan16,
  17. Joao Carlos Winck17,18,
  18. Antonino Giarratano4,5,
  19. Annalisa Carlucci19,20,
  20. Cesare Gregoretti4,21,
  21. Paolo Groff7,
  22. Andrea Cortegiani4,5
  23. on behalf of the COVID-HIGH Investigators
    1. 1 Respiratory Medicine Unit, Policlinico “G. Rodolico-San Marco” University Hospital, Catania, Italy
    2. 2 Department of Human Pathology of the Adult and Evolutive Age “Gaetano Barresi”, Division of Anesthesia and Intensive Care, University of Messina, Policlinico “G. Martino”, Messina, Italy
    3. 3 Value-Based Healthcare Unit, IRCCS MultiMedica, Sesto San Giovanni, Milan, Italy
    4. 4 Department of Surgical, Oncological and Oral Science (Di.Chir.On.S.), University of Palermo, Palermo, Italy
    5. 5 Department of Anesthesia, Intensive Care and Emergency, University Hospital Policlinico Paolo Giaccone, Palermo, Italy
    6. 6 Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy
    7. 7 Emergency Department, “S. Maria della Misericordia” Hospital, Perugia, Italy
    8. 8 UOC Fisiopatologia e Riabilitazione Respiratoria, AO dei Colli, Naples, Italy
    9. 9 Department of Emergency Medicine, Faculty of Medicine, University of Thessaly, Larisa, Greece
    10. 10 Department of Anesthesiology, Faculty of Medicine, University of Thessaly, Larisa, Greece
    11. 11 Outcomes Research Consortium, Cleveland, Ohio, USA
    12. 12 Cardio-Thoracic Department, AOU Città della Salute e della Scienza, Molinette Hospital, Turin, Italy
    13. 13 Pulmonology and Respiratory Intensive Care Unit, S. Donato Hospital, Arezzo, Italy
    14. 14 Respiratory Diseases Unit, Department of Medical and Surgical Sciences, University Hospital of Modena, University of Modena Reggio Emilia, Modena, Italy
    15. 15 Department of Pulmonary and Critical Care, Dokuz Eylul University, İzmir, Turkey
    16. 16 Pneumology Service, CIBERES, Hospital de Sabadell, Barcelona, Spain
    17. 17 Department of Medicine, Faculty of Medicine, University of Porto, Porto, Portugal
    18. 18 Centro De Reabilitação Do Norte, Centro Hospitalar de Vila Nova de Gaia/Espinho, Vila Nova De Gaia, Portugal
    19. 19 Department of Medicina e Chirurgia, Università Insubria Varese-Como, Varese, Italy
    20. 20 Pulmonary Rehabilitation Unit, Istituti Clinici Scientifici Maugeri, Pavia, Italy
    21. 21 Fondazione ‘Giglio’, Cefalù, Palermo, Italy
    1. Correspondence to Prof. Andrea Cortegiani, Department of Surgical, Oncological and Oral Science (Di.Chir.On.S.), University of Palermo, Via del vespro 129, 90127, Palermo, Italy; andrea.cortegiani{at}unipa.it

    Abstract

    Rationale In patients with COVID-19 pneumonia and mild hypoxaemia, the clinical benefit of high-flow nasal oxygen (HFNO) remains unclear. We aimed to examine whether HFNO compared with conventional oxygen therapy (COT) could prevent escalation of respiratory support in this patient population.

    Methods In this multicentre, randomised, parallel-group, open-label trial, patients with COVID-19 pneumonia and peripheral oxygen saturation (SpO2) ≤92% who required oxygen therapy were randomised to HFNO or COT. The primary outcome was the rate of escalation of respiratory support (ie, continuous positive airway pressure, non-invasive ventilation or invasive mechanical ventilation) within 28 days. Among secondary outcomes, clinical recovery was defined as the improvement in oxygenation (SpO2 ≥96% with fractional inspired oxygen (FiO2) ≤30% or partial pressure of arterial carbon dioxide/FiO2 ratio >300 mm Hg).

    Results Among 364 randomised patients, 55 (30.3%) of 181 patients assigned to HFNO and 70 (38.6%) of 181 patients assigned to COT underwent escalation of respiratory support, with no significant difference between groups (absolute risk difference −8.2% (95% CI −18% to +1.4%); RR 0.79 (95% CI 0.59 to 1.05); p=0.09). There was no significant difference in clinical recovery (69.1% vs 60.8%; absolute risk difference 8.2% (95% CI −1.5% to +18.0%), RR 1.14 (95% CI 0.98 to 1.32)), intensive care unit admission (7.7% vs 11.0%, absolute risk difference −3.3% (95% CI −9.3% to +2.6%)), and in hospital length of stay (11 (IQR 8–17) vs 11 (IQR 7–20) days, absolute risk difference −1.0% (95% CI −3.1% to +1.1%)).

    Conclusions Among patients with COVID-19 pneumonia and mild hypoxaemia, the use of HFNO did not significantly reduce the likelihood of escalation of respiratory support.

    Trial registration number NCT04655638.

    • COVID-19
    • Critical Care
    • Pneumonia

    Data availability statement

    Data are available on reasonable request.

    This article is made freely available for personal use in accordance with BMJ’s website terms and conditions for the duration of the covid-19 pandemic or until otherwise determined by BMJ. You may use, download and print the article for any lawful, non-commercial purpose (including text and data mining) provided that all copyright notices and trade marks are retained.

    https://bmj.com/coronavirus/usage

    https://doi.org/10.1136/thoraxjnl-2022-218806

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      Data availability statement

      Data are available on reasonable request.

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      Footnotes

      • Twitter @Crimillina, @nolascos91, @chiccoclini, @AndCorteg

      • Collaborators COVID-HIGH trial collaborators: Drs. Sokol Berisha, Patrizia Pierini, Maria Rita Taliani, Francesco Balducci, Pasquale Cianci, Alessandra Lignani from Emergency Department, Santa Maria della Misericordia Hospital, Perugia, Italy; Drs. Pasquale Imitazione, Angela Mirizzi, Anna Annunziata, Antonietta Coppola, Francesca Simioli, Antonella Marotta from UOC Fisiopatologia e Riabilitazione Respiratoria AO dei Colli, Naples, Italy; Drs. Konstantinos Gourgoulianis, Athanasios Pagonis from Department of Emergency Medicine, Faculty of Medicine, University of Thessaly, Larissa, Greece; Drs. Eleni Laou, Konstantinos Tourlakopoulos from Department of Anesthesiology, Faculty of Medicine, University of Thessaly, Larisa, Greece; Drs. Ada Vancheri, Nicola Ciancio, Pietro Impellizzeri, Rossella Intravaia from Respiratory Medicine Unit, Policlinico ‘G. Rodolico-San Marco’ University Hospital, Catania, Italy; Drs. Ernesto Crisafulli, Giulia Sartori from Respiratory Medicine Unit, Department of Medicine, University of Verona, Verona, Italy; Drs. Valentina Musella, Leonello Fuso, Luciana Paladini, Gabriele Valli from UOC Malattie Apparato Respiratorio ed Endoscopia Bronchiale, AO San Giovanni, Roma, Italy; Drs. José Pedro Boléo-Tomé, Énia Ornelas, Miguel Filipe Guia from Pulmonology Department, Hospital Prof. Doutor Fernando Fonseca, Amadora, Portugal; Drs. Chiara Chiappero, Marco Bardessono, Mauro Mangiapia from Cardio-Thoracic Department, AOU Città della Salute e della Scienza, Molinette Hospital, Turin, Italy; Drs. Margherita Marelli, Cinzia Gambarini, Dania Mazzola, Giuditta Riganti from UO Pneumologia ASST-Settelaghi, Varese, Italy; Drs. Alberto Perboni, Sara Demichelis, Massimo Comune, Giulia Rovere from Pulmonology Department; San Luigi Gonzaga Hospital, Orbassano (TO), Italy; Drs. Luca Guidelli, Giacomo Ghinassi, Nicoletta Golfi from Pulmonology and Respiratory Intensive Care Unit, S. Donato Hospital, Arezzo, Italy; Drs. Antonella Spacone, Antonietta Esposito, Giorgia Rapacchiale from Respiratory Medicine Unit, General Hospital, Pescara, Italy; Drs. Antonio Voza, Carlo Fedeli, Sara Sauro from Dipartimento di Medicina d’Urgenza, Istituto Clinico Humanitas Research Hospital, Milano, Italy; Drs. Gianfilippo Gangitano, Ilaria Gessaroli, Davide Francia from AUSL Romagna, Emergency Department, Infermi Hospital, Rimini; Drs. Pablo Flórez, Cristina Lalmolda from Pneumology Service, Hospital de Sabadell, Spain, CIBERES; Drs. Valentina Pinelli, Stefania Artioli, Massimiliano Meazza from Division of Pneumology, Ospedale San Bartolomeo, Sarzana, La Spezia, Italy; Drs. Donato Lacedonia, Giulia Scioscia, Marcello Stomaci from Department of Medical and Surgical Sciences, ‘Policlinico Riuniti’ University Hospital, University of Foggia, Italy; Drs. Silvia Marani, Mara Bozzoli from Medicina Interna, Ospedale Ramazzini, Carpi, Ausl Modena, Italy; Dr. Mehmet Nuri Yakar from Dokuz Eylul University, Department of Pulmonary and Critical Care, İzmir, Turkey; Drs. Elisiana Carpagnano, Valentina Di Lecce from Institute of Respiratory Disease, Department of Basic Medical Science, Neuroscience, and Sense Organs, University of Bari ‘Aldo Moro’, Bari, Italy; Drs. Erika Zanardi, Monica Trentin from Aulss 7 Pedemontana, Ospedale Santorso, Santorso (VI), Italia; Drs. Szymon Skoczyński, Aleksandra Oraczewska from Department of Pneumonology, Faculty of Medical Sciences in Katowice, Medical University of Silesia - Katowice, Poland; Drs. Marco Contoli, Brunilda Marku from Respiratory Section, Department of Translational Medicine, University of Ferrara, Italy; Drs. Paola Noto, Eugenia Di Fazio from Emergency Medicine Unit, AOU Policlinico ‘G. Rodolico-San Marco’ University Hospital, Catania, Italy; Drs. Pierachille Santus, Dejan Radovanovic from Division of Respiratory Diseases, Ospedale Luigi Sacco, ASST Fatebenefratelli-Sacco, Department of Biomedical and Clinical Sciences (DIBIC), University of Milan, Italy; Dr. Luigi Marino, U.O. Pneumotisiologia, Ospedale di Vittorio Veneto, ULSS 2 Marca Trevigiana, Vittorio Veneto, Treviso, Italy.

      • Contributors PG, ACo and CC contributed to the concept and design of the trial. CC, ACh, FM, MI and SN wrote the first draft. FM performed the statistical analysis. All authors contributed to the data analysis and interpretation, critical revision of the publication, and final approval to submit. ACo, CC, AN and FM accessed and verified the data in this study and take responsibility for the integrity of the data and the accuracy of the data analysis. ACo and CC are responsable for the overall content as the guarantors. The COVID-HIGH trial collaborators consist of local investigators who were responsible for participant recruitment and local ethical board approval.

      • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

      • Competing interests ACh, AG and CG declare a patent, in association with the University of Palermo—Italy (No 102019000020532—Italian Ministry of Economic Development), not discussed in the present study. ACa received honoraria for lectures or consultancies from Breas, Philips (outside the submitted work). CC received honoraria for lectures from Philips, Resmed (outside the submitted work). CG received honoraria for lectures or consultancies from Vivisol, Philips, Mindray, Air Liquide (outside the submitted work). JCW received honoraria for lectures from Vitalaire, Nippon Gases, Philips, Breas and Armstrong Medical (outside the submitted work). The remaining authors declared no competing interests.

      • Provenance and peer review Not commissioned; externally peer reviewed.

      • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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