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Cited by 2,342Respiratory Support and MechanismsAirway Management and Intubation TechniquesNeonatal Respiratory Health Research

High-Flow Oxygen through Nasal Cannula in Acute Hypoxemic Respiratory Failure

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Frat, Jean-Pierre, Thille, Arnaud W., Mercat, Alain, Girault, Christophe, Ragot, Stéphanie, Perbet, Sébastien, Prat, Gwénael, Boulain, Thierry +22 more·2015·New England Journal of Medicine
DOI 10.1056/nejmoa1503326
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Abstract

BACKGROUND: Whether noninvasive ventilation should be administered in patients with acute hypoxemic respiratory failure is debated. Therapy with high-flow oxygen through a nasal cannula may offer an alternative in patients with hypoxemia. METHODS: We performed a multicenter, open-label trial in which we randomly assigned patients without hypercapnia who had acute hypoxemic respiratory failure and a ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen of 300 mm Hg or less to high-flow oxygen therapy, standard oxygen therapy delivered through a face mask, or noninvasive positive-pressure ventilation. The primary outcome was the proportion of patients intubated at day 28; secondary outcomes included all-cause mortality in the intensive care unit and at 90 days and the number of ventilator-free days at day 28. RESULTS: A total of 310 patients were included in the analyses. The intubation rate (primary outcome) was 38% (40 of 106 patients) in the high-flow-oxygen group, 47% (44 of 94) in the standard group, and 50% (55 of 110) in the noninvasive-ventilation group (P=0.18 for all comparisons). The number of ventilator-free days at day 28 was significantly higher in the high-flow-oxygen group (24±8 days, vs. 22±10 in the standard-oxygen group and 19±12 in the noninvasive-ventilation group; P=0.02 for all comparisons). The hazard ratio for death at 90 days was 2.01 (95% confidence interval [CI], 1.01 to 3.99) with standard oxygen versus high-flow oxygen (P=0.046) and 2.50 (95% CI, 1.31 to 4.78) with noninvasive ventilation versus high-flow oxygen (P=0.006). CONCLUSIONS: In patients with nonhypercapnic acute hypoxemic respiratory failure, treatment with high-flow oxygen, standard oxygen, or noninvasive ventilation did not result in significantly different intubation rates. There was a significant difference in favor of high-flow oxygen in 90-day mortality. (Funded by the Programme Hospitalier de Recherche Clinique Interrégional 2010 of the French Ministry of Health; FLORALI ClinicalTrials.gov number, NCT01320384.).

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  • In the SALT pilot trial, the primary composite outcome (MAKE30) was similar between balanced solutions and normal saline (24.6% vs. 24.7%).

    “In 2016, the SALT pilot trial (n = 974) compared balanced solutions versus normal saline; with septic patients comprising 25% and 28% of the population, respectively (333).The primary outcome, a composite outcome including mortality, new RRT or persistent renal dysfunction (major adverse kidney event within 30 days, MAKE30), was similar between groups (24.6% vs. 24.7%).”

    From Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021. (2021) · cites this paper as [333]

    The Study Outcomes section identifies this paper’s primary outcome as endotracheal intubation within 28 days, not MAKE30. Its reported groups received high-flow oxygen, standard oxygen, or noninvasive ventilation, rather than balanced solutions or saline; it does not report the attributed 24.6% versus 24.7% comparison. (LLM, conf=0.90)

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  • In a post hoc analysis of patients with severe hypoxemia (PaO2/FiO2 ≤ 200 mmHg) from that trial, HFNC resulted in lower intubation rates compared with NIV (35 versus 58 percent).

    “In a post hoc analysis of patients with severe hypoxemia (PaO2/FiO2 ≤ 200 mmHg) from the above trial, HFNC resulted in lower intubation rates compared with NIV (35 versus 58 percent, respectively).”

    From Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021 (2021) · cites this paper as [411]

  • A single, large randomised trial has directly compared NIV versus HFNC for acute hypoxemic respiratory failure despite conventional oxygen.

    “When comparing the strategies of NIV versus HFNC for acute hypoxemic respiratory failure despite conventional oxygen, a single, large randomised trial has been conducted for direct comparison [411].”

    From Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021 (2021) · cites this paper as [411]

  • In that trial, the primary outcome of intubation rate at 28 days was not different between HFNC and NIV, but 90-day survival was improved with HFNC (OR 0.42; 95% CI 0.21-0.85) and HFNC patients had significantly more days free of mechanical ventilation during a 28-day study period.

    “Although the primary outcome of intubation rate at 28 days was not different, this study demonstrated improved 90-day survival with HFNC compared with NIV (OR 0.42; 95% CI 0.21–0.85) and HFNC patients experienced significantly more days free of mechanical ventilation during a 28-day study period [411].”

    From Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021 (2021) · cites this paper as [411]

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Research works printed but not linked: 3

  1. Masip J, Roque M, Sánchez B, Fernán- dez R, Subirana M, Expósito JA. Noninva- sive ventilation in acute cardiogenic pul- monary edema: systematic review and meta-analysis. JAMA 2005;294:3124-30.
  2. Roca O, Riera J, Torres F, Masclans JR. High-flow oxygen therapy in acute respira- tory failure. Respir Care 2010;55:408-13.
  3. Slutsky AS, Ranieri VM. Ventilator- induced lung injury. N Engl J Med 2014; 370:980.

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Authors
Frat, J.-P., Thille, A. W., Mercat, A., Girault, C., Ragot, S., Perbet, S., Prat, G., Boulain, T., Morawiec, E., Cottereau, A., Devaquet, J., Nseir, S., Razazi, K., Mira, J.-P., Argaud, L., Chakarian, J.-C., Ricard, J.-D., Wittebole, X., Chevalier, S., Herbland, A., Fartoukh, M., Constantin, J.-M., Tonnelier, J.-M., Pierrot, M., Mathonnet, A., Béduneau, G., Delétage-Métreau, C., Richard, J.-C. M., Brochard, L., & Robert, R.
Affiliations
  • Inserm (FR)
  • Centre Hospitalier Universitaire d'Angers (FR)
  • Hôpital Charles-Nicolle (FR)
  • Université Clermont Auvergne (FR)
  • Centre hospitalier universitaire d'Orléans (FR)
  • Hôpital Foch (FR)
  • Centre Hospitalier Universitaire de Lille (FR)
  • Hôpital Cochin (FR)
  • Hospices Civils de Lyon (FR)
  • Cliniques Universitaires Saint-Luc (BE)
  • Centre Hospitalier de Saint-Malo (FR)
  • Centre Hospitalier de La Rochelle (FR)
  • Assistance Publique – Hôpitaux de Paris (FR)
  • St. Michael's Hospital (CA)
ORCID
Venue
New England Journal of Medicine
Publisher
Massachusetts Medical Society
Published
2015-06-04
Volume
372
Issue
23
Pages
2185-2196
ISSN
  • 0028-4793 (ISSN-L)
  • 1533-4406
DOI
10.1056/nejmoa1503326
OpenAlex
W2148218430
Cited by
2,342
References
35
Citations by year
2026: 159 · 2025: 175 · 2024: 179 · 2023: 215 · 2022: 279 · 2021: 312 · 2020: 307 · 2019: 164 · 2018: 154 · 2017: 182 · 2016: 156 · 2015: 55 · 2014: 1 · 2012: 1
FWCI
144.22
Type
journal article
Language
en
Open access
Locations
  • New England Journal of Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • HAL (submittedVersion)
  • Digital Access to Libraries (submittedVersion)
  • INFM-OAR (INFN Catania) (submittedVersion, other-oa)
  • Zenodo (CERN European Organization for Nuclear Research) (other-oa)
Topics
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Respiratory Support and Mechanisms
  • Health Sciences › Medicine › Anesthesiology and Pain Medicine › Airway Management and Intubation Techniques
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Neonatal Respiratory Health Research
Keywords
high-flow oxygen therapy, nasal cannula, acute hypoxemic respiratory failure, noninvasive positive pressure ventilation, standard oxygen therapy, intubation rate, ventilator-free days, 90-day mortality, mechanical ventilation avoidance, acute respiratory distress syndrome, acute lung injury, acute respiratory failure, non-invasive ventilation, ICU mortality
MeSH terms
Acute Disease, Adult, Aged, Hypoxia, Female, Humans, Intubation, Intratracheal, Male, Middle Aged, Oxygen, Oxygen Inhalation Therapy, Positive-Pressure Respiration, Respiratory Insufficiency, Kaplan-Meier Estimate

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