[Skip to Content]
[Skip to Content Landing]

Effect of High-Flow Nasal Cannula Oxygen vs Standard Oxygen Therapy on Mortality in Patients With Respiratory Failure Due to COVID-19The SOHO-COVID Randomized Clinical Trial

Educational Objective
To identify the key insights or developments described in this article
1 Credit CME
Key Points

Questions  In patients with respiratory failure due to COVID-19, does the use of high-flow nasal cannula oxygen reduce the risk of mortality compared with standard oxygen therapy?

Findings  In this randomized clinical trial that included 711 patients, mortality at day 28 was 10% in the high-flow oxygen group and 11% in the standard oxygen therapy group, a difference that was not statistically significant.

Meaning  In patients with respiratory failure due to COVID-19, high-flow nasal cannula oxygen did not significantly reduce mortality at day 28 compared with standard oxygen therapy.

Abstract

Importance  The benefit of high-flow nasal cannula oxygen (high-flow oxygen) in terms of intubation and mortality in patients with respiratory failure due to COVID-19 is controversial.

Objective  To determine whether the use of high-flow oxygen, compared with standard oxygen, could reduce the rate of mortality at day 28 in patients with respiratory failure due to COVID-19 admitted in intensive care units (ICUs).

Design, Setting, and Participants  The SOHO-COVID randomized clinical trial was conducted in 34 ICUs in France and included 711 patients with respiratory failure due to COVID-19 and a ratio of partial pressure of arterial oxygen to fraction of inspired oxygen equal to or below 200 mm Hg. It was an ancillary trial of the ongoing original SOHO randomized clinical trial, which was designed to include patients with acute hypoxemic respiratory failure from all causes. Patients were enrolled from January to December 2021; final follow-up occurred on March 5, 2022.

Interventions  Patients were randomly assigned to receive high-flow oxygen (n = 357) or standard oxygen delivered through a nonrebreathing mask initially set at a 10-L/min minimum (n = 354).

Main Outcomes and Measures  The primary outcome was mortality at day 28. There were 13 secondary outcomes, including the proportion of patients requiring intubation, number of ventilator-free days at day 28, mortality at day 90, mortality and length of stay in the ICU, and adverse events.

Results  Among the 782 randomized patients, 711 patients with respiratory failure due to COVID-19 were included in the analysis (mean [SD] age, 61 [12] years; 214 women [30%]). The mortality rate at day 28 was 10% (36/357) with high-flow oxygen and 11% (40/354) with standard oxygen (absolute difference, –1.2% [95% CI, –5.8% to 3.4%]; P = .60). Of 13 prespecified secondary outcomes, 12 showed no significant difference including in length of stay and mortality in the ICU and in mortality up until day 90. The intubation rate was significantly lower with high-flow oxygen than with standard oxygen (45% [160/357] vs 53% [186/354]; absolute difference, –7.7% [95% CI, –14.9% to –0.4%]; P = .04). The number of ventilator-free days at day 28 was not significantly different between groups (median, 28 [IQR, 11-28] vs 23 [IQR, 10-28] days; absolute difference, 0.5 days [95% CI, –7.7 to 9.1]; P = .07). The most common adverse events were ventilator-associated pneumonia, occurring in 58% (93/160) in the high-flow oxygen group and 53% (99/186) in the standard oxygen group.

Conclusions and Relevance  Among patients with respiratory failure due to COVID-19, high-flow nasal cannula oxygen, compared with standard oxygen therapy, did not significantly reduce 28-day mortality.

Trial Registration  ClinicalTrials.gov Identifier: NCT04468126

Sign in to take quiz and track your certificates

Buy This Activity

JN Learning™ is the home for CME and MOC from the JAMA Network. Search by specialty or US state and earn AMA PRA Category 1 Credit(s)™ from articles, audio, Clinical Challenges and more. Learn more about CME/MOC

CME Disclosure Statement: Unless noted, all individuals in control of content reported no relevant financial relationships. If applicable, all relevant financial relationships have been mitigated.

Article Information

Corresponding Author: Jean-Pierre Frat, MD, PhD, CHU de Poitiers, Médecine Intensive Réanimation, 2 rue de la Milétrie, CS 90577, 86021 POITIERS cedex, France (jean-pierre.frat@chu-poitiers.fr).

Accepted for Publication: August 21, 2022

Author Contributions: Dr Ragot and Mr de Keizer had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Frat, Coudroy, Guesdon, Ragot, Thille.

Acquisition, analysis, or interpretation of data: Frat, Quenot, Badie, Coudroy, Guitton, Ehrmann, Gacouin, Merdji, Auchabie, Daubin, Dureau, Thibault, Sedillot, Rigaud, Demoule, Fatah, Terzi, Simonin, Danjou, Carteaux, Pradel, Besse, Reignier, Beloncle, La Combe, Prat, Nay, De Keizer, Ragot, Thille.

Drafting of the manuscript: Frat, Badie, Sedillot, Fatah, Guesdon, De Keizer, Ragot, Thille.

Critical revision of the manuscript for important intellectual content: Frat, Quenot, Coudroy, Guitton, Ehrmann, Gacouin, Merdji, Auchabie, Daubin, Dureau, Thibault, Rigaud, Demoule, Fatah, Terzi, Simonin, Danjou, Carteaux, Pradel, Besse, Reignier, Beloncle, La Combe, Prat, Nay, De Keizer, Ragot, Thille.

Statistical analysis: Coudroy, De Keizer, Ragot, Thille.

Obtained funding: Frat, Demoule, Thille.

Administrative, technical, or material support: Frat, Quenot, Badie, Dureau, Carteaux, Guesdon, Besse.

Supervision: Frat, Merdji, Ragot.

Conflict of Interest Disclosures: Dr Frat reported receiving grants from the French Ministry of Health and Fisher & Paykel Healthcare during the conduct of the study and personal fees and nonfinancial support from Fisher & Paykel Healthcare and SOS Oxygène outside the submitted work. Dr Coudroy reported receiving grants from the European Respiratory Society and the French Intensive Care Society, and travel expense coverage to attend scientific meetings from Fisher & Paykel Healthcare and Merck Sharp & Dohme. Dr Ehrmann reported receiving personal fees, grants, and nonfinancial support from Fisher & Paykel Healthcare and Aerogen Ltd. Dr Auchabie reported receiving grants from the French Ministry of Health. Dr Demoule reported receiving personal fees from Respinor, Baxter, Fisher & Paykel Healthcare, Lungpacer, Lowenstein, Getinge, Gilead, and Mindray; grants from the French Ministry of Health; and nonfinancial support from Philips. Dr Terzi reported receiving personal fees from Pfizer. Dr Carteaux reported receiving personal fees from Dräger, Medtronic, and Lowenstein and nonfinancial support from Air Liquide Medical System. Dr Beloncle reported receiving nonfinancial support from GE Healthcare and Covidien, travel expenses from Draeger, and personal fees from Lowenstein. Dr Nay reported receiving personal fees for lectures from Fisher & Paykel Healthcare. Dr Ragot reported receiving grants from the French Ministry of Health and Fisher & Paykel Healthcare. Dr Thille reported receiving travel expense coverage to attend scientific meetings and payment for lectures from Fisher & Paykel Healthcare, Covidien, Maquet-Getinge, Dräger Medical, and GE Healthcare. No other disclosures were reported.

Funding/Support: Financial support was provided by the “Programme Hospitalier de Recherche Clinique National” 2019 from the French Ministry of Health (PHRC-19-0305) and a grant from Fisher & Paykel Healthcare.

Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Group Information: The SOHO-COVID Study Group and the REVA Network members are listed in Supplement 4.

Additional Contributions: We thank Mr Jeffrey Arsham, translator, CHU de Poitiers, Poitiers, France, for reviewing and editing the original English-language manuscript. He did not receive compensation for his role in the study.

Data Sharing Statement: See Supplement 5.

References
1.
World Health Organization. WHO coronavirus (COVID-19) dashboard. Accessed January 12, 2022. https://covid19.who.int
2.
Islam  N , Shkolnikov  VM , Acosta  RJ ,  et al.  Excess deaths associated with covid-19 pandemic in 2020: age and sex disaggregated time series analysis in 29 high income countries.   BMJ. 2021;373(1137):n1137. doi:10.1136/bmj.n1137 PubMedGoogle ScholarCrossref
3.
Grasselli  G , Zangrillo  A , Zanella  A ,  et al; COVID-19 Lombardy ICU Network.  Baseline characteristics and outcomes of 1591 patients infected with SARS-CoV-2 admitted to ICUs of the Lombardy Region, Italy.   JAMA. 2020;323(16):1574-1581. doi:10.1001/jama.2020.5394 PubMedGoogle ScholarCrossref
4.
COVID-ICU Group on behalf of the REVA Network and the COVID-ICU Investigators.  Clinical characteristics and day-90 outcomes of 4244 critically ill adults with COVID-19: a prospective cohort study.   Intensive Care Med. 2021;47(1):60-73. doi:10.1007/s00134-020-06294-x PubMedGoogle ScholarCrossref
5.
Cummings  MJ , Baldwin  MR , Abrams  D ,  et al.  Epidemiology, clinical course, and outcomes of critically ill adults with COVID-19 in New York City: a prospective cohort study.   Lancet. 2020;395(10239):1763-1770. doi:10.1016/S0140-6736(20)31189-2 PubMedGoogle ScholarCrossref
6.
Maslo  C , Friedland  R , Toubkin  M , Laubscher  A , Akaloo  T , Kama  B .  Characteristics and outcomes of hospitalized patients in South Africa during the COVID-19 Omicron wave compared with previous waves.   JAMA. 2022;327(6):583-584. doi:10.1001/jama.2021.24868 PubMedGoogle ScholarCrossref
7.
Demoule  A , Vieillard Baron  A , Darmon  M ,  et al.  High-flow nasal cannula in critically ill patients with severe COVID-19.   Am J Respir Crit Care Med. 2020;202(7):1039-1042. doi:10.1164/rccm.202005-2007LE PubMedGoogle ScholarCrossref
8.
Bonnet  N , Martin  O , Boubaya  M ,  et al.  High flow nasal oxygen therapy to avoid invasive mechanical ventilation in SARS-CoV-2 pneumonia: a retrospective study.   Ann Intensive Care. 2021;11(1):37. doi:10.1186/s13613-021-00825-5 PubMedGoogle ScholarCrossref
9.
Franco  C , Facciolongo  N , Tonelli  R ,  et al.  Feasibility and clinical impact of out-of-ICU noninvasive respiratory support in patients with COVID-19-related pneumonia.   Eur Respir J. 2020;56(5):2002130. doi:10.1183/13993003.02130-2020 PubMedGoogle ScholarCrossref
10.
Grieco  DL , Menga  LS , Cesarano  M ,  et al; COVID-ICU Gemelli Study Group.  Effect of helmet noninvasive ventilation vs high-flow nasal oxygen on days free of respiratory support in patients with COVID-19 and moderate to severe hypoxemic respiratory failure: the HENIVOT randomized clinical trial.   JAMA. 2021;325(17):1731-1743. doi:10.1001/jama.2021.4682 PubMedGoogle ScholarCrossref
11.
Ospina-Tascón  GA , Calderón-Tapia  LE , García  AF ,  et al; HiFLo-Covid Investigators.  Effect of high-flow oxygen therapy vs conventional oxygen therapy on invasive mechanical ventilation and clinical recovery in patients with severe COVID-19: a randomized clinical trial.   JAMA. 2021;326(21):2161-2171. doi:10.1001/jama.2021.20714 PubMedGoogle ScholarCrossref
12.
Perkins  GD , Ji  C , Connolly  BA ,  et al; RECOVERY-RS Collaborators.  Effect of noninvasive respiratory strategies on intubation or mortality among patients with acute hypoxemic respiratory failure and COVID-19: the RECOVERY-RS randomized clinical trial.   JAMA. 2022;327(6):546-558. doi:10.1001/jama.2022.0028 PubMedGoogle ScholarCrossref
13.
Frat  JP , Thille  AW , Mercat  A ,  et al; FLORALI Study Group; REVA Network.  High-flow oxygen through nasal cannula in acute hypoxemic respiratory failure.   N Engl J Med. 2015;372(23):2185-2196. doi:10.1056/NEJMoa1503326 PubMedGoogle ScholarCrossref
14.
Azoulay  E , Lemiale  V , Mokart  D ,  et al.  Effect of high-flow nasal oxygen vs standard oxygen on 28-day mortality in immunocompromised patients with acute respiratory failure: the HIGH randomized clinical trial.   JAMA. 2018;320(20):2099-2107. doi:10.1001/jama.2018.14282PubMedGoogle ScholarCrossref
15.
Tobin  MJ , Laghi  F , Jubran  A .  Why COVID-19 silent hypoxemia is baffling to physicians.   Am J Respir Crit Care Med. 2020;202(3):356-360. doi:10.1164/rccm.202006-2157CP PubMedGoogle ScholarCrossref
16.
Swenson  KE , Ruoss  SJ , Swenson  ER .  The pathophysiology and dangers of silent hypoxemia in COVID-19 lung injury.   Ann Am Thorac Soc. 2021;18(7):1098-1105. doi:10.1513/AnnalsATS.202011-1376CME PubMedGoogle ScholarCrossref
17.
Coudroy  R , Frat  JP , Girault  C , Thille  AW .  Reliability of methods to estimate the fraction of inspired oxygen in patients with acute respiratory failure breathing through non-rebreather reservoir bag oxygen mask.   Thorax. 2020;75(9):805-807. doi:10.1136/thoraxjnl-2020-214863 PubMedGoogle ScholarCrossref
18.
Rodriguez  M , Thille  AW , Boissier  F ,  et al.  Predictors of successful separation from high-flow nasal oxygen therapy in patients with acute respiratory failure: a retrospective monocenter study.   Ann Intensive Care. 2019;9(1):101. doi:10.1186/s13613-019-0578-8 PubMedGoogle ScholarCrossref
19.
Hernandez-Romieu  AC , Adelman  MW , Hockstein  MA ,  et al; Emory COVID-19 Quality and Clinical Research Collaborative.  Timing of intubation and mortality among critically ill coronavirus disease 2019 patients: a single-center cohort study.   Crit Care Med. 2020;48(11):e1045-e1053. doi:10.1097/CCM.0000000000004600 PubMedGoogle ScholarCrossref
20.
Patel  M , Gangemi  A , Marron  R ,  et al.  Retrospective analysis of high flow nasal therapy in COVID-19-related moderate-to-severe hypoxaemic respiratory failure.   BMJ Open Respir Res. 2020;7(1):e000650. doi:10.1136/bmjresp-2020-000650 PubMedGoogle ScholarCrossref
21.
Perkins  GD , Ji  C , Connolly  BA ,  et al; RECOVERY-RS Collaborators.  Effect of noninvasive respiratory strategies on intubation or mortality among patients with acute hypoxemic respiratory failure and COVID-19: the RECOVERY-RS randomized clinical trial.   JAMA. 2022;327(6):546-558. doi:10.1001/jama.2022.0028PubMedGoogle ScholarCrossref
22.
Sterne  JAC , Murthy  S , Diaz  JV ,  et al; WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group.  Association between administration of systemic corticosteroids and mortality among critically ill patients with COVID-19: a meta-analysis.   JAMA. 2020;324(13):1330-1341. doi:10.1001/jama.2020.17023 PubMedGoogle ScholarCrossref
23.
Mauri  T , Turrini  C , Eronia  N ,  et al.  Physiologic effects of high-flow nasal cannula in acute hypoxemic respiratory failure.   Am J Respir Crit Care Med. 2017;195(9):1207-1215. doi:10.1164/rccm.201605-0916OC PubMedGoogle ScholarCrossref
24.
Möller  W , Feng  S , Domanski  U ,  et al.  Nasal high flow reduces dead space.   J Appl Physiol (1985). 2017;122(1):191-197. doi:10.1152/japplphysiol.00584.2016PubMedGoogle ScholarCrossref
Close
Want full access to the AMA Ed Hub?
After you sign up for AMA Membership, make sure you sign in or create a Physician account with the AMA in order to access all learning activities on the AMA Ed Hub
Buy this activity
Close
Want full access to the AMA Ed Hub?
After you sign up for AMA Membership, make sure you sign in or create a Physician account with the AMA in order to access all learning activities on the AMA Ed Hub
Buy this activity
Close
With a personal account, you can:
  • Access free activities and track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
Education Center Collection Sign In Modal Right
Close

Name Your Search

Save Search
With a personal account, you can:
  • Access free activities and track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
Close
Close

Lookup An Activity

or

My Saved Searches

You currently have no searches saved.

Close

My Saved Courses

You currently have no courses saved.

Close