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Original Investigation
Caring for the Critically Ill Patient
November 27, 2018

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

Author Affiliations
  • 1Medical Intensive Care Unit and Department of Biostatistics, APHP, Hôpital St-Louis, Paris, France.
  • 2Intensive Care Unit, Paoli Calmettes Institut, Marseille, France
  • 3Critical Care Center, CHU de Lille, Lille, France
  • 4Medical Intensive Care Unit, Hospices Civils de Lyon, Hôpital Edouard Herriot, Lyon, France
  • 5Medical Intensive Care Unit, Hôpital Cochin, APHP, Université Paris Descartes, Paris, France
  • 6Medical Intensive Care Unit, INSERM U1088, Amiens University Hospital, Amiens, France
  • 7Medical Intensive Care Unit, André Mignot Hospital, Versailles, France
  • 8Medical Intensive Care Unit, CHU de Montpellier, Montpellier, France
  • 9Medical Intensive Care Unit, La Source Hospital, CHR Orléans, Orléans, France
  • 10Medical Intensive Care Unit, Hotel Dieu, CHU de Nantes, Nantes, France
  • 11Intensive Care Unit, Institut Gustave Roussy, Villejuif, France
  • 12Intensive Care Unit, CHR de Metz-Thionville, Metz, France
  • 13Department of Perioperative Medicine, CHU Clermont-Ferrand, Clermont-Ferrand, France
  • 14Medical Intensive Care Unit and Respiratory Division, APHP, Hôpital Pitié-Salpêtrière, Sorbonne University, Paris, France
  • 15Intensive Care Unit, Lyon Sud Medical Center, Lyon, France
  • 16Medical Intensive Care Unit, CHRU, Angers, France
  • 17Intensive Care Unit, Centre Hospitalier Métropole-Savoie, Chambery, France
  • 18Medical Intensive Care Unit, Hôpital Brabois, Vandoeuvre Les Nancy, France
  • 19Medical Intensive Care Unit, Hôpital Charles Nicolle, Rouen, France
  • 20Montpellier University Hospital, PhyMedExp, INSERM U-1046, CNRS 34295 Montpellier, France
  • 21Medical Intensive Care Unit, Avicenne University Hospital, Bobigny, France
  • 22Intensive Care Unit, Roubaix hospital, Roubaix, France
  • 23Medical Intensive Care Unit, CHU de Grenoble Alpes, Grenoble, France
  • 24Medical Intensive Care Unit, CHU Bichat, Paris, France
  • 25Intensive Care Unit, Centre Hospitalier Départemental Les Oudairies, La Roche Sur Yon, France
  • 26Medical Intensive Care Unit, Gabriel-Montpied University Hospital, Clermont-Ferrand, France
  • 27Medical Intensive Care Unit, CHU St-Antoine, Paris, France
  • 28Department of Anesthesia and Critical Care, Necker Hospital, Paris, France
  • 29Réanimation des Détresses Respiratoires et Infections Sévères, Assistance Publique–Hôpitaux de Marseille, Hôpital Nord, Aix-Marseille Université, Faculté de Médecine, Marseille, France
  • 30Respiratory Intensive Care Unit, Hôpital Cochin, Paris, France
JAMA. 2018;320(20):2099-2107. doi:10.1001/jama.2018.14282
Key Points

Question  In immunocompromised patients with acute hypoxemic respiratory failure, is high-flow nasal oxygen therapy superior to standard oxygen therapy with respect to mortality at day 28?

Findings  In this randomized clinical trial that included 776 critically ill immunocompromised patients receiving at least 6 L/min of oxygen, high-flow oxygen therapy compared with standard oxygen therapy did not significantly reduce day-28 mortality (35.6% vs 36.1%, respectively).

Meaning  Among immunocompromised patients with acute respiratory failure, high-flow oxygen therapy did not significantly reduce mortality compared with standard oxygen therapy.


Importance  High-flow nasal oxygen therapy is increasingly used for acute hypoxemic respiratory failure (AHRF).

Objective  To determine whether high-flow oxygen therapy decreases mortality among immunocompromised patients with AHRF compared with standard oxygen therapy.

Design, Setting, and Participants  The HIGH randomized clinical trial enrolled 776 adult immunocompromised patients with AHRF (Pao2 <60 mm Hg or Spo2 <90% on room air, or tachypnea >30/min or labored breathing or respiratory distress, and need for oxygen ≥6 L/min) at 32 intensive care units (ICUs) in France between May 19, 2016, and December 31, 2017.

Interventions  Patients were randomized 1:1 to continuous high-flow oxygen therapy (n = 388) or to standard oxygen therapy (n = 388).

Main Outcomes and Measures  The primary outcome was day-28 mortality. Secondary outcomes included intubation and mechanical ventilation by day 28, Pao2:Fio2 ratio over the 3 days after intubation, respiratory rate, ICU and hospital lengths of stay, ICU-acquired infections, and patient comfort and dyspnea.

Results  Of 778 randomized patients (median age, 64 [IQR, 54-71] years; 259 [33.3%] women), 776 (99.7%) completed the trial. At randomization, median respiratory rate was 33/min (IQR, 28-39) vs 32 (IQR, 27-38) and Pao2:Fio2 was 136 (IQR, 96-187) vs 128 (IQR, 92-164) in the intervention and control groups, respectively. Median SOFA score was 6 (IQR, 4-8) in both groups. Mortality on day 28 was not significantly different between groups (35.6% vs 36.1%; difference, −0.5% [95% CI, −7.3% to +6.3%]; hazard ratio, 0.98 [95% CI, 0.77 to 1.24]; P = .94). Intubation rate was not significantly different between groups (38.7% vs 43.8%; difference, −5.1% [95% CI, −12.3% to +2.0%]). Compared with controls, patients randomized to high-flow oxygen therapy had a higher Pao2:Fio2 (150 vs 119; difference, 19.5 [95% CI, 4.4 to 34.6]) and lower respiratory rate after 6 hours (25/min vs 26/min; difference, −1.8/min [95% CI, −3.2 to −0.2]). No significant difference was observed in ICU length of stay (8 vs 6 days; difference, 0.6 [95% CI, −1.0 to +2.2]), ICU-acquired infections (10.0% vs 10.6%; difference, −0.6% [95% CI, −4.6 to +4.1]), hospital length of stay (24 vs 27 days; difference, −2 days [95% CI, −7.3 to +3.3]), or patient comfort and dyspnea scores.

Conclusions and Relevance  Among critically ill immunocompromised patients with acute respiratory failure, high-flow oxygen therapy did not significantly decrease day-28 mortality compared with standard oxygen therapy.

Trial Registration  clinicaltrials.gov Identifier: NCT02739451.