Benefits and Risks of Non-invasive Oxygenation Strategy in COVID-19

A Multicenter, Prospective Cohort Study (COVID-ICU) in 137 Hospitals

COVID-ICU group, for the REVA network, COVID-ICU investigators


Crit Care. 2021;25(421) 

In This Article

Abstract and Introduction


Rational: To evaluate the respective impact of standard oxygen, high-flow nasal cannula (HFNC) and noninvasive ventilation (NIV) on oxygenation failure rate and mortality in COVID-19 patients admitted to intensive care units (ICUs).

Methods: Multicenter, prospective cohort study (COVID-ICU) in 137 hospitals in France, Belgium, and Switzerland. Demographic, clinical, respiratory support, oxygenation failure, and survival data were collected. Oxygenation failure was defined as either intubation or death in the ICU without intubation. Variables independently associated with oxygenation failure and Day-90 mortality were assessed using multivariate logistic regression.

Results: From February 25 to May 4, 2020, 4754 patients were admitted in ICU. Of these, 1491 patients were not intubated on the day of ICU admission and received standard oxygen therapy (51%), HFNC (38%), or NIV (11%) (P < 0.001). Oxygenation failure occurred in 739 (50%) patients (678 intubation and 61 death). For standard oxygen, HFNC, and NIV, oxygenation failure rate was 49%, 48%, and 60% (P < 0.001). By multivariate analysis, HFNC (odds ratio [OR] 0.60, 95% confidence interval [CI] 0.36–0.99, P = 0.013) but not NIV (OR 1.57, 95% CI 0.78–3.21) was associated with a reduction in oxygenation failure). Overall 90-day mortality was 21%. By multivariable analysis, HFNC was not associated with a change in mortality (OR 0.90, 95% CI 0.61–1.33), while NIV was associated with increased mortality (OR 2.75, 95% CI 1.79–4.21, P < 0.001).

Conclusion: In patients with COVID-19, HFNC was associated with a reduction in oxygenation failure without improvement in 90-day mortality, whereas NIV was associated with a higher mortality in these patients. Randomized controlled trials are needed.


Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the ongoing coronavirus disease 2019 (COVID-19) pandemic. Understanding how clinicians can address the demand for emergency mass critical care and fine-tune the standard of care regarding oxygenation management is of the utmost importance. For instance, guidance about how to allocate scarce critical care resources such as ventilators should be made using data showing that safe alternatives to standard oxygen therapy can avoid intubation without lessening survival probabilities.

In patients with de novo acute respiratory failure admitted to the intensive care unit (ICU), high-flow nasal cannula oxygen (HFNC) and noninvasive mechanical ventilation (NIV) improve oxygenation and reduce inspiratory effort and the work of breathing.[1–3] High-flow nasal cannula oxygen has shown clinical benefit by reducing the intubation rate,[4] and its use is now recommended in de novo acute respiratory failure.[5] Noninvasive ventilation decreases the intubation rate,[6] but NIV failure and subsequent intubation is associated with higher mortality compared to first-line intubation,[7] and NIV is not recommended in de novo acute respiratory failure.[6]

In COVID-19 patients, recent data suggest that HFNC and NIV are associated with a reduction in intubation rate, but without a clear benefit on mortality.[8,9]

We hypothesized that HFNC and NIV could be beneficial to the outcome of COVID-19 patients admitted to the ICU for acute respiratory failure. This study comprised a secondary analysis of the large international COVID-ICU study[10] with the following specific objectives: 1) to quantify the respective use of standard oxygen, HFNC, and NIV; 2) to determine oxygenation failure rate (i.e., intubation rate or death in the ICU without intubation) of standard oxygen, HFNC, and NIV and to evaluate the impact of HFNC and NIV on oxygen failure; and 3) to evaluate whether HFNC and NIV use is associated with a reduction in mortality.