High-Flow Nasal Oxygen in Patients With COVID-19-Associated Acute Respiratory Failure

Ricard Mellado-Artigas; Bruno L. Ferreyro; Federico Angriman; Maria Hernandez-Sanz; Egoitz Arruti; Antoni Torres; Jesus Villar; Laurent Brochard; Carlos Ferrando


Crit Care. 2021;25(58) 

In This Article

Abstract and Introduction


Purpose: Whether the use of high-flow nasal oxygen in adult patients with COVID-19 associated acute respiratory failure improves clinically relevant outcomes remains unclear. We thus sought to assess the effect of high-flow nasal oxygen on ventilator-free days, compared to early initiation of invasive mechanical ventilation, on adult patients with COVID-19.

Methods: We conducted a multicentre cohort study using a prospectively collected database of patients with COVID-19 associated acute respiratory failure admitted to 36 Spanish and Andorran intensive care units (ICUs). Main exposure was the use of high-flow nasal oxygen (conservative group), while early invasive mechanical ventilation (within the first day of ICU admission; early intubation group) served as the comparator. The primary outcome was ventilator-free days at 28 days. ICU length of stay and all-cause in-hospital mortality served as secondary outcomes. We used propensity score matching to adjust for measured confounding.

Results: Out of 468 eligible patients, a total of 122 matched patients were included in the present analysis (61 for each group). When compared to early intubation, the use of high-flow nasal oxygen was associated with an increase in ventilator-free days (mean difference: 8.0 days; 95% confidence interval (CI): 4.4 to 11.7 days) and a reduction in ICU length of stay (mean difference: − 8.2 days; 95% CI − 12.7 to − 3.6 days). No difference was observed in all-cause in-hospital mortality between groups (odds ratio: 0.64; 95% CI: 0.25 to 1.64).

Conclusions: The use of high-flow nasal oxygen upon ICU admission in adult patients with COVID-19 related acute hypoxemic respiratory failure may lead to an increase in ventilator-free days and a reduction in ICU length of stay, when compared to early initiation of invasive mechanical ventilation. Future studies should confirm our findings.


High-flow nasal oxygen (HFNO) reduces the need for intubation in adult patients with acute respiratory failure.[1–4] This may in turn help to avoid the associated risks of invasive mechanical ventilation, such as delirium and cognitive impairment, intensive care unit (ICU) acquired weakness and secondary infections. However, through vigorous breathing efforts, spontaneous ventilation could theoretically promote further lung injury (e.g., patient self-inflicted lung injury).[5–9]

A novel coronavirus disease (COVID-19) has spread worldwide causing thousands of cases of acute respiratory failure with a high mortality rate.[10,11] Thus far, the use of HFNO has been limited, despite the fact it may represent an appropriate initial therapy.[12,13] Conversely, several studies have shown that the use of invasive mechanical ventilation remains high in this population, and patients usually receive it for prolonged periods of time.[14–16] In daily clinical practice, the decision to intubate is usually based on several clinical markers, including blood oxygenation,[17] and may differ across institutions.[18] Furthermore, based on experimental[19,20] and observational data,[5,6] a so-called "early approach" to invasive mechanical ventilation has been advocated for patients with non-COVID related ARDS.[5] Critically ill patients with COVID-19 often have profound hypoxemia which may partially explain the extremely high use of invasive ventilatory support in this patient population. This scenario, combined with the sharp rise in the incidence of COVID-19, has led to an unprecedented pressure on healthcare systems.[14,15,21–23]

Previous reports on the use of HFNO in patients with COVID-19 have been mainly limited by small sample sizes and the reporting of unadjusted effect estimates.[24] Whether HFNO decreases the need for invasive mechanical ventilation in these patients remains unknown. In this study, we aimed to estimate the effect of HFNO on ventilator-free days (VFDs), ICU length of stay and in-hospital mortality, when compared to an early intubation strategy in adult patients with COVID-19 related acute respiratory failure. Our overall aim is to better inform the use of non-invasive oxygenation/ventilation strategies and the rational allocation of invasive mechanical ventilation.