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The use of High-Flow Nasal Oxygen (HFNO) in the intensive care unit (ICU) setting has increased across a variety of clinical scenarios, including early management of patients with de novo acute respiratory failure (ARF). The last European Respiratory Society (ERS) guidelines for HFNO in ARF provided a conditional recommendation for the use of HFNO over conventional oxygen therapy (COT) and over non-invasive mechanical ventilation (NIV) in adults experiencing ARF [1].

HFNO delivers up to 80 liters/min of heated and fully humidified gas with a FIO2 ranging between 21% and 100%; it generates different values of positive airway pressure (ranging between 2.7 and 7.4 cmH2O) based on the flow delivered, decreases the resistive breathing effort and then the work of breathing [2].

During the ongoing SARS-CoV2 pandemic, a significant number of patients with ARF were treated with HFNO as first line treatment, irrespectively of gas exchange impairment. The “Berlin definition” of acute respiratory distress syndrome (ARDS) does not include patients receiving HFNO, as it requires that patients must be assessed while being given a positive end expiratory pressure (PEEP) of at least 5 cmH2O [3]. Ranieri and colleagues [4] compared the proportion of patients fulfilling ARDS criteria during HFNO and soon after intubation, and 28-day mortality between patients treated exclusively with HFNO and patients transitioned from HFNO to invasive mechanical ventilation (IMV). This study is a secondary analysis of data from four previously published studies performed in Italy. Inclusion criteria selected 315 patients treated exclusively with HFNO as first line treatment (n=184) using gas flows of ≥ 40 L/min or treated with NIV (n=131) with PEEP of ≥ 5 cmH2O.


  • Most patients progressed to the need of IMV (61% in the HFNO and 53% in the NIV group).
  • Shortly after intubation, 92.9% (104/112) of patients on HFNO and 95.7% (66/69) on NIV, continued to have PaO2/FIO2 of < 300 mmHg maintaining ARDS criteria, even if ARDS severity decreased significantly after intubation.
  • Mortality in patients treated with HFNO who were not intubated was 4.2% (3/72), whereas in patients transitioned from HFNO to IMV, mortality was 28.6% (32/112) (p < 0.001). Mortality in patients treated with NIV but not intubated was 1.6% (1/62), whereas in patients who transitioned to IMV, mortality was 44.9% (31/69) (p < 0.001)


  • The patient population was small and highly selected.
  • Many patients were managed outside the ICU, which may have selected for less acutely ill patients.
  • This study included only patients with COVID-19 ARDS, thus results cannot be generalized to all ARDS patients, due to the peculiar pathophysiology of COVID-19 ARDS.


After institution of IMV, 7.1% of HFNO patients and 4.3% of NIV patients lost ARDS criteria because of the improvement PaO2/FIO2 ratio > 300 mmHg. Thus, allowing the diagnosis of ARDS in patients on HFNO may enable to detect a subgroup of patients at an earlier stage of this notable syndrome but with lower mortality.


Should the Berlin ARDS definition be broadened to include High-Flow Nasal Oxygen?  Even before the pandemic, it was clear that some patients who otherwise met the Berlin criteria for ARDS could be managed, at least initially, with HFNO rather than IMV. This has led several groups to propose that HFNO should be added to the definition of ARDS, based on the fact that low levels of positive airway pressure, provided by HFNO, fulfill the requirement for PEEP specified in the Berlin definition. Ranieri’s work observed a low mortality in both HFNO and NIV patients who did not ever require intubation. Patients who progressed to IMV had substantial mortality (29% for HFNO and 45% for NIV), suggesting that earlier diagnosis of ARDS, in these patients, could provide an important window for early monitoring and intervention in a group at high risk of poor outcomes. In this specific category, one of the mechanisms hypothesized to be involved is the Patient-Self Inflicted Lung Injury (P-SILI) generated by the strenuous respiratory effort of the patient during spontaneous breathing and the importance of monitoring it to identify promptly (e.g. Esophageal pressure monitoring) patients at risk of failure where it is recommended to start IMV with a protective protocol and to avoid an unduly continuation of non-invasive ventilatory support.


[1] Oczkowski S, Ergan B, Bos L et al. ERS Clinical Practice Guidelines: High-flow nasal cannula in acute respiratory failure. Eur Respir J. 2021 Oct 28; 2101574.

[2] Renda T, Corrado A, Iskandar G et al. High-flow nasal oxygen therapy in intensive care and anesthesia. Br J Anaesth. 2018 Jan; 120(1): 18-27.

[3] Ranieri VM, Rubenfeld GD, Thompson BT, Ferguson ND, Caldwell E, Fan E, et al. ARDS Definition Task Force. Acute respiratory distress syndrome: the Berlin definition. JAMA 2012; 307:2526–2533.

[4] Ranieri VM, Tonetti T, Navalesi P, Nava S, Antonelli M, Pesenti A, et al. High-flow nasal oxygen for severe hypoxemia: oxygenation response and outcome in patients with COVID-19. Am J Respir Crit Care Med 2022; 205:431–439.