High-flow nasal cannula prevents intubation, occasionally (Review)

But any patient could be lucky number 17, you know?

Beginning in the 2010s, high-flow nasal cannula oxygen became widely used in acutely ill patients in developed countries, driven by clinicians’ perceptions and strong intuition that it delays or prevents the need for intubation in many patients.

There were good reasons to believe this.

You see (stay with me, now), in the context of supplemental oxygen therapy, the phrase “high-flow” means flow that is higher than some other flow, viz., that of standard oxygen therapy, whose flow is lower by comparison.

Recapping that: high-flow is high. Regular flow is lower (not high).

Wait: it gets more complicated. Flow is volume per unit of time; ergo, higher flow delivers a greater volume of a fluid (gaseous oxygen in this case) per unit of time, into the respiratory system of spontaneously breathing, acutely ill people in this instance. More flow. More oxygen. Oxygen good. Illness bad. Are you getting all this?

Tedious blogsplaining aside, HFNC O2’s higher flow rate conveys some experimentally demonstrated additional advantages over conventional nasal cannula or facemask oxygen.

High-flow nasal cannula oxygen can reliably deliver high FiO2 close to 100%, while also providing low-dose PEEP (~3-5 cm H2O), and washing out nasopharyngeal dead space with its high flow rate. Nonrebreather oxygen, by contrast, does not provide PEEP and is subject to room air entrainment into the breathing circuit, diminishing the delivered FiO2 to an unpredictable degree.

For a walk further into the weeds, read Jon’s excellent review here:

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Although many physicians consider the benefits of HFNC O2 to be self-evident, it’s easy to imagine a counterfactual: perhaps, above some threshold of acute hypoxemia, the events of progressive respiratory failure, the need for mechanical ventilation, and mortality occur equally often, such that marginal improvements in oxygenation (e.g., from SpO2 85% to 90%) have no real influence on those outcomes.

You could even go Full Contrarian and wonder if by supporting oxygenation so well in deteriorating patients, HFNC O2 might inappropriately delay intubation and lead to worse outcomes.

If HFNC O2 does have benefits in acute respiratory failure, it would be helpful to understand their magnitude, which could inform the strength of the indications for HFNC O2 in specific clinical situations.

Considering the success and speed with which HFNC O2 conquered the field, there’s surprisingly little evidence to support its use. That said, the overall body of data points in the same direction as clinical intuition and common sense.

FLORALI and HOT-ER Trials

In the FLORALI trial (NEJM 2017), among 313 patients with acute hypoxemic respiratory failure without hypercapnia or cardiogenic pulmonary edema, the 106 who were randomized to HFNC O2 had about half the mortality at 90 days than those randomized to noninvasive ventilation or standard/facemask oxygen (statistically significant). They also had a lower intubation rate (38%) than those treated with NIV (50%) or standard oxygen (47%), although this did not reach statistical significance.

In HOT-ER (n~320), patients with hypoxemic respiratory failure in the ED randomized to HFNC required numerically fewer intubations within 24 hours compared to patients treated with standard oxygen, just missing significance (p=0.053).

Colombian RCT and Meta-Analysis

During the Covid-19 pandemic, it seemed clear that HFNC oxygen prevented intubations, and this intuition was supported by the results of a small multicenter RCT in Colombia (JAMA 2021), in which HFNC O2 reduced intubation rates by about one-third (34% vs 51%) in patients with Covid-related respiratory failure.

A meta-analysis of nine RCTs (n=2,093) also suggested that HFNC O2 reduced the need for intubation (relative risk 0.85), but noted a high risk of bias in the included trials. There was no signal that HFNC O2 reduced mortality (RR 0.94).

Some trials have also suggested a benefit of HFNC at preventing the need for reintubation after an episode of mechanical ventilation.

SOHO Trial

In March 2026, the large and rigorous SOHO trial, conducted at 42 French ICUs by the same group as FLORALI (Frat et al), randomized 1,110 patients with de novo respiratory failure (mostly due to pneumonia, without hypercarbia or cardiogenic pulmonary edema) to either HFNC O2 or standard oxygen therapy (e.g., nonrebreather mask).

The mortality rate at 28 days was precisely equal at 14.6% in each arm.

HFNC O2 patients had an absolute 6% reduced incidence for intubation within 28 days (42% vs 48%). This corresponds to a number needed to treat with HFNC O2 of 17 to prevent one intubation, in this patient group.

An excess of only about one in 40 patients treated with conventional oxygen had severe hypoxemia during intubation (SpO2 <80%). Adverse events (e.g., cardiac arrest during intubation and in the ICU) occurred at rates too low for valid comparisons.

Besides its size, SOHO had the strength of methodological rigor, which included objective criteria for intubation. This standardization should have reduced the risk for bias (e.g., unblinded clinicians intubating more often in standard oxygen groups in previous trials, inflating the apparent benefit of HFNC O2).

U.S. critical care society guidelines are largely silent on the use of high-flow nasal cannula oxygen. European guidelines endorse the use of HFNC O2 in a variety of settings.

Discussion

High-flow oxygen delivers, well, a higher flow of oxygen into the respiratory system than lower-flow conventional oxygen. Oxygen good. More oxygen better?

HFNC O2 intuitively should improve mortality over conventional oxygen, but doesn’t seem to.

It should prevent the need for intubation, and it does seem to—but only occasionally, in about one in 17 patients with de novo respiratory failure (without hypercarbia or cardiogenic pulmonary edema).

It’s hard to reconcile the huge reduction in 90-day mortality (and numeric intubation rates) with HFNC O2 in the first Frat et al trial (FLORALI) with the finding of zero difference between groups in SOHO and in pooled results of multiple other randomized trials … other than to simply believe SOHO over FLORALI.

But that take itself casts significant doubt on the supposed harms of noninvasive ventilation in de novo respiratory failure (without hypercarbia or pulmonary edema), a belief among clinicians which derives in large part from FLORALI.

Because of SOHO’s size, rigor, and recency reflecting current practice, the most plausible takeaway from the trial (in the context of the larger body of research) is that high-flow nasal cannula has marginal but meaningful benefits in preventing the need for intubation and mechanical ventilation.

High-flow nasal cannula oxygen’s current widespread use in developed countries as an effective, safe, and beneficial method of noninvasive respiratory support is fully justified.

References

Frat JP, Quenot JP, Guitton C, et al. High-Flow or Standard Oxygen in Acute Hypoxemic Respiratory Failure. New England Journal of Medicine. Published online March 17, 2026. doi:https://doi.org/10.1056/nejmoa2516087

‌Frat JP, Thille AW, Mercat A, et al. High-Flow Oxygen through Nasal Cannula in Acute Hypoxemic Respiratory Failure. New England Journal of Medicine. 2015;372(23):2185-2196. doi:https://doi.org/10.1056/nejmoa1503326

Ospina-Tascón GA, Calderón-Tapia LE, García AF, et al. 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:https://doi.org/10.1001/jama.2021.20714

‌Rochwerg B, et al. High flow nasal cannula compared with conventional oxygen therapy for acute hypoxemic respiratory failure: a systematic review and meta-analysis. Intensive Care Med. 2019 May;45(5):563-572. doi: 10.1007/s00134-019-05590-5. Epub 2019 Mar 19. PMID: 30888444.

Drake MG. High-Flow Nasal Cannula Oxygen in Adults: An Evidence-based Assessment. Annals of the American Thoracic Society. 2018;15(2):145-155. doi:https://doi.org/10.1513/annalsats.201707-548fr

‌Jones PG, Kamona S, Doran O, Sawtell F, Wilsher M. Randomized Controlled Trial of Humidified High-Flow Nasal Oxygen for Acute Respiratory Distress in the Emergency Department: The HOT-ER Study. Respir Care. 2016 Mar;61(3):291-9. doi: 10.4187/respcare.04252. Epub 2015 Nov 17. PMID: 26577199.

Oczkowski S, Ergan B, Bos L, et al. ERS Clinical Practice Guidelines: high-flow nasal cannula in acute respiratory failure. European Respiratory Journal. 2021;59(4). doi:‌