Washington University Emergency Medicine Journal Club – February 19th, 2026
Dr. Brian Cohn
Hello all,
This month’s journal club will focus on the use of high-flow nasal cannula for respiratory failure in the ED.
The PGY-1 paper will be appraised using the Meta-Analysis form.
The PGY-2, PGY-3, and PGY-4 papers will be appraised using the Therapy form.
Vignette
A 64-year-old man presents to the emergency department with acute worsening shortness of breath over the past 12 hours. His medical history includes chronic obstructive pulmonary disease (COPD) and hypertension. He reports increased cough with sputum production and progressive dyspnea despite frequent use of his rescue inhaler. He does not use home oxygen.
On arrival, he appears uncomfortable and tachypneic, speaking in short phrases. Vital signs show a temperature of 36.7 °C, heart rate 110 beats per minute, blood pressure 150/88 mm Hg, respiratory rate 32 breaths per minute, and oxygen saturation 84% on room air. Physical examination reveals diffuse wheezing and use of accessory respiratory muscles. Venous blood gas analysis demonstrates a pH of 7.28 and PaCO₂ of 55 mm Hg, consistent with mild acute hypercapnic respiratory failure. A chest radiograph shows hyperinflation without focal infiltrates.
Despite initial treatment with bronchodilators, systemic corticosteroids, and supplemental oxygen, the patient remains tachypneic and hypoxemic. The emergency physician considers escalating respiratory support. Traditionally, bilevel positive airway pressure (BiPAP) would be initiated in this setting; however, high-flow nasal cannula (HFNC) therapy is also available and is often better tolerated.
Based on current evidence in patients with acute respiratory failure, you wonder if high-flow nasal cannula would be expected to work better for this patient than BiPAP in preventing clinical deterioration requiring endotracheal intubation, and proceed to check the literature for clues…
PICO Question
Population: Adult patients with respiratory failure requiring noninvasive, positivepressure
ventilation
Intervention: High-flow oxygen delivered by nasal cannula
Comparison: Standard noninvasive, positive-pressure ventilation via face mask or
helmet
Outcome: Need for intubation, worsening hypoxia or hypercapnia, mortality, ICUfree
days, hospital length of stay
Search Strategy
PubMed was searched using the terms “(“high flow”) AND “respiratory failure””,
which resulted in 228 citations (https://tinyurl.com/mub8ut9w). Among these,
three relevant randomized controlled trials and one meta-analysis were chosen.
Article 1: Ovtcharenko N, Ho E, Alhazzani W, et al. High-flow nasal cannula versus
non-invasive ventilation for acute hypercapnic respiratory failure in adults: a
systematic review and meta-analysis of randomized trials. Crit Care. 2022 Nov
9;26(1):348. [Answer Key].
Article 2: Doshi P, Whittle JS, Bublewicz M, et al. High-Velocity Nasal Insufflation in
the Treatment of Respiratory Failure: A Randomized Clinical Trial. Ann Emerg Med.
2018 Jul;72(1):73-83.e5. [Answer Key].
Article 3: Li XY, Tang X, Wang R, et al. High-Flow Nasal Cannula for Chronic
Obstructive Pulmonary Disease with Acute Compensated Hypercapnic Respiratory
Failure: A Randomized, Controlled Trial. Int J Chron Obstruct Pulmon Dis. 2020 Nov
24;15:3051-3061. [Answer Key].
Article 4: RENOVATE Investigators and the BRICNet Authors; Maia IS, Kawano-
Dourado L, Tramujas L, et al. High-Flow Nasal Oxygen vs Noninvasive Ventilation in
Patients With Acute Respiratory Failure: The RENOVATE Randomized Clinical Trial.
JAMA. 2025 Mar 11;333(10):875-890. [Answer Key].
Bottom Line
Both high-flow nasal cannula (HFNC) and bilevel positive airway pressure (BiPAP) provide positive pressure support in patients with respiratory failure (Sharma 2023). HFNC offers a few key advantages over BiPAP, including decreased risk of skin breakdown (Stéphan 2015), increased patient comfort (Pantazopoulos 2024), and the ability to eat and drink without interruption of flow (Charlton 2023). We reviewed three randomized controlled trials and one meta-analysis on the efficacy of HFNC, primarily attempting to establish noninferiority with traditional modes of noninvasive ventilation (e.g. BiPAP and CPAP).
One multicenter, parallel-group, noninferiority trial comparing HFNC to noninvasive positive-pressure ventilation (NIPPV) using an oronasal mask in patients requiring noninvasive ventilatory support—as determined by the treating clinician—was conducted at five centers in the southeastern US (Doshi 2018). The authors found no significant difference in intubation rates (7% vs. 13%, risk difference of -6%; 95% CI -14% to 2%). The CI did not cross the noninferiority margin of 15% and hence HFNC was found to be noninferior to NIPPV. There was also no significant difference in treatment failure rate, changes in blood gas measurements, changes in dyspnea score, or ED/hospital/ICU lengths of stay. There were trends toward improved patients comfort and greater simplicity of use.
The recently published RENOVATE trial was a multicenter, noninferiority randomized controlled trial conducted at 33 hospitals in Brazil that enrolled adult patients in the ICU, ED, or medical ward with acute respiratory failure, defined by hypoxemia and either increased respiratory effort or tachypnea. Patients were categorized into four mutually exclusive groups: non-immunocompromised with hypoxemia, immunocompromised with hypoxemia, COPD exacerbation with respiratory acidosis, or acute cardiogenic pulmonary edema. Patients were randomized to high-flow nasal oxygen via Airvo-2 or NIV via facemask. For the primary outcome (intubation or death within 7 days) the noninferiority criterion (a posterior probability higher than 0.992 for an odds ratio less than 1) was met in all groups except patients who were immunocompromised with hypoxemia. The incidence of serious adverse events was similar between the HFNO group (9.4%) and the NIV group (9.9%).
A systematic review and meta-analysis parallel-group and crossover RCTs enrolling adults with acute hypercapnic respiratory failure (defined as pH < 7.35 or PaCO2 > 45 mmHg) regardless of etiology, was published in 2022. The authors included eight studies in the final analysis comprising 528 total patients. Pooled results of 4 studies (n=250) found no significant difference in mortality (RR 0.86, 95% CI 0.48–1.56, I² = 0%, low certainty); pooled results of four studies (n=275) found no significant difference in rates of endotracheal intubation (RR 0.80, 95% CI 0.46–1.39, I² = 0%, low certainty). There was also no significant difference in ICU or hospital length of stay, measures of comfort, dyspnea, respiratory rate, PaO2, or PaCO2 between groups. Unfortunately, while the authors theorized that HFNC would be non-inferior to NIV for treatment of hypercapnic respiratory failure, they did not perform a noninferiority analysis to confirm or refute this hypothesis (Trone 2020).
Rather than compare HFNC with other modes of NIV, a fourth paper compared HFNC with conventional oxygen therapy (COT) in patients with acute exacerbations of COPD (AECOPD). This multicenter, prospective, randomized controlled clinical trial conducted at three tertiary hospitals in Beijing, China (Li 2020) enrolled patient from the general wards of respiratory departments with AECOPD accompanied by compensated hypercapnic respiratory failure (pH ≥ 7.35, PaO2 < 60 mmHg, and PaCO2 > 45 mmHg). Patients were randomized to HFNC or COT. Treatment failure (defined as the need for NIV or invasive mechanical ventilation) occurred in 10.0% of patients in the HFNC group and 19.4% in the COT group, for a risk difference of 9.4% (95% CI 1.7% to 17%; p=0.026). All treatment failure was driven by the need for NIV, as no patient in either group required intubation.
These studies all suffered from an understandable lack of blinding, which would not be possible given the intervention being studied. Additionally, much of the evicdence comes from outside the US, where differences in ethnicity, body habitus, and medical comorbidities make it difficult to generalize these results to our patient population (external validity). While not definitive, this evidence strongly suggests that HFNC is not inferior to other forms of NIV, such as BiPAP, in the management of respiratory failure of multiple etiologies. Given the improved comfort and ease of use of HFNF, it seems reasonable in select patients to begin with this modality, understanding that BiPAP remains an option if expected improvement is not seen.