IMPORTANCE: High-flow nasal oxygen (HFNO) and noninvasive ventilation (NIV) are commonly used respiratory support therapies for patients with acute respiratory failure (ARF).
OBJECTIVE: To assess whether HFNO is noninferior to NIV on the rates of endotracheal intubation or death at 7 days in 5 patient groups with ARF.
DESIGN, SETTING, AND PARTICIPANTS: This noninferiority, randomized clinical trial enrolled hospitalized adults (aged =18 years; classified as 5 patient groups with ARF: nonimmunocompromised with hypoxemia, immunocompromised with hypoxemia, chronic obstructive pulmonary disease [COPD] exacerbation with respiratory acidosis, acute cardiogenic pulmonary edema [ACPE], or hypoxemic COVID-19, which was added as a separate group on June 26, 2023) at 33 hospitals in Brazil between November 2019 and November 2023 (final follow-up: April 26, 2024).
INTERVENTIONS: High-flow nasal oxygen (n = 883) or NIV (n = 883).
MAIN OUTCOMES AND MEASURES: The primary outcome was endotracheal intubation or death within 7 days assessed using a bayesian hierarchical model with dynamic borrowing across patient groups. Noninferiority was defined by a posterior probability of 0.992 or greater for an odds ratio (OR) less than 1.55.
RESULTS: Among 1800 patients, 1766 completed the study (mean age, 64 [SD, 17] years; 707 [40%] were women). The primary outcome of endotracheal intubation or death at 7 days occurred in 39% (344/883) in the HFNO group vs 38% (336/883) in the NIV group. In the immunocompromised with hypoxemia patient group, the primary outcome occurred in 57.1% (16/28) in the HFNO group vs 36.4% (8/22) in the NIV group; enrollment was stopped for futility (final OR, 1.07; 95% credible interval [CrI], 0.81-1.39; noninferiority posterior probability [NPP], 0.989). In the nonimmunocompromised with hypoxemia group, the primary outcome occurred in 32.5% (81/249) in the HFNO group vs 33.1% (78/236) in the NIV group (OR, 1.02 [95% CrI, 0.81-1.26]; NPP, 0.999). In the ACPE group, the primary outcome occurred in 10.3% (14/136) in the HFNO group vs 21.3% (29/136) in the NIV group (OR, 0.97 [95% CrI, 0.73-1.23]; NPP, 0.997). In the hypoxemic COVID-19 group, the primary outcome occurred in 51.3% (223/435) in the HFNO group vs 47.0% (210/447) in the NIV group (OR, 1.13 [95% CrI, 0.94-1.38]; NPP, 0.997). In the COPD exacerbation with respiratory acidosis group, the primary outcome occurred in 28.6% (10/35) in the HFNO group vs 26.2% (11/42) in the NIV group (OR, 1.05 [95% CrI, 0.79-1.36]; NPP, 0.992). However, a post hoc analysis without dynamic borrowing across the 5 ARF patient groups revealed some qualitatively different results in patients with COPD, immunocompromised patients, and patients with ACPE. The incidence of serious adverse events was similar (9.4% of patients in HFNO group vs 9.9% in NIV group).
CONCLUSIONS AND RELEVANCE: Compared with NIV, HFNO met prespecified criteria for noninferiority for the primary outcome of endotracheal intubation or death within 7 days in 4 of the 5 patient groups with ARF. However, the small sample sizes in some patient groups and the sensitivity of the findings to the choice of analysis model suggests the need for further study in patients with COPD, immunocompromised patients, and patients with ACPE.
TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03643939.
| Discipline Area | Score |
|---|---|
| Emergency Medicine |  |
| Cardiology | |
| Hospital Doctor/Hospitalists |  |
| Internal Medicine | |
| Intensivist/Critical Care | |
| Respirology/Pulmonology | |
Overall pretty big "n" suggesting "dealer's choice" in most cases would work. Although based on the mode of action in some cases, we would select one modality over another depending on suspected pathophysiology.
This is an ambitious RCT to answer the question: Is high-flow nasal oxygen (HFNO) noninferior to noninvasive ventilation (NIV) for rate of endotracheal intubation or death at 7 days in patients with acute respiratory failure? This was done in 33 Brazilian hospitals over a 4-year period using sophisticated statistical planning and analysis. The patient groups analyzed separately were nonimmunocompromised with hypoxemia, immunocompromised with hypoxemia, COPD exacerbation with respiratory acidosis, acute cardiogenic pulmonary edema, or hypoxemic COVID-19. No difference was found between HFNO and NIV for 4 of the groups. One patient group (immunocompromised with hypoxemia) was stopped for futility; only 50 patents enrolled. (The primary outcome occurred in 57% in the HFNO group vs 36% in the NIV group.) Overall, no difference in the incidence of serious adverse events was found.
The non-inferiority conclusions among those with COPD and acute cardiogenic pulmonary edema is concerning when there is biologic plausibility for NIV to be superior, and the point estimates favor NIV when NIV is widely available with no clear signal of NIV harms. The results in the nonimmunocompromised with hypoxemia and hypoxemic COVID-19 groups are interesting, although sometimes in the acute care setting the etiology of dyspnea (CHF vs COPD vs COVID) is unclear, so uncertain how these results might be used amid that diagnostic uncertainty.
HFNC is non-inferior compared with non-invasive positive pressure ventilation (e.g., BiPAP/CPAP) for hypoxic respiratory failure. While this is at least consistent with other recent literature, there are a number of caveats: 1) patients who were immunocompromised, did not meet non-inferiority and thus cannot be included in this; 2) it's unclear whether "sicker" patients with COPD or pulmonary edema would also benefit as some analysis would suggest otherwise (e.g., a large number of patients in the COPD had crossed over into non-invasive); 3) since this treatment isn't "superior", it's unclear whether this is more cost-effective versus non-invasive PPV; and 4) secondary outcomes were not statistically significant, thus a bigger picture of benefit is unclear. Regardless, it is an option and at least for some scenarios, is non-inferior (and easier to tolerate) than NIPPV.
The definition of non-inferiority in this study was generous at an OR < 1.55. That being said the point estimates were well centered and the upper ends of the 95% CIs were quite reasonable.
Useful information for almost any hospitalist as ARF is exceedingly common. Being aware of the benefits (or lack thereof) of therapy escalation is important!
Interesting trial but complicated to apply to practice and not sure it's practice-changing.
The comparative effectiveness of noninvasive ventilation versus high flow nasal cannula (HFNC) in hypoxemic respiratory failure has been much debated. This article should reassure clinicians about using HFNC, even in some surprising conditions (e.g., COPD with acidosis) in patients intolerant of noninvasive ventilation. The main concerns are: 1) the eligibility criteria do not necessarily reflect routine practice (patients were initiated on HFNC or noninvasive with modest degrees of hypoxemia); and 2) the primary analysis and the post-hoc sensitivity analysis have discrepant results, suggesting that the underlying assumptions about similarities in treatment effect in the primary analysis may not be valid
The authors should be commended for enrolling a large number of participants over several years. The choice between high-flow nasal oxygen (HFNC) and noninvasive ventilation (NIV) in acute respiratory failure primarily rests on the work of breathing and relies on clinical judgment. The results of the study are not surprising, considering NIV is known to be most helpful for those with increased work of breathing or hypercapnic respiratory failure and the minimal proportion of the participants was hypercarbic. This study reassures that HFNC is noninferior to NIV in acute hypoxemic respiratory failure, which is consistent with the existing literature.
This adaptive RCT finds that oxygen by high-flow nasal cannula was noninferior to noninvasive ventilation in patients with acute respiratory failure. This is important validation of HFNC, which is now widely used in practice as it is much more comfortable for patients and may allow management in less closely monitored settings.
