SGEM#505: Close Enough for (ARF) Acute Respiratory Failure (HFNO vs NIV)

Date: March 11, 2026 Reference: RENOVATE Investigators and the BRICNet Authors; High-Flow Nasal Oxygen vs Noninvasive Ventilation in Patients With Acute Respiratory Failure: The RENOVATE Randomized Clinical Trial. JAMA March 2025 Guest Skeptic: Dr. Rory Spiegel is an emergency medicine and critical care physician known for his work in evidence-based medicine and critical care. He is widely recognized for translating emerging research into practical bedside insights through lectures, writing, and digital medical education. His work focuses on resuscitation science, airway management, and the critical appraisal of medical literature. I’m in Maui at the Centre for Continuing Medical Education Year in Review Course. CCME has been doing courses for almost 40 years. The courses take place at amazing locations in the US, including Maui, Hilton Head, Key West, and NYC. CCME recruits four outstanding educators to review ~260 articles from the past year. It’s a unique course because there are no PowerPoint slides to get in the way of the attendees and the speakers. Two faculty members summarize a few articles on a topic in ½ hour with direct interaction with the speakers. You come to this course…you are up to date on the latest EM literature.   Case: A 64-year-old woman with a history of COPD (GOLD stage III) and hypertension presents to the emergency department (ED) with worsening shortness of breath over the past 24 hours. She reports increased sputum production and wheezing. On arrival, she is tachypneic and speaking in short phrases. Her vital signs are heart rate 104 beats per minute, blood pressure 148/86 mm Hg, respiratory rate 30 breaths per minute, and SpO₂ 88% on 4 L nasal cannula. She is using accessory muscles and has diffuse expiratory wheezes on auscultation. An arterial blood gas reveals pH 7.29, PaCO₂ 58 mm Hg, and PaO₂ 62 mm Hg. Chest X-ray shows hyperinflation without focal consolidation. Background: Acute respiratory failure (ARF) is one of the most common serious respiratory problems managed in emergency medicine and critical care. For decades, noninvasive ventilation (NIV) has been a central part of therapy for selected patients. This is particularly true for those with COPD exacerbations and acute cardiogenic pulmonary edema. By delivering positive pressure, NIV reduces the work of breathing, improves oxygenation and ventilation. This intervention has been shown to reduce intubation rates and mortality in specific populations. However, NIV can be poorly tolerated, requires a tight mask seal and monitoring, and is resource-intensive [1-3]. These downsides can become more problematic in disease states that are not readily reversible over the first few hours. High-flow nasal oxygen (HFNO) has emerged over the past decade as an attractive potential alternative. By delivering heated, humidified oxygen at high flow rates, HFNO improves oxygenation, improves ventilator efficiency by reducing dead space, and is often better tolerated than mask-based ventilation. Its physiologic appeal and ease of use have led to widespread adoption, particularly during the COVID-19 pandemic. Yet enthusiasm has at times outpaced evidence, and important clinical questions remain:  Is HFNO equivalent/non-inferior to NIV in preventing intubation or death? How does it perform across different types of respiratory failure? And when should clinicians choose one over the other? Clinical Question: Is HFNO noninferior to NIV regarding the rates of endotracheal intubation or death at 7 days across five distinct patient groups with ARF? Reference: RENOVATE Investigators and the BRICNet Authors; High-Flow Nasal Oxygen vs Noninvasive Ventilation in Patients With Acute Respiratory Failure: The RENOVATE Randomized Clinical Trial. JAMA March 2025 Population: Hospitalized adults with ARF (hypoxemia plus respiratory effort or tachypnea) classified into 5 groups: Nonimmunocompromised with hypoxemia Immunocompromised with hypoxemia COPD exacerbation with respiratory acidosis Acute cardiogenic pulmonary edema (ACPE) Hypoxemic COVID-19 Exclusions: The main exclusion criteria were if there was an urgent need for endotracheal intubation, hemodynamic instability or contraindications to NIV. Intervention: High-flow nasal oxygen (HFNO) delivered continuously, titrated toward 60 L/min. Comparison: Noninvasive ventilation (NIV) delivered through a face mask. Outcome: Primary Outcome: Endotracheal intubation or death within 7 days. Secondary Outcomes: 28-day and 90-day mortality, mechanical ventilation-free days, and ICU-free days. Type of Study: Multicenter, adaptive, noninferiority randomized clinical trial using a Bayesian hierarchical model with dynamic borrowing across patient groups. Authors’ Conclusions: “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.” Quality Checklist for Randomized Clinical Trials: The study population included or focused on those in the emergency department. Yes The patients were adequately randomized. Yes  The randomization process was concealed. Yes  The patients were analyzed in the groups to which they were randomized. Yes The study patients were recruited consecutively (i.e. no selection bias). Yes The patients in both groups were similar with respect to prognostic factors. Unsure All participants (patients, clinicians, outcome assessors) were unaware of group allocation. No  All groups were treated equally except for the intervention. Unsure  Follow-up was complete (i.e. at least 80% for both groups). Yes  All patient-important outcomes were considered. Yes The treatment effect was large enough and precise enough to be clinically significant. Unsure  Funding: Supported by a grant from the Brazilian Ministry of Health. Fisher & Paykel Healthcare provided the high-flow nasal oxygen equipment and associated disposables. The trial coordinating center and sponsor were the Hcor Research Institute. “The funders/sponsors had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.” Financial conflicts of interest. Multiple authors reported multiple COIs, with one author receiving personal fees from Fisher & Paykel Healthcare. Results: RENOVATE randomized 1,800 hospitalized adults with ARF across 33 hospitals in Brazil, with 1,766 completing the trial. The mean age was 64 years, and 40% of participants were women. The population was primarily older adults with moderate to severe respiratory failure. The largest of the five pre-defined subgroups (almost half) consisted of patients with hypoxemic COVID-19. Key Result: HFNO was noninferior to NIV for the composite outcome of endotracheal intubation or death within 7 days in four out of five subgroups. Primary Outcome: Endotracheal intubation or death Overall, 39% HFNO vs 38% NIV Noninferiority: Met in four of the pre-specified groups (Nonimmunocompromised, COPD, ACPE, and COVID-19). Immunocompromised Group: Stopped for futility (57.1% HFNO vs 36.4% NIV). Secondary Outcomes: There were no statistically or clinically meaningful differences in 28-day mortality, 90-day mortality, mechanical ventilation-free days, or ICU-free days overall. However, subgroup-specific secondary outcome estimates were imprecise and should be interpreted cautiously. 1. Diverse Etiology: The authors enrolled all adult patients presenting with hypoxic respiratory failure to non-invasive support with either HFNO or NIV. Using such a broad enrollment criterion led them to enroll a wide variety of clinical etiologies in this trial. The advantages of such broad inclusion criteria mean that the results can be applied broadly to patients presenting with hypoxic respiratory failure. In this case, it is likely accurate to say that neither NIV nor HFNO is superior when treating an undifferentiating population of patients with hypoxic respiratory failure. A disadvantage is that the 5 subtypes of respiratory failure represent very different physiological causes of ARF, which may respond differently to different forms of respiratory support. There may, in fact, exist potential benefits for either NIV or HFNO in one or more of these specific subgroups that are obscured when looking at this greater population. The authors address this by performing subgroup analyses for each of the 5 predefined subgroups. Unfortunately, due to the small sample sizes in each subgroup, there were too few patients to confidently demonstrate that one form of non-invasive support is preferred over the other. Therefore, the broad inclusion criteria used by these authors make it very difficult to identify a potential benefit of NIV or HFNO in any one subtype of hypoxic respiratory failure. For example, among immunocompromised patients with hypoxemia, the primary outcome (endotracheal intubation and death within 7 days) occurred in 57.1% of patients in the HFNO group vs 36.4% of patients in the NIV group. Due to the small sample sizes (28 and 22 patients in the two groups, respectively), the 20.7% difference met criteria for futility, as the confidence intervals were too wide to demonstrate non-inferiority or superiority. Open Label 2. Lack of Masking: This was an open-label trial where both clinicians and patients knew which treatment was assigned.