REBEL Core Cast 135.0: A Simple Approach to Hypoxemia (vs. Hypoxia)
In this episode, we break down a practical bedside approach to hypoxemia. We ...

REBEL Cast
οΈ Rescue BPAP use, subgroup-specific exclusion criteria, and non-standardized BPAP delivery are important contextual factors that influence how subgroup results should be interpreted.Bilevel Positive Airway Pressure (BPAP) has long been a foundational modality in the management of acute respiratory failure (ARF), particularly in COPD exacerbations and cardiogenic pulmonary edema, where it can rapidly reduce work of breathing and improve gas exchange. It remains a core tool in our respiratory support arsenal.
High-flow nasal cannula (HFNC), however, has expanded what we can offer patients by delivering many of the same physiologic benefits through a far more comfortable interface. With high flows, modest PEEP, and effective dead-space washout, HFNC can improve oxygenation and decrease work of breathing while preserving the ability to talk, cough, eat, and interact with staff and family. This combination of physiologic support and tolerability makes HFNC especially attractive in patients where comfort, anxiety, or cardiovascular stability are key considerations, and in settings where prolonged noninvasive support may be needed. Rather than competing with BPAP, HFNC broadens our options in ARF and allows us to better match the modality to the patient and their underlying disease process.
The RENOVATE trial set out to answer a high-impact question across five distinct etiologic groups: Is HFNC non-inferior to BPAP (NIV) for preventing intubation or death in acute respiratory failure?
Azoulay Γ, et al. High-Flow Nasal Oxygen vs Noninvasive Ventilation in Patients With Acute Respiratory Failure: The RENOVATE Randomized Clinical Trial. JAMA. 2025 PMID: 39657981
οΈ What They DidIs HFNC non-inferior to BPAP for rate of endotracheal intubation or death at 7 days in patients with acute respiratory failure due to a variety of causes?
1. Non-immunocompromised hypoxemia
2. Immunocompromised hypoxemia
Defined as:
3. COPD exacerbation with acidosis
4. Acute cardiogenic pulmonary edema (ACPE)
5. Hypoxemic COVID-19 (added June 2023)
Inclusion Criteria:
| Exclusion Criteria:
|
Intervention (HFNC Group):
| Comparator (BPAP Group):
|
Primary Outcome:
| Secondary Outcomes:
| Tertiary Outcomes:
|


MOR: Median Odds Ratio
MHR: Median Hazard Ratio
βHFNC met criteria for noninferiority to NIV for the primary outcome in 4 of the 5 patient groups. Small sample sizes and sensitivity to the analysis model suggest further study is needed in COPD, immunocompromised patients, and ACPE.β
HFNC appears to perform comparably to BPAP in non-immunocompromised hypoxemic and COVID-positive patients. However, the data in COPD, ACPE, and immunocompromised patients are limited and statistically fragileβheavily influenced by small numbers and modeling assumptionsβso BPAP should remain the preferred modality when ventilatory support is clearly required and may offer more reliable benefit in these groups.
HFNC is a great option for many patients with acute respiratory failure, but some patients clearly need BPAP up front. In patients with obvious BPAP-responsive physiologyβsuch as COPD with acidosis, ACPE with increased work of breathing, or frank hypercapniaβor in those who are crashing at the door, BPAP remains the first-line choice. In more stable patients, especially those without a strong indication for BPAP, with limited hypercapnia, or where comfort and longer-term tolerance matter, HFNC is a reasonable first-line option for extra respiratory support while you closely watch their trajectory and stay ready to escalate.

Jonathan Bradshaw, DO
Emergency Medicine Resident (PGY-3)
Cape Fear Valley Medical Center
Fayetteville, NC
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