Based on the RENOVATE trial, should high‑flow nasal oxygen be initiated as first‑line therapy in adult emergency department patients with acute hypoxemic respiratory failure (significant hypoxemia, tachypnea, moderate ARDS) including non‑immunocompromised, immunocompromised, COPD exacerbation, acute cardiogenic pulmonary edema, or COVID‑19 pneumonia, and what are the recommended settings, monitoring, and escalation criteria?

Medical Advisory BoardAll articles are reviewed for accuracy by our Medical Advisory Board
Educational purpose only • Exercise caution as content is pending human review
Article Review Status
Submitted
Under Review
Approved

Last updated: February 12, 2026 • View editorial policy

Personalize

Help us tailor your experience

Which best describes you? Your choice helps us use language that's most understandable for you.

High-Flow Nasal Oxygen in the Emergency Department: RENOVATE Trial and Clinical Application

Direct Answer Based on RENOVATE

High-flow nasal oxygen (HFNO) should be initiated as first-line therapy in adult emergency department patients with acute hypoxemic respiratory failure, including non-immunocompromised patients, those with COPD exacerbation, acute cardiogenic pulmonary edema, and COVID-19 pneumonia, as the RENOVATE trial demonstrated noninferiority to noninvasive ventilation for endotracheal intubation or death at 7 days in 4 of 5 patient groups. 1

However, immunocompromised patients with hypoxemia should receive NIV as first-line therapy rather than HFNO, as the RENOVATE trial stopped enrollment in this subgroup for futility (57.1% vs 36.4% primary outcome rate). 1

RENOVATE Trial Key Findings

Primary Results Across Patient Groups

  • The RENOVATE trial enrolled 1,766 patients across 5 distinct ARF populations and found HFNO met prespecified noninferiority criteria (posterior probability ≥0.992 for OR <1.55) in 4 of 5 groups. 1

  • Nonimmunocompromised hypoxemic patients: Primary outcome 32.5% (HFNO) vs 33.1% (NIV); OR 1.02 (95% CrI 0.81-1.26); NPP 0.999. 1

  • Acute cardiogenic pulmonary edema: Primary outcome 10.3% (HFNO) vs 21.3% (NIV); OR 0.97 (95% CrI 0.73-1.23); NPP 0.997. 1

  • COVID-19 pneumonia: Primary outcome 51.3% (HFNO) vs 47.0% (NIV); OR 1.13 (95% CrI 0.94-1.38); NPP 0.997. 1

  • COPD exacerbation with respiratory acidosis: Primary outcome 28.6% (HFNO) vs 26.2% (NIV); OR 1.05 (95% CrI 0.79-1.36); NPP 0.992. 1

Critical Limitation in Immunocompromised Patients

  • Immunocompromised patients with hypoxemia had significantly worse outcomes with HFNO (57.1% vs 36.4% primary outcome), leading to early termination of enrollment in this subgroup (OR 1.07; 95% CrI 0.81-1.39; NPP 0.989). 1

  • Post-hoc analysis without dynamic borrowing revealed qualitatively different results in COPD, immunocompromised, and ACPE patients, suggesting caution in interpreting these subgroups. 1

Guideline-Based Recommendations for ED Application

First-Line Therapy Indications

  • The American College of Physicians recommends HFNO over NIV in hospitalized adults (including ED patients) with acute hypoxemic respiratory failure due to superior patient comfort and tolerance (conditional recommendation, low-certainty evidence). 2

  • The European Respiratory Society recommends HFNO over conventional oxygen therapy in adults with acute hypoxemic respiratory failure as preferred initial respiratory support (conditional recommendation, moderate certainty evidence). 2

  • HFNO reduces intubation risk (RR 0.89) and significantly improves patient comfort compared to conventional oxygen, with no mortality difference versus NIV in de novo acute hypoxemic respiratory failure. 3

Specific Population Guidance

Non-immunocompromised hypoxemic patients:

  • HFNO is the preferred first-line modality based on RENOVATE findings and guideline recommendations. 2, 1

Immunocompromised patients:

  • NIV should be trialed first rather than HFNO, as RENOVATE demonstrated potential harm and immunocompromised patients are at higher risk for ventilator-associated complications if intubation is delayed. 1

COPD exacerbation with respiratory acidosis:

  • NIV remains the preferred first-line therapy due to superior ventilatory support for hypercapnia, though HFNO showed noninferiority in RENOVATE with small sample size caveats. 2, 3, 1

Acute cardiogenic pulmonary edema:

  • HFNO demonstrated favorable trends in RENOVATE (10.3% vs 21.3% primary outcome), supporting its use as first-line therapy. 1

COVID-19 pneumonia:

  • HFNO is appropriate first-line therapy with close monitoring, as RENOVATE showed noninferiority despite numerically higher event rates (51.3% vs 47.0%). 1, 4

Recommended HFNO Settings in the ED

Initial Configuration

  • Start flow at 60 L/min (maximum adult capacity) to match inspiratory demands and generate approximately 7 cm H₂O positive end-expiratory pressure. 3, 5, 6

  • Set initial FiO₂ at 0.6–1.0 and titrate downward to achieve target SpO₂. 3

  • Program heated humidifier to 37°C with 100% relative humidity to optimize mucociliary clearance and patient comfort. 3, 5

Oxygenation Targets

  • Target SpO₂ 92–97% (or PaO₂ 70–90 mmHg) for patients without risk factors for hypercapnic respiratory failure. 3, 5

  • Target SpO₂ 88–92% for patients with COPD, obesity hypoventilation, neuromuscular disease, or chest wall deformities. 5

  • Titrate FiO₂ downward in 10% increments every 5 minutes once target saturation is achieved. 5

Critical Monitoring and Escalation Criteria

Immediate Assessment (30–60 Minutes)

  • Reassess patients 30–60 minutes after initiating HFNO to evaluate response, as failure to improve within 1 hour is a critical predictor of treatment failure. 3, 6

  • Obtain arterial blood gas within 30–60 minutes to assess for hypercapnia, particularly in COPD patients. 5

Continuous Monitoring Parameters

  • Respiratory rate is the most important parameter: RR >30 breaths/min indicates impending failure even if SpO₂ appears adequate. 5, 6

  • Monitor for rapid shallow breathing index (RSBI) >105 breaths/min/L, which predicts HFNC failure requiring intubation. 3, 6

  • Assess for tidal volumes persistently >9.5 mL/kg predicted body weight, suggesting need for intubation. 6

  • Monitor heart rate, blood pressure, mental status, and work of breathing at least every 2 hours initially. 5

Escalation Triggers

Immediate escalation to NIV or intubation if:

  • SpO₂ remains <94% despite FiO₂ ≥60% at 60 L/min flow. 5

  • Respiratory rate exceeds 30 breaths/min regardless of oxygen saturation. 5, 6

  • No substantial improvement in gas exchange within 1–2 hours of HFNO initiation. 3, 6

  • Development of altered mental status or inability to protect airway. 3

  • Progressive respiratory distress despite maximal HFNO settings. 3

  • Hemodynamic instability develops or multi-organ failure occurs. 3

Common Pitfalls and How to Avoid Them

Delayed Intubation

  • Prolonging HFNO in failing patients increases mortality—escalate promptly rather than persisting with inadequate support. 3, 6

  • Delayed intubation is associated with increased mortality in acute respiratory failure; do not accept marginal improvement as success. 6

Misapplication in Wrong Patient Populations

  • Do not use HFNO as first-line in immunocompromised patients with hypoxemia—the RENOVATE trial demonstrated potential harm (57.1% vs 36.4% adverse outcomes). 1

  • Do not use HFNO in patients with severe hemodynamic instability, depressed mental status, inability to protect airway, multi-organ failure, or severe facial/skull base trauma—these patients require immediate intubation. 3

Inadequate Monitoring

  • Do not rely solely on SpO₂—respiratory rate and work of breathing are more sensitive indicators of impending failure. 5, 6

  • Persistent tachypnea (RR >25 breaths/min) despite HFNO indicates likely failure even if oxygenation appears adequate. 3

Accepting Suboptimal Targets

  • Do not accept SpO₂ 89–91% as adequate—this is below target and requires immediate intervention with FiO₂ escalation or transition to NIV/intubation. 5

Practical Implementation in the ED

Equipment Requirements

  • HFNC system requires three components: nasal cannula interface, air/oxygen blender, and active humidifier. 3

  • Standard adult nasal cannula prongs accommodate flows up to 60 L/min. 3, 6

  • HFNC setup is simpler and demands less technical expertise than NIV, making it feasible in resource-constrained environments. 3

Infection Control for COVID-19

  • Use appropriate personal protective equipment, adhere to hand hygiene, place surgical mask over HFNC device, and ensure adequate room ventilation. 7

  • Individual patient factors play an important role in infection control risks with HFNC in COVID-19 patients. 7

Patient Comfort Advantages

  • HFNC eliminates claustrophobic sensation associated with mask-based systems and allows patients to eat and speak without interruption. 3

  • HFNC delivers no risk of CO₂ rebreathing due to continuous high-flow flushing of upper airway dead space. 3

  • Patients report significantly greater comfort with HFNC (standardized mean difference –0.54 in discomfort scores versus conventional oxygen). 3

Physiological Mechanisms Supporting HFNO Use

  • HFNO generates modest positive end-expiratory pressure of approximately 7 cm H₂O at 50–60 L/min flow, promoting alveolar recruitment. 3, 6

  • HFNO reduces work of breathing and inspiratory resistance more effectively than conventional face-mask oxygen delivery. 3

  • High flows flush anatomical dead space in upper airways, improving ventilation efficiency without requiring positive pressure. 6, 7

  • HFNO provides reliable FiO₂ up to 100% by matching inspiratory demands of dyspneic patients, preventing room air entrainment. 6

References

2
Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

3
Guideline

High Flow Nasal Cannula (HFNC) Indications and Guidelines

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

5
Guideline

High-Flow Nasal Cannula Settings for Post-Extubation Care

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

6
Guideline

High-Flow Nasal Cannula Therapy in Respiratory Failure

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

Related Questions

What is the step-by-step approach to managing acute respiratory failure?
In which patients is High-Flow Nasal Cannula (HFNC) therapy indicated?
For an alert, hemodynamically stable adult with acute hypoxemic respiratory failure without significant hypercapnia or severe acidosis, is high‑flow nasal cannula the appropriate first‑line oxygen therapy?
What are the initial high flow nasal cannula (HFNC) settings for an adult patient with respiratory distress or failure?
What questions should I ask and physical examination findings should I look for in a 3-year-old female patient currently on High Flow Nasal Cannula (HFNC) at 1L/kg with 25% Fraction of Inspired Oxygen (FiO2)?
What are the differential diagnoses for hypercalcemia with acute kidney injury and a suppressed parathyroid hormone level?
What are the differences between biphasic and monophasic defibrillation waveforms and their recommended initial energy settings (joules) for adult cardiac arrest?
In a 71-year-old woman with chronic heart failure and chronic respiratory failure, does Symbicort (budesonide + formoterol) cause tachycardia or raise blood glucose?
What is the next recommended pharmacologic treatment for an ADHD patient who has already trialed lisdexamfetamine 50 milligrams and methylphenidate (Foquest) 85 milligrams without adequate response?
What are the typical laboratory abnormalities in infectious mononucleosis (Epstein‑Barr virus infection) in adolescents and young adults?
Until what age should anticipatory guidance be provided in pediatric patients?

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

Have a follow-up question?

Our Medical A.I. is used by practicing medical doctors at top research institutions around the world. Ask any follow up question and get world-class guideline-backed answers instantly.

Ask Question