HOT-ER
Randomised Controlled Trial of Humidified High-Flow Nasal Oxygen for Acute Respiratory Distress in the Emergency Department
Jones. Respiratory Care 2016; 61(3):291-299. doi:10.4187/respcare.04252
Clinical Question
- In hypoxic adults presenting to the emergency department, does nasal high-flow oxygen compared to standard oxygen therapy reduce the need for advanced respiratory support?
Design
- Single-centre, randomised, controlled trial
- Randomised by custom Microsoft Access application
- Sequence concealed by sealed, opaque envelopes
- Data collected from clinical notes by non-blinded study assessor
- Intention to treat analysis
- 80% power at α=0.05 if 390 patients recruited
- Baseline conversion to advanced respiratory support of 24% based upon pilot observational study
- Expected relative reduction of 33% with nasal high-flow oxygen
Setting
- Single tertiary academic city hospital in New Zealand
- July 2012 to May 2014
Population
- Inclusion: Patient presenting to hospital via the emergency department with
- Arrival or pre-hospital SpO2 < 92% (<90% if known chronic CO2 retention)
- And respiratory rate > 22 breaths/minute
- Exclusion: Intubated pre-hospital or received non-invasive ventilation (NIV) immediately upon arrival; bullous lung disease; pneumothorax; facial abnormalities including trauma or trans-nasal neurosurgery; epistaxis within last 2 weeks
- 1,287 patients screened, 322 were randomised, 303 were analysed (19 excluded from analysis)
Intervention
- High-flow nasal oxygen
- Airvo1 or Airvo2 (Fisher & Paykel Healthcare)
- Starting 40 l/min at 37°C and FiO2 0.28
- Titrated according to clinical need
Control
- Standard oxygen therapy
- Hudson mask, Venturi device or nasal prongs
- Administered at 1-15 l/min
- Titrated according to clinical need
Management common to both groups
- The decision to convert to non-invasive ventilation (NIV) was according to the British Thoracic Society’s guidelines
- Persistent or worsening hypoxaemia
- Worsening tachypnoea
- Rising arterial PCO2
- Persistent respiratory acidosis with pH < 7.30 despite 30 minutes of optimised standard acute medical therapy
- Worsening fatigue or confusion
- Decision by the treating clinician that escalation of therapy was necessary
- Choice of NIV strategy (CPAP 5 cmH2O or BIPAP 5 and 10 cmH2O) was at clinician’s discretion
- The decision to convert to invasive positive pressure ventilation (IPPV) was also according to the BTS guidelines
- NIV criteria met and clinician anticipated that invasive ventilation will be required
- Failure of NIV
- Patient unable to maintain a patent airway or manage secretions
Outcome
- Primary outcome: no difference was seen in the rate of conversion to non-invasive ventilation (NIV) or invasive positive-pressure ventilation (IPPV)
- HFNC: 3.6%
- Standard O2: 7.3%
- P = 0.20 by Fisher’s exact test
- Absolute risk reduction: 3.6% (95% CI -1.57% to 8.79%)
- Fragility Index: -3 patients
- This means, if 3 patients who received NIV/IPPV in the HFNC group had the opposite outcome, this trial would then demonstrate a statistically significant difference
- Secondary outcome:
- Failure to tolerate therapy: clinically significant rate in HFNC group
- HFNC: 8.5% (1 in 12 patients)
- Standard O2: 0%
- Emergency department length of stay: no difference
- Hospital length of stay: no difference
- 90 day mortality: no difference
- HFNC: 21.2%
- Standard O2: 17.4%
- P = 0.47 by Fisher’s exact test
- Absolute risk reduction: 3.82% (95% CI -5.06% to 12.7%)
- Patients satisfaction survey: Overall, patients rated Standard O2 better than HFNC
- However, 48% lost-to-follow-up
- More patients described Standard O2 therapy as ‘comfortable’:
- HFNC: 73.4%
- Standard O2: 85.9%
- P = 0.076
- Failure to tolerate therapy: clinically significant rate in HFNC group
Authors’ Conclusions
- Oxygen therapy delivered by high-flow nasal cannulae did not reduce the need for non-invasive or invasive ventilation when compared against standard oxygen therapy
- However, the trial was unexpectedly underpowered and a true, clinically important benefit may exist, therefore this trial should be considered a pilot for a larger (~900 patient) trial
- One in 12 patients are intolerant of oxygen delivery via high-flow nasal cannulae
Strengths
- Important theory given increasing use of nasal high-flow oxygen therapy
- Sensible inclusion and exclusion list with good generalisability to most Emergency Departments
- Randomised, controlled trial
- Intention-to-treat analysis
Weaknesses
- Non-blinded with subjective primary outcome at clinician’s discretion
- Failed to recruit target number, so under-powered to detect the expected or a smaller difference
- Significant loss-to-follow-up for patient experience survey – strong likelihood of bias in reporting
The Bottom Line
- This trial did not demonstrate a difference between nasal high-flow oxygen and standard oxygen therapy in hypoxic and dyspneic patients arriving in the Emergency Department
- Significant weaknesses in the methodology mean that no firm conclusion can be drawn, as a false negative result may have occurred
External Links
- [article] Randomized Controlled Trial of Humidified High-Flow Nasal Oxygen for Acute Respiratory Distress in the Emergency Department: The HOT-ER Study
- [TBL summary] FLORALI trial
- [further reading] High-flow nasal cannula oxygen therapy in adults
Metadata
Summary author: Duncan Chambler
Summary date: 5th July 2016
Peer-review editor: Steve Mathieu
From a post-publication comment, I have realised that I meant to write “a false NEGATIVE result may have occurred” in my Bottom Line. Sorry everyone, and thanks to David Slessor’s sharp eye for noticing that error.
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