The FLORALI Trial

Non-invasive positive pressure ventilation (NIV) has been shown to decrease the work of breathing and improve gas exchange. It has been shown to reduce the need for intubation in COPD and in cardiogenic pulmonary oedema. However we don't have the evidence for the effectiveness of NIV in preventing intubation and improving outcomes for patients acute hyperaemic respiratory failure

The FLORALI Trial looked at high flow oxygen and compared it to NIV and standard oxygen therapy, in patients admitted to the ICU with acute hypoxemic respiratory failure to determine the impact on intubation rates and outcomes. The study states that it looked at patients with 'acute lung injury', however most of the patients had severe pneumonia. This is very helpful for us, as we have had little in the literature in respect to pneumonia patients. This is a good study to read.

The Study
Frat JP, et al. High Flow Oxygen Through Nasal Cannula in Acute Hypoxaemic Respiratory Failure, NEJM 2015. 372;23: 2185-2196.

What They Did

This was a prospective, multicenter, randomized, controlled trial conducted in 23 ICUs in France and Belgium.

N = 310 patients randomised to the treatments below.

Inclusion Criteria included:

• > 18 years of age
• The following four criteria had to be met
  • Respiratory rate > 25
  • PaO2: Fio2 ratio of of 300 mm Hg or less on oxygen at a flow rate of >  10 liters/min for >  15 minutes
  • PaCo2 < 45 mmHg,
  • No history of chronic respiratory failure.

Exclusion Criteria:

• PaCO2 >45 mm Hg,
• Exacerbation of asthma
• Chronic respiratory failure
• Cardiogenic pulmonary edema
• Severe neutropenia
• Hemodynamic instability
• Use of vasopressors
• Glasgow Coma Score of < 13
• Contraindications to NIV
• Urgent need for intubation
• Do-not-intubate order

Treatment Options:

1. Standard-oxygen group: non-rebreather mask at a flow rate of > 10 L/min, to maintain SpO2 > 92%
2. High-flow–oxygen group: heated humidified oxygen via large-bore binasal prongs, with a gas flow rate of 50 L/min and Fio2 of 1.0 at commencement, titrated to maintain SpO2 > 92% or more.
3. NIV: via facemask to an ICU ventilator, with pressure support to maintain expired tidal volume of 7 to 10 ml/kg, with a PEEP of 2-10 cm of water. FiO2 and/or PEEP were adjusted to maintain an SpO2 of > 92%

Primary Outcome

Proportion of patients requiring endotracheal intubation within 28 days after randomization. Prespecified criteria were used that included:

• Hemodynamic instability
• Deterioration of neurologic status
• Signs of persisting or worsening respiratory failure defined by > 2 of the following:
  • Respiratory rate > 40 breaths per minute
  • Lack of improvement in signs of high respiratory-muscle workload
  • Development of copious tracheal secretions
  • pH < 7.35
  • SpO2 < 90% for > 5 minute

Secondary outcomes

• Mortality in the ICU
• Mortality at 90 days
• Number of ventilator-free days (i.e., days alive and without invasivemechanical ventilation)
• Duration of ICU stay.

What They Found

The intubation rate:

• 47% in the standard-oxygen group
• 38% in the high-flow oxygen group
• 50% in the noninvasive-ventilation group

ICU Mortality and 90 day Mortality

• Hazard ratio for death at 90 days with standard-oxygen, compared with the high-flow–oxygen was 2.01
• Hazard ratio for death with NIV compared with the high-flow–oxygen  was 2.50

The risk of death at 90 days was significantly lower in the high-flow–oxygen group. In patients requiring intubation, the 90-day mortality did not differ between groups.

Author's Conclusion

"..treatment with high-flow oxygen improved the survival rate among patients with acute hypoxemic respiratory failure, even though no difference in the primary outcome (i.e., intubation rate) was observed with high-flow oxygen therapy, as compared with standardoxygen therapy or noninvasive ventilation."

My Take on This

This study shows me that HFNC is not inferior to NIV or high flow oxygen by rebreather, in terms of intubation rate. There was a positive effect on mortality, when using HFNC.

The study doesn't look at all lung injury however, but mostly at patients with severe pneumonia. The fact that patients on high flow were allowed 'rescue therapy' BiPAP, may affect the differences in performance of the groups.

For me, I think this is a study that has reinforced my practice of using HFNC in severe pneumonia.