FLORALI – breathe (HFHO2) in through the nose

High flow humidified nasal oxygen for respiratory failure has been gaining popularity both in adult and paediatric care in recent years. A number of studies have shown promising results.

Announced last year but published this month, FLORALI was a multicenter, sealed randomization, pragmatic RCT with a well-defined study protocol, performed in more than 20 ICUs in France and Belgium. Patients with hypoxic respiratory failure (Pa/FiO2 <39.9 KPa) almost entirely due to pneumonia) but without chronic lung disease, pulmonary oedema, shock GCS<12, hypercapnia or neutropoenia, were included. Obviously those needing emergent intubation were also excluded. 313 patients were randomised to receive:

1. face mask oxygen at 10l/min
2. high-flow (warm humidified) nasal oxygen (starting at 50l/min)
3. NIV (for at least 8hr/day, PEEP 2-10, Vt 7-10ml/kg, high-flow nasal oxygen when not on NIV)

The primary outcome was intubation within 28 days.

Of 4777 admissions with respiratory failure only 512 were eligible, and 313 randomised successfully.

• Overall there was no significant difference in the primary outcome between the 3 groups. There was an overall trend towards superiority of high-flow nasal oxygen, but the subgroup with more severe hypoxia (PaO2:FiO2 ratio of <26.7KPa) showed a significant benefit.
• 90 day mortality was a lower in the high-flow nasal oxygen group. But what does this mean if the intubation rate was no different? It was also a secondary outcome so suffers from our usual concerns.
• High flow nasal oxygen was clearly more comfortable.

Interestingly there was no significant difference among the groups in terms of the time until intubation or the reasons for intubation, suggesting NIV failure per se was not necessarily deleterious.

The lack of difference for intubation rates could have been due to slight under-powering from an over-estimation of the likely intubation rate when using standard oxygen therapy.Once intubated the excess mortality rate in NIV could possibly have been related to the relatively high tidal volumes in the NIV group, at around 9ml/Kg.

The exclusion criteria, although on the face of it sensible, actually meant just 525 of the 4777 patients were eligible for inclusion and only 313 received a treatment protocol. Being strict this study applies to around just 1 in 10 of our patients with respiratory failure. All in all a well-designed and well-enacted, important RCT that falls short of being practice-changing, so is hypothesis-generating.

Perhaps the benefits of additional pressure support are offset by the dangers of additional baro/volu/atelectatrauma. Maybe BiPAP subdues cough or gives rise to more persistent secretions.

High flow humidified nasal oxygen provides a tolerable way of delivering a small amount of PEEP, maybe helps clear CO2, and is at least beneficial as a first line therapy in the more severely hypoxaemic patient. The questions of whether early intubation is beneficial, whether NIV is actually detrimental

Many of us extrapolate the benefits beyond the tight confines of this trial already, but studies now need to focus on the subgroups in the exclusion set.

Others’ words:

The statistically awesome EMnerd review

PulmCrit – Pneumonia, BiPAP, secretions and HFNC: new lessons from FLORALI

Author JP Frat talks on the ESICM site

PulmCCM review

Bottom Line review