High Flow Nasal Oxygen or NIV in the Immunocompromised?

There are numerous guidelines that have been published over the recent years regarding the use of high-flow nasal cannula. Those guidelines address different populations and can be found HERE. In addition, there are studies currently cooking to look at using high-flow in COPD patients. Colleagues are also looking into include high flow oxygen in the definition of ARDS. One can’t forget, of course, that the ROX Index helps predict who is going to do well, and who is likely going to need intubation when using high flow. A question that still lacks an answer, however, is regarding immunocompromised patients.Do immunocompromised patients do better when receiving either high flow nasal cannula or non-invasive ventilation (NIV, BPAP, BiPAP, CPAP)?

Previous Data Regarding High Flow in the Immunocompromised

The landmark trial looking at high flow oxygen in patients with hypoxemic respiratory failure not attributed to heart failure exacerbations and hypercapnic respiratory failure was the FLORALI trial in 2015. I covered the FLORALI trial in an older post so going into the gritty details here is beyond the scope of this post. Out of the FLORALI trial, however, the authors were able to conduct a post-hoc analysis on the patients who were immunocompromised. For historical context, that analysis was published in 2016.

In this post-hoc analysis including 82 patients out of the 310 patients from the FLORALI trial, the authors were able to determine that non-invasive ventilation was harmful for patients who are immunocompromised compared to those using high flow nasal oxygen. A question I always ask myself in studies comparing NIV to any other oxygen device is how much pressure are we providing these patients. The now-older but still extremely relevant ARDS data states that we should target 4-6cc/kg of ideal body weight. In this post-hoc analysis, however, they noted that the patients were provided with 9cmH2O over 5cmH2O with a tidal volume of 9cc/kg of ideal body weight. One could see how this is an issue as these volumes can cause barotrauma and volutrauma.

It should come as no surprise, then that “patients treated with oxygen via high-flow nasal cannula alone had lower rates of intubation and mortality compared with patients treated by non-invasive ventilation interspaced with high-flow nasal cannula”. There are limitations that come with post-hoc analyses which is why this great team of clinicians proposed and completed a prospective study called FLORALI-IM.

FLORALI-IM: High Flow alone or with NIV for the immunocompromised

The same team took a dedicated crack at sorting out which mode of providing oxygen is best for our immunocompromised patients. There was no standard oxygen group in the FLORALI-IM trial as there was in the FLORALI trial. They looked at immunocompromised patients on high flow nasal oxygen versus high flow alternating with NIV. Unfortunately, the FLORALI-IM paper is not free for you to download. It was published in March of 2022 for historical context.

They randomized 299 patients and did their statistical jumping jacks. Earlier in this post, I mentioned that the post-hoc analysis of the FLORALI trial had patients receiving 9cc/kg of IBW as their tidal volume. In the FLORALI-IM trial, they targeted 8cc/kg of IBW. FLORALI did 9 over 5. FLORALI kept the pressure support level as low as possible. They also kept the PEEP (the lower number) at at least 8cmH2O. This was done to “promote alveolar recruitment”. In other words, they gave the patients on NIV a little more TLC to avoid the barotrauma and volutrauma. In the high-flow oxygen group, they attempted to have the patients on 60L of flow. That should equal, extremely roughly speaking, a PEEP-equivalent of about 6cmH2O. This obviously has numerous caveat such as the mouth being open, etc.

One could make the argument that the reason why the FLORALI trial was a positive trial for high flow nasal oxygen because the NIV devices were managed in a suboptimal manner. This argument has been at least partially addressed here. Those critics should feel a little better of how they were managed here.

Results of the FLORALI-IM Trial

The authors listed a number of limitations and reasons why these data should be “interpreted with caution”. There was no difference in their primary nor secondary outcomes. The primary outcome was mortality at 28 days. No difference. The secondary outcomes included intubation at day 28, mortality in different subgroups (ICU, hospital, at 90 day and 180 day), ICU and hospital length of stay, etc. No difference in these either.

How do I interpret these data in high flow in the immunocompromised?

The question should then should be do all intensivists pay this level of attention to the NIV machines? Do we have protocols in place to avoid the generation of tidal volumes >8cc/kg IBW? Do we have the resources to constantly monitor these devices in order to optimize our patient care and avoid harm? Sure, there’s no difference in the multiple end-points, which is fantastic for those institutions that lack certain resources and only have NIV in house. But let’s say that you or a family member had hypoxemic respiratory failure and were immunocompromised. Would you prefer to be wearing the high flow nasal oxygen setup, or NIV? I know which one I would choose.


Frat JP, Thille AW, Mercat A, Girault C, Ragot S, Perbet S, Prat G, Boulain T, Morawiec E, Cottereau A, Devaquet J, Nseir S, Razazi K, Mira JP, Argaud L, Chakarian JC, Ricard JD, Wittebole X, Chevalier S, Herbland A, Fartoukh M, Constantin JM, Tonnelier JM, Pierrot M, Mathonnet A, Béduneau G, Delétage-Métreau C, Richard JC, Brochard L, Robert R; FLORALI Study Group; REVA Network. High-flow oxygen through nasal cannula in acute hypoxemic respiratory failure. N Engl J Med. 2015 Jun 4;372(23):2185-96. doi: 10.1056/NEJMoa1503326. Epub 2015 May 17. PMID: 25981908.
Link to Article

Frat JP, Ragot S, Girault C, Perbet S, Prat G, Boulain T, Demoule A, Ricard JD, Coudroy R, Robert R, Mercat A, Brochard L, Thille AW; REVA network. Effect of non-invasive oxygenation strategies in immunocompromised patients with severe acute respiratory failure: a post-hoc analysis of a randomised trial. Lancet Respir Med. 2016 Aug;4(8):646-652. doi: 10.1016/S2213-2600(16)30093-5. Epub 2016 May 27. PMID: 27245914.
Link to (NOT FREE) Article

Coudroy R, Frat JP, Ehrmann S, Pène F, Decavèle M, Terzi N, Prat G, Garret C, Contou D, Gacouin A, Bourenne J, Girault C, Vinsonneau C, Dellamonica J, Labro G, Jochmans S, Herbland A, Quenot JP, Devaquet J, Benzekri D, Vivier E, Nseir S, Colin G, Thevenin D, Grasselli G, Bougon D, Assefi M, Guérin C, Lherm T, Kouatchet A, Ragot S, Thille AW; FLORALI-IM study group and the REVA Research Network. High-flow nasal oxygen alone or alternating with non-invasive ventilation in critically ill immunocompromised patients with acute respiratory failure: a randomised controlled trial. Lancet Respir Med. 2022 Mar 21:S2213-2600(22)00096-0. doi: 10.1016/S2213-2600(22)00096-0. Epub ahead of print. PMID: 35325620.
Link to Article (NOT FREE)

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