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Effect of High-Flow Nasal Oxygen vs. Standard Oxygen on 28-Day Mortality in Immunocompromised Patients With Acute Respiratory Failure The HIGH Randomized Clinical Trial

Original: JAMA. 2018; 320: 2099-2107

Author(s): Azoulay E, Lemiale V, Mokart D, Nseir S, Argaud L, Pène F, Kontar L, Bruneel F, Klouche K, Barbier F, Reignier J, Berrahil-Meksen L, Louis G, Constantin JM, Mayaux J, Wallet F, Kouatchet A, Peigne V, Théodose I, Perez P, Girault C, Jaber S, Oziel J, Nyunga M, Terzi N, Bouadma L, Lebert C, Lautrette A, Bigé N, Raphalen JH, Papazian L, Darmon M, Chevret S, Demoule A.

Reviewer: Claudia Crimi

Acute hypoxemic respiratory failure (ARF) is one of the major cause of critical illness in immunocompromized patients. High flow nasal cannula (HFNC) is a relatively novel strategy to improve gas exchange in patients with ARF and might represent an appealing option for these subsets of patients.

Indeed, HFNC has shown to reduce 90-day mortality in patients with ARF compared to conventional oxygen therapy (COT) in the FLORALI trial1. However, a subsequent subgroup analysis of the trial showed no benefit in immunocompromised patients2.
The HIGH trial3 is a multicenter randomized controlled trial (RCT) conducted in 32 ICU in France that compared the use of HFNT vs. COT in 778 immunocompromized patients with ARF needing at least 6L/min oxygen with nasal cannula.
In the intervention group, HFNC was initiated at 50 L/min and FiO2 titrated to achieve SpO2  95%. In the control group, oxygen was delivered using any device (nasal prong or mask) and flow set to achieve SpO2  95%. The primary outcome was overall mortality within 28 days. The secondary outcomes were need for invasive ventilation, respiratory rate, PaO2/FIO2 ratio, patient comfort score and dyspnea score (on a visual scale), ICU and hospital lengths of stay, and incidence of ICU-acquired infections.

There was no difference in 28-day mortality: HFNC 35.6% (138/388) vs. COT 36.1% (140/388); Hazard Ratio (HR), 0.98 [95% CI, 0.77-1.24; p = .94]. No significant difference was found in intubation rate (38.7% vs. 43.8%) – HR, 0.85 [95% C.I., 0.68 to 1.06, p = 0.17], hospital length of stay (24 vs. 27 days, mean difference -2 days [95% C.I. -7.3 to 3.3], ICU length of stay (8 vs. 6 days, p=.07), ICU-acquired infections (10.0% vs. 10.6%, p=.91)], comfort and dyspnea. Respiratory rate was lower and PaO2/FIO2 was higher (150 vs. 119; mean difference, 19.5 [95% CI, 4.4-34.6] in the HFNC group.

The HIGH trial showed no mortality benefit from the use of HFNC nor a significant reduction of intubation rate. Nevertheless, it has to be considered that mortality is a very complex outcome in immunocompromized patients and that probably the study was underpowered for intubation rate (5.1% mean difference with large CI 12.3% to 2.0%, p=0.17). Moreover, as shown in a very recent metanalysis4, the HIGH trial was the first RCT on this topic and all the published studies so far, have very different methodological design; therefore, further research is needed to better address this subject.

References

  1. 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. Link: https://www.nejm.org/doi/10.1056/NEJMoa1503326?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dwww.ncbi.nlm.nih.gov
  2. 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;4(8): 646-652. doi:10.1016/S2213-2600(16)30093-5
    Link: https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(16)30093-5/fulltext
  3. Azoulay E, Lemiale V, Mokart D, Nseir S, Argaud L, Pène F, Kontar L, Bruneel F, Klouche K, Barbier F, Reignier J, Berrahil-Meksen L, Louis G, Constantin JM, Mayaux J, Wallet F, Kouatchet A, Peigne V, Théodose I, Perez P, Girault C, Jaber S, Oziel J, Nyunga M, Terzi N, Bouadma L, Lebert C, Lautrette A, Bigé N, Raphalen JH, Papazian L, Darmon M, Chevret S, Demoule A. Effect of High-Flow Nasal Oxygen vs Standard Oxygen on 28-Day Mortality in Immunocompromised Patients With Acute Respiratory Failure: The HIGH Randomized Clinical Trial. JAMA. 2018 Oct 24. doi: 10.1001/jama.2018.14282 Link: https://jamanetwork.com/journals/jama/article-abstract/2710775
  4. Cortegiani A, Crimi C, Sanfilippo F, Noto A, Di Falco D, Grasselli G, Gregoretti C, Giarratano A. High flow nasal therapy in immunocompromised patients with acute respiratory failure: A systematic review and meta-analysis. J Crit Care. 2019 Apr;50:250-256. doi: 10.1016/j.jcrc.2018.12.015. Epub 2018 Dec 29. Link:https://www.sciencedirect.com/science/article/pii/S088394411831675?via%3Dihub
Respiratory critical care
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