The Role of High-Flow Nasal Cannula in Acute Hypoxemic Respiratory Failure: A Systematic Review and Meta-Analysis of Mortality, Intubation Rates, and ICU Outcomes

Ifrah Ul Ain; Ali Kashmoola; Preety Sainani; Aliha Rizwan; Randa Harbi; Baidaa Jasem Alakasheh; Salman Rafiq Farooqi; Shirin Alansari; Ankita Sunil; Muqtasid Khan

doi:10.70749/ijbr.v3i10.2359

Authors

Ifrah Ul Ain Jinnah Hospital, Lahore, Punjab, Pakistan.
Ali Kashmoola Alqassimi Hospital, Sharjah, UAE.
Preety Sainani Ziauddin Medical College, Karachi, Sindh, Pakistan.
Aliha Rizwan Amna Inayat Medical College, Sheikhupura, Punjab, Pakistan.
Randa Harbi Alqassimi Hospital, Sharjah, UAE.
Baidaa Jasem Alakasheh Emirates Health Service, Sharjah, UAE.
Salman Rafiq Farooqi Sindh Government Lyari General Hospital, Karachi, Sindh, Pakistan.
Shirin Alansari Sheikh Tahnoon Medical City Hospital, Alain, UAE.
Ankita Sunil Thumbay University Hospital, Ajman, UAE.
Muqtasid Khan Khyber Medical College, Peshawar, KP, Pakistan.

DOI:

https://doi.org/10.70749/ijbr.v3i10.2359

Keywords:

High-flow Nasal Cannula, Acute Hypoxemic Respiratory Failure, Intubation, Mortality, ICU Outcomes, Oxygen Therapy, Systematic Review, Meta-analysis, Randomized Controlled Trial.

Abstract

Background: Acute hypoxemic respiratory failure (AHRF) is a common reason to be admitted and die in the intensive care unit (ICU). Traditional Oxygen therapy might be unable to reverse hypoxemia and early intubation may be needed. High-flow nasal cannula (HFNC) therapy provides high flow rates of warmed, humidified oxygen and has possible physiologic and clinical advantages. Albeit there have been several randomized controlled trials (RCTs) devoted to its role, the outcomes have not been reported consistently. Objectives: To conduct a systematic review and quantitative analysis of the effects of high-flow nasal cannula versus conventional oxygen therapy on mortality, intubation rate and mortality in the ICU, in adult patients with acute hypoxemic respiratory failure. Methodology: The present systematic review and meta-analysis have been conducted in accordance with PRISMA. A search of PubMed, Scopus and Cochrane CENTRAL was conducted in full until October 2025. A total of six large RCTs were incorporated: FLORALI (Frat et al., 2015), HiFLo-COVID (Ospina-Tascgon et al., 2021), HENIVOT (Grieco et al., 2021), RECOvery-RS (Perkins et al., 2022), SOHO-COVID (Frat et al., 2022) and Covid-High (Crimi et al., 2023). Data were abstracted on mortality, intubation, and ICU related outcomes. Pooled risk ratios (RRs) were computed by means of a random-effects model [DerSimonian- Laird] with 95% confidence intervals (CIs). Results: There were six RCTs (HFNC: 1,267; Control: 1,313) that included 2,580 patients. The probability of endotracheal intubation was much lower in HFNC compared with standard oxygen therapy (RR = 0.861; 95% CI, 0.751-0.987; p = 0.032; I2 = 36%). No meaningful tendency towards a decrease in mortality was observed with HFNC (RR = 0.786; 95% CI, 0.591-1.045; p = 0.097; I2 = 31%). Outcomes associated with the ICU (escalation of respiratory support or length of stay) were positive (though not homogeneous). Conclusion: Compared to standard oxygen therapy, high-flow nasal cannula therapy reduces endotracheal intubation use in patients with acute hypoxemic respiratory failure and has a no significant possible mortality reduction. The findings of this research help to support the early use of HFNC as one of the strategies of choice in noninvasive oxygenation. More extensive studies are justified to establish its impact on outcome in the long run and in ICU.

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References

1. Azoulay, E., Lemiale, V., Mokart, D., et al. (2018). 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, 320(20), 2099–2107.

https://doi.org/10.1001/jama.2018.14282

2. Coudroy, R., Frat, J.-P., Girault, C., & Thille, A. W. (2020). Reliability of methods to estimate the fraction of inspired oxygen in patients with acute respiratory failure breathing through non-rebreather reservoir bag oxygen mask. Thorax, 75(9), 805–807.

https://doi.org/10.1136/thoraxjnl-2020-214863

3. Delclaux, C., L’Her, E., Alberti, C., et al. (2000). Treatment of acute hypoxemic nonhypercapnic respiratory insufficiency with continuous positive airway pressure delivered by a face mask: A randomized controlled trial. JAMA, 284(18), 2352–2360.

https://doi.org/10.1001/jama.284.18.2352

4. Ferrer, M., Esquinas, A., Leon, M., et al. (2003). Noninvasive ventilation in severe hypoxemic respiratory failure: A randomized clinical trial. American Journal of Respiratory and Critical Care Medicine, 168, 1438–1444.

https://doi.org/10.1164/rccm.200301-072OC

5. Ferreyro, B. L., Angriman, F., Munshi, L., et al. (2020). Association of noninvasive oxygenation strategies with all-cause mortality in adults with acute hypoxemic respiratory failure: A systematic review and meta-analysis. JAMA, 324(1), 57–67.

https://doi.org/10.1001/jama.2020.9524

6. Frat, J.-P., Girault, C., Ragot, S., Perbet, S., Prat, G., Boulain, T., … Thille, A. W. (2022). Effect of high-flow nasal cannula oxygen vs standard oxygen therapy on mortality in patients with respiratory failure due to COVID-19: The SOHO-COVID randomized clinical trial. JAMA, 328(12), 1212–1222.

https://doi.org/10.1001/jama.2022.15613

7. Frat, J.-P., Thille, A. W., Mercat, A., et al.; FLORALI Study Group; REVA Network. (2015). High-flow oxygen through nasal cannula in acute hypoxemic respiratory failure. New England Journal of Medicine, 372(23), 2185–2196.

https://doi.org/10.1056/NEJMoa1503326

8. Freitas, D. L. C., Delivoria-Papadopoulos, M., Mendelsohn, A. R., & Finger, J. (1999). Effects of increasing respiratory rate on ventilatory pattern and gas exchange in infants. Pediatric Pulmonology, 27(4), 252–260.

https://doi.org/10.1002/(SICI)1099-0496(199904)27:4<252::AID-PPUL4>3.0.CO;2-E

9. Hernandez-Romieu, A. C., Adelman, M. W., Hockstein, M. A., Robichaux, C. J., Edwards, J. A., Fazio, J. C., Blum, J. M., Jabaley, C. S., Caridi-Scheible, M., Martin, G. S., Murphy, D. J., & Auld, S. C. (2020). Timing of Intubation and Mortality Among Critically Ill Coronavirus Disease 2019 Patients: A Single-Center Cohort Study. Critical Care Medicine, 48(11), e1045–e1053.

https://doi.org/10.1097/ccm.0000000000004600

10. Jentzer, J., Dezfulian, C., & Emlet, L. (2016). High-flow oxygen through nasal cannula in acute hypoxemic respiratory failure: The FLORALI study [version 1; peer review: not peer reviewed]. F1000Research, 5, Article 41.

https://doi.org/10.12688/f1000research.7360.1

11. Kow, C. S., & Hasan, S. S. (2021). Pitfalls in reporting sample size calculation across randomized controlled trials involving ivermectin for the treatment of COVID-19. American Journal of Therapeutics, 28(5), e616–e619.

https://doi.org/10.1097/MJT.0000000000001441

12. Marciniak, S. J., Farrell, J., Rostron, A., et al. (2021). COVID-19 pneumothorax in the UK: A prospective observational study using the ISARIC WHO clinical characterization protocol. European Respiratory Journal.

https://doi.org/10.1183/13993003.00929-2021

13. Mauri, T., Turrini, C., Eronia, N., et al. (2017). Physiologic effects of high-flow nasal cannula in acute hypoxemic respiratory failure. American Journal of Respiratory and Critical Care Medicine, 195(9), 1207–1215.

https://doi.org/10.1164/rccm.201605-0916OC

14. Ospina-Tascón, G. A., Calderón-Tapia, L. E., García, A. F., et al.; HiFLo-COVID Investigators. (2021). Effect of high-flow oxygen therapy vs conventional oxygen therapy on invasive mechanical ventilation and clinical recovery in patients with severe COVID-19. JAMA, 326(21), 2161–2171.

https://doi.org/10.1001/jama.2021.20714

15. Patel, B. K., Wolfe, K. S., Pohlman, A. S., et al. (2016). Effect of noninvasive ventilation delivered by helmet vs face mask on the rate of endotracheal intubation in patients with acute respiratory distress syndrome. JAMA, 315(17), 2435–2441.

https://doi.org/10.1001/jama.2016.6338

16. Perkins, G. D., Ji, C., Connolly, B. A., Couper, K., Lall, R., Baillie, K., … McAuley, D. F.; RECOVERY-RS Collaborators. (2022). Effect of noninvasive respiratory strategies on intubation or mortality among patients with acute hypoxemic respiratory failure and COVID-19: The RECOVERY-RS randomized clinical trial. JAMA, 327(6), 546–558.

https://doi.org/10.1001/jama.2022.0028

17. Rodriguez, M., Thille, A. W., Boissier, F., et al. (2019). Predictors of successful separation from high-flow nasal oxygen therapy in patients with acute respiratory failure: A retrospective monocenter study. Annals of Intensive Care, 9(1), 101.

https://doi.org/10.1186/s13613-019-0578-8

18. Wilcox, S. R., Aydin, A., & Marcolini, E. G. (2019). Noninvasive respiratory support. In Mechanical Ventilation in Emergency Medicine (pp. 88–108). Springer, Cham.

https://doi.org/10.1007/978-3-319-98410-0_4