
==== Front
Indian J Crit Care Med
Indian J Crit Care Med
IJCCM
Indian Journal of Critical Care Medicine : Peer-reviewed, Official Publication of Indian Society of Critical Care Medicine
0972-5229
1998-359X
Jaypee Brothers Medical Publishers

10.5005/jp-journals-10071-24779
Editorial
High Flow, High Hope: HFNO in Acute Hypoxemic Respiratory Failure
Pachisia Anant V 1https://orcid.org/0000-0003-1292-1141

Govil Deepak 2https://orcid.org/0000-0002-4624-1614

1 Department of Critical Care Medicine, Medanta–The Medicity, Gurugram, Haryana, India
2 Department of Critical Care Medicine and Anesthesia, Medanta–The Medicity, Gurugram, Haryana, India
Deepak Govil, Department of Critical Care Medicine and Anesthesia, Medanta–The Medicity, Gurugram, Haryana, India, Phone: +91 1126692531, e-mail: drdeepak_govil@yahoo.co.in
8 2024
31 7 2024
28 8 726728
Copyright © 2024; The Author(s).
2024
https://creativecommons.org/licenses/by-nc/4.0/ © The Author(s). 2024 Open Access. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted use, distribution, and non-commercial reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
How to cite this article: Pachisia AV, Govil D. High Flow, High Hope: HFNO in Acute Hypoxemic Respiratory Failure. Indian J Crit Care Med 2024;28(8):726–728.

Keywords

Acute hypoxemic respiratory failure
Covid pandemic
High-flow nasal oxygen
Humidified inhaled gases
Supplemental oxygenation
Work of breathing
==== Body
pmcSince the late 18th century, supplemental oxygen has been utilized as a treatment, and its use for acute hypoxemia dates back to 1887.1 In an acutely hypoxic patient, the benefit of offering supplemental oxygenation may be limited by a high inspiratory flow which results in entrainment of ambient air. In the last few years after the COVID pandemic, high-flow nasal oxygen (HFNO) has evolved, as the need for respiratory support during acute hypoxemic respiratory failure (AHRF) increased. HFNO by design is an interesting device providing the patient with heated and humidified oxygen at high flows.

High-flow nasal oxygen has several advantages over conventional supplemental oxygenation (Fig. 1):2

Fig. 1 Advantages of high-flow nasal oxygen

Heated and humidified inhaled gases increase the clearance of secretions and decrease bronchoconstriction. By heating the inhaled oxygen to 37°C and humidifying it, the mucosal function in the airway is maintained. This helps maximize the mucus removal by the cilia without the risk of thermal injury.3 Delivery of heated and humidified oxygen not only increases patient's comfort, but also decreases the risk of bronchoconstriction that occurs because of dry and cold gases.4 In a study conducted by Roca et al., involving 20 patients, it was discovered that the use of HFNO resulted in improved comfort, reduced oxygenation rate, and enhanced oxygenation.5

Dead space washout decreases minute ventilation requirements, thus decreasing respiratory rate and work of breathing. Because of its high flow, HFNO can continuously flush carbon dioxide (CO2) from the upper airway increasing the FiO2 and decreasing the fraction of inspired CO2.6

High inspiratory flow compensates for the increased peak inspiratory flow observed during respiratory distress, thereby decreasing entrainment of ambient air, hence providing a high fraction of inspired oxygen (FiO2). However, open-mouth breathing leads to lower FiO2 because of the mixing of room air with the inspired oxygen.7

Positive airway pressure may result in the recruitment of atelectatic lung fields, thus enhancing the ventilation-perfusion (V/Q) ratio. Groves and Tobin were among the first to demonstrate positive airway pressure by using HFNO. They concluded that when the mouth is closed, the expiratory pressures are higher compared to when the mouth is open, and this is dependent on the flow.8 Parke and McGuinness found that when the subjects kept their mouths closed while breathing, an increase of 10 L/min in the flow rate led to an increase of 0.69 cm H2O in the mean airway pressure (p < 0.01). When subjects breathed with their mouths open, the same increase in flow rate led to a rise in mean airway pressure by 0.35 cm H2O (p < 0.03).9 The same group in a later study also found that expiratory pressures were higher compared to mean pressures.10

The scientific evidence on the use of HFNO in AHRF started with some anecdotal reports of improved patient comfort and oxygenation. In an early prospective observational study, Sztrymf et al. compared clinical parameters and arterial blood gas in patients on conventional facemasks and HFNO having AHRF. With the use of HFNO, researchers observed a notable reduction in the respiratory rate, along with an elevation in both oxygen saturation (SpO2) and the partial pressure of oxygen (PaO2).11 In a multicenter RCT, Frat et al. studied 310 patients with AHRF and compared the effectiveness of high-flow oxygen therapy, standard oxygen therapy via a face mask, and non-invasive ventilation (NIV). They found that while there was no significant difference in intubation rates between the groups, the HFNO group had a significantly higher number of ventilation-free days at day 28 (24 ± 8 days) compared to the standard oxygen-by-face mask group (22 ± 10 days) and the NIV group (19 ± 12 days), with a p-value of 0.02 for all comparisons. There was a notable difference in the 90-day mortality rate, with the HFNO group showing more favorable results. The primary endpoint of the study was underpowered because the study was designed with the assumption that the intubation rate among standard oxygen would be 60%, but the actual rate was found to be 47%.12 A later meta-analysis of 9 RCTs of 2093 patients with AHRF found results contrary to that of the trial by FLORALI study group. The meta-analysis found a decreased risk of intubation with HFNO or escalation of oxygen therapy. They also found that HFNO has no impact on intensive care unit (ICU) length of stay (LOS), hospital LOS, patient comfort, or patient-reported dyspnea.13 The COVID pandemic expanded the use of HFNO outside of ICUs. In a prospective observational trial, 608 patients from the ward and ICU who were started on HFNO were compared. The intubation rates between the two groups were not different. The rate of mortality between the two groups was similar. Significantly more ICU-free days were seen in patients in whom HFNO was started in the ward.14 The ratio of pulse oximetry/fraction of inspired oxygen to respiratory rate is defined as the ROX index. Roca et al. found that at 12 hours the ROX index had the best prediction accuracy. ROX score of 4.88 or more after 12 hours of initiating HFNO was associated with a reduced risk of mechanical ventilation.15 In a subsequent study, it was discovered that the ROX index's ability to predict outcomes improved over time, as indicated by the increasing area under the receiver operating characteristic curve at 2 hours (0.679), 6 hours (0.703), and 12 hours (0.759). Additionally, a ROX index of 4.88 or more at 2, 6, or 12 hours was consistently linked to a reduced likelihood of requiring mechanical ventilation.16

where RR, respiratory rate; SpO2/FiO2, ratio of pulse oximetry/fraction of inspired oxygen

Magdy in their RCT on early initiated HFNO in patients with pneumonia presenting with AHRF included 160 patients. They have compared HFNO to NIV. The primary outcome was similar to the FLORALI study group i.e., the number of patients who need intubation. They found that the intubation rate between HFNO (15%) and NIV(18.7%) was not statistically different. However, they found that for the 48-hour time period, in the HFNO group, the partial pressure of oxygen (PaO2)/FiO2 ratio was significantly higher. Also observed was a significantly lower respiratory rate with HFNO at 48 hours [HFNC 20.1 ± 3.4, NIV 23.4 ± 4.2, mean difference 3.3 (95% CI 1.38–4.2, p = 0.01)]. There was no significant difference in the length of stay in the ICU or hospital between the two groups. It was concluded that ROX index value below 5.4 at the 12-hour mark was consistently linked to an increased likelihood of intubation.17

Conclusion

So we conclude that HFNO is relatively a new device with a limited number of RCTs. Though the device has been extensively used during the COVID pandemic and thereafter, evidence for prevention of intubation, mortality benefit, or LOS is inconsistent. The largest RCT was underpowered in this regard. The use of HFNO outside the ICU is also an area that can change the outcome of patients and prevent ICU admission. There is no doubt that HFNO is here to stay because of its physiological benefits and patient comfort, but the exact outcome gain requires more research.

Orcid

Anant V Pachisia https://orcid.org/0000-0003-1292-1141

Deepak Govil https://orcid.org/0000-0002-4624-1614

Source of support: Nil

Conflict of interest: None
==== Refs
References

1. Heffner JE The story of oxygen Respir Care 2013 58 1 18 31 10.4187/respcare.01831 23271817
2. Goligher EC Slutsky AS Not just oxygen? Mechanisms of benefit from high-flow nasal cannula in hypoxemic respiratory failure Am J Respir Crit Care Med 2017 195 9 1128 1131 10.1164/rccm.201701-0006ED 28459344
3. Williams R Rankin N Smith T Galler D Seakins P Relationship between the humidity and temperature of inspired gas and the function of the airway mucosa Crit Care Med 1996 24 11 1920 1929 10.1097/00003246-199611000-00025 8917046
4. Richards GN Cistulli PA Ungar RG Berthon-Jones M Sullivan CE Mouth leak with nasal continuous positive airway pressure increases nasal airway resistance Am J Respir Crit Care Med 1996 154 1 182 186 10.1164/ajrccm.154.1.8680678 8680678
5. Roca O Riera J Torres F Masclans JR High-flow oxygen therapy in acute respiratory failure Respir Care 2010 55 4 408 413 20406507 20406507
6. Spoletini G Alotaibi M Blasi F Hill NS Heated humidified high-flow nasal oxygen in adults: Mechanisms of action and clinical implications Chest 2015 148 1 253 261 10.1378/chest.14-2871 25742321
7. Ritchie JE Williams AB Gerard C Hockey H Evaluation of a humidified nasal high-flow oxygen system, using oxygraphy, capnography and measurement of upper airway pressures Anaesth Intensive Care 2011 39 6 1103 1110 10.1177/0310057X1103900620 22165366
8. Groves N Tobin A High flow nasal oxygen generates positive airway pressure in adult volunteers Aust Crit Care 2007 20 4 126 131 10.1016/j.aucc.2007.08.001 17931878
9. Parke RL Eccleston ML McGuinness SP The effects of flow on airway pressure during nasal high-flow oxygen therapy Respir Care 2011 56 8 1151 1155 10.4187/respcare.01106 21496369
10. Parke RL McGuinness SP Pressures delivered by nasal high flow oxygen during all phases of the respiratory cycle Respir Care 2013 58 10 1621 1624 10.4187/respcare.02358 23513246
11. Sztrymf B Messika J Mayot T Lenglet H Dreyfuss D Ricard JD Impact of high-flow nasal cannula oxygen therapy on intensive care unit patients with acute respiratory failure: A prospective observational study J Crit Care 2012 27 3 324.e9 e13 10.1016/j.jcrc.2011.07.075
12. Frat JP Thille AW Mercat A Girault C Ragot S Perbet S et al. FLORALI Study Group; REVA Network. High-flow oxygen through nasal cannula in acute hypoxemic respiratory failure N Engl J Med 2015 372 23 2185 2196 10.1056/NEJMoa1503326 25981908
13. Rochwerg B Granton D Wang DX Helviz Y Einav S Frat JP et al. High flow nasal cannula compared with conventional oxygen therapy for acute hypoxemic respiratory failure: A systematic review and meta-analysis Intensive Care Med 2019 45 5 563 572 10.1007/s00134-019-05590-5 30888444
14. Janssen ML Türk Y Baart SJ Hanselaar W Aga Y van der Steen-Dieperink M et al Dutch HFNO COVID-19 Study Group Safety and outcome of high-flow nasal oxygen therapy outside ICU setting in hypoxemic patients with COVID-19 Crit Care Med 2024 52 1 31 43 10.1097/CCM.0000000000006068 37855812
15. Roca O Messika J Caralt B García-de-Acilu M Sztrymf B Ricard JD et al. Predicting success of high-flow nasal cannula in pneumonia patients with hypoxemic respiratory failure: The utility of the ROX index J Crit Care 2016 35 200 205 10.1016/j.jcrc.2016.05.022 27481760
16. Roca O Caralt B Messika J Samper M Sztrymf B Hernández G et al. An index combining respiratory rate and oxygenation to predict outcome of nasal high-flow therapy Am J Respir Crit Care Med 2019 199 11 1368 1376 10.1164/rccm.201803-0589OC 30576221
17. Magdy DM Outcome of early initiation of high-flow nasal oxygen therapy among pneumonia patients presenting with acute hypoxemic respiratory failure Indian J Crit Care Med 2024 28 8 753 759
