Edited by: Murali Shyamsundar, Queen's University Belfast, United Kingdom
Reviewed by: Claudia Crimi, Gaspare Rodolico Hospital, Italy; Bairbre AIne Mcnicholas, Saolta University Health Care Group, Ireland; Alison Bell, Saolta Hospital Group, Ireland, in collaboration with reviewer BM
This article was submitted to Intensive Care Medicine and Anesthesiology, a section of the journal Frontiers in Medicine
This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
High flow nasal oxygen is a relatively new option for treating patients with respiratory failure, which decreases work of breathing, improves tidal volume, and modestly increases positive end expiratory pressure. Despite well-described physiologic benefits, the clinical impact of high flow nasal oxygen is still under investigation. In this article, we review the most recent findings on the clinical efficacy of high flow nasal oxygen in Type I, II, III, and IV respiratory failure within adult and pediatric patients. Additionally, we discuss studies across clinical settings, including emergency departments, intensive care units, outpatient, and procedural settings.
High flow nasal oxygen (HFNO) is a relatively new modality for treating patients with respiratory failure. Historically, the term 'high-flow' referred to an increased bore size of the nasal cannula with associated gas flow. Technological advancements have significantly augmented this concept creating a class of devices called “high flow nasal oxygen.” While there are a variety of HFNO machines available, they can broadly be divided into two groups. Classic HFNO utilizes a high-flow nasal cannula providing heated, humidified air at flow rates up to 60 Liters/min with a corresponding fraction of inspired oxygen from 21 to 100%. The second category is high-velocity nasal insufflation (HVNI), which utilizes small-bore nasal cannulas to flush large airways, reducing anatomic dead space and increasing oxygen. Flow levels are limited to 40 L/min, but the air has greater kinetic energy resulting in a larger flush at equivalent flow rates (
The physiological benefits of HFNO are well-described, including decreased work of breathing, improved tidal volumes, modest increases in positive end-expiratory pressure, enhanced mucociliary clearance of secretions, and accurate delivery of FiO2 (
Acute hypoxemic respiratory failure (AHRF) describes patients with inadequate tissue oxygenation associated with partial pressures of oxygen < 60 mmHG. Non-invasive positive pressure ventilation (NIPPV) is associated with improved oxygenation but may cause lung damage through overdistention (
One of the significant recent studies was the FLORALI trial which compared intubation rates in 310 adult ICU patients with AHRF (
Overview of key clinical trials and studies.
Acute hypoxemic respiratory failure (AHRF) | Frat et al. ( |
FLORALI |
310 adult ICU patients | • No statistically significant difference in 28-day intubation rate between HFNO (38%), NIV (50%), and COT (47%). |
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Azoulay et al. ( |
HIGH – RCT |
776 adult immunocompromised ICU patients | • No significant difference in 28 or 90-day mortality between HFNO and COT. |
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Andino et al. ( |
Open-label, controlled, and single-center clinical trial | 46 ICU patients | • HFNO-treated patients required significantly less intubations (33%) than COT (63%). |
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Coudroy et al. ( |
FLORALI-IM |
300 adult immunocompromised ICU patients | • No significant difference in 28-day mortality rate between HFNO alone (36%) and alternating NIV with HFNO (35%). |
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AHRF–emergency department | Jones et al. ( |
HOT-ER |
303 patients with acute hypoxia | • No difference in HFNO or COT required NIV or IMV. |
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Macé et al. ( |
Bi-center, Prospective before-after study | 102 patients in respiratory failure | • HFNO-treated patients showed significant improvement in respiratory failure signs (61%) vs. COT (15%). |
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COVID-19 | Perkins et al. ( |
RECOVERY-RS |
1,273 patients with AHRF and COVID-19 | • Significantly less tracheal intubations or mortality within 30 days occurred in CPAP-treated patients (36.3%) than within COT-treated patients (44.4%). |
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Crimi et al. ( |
COVID-HIGH |
364 patients with COVID-19 pneumonia and mild hypoxemia | • No significant difference in escalation of respiratory support between HFNO (30.3%) and COT (38.6%). |
Lee et al. ( |
Prospective, observational study | 92 AECOPD patients | • No significant difference in intubation rate between NIV (27.3%) and HFNO (25%) at day 30. |
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Crimi et al. ( |
Prospective, observational study | 15 Patients with AECOPD and bronchiectasis | • Patients treated with HFNO over 72 h had significant improvements in RR, pCO2, pO2, Borg score, mucus production, and subjective ease of expectoration. | |||||
Post-operative respiratory failure | Stéphan et al. ( |
BIPOP study |
830 cardiothoracic surgery patients | • HFNO was not inferior to BIPAP; treatment failure occurred in 21.9% of BiPAP patients and 21.0% of HFNO. |
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Type IV Respiratory Failure | Mauri et al. ( |
Explorative physiologic study | 25 non-intubated patients with extrapulmonary sepsis or septic shock | • Respiratory effort and drive were significantly improved with HFNO in comparison to LFO. | ||||
Procedures | Frat et al. ( |
FLORALI-2 |
313 patients preoxygenated prior to intubation for acute hypoxemic respiratory failure | • No significant difference in patients with severe hypoxemia after preoxygenation with NIV (23%) or HFNO (27%). | ||||
Nay et al. ( |
ODEPHI trial |
380 gastrointestinal endoscopy patients | • HFNO significantly decreased the rate of hypoxemia SpO2 ≤ 92% compared to COT. | |||||
Thiruvenkatarajan et al. ( |
OTHER ( |
132 patients undergoing procedural sedation | • No significant difference in hypoxemic events in HFNO (7.7%) or COT with mouthguard patients (9.1%). |
The data are less clear in critically ill, immunocompromised patients. In a study of 776 such patients with AHRF, HFNO was not superior to COT in reducing 28-day mortality (
Mace et al., 2019 compared oxygen treatments in 102 ED patients with acute hypoxemia. 61% of HFNO patients showed improvement in respiratory failure symptoms after 1 h compared to 15% improvement in COT-treated (
In 204 ED patients, HVNI was non-inferior to NIPPV for all-cause respiratory distress in patients without a need for emergency intubation (
Respiratory support for preterm infants and young children in respiratory failure can be provided through non-invasive methods prior to endotracheal intubation. Recent studies have sought to evaluate the efficacy of HFNO compared to non-invasive options to ensure clinical outcomes are not worse than standard practices. Unfortunately, many studies provide contradictory evidence, which may be due to variability of methods, flow rates, and patient populations. Recent meta-analyses suggest HFNO has a higher risk of treatment failure in infants (
Individual studies have found HFNO non-inferior to nCPAP or BiPAP (
COVID-19 infections resulted in critically-ill patients with AHRF worldwide (
Recent studies have evaluated whether HFNO has a specific benefit over COT during COVID-19. HFNO-treated adults with COVID-19 had significantly reduced need for intubation (
Acute respiratory failure with hypercapnia is common in chronic obstructive pulmonary disease (COPD) patients, and NIV is the current gold standard for care (
In patients with severe COPD and ventilatory limitations during exercise, HFNO improved endurance time and dyspnea rates over COT (
In the acute care setting, NIPPV has significant benefits and remains strongly recommended for acute exacerbation of COPD (AECOPD) (
HVNI was shown to have comparable efficacy to NIPPV in hypercapnic respiratory failure, with no significant difference in treatment failure or intubation rate (
Hypercapnia is relatively rare in children and is typically associated with advanced lung diseases, such as cystic fibrosis or neuromuscular diseases (
Post-operative respiratory failure is associated with morbidity and mortality in surgical patients. HFNO was given a conditional recommendation with moderate certainty using GRADE guidelines by a joint panel of experts within the European Society of Intensive Care Medicine for usage post-operatively in high-risk and obese patients after cardiac and thoracic surgery (
In a multicenter, non-inferiority trial of patients after cardiothoracic surgery, HFNO was non-inferior to BiPAP with similar levels of treatment failure (21.9% BiPAP, 21.0% HFNO), reintubation rates (13.7% BiPAP, 14.0% HFNO) and ICU mortality (5.5% BiPAP, 6.8% HFNO) (
Patients are also at risk for type 3 respiratory failure in the immediate post-extubation period. HFNO significantly reduced reintubation rates and post-extubation respiratory failure incidence compared to COT and performed similarly to NIPPV (
Type 4 respiratory failure occurs due to failure of respiratory muscles resulting from hypoperfusion in shock. The physiologic concept behind using HFNO in this setting would provide supplemental oxygen and reduce work of breathing, allowing for lower cardiac output requirements to support respiration. This may enhance the ability of the patient to resolve metabolic acidosis through typical respiratory compensation methods. Treatment focuses on supporting respiration while identifying and correcting the source of shock. Few studies examined the clinical role of HFNO during shock-induced respiratory failure. Mauri et al. (
The authors measured respiratory effort by esophageal pressure and correlated it with plasma lactate levels and dynamic lung compliance. Both factors independently increased respiratory effort when plasma lactate levels increase, or dynamic lung compliance worsens (
Many patients benefit from preoxygenation prior to endotracheal intubation (
In a recent meta-analysis, patients preoxygenated with HFNO prior to endotracheal intubation had significantly shortened ICU LOS (mean = 1.8 days). Subgroup analysis demonstrated that HFNO significantly reduced severe hypoxemia incidence during endotracheal intubation in patients with mild hypoxemia (PaO2/FiO2 > 200 mmHg), with a number needed to treat (NNT) = 16.7. The authors concluded that there was no apparent benefit to HFNO use compared to standard care for non-hypoxic patients (
HFNO usage during apnea has recently been studied using the newly coined “Transnasal Humidified Rapid Insufflation Ventilatory Exchange” (THRIVE) technique, where HFNO maintains oxygenation during intubation and extends apnea time (
The THRIVE technique (HFNO with jaw support) was studied in 48 healthy children (0–10 yo) undergoing general anesthesia; results showed significantly longer apnea without desaturation times during intubation compared to jaw support alone (
Gastrointestinal (GI) endoscopy procedures may have complications stemming from sedation, such as respiratory depression, airway obstruction, and decreased chest wall compliance, which may induce hypoxia (
Evidence from other GI procedures produced similar results; patients undergoing advanced esophagogastroduodenoscopy with HFNO had an absolute risk reduction of 11.9% of hypoxic events compared to patients provided oxygen with low flow nasal cannulas (LFNC); NNT = 8.4 (
However, high-risk patient studies failed to observe any benefits. Morbidly obese (BMI >40 kg/m2) patients undergoing elective colonoscopy with propofol sedation were supported with HFNO or LFNO with no significant differences in desaturation incidence (
HFNO is a valuable addition to the options for managing respiratory distress. HFNO is more often portable than NIPPV, allowing greater freedom of movement for the patient and the ability to eat and speak with healthcare providers and loved ones. Additionally, HFNO patients may be managed in a range of hospital bedding areas due to mechanical constraints of NIPPV machines. Overall, more studies are needed in pediatrics, peri-operative patients, during medical procedures, type 4 respiratory distress, COVID-19, and unique patient populations.
KW, NG, and JW participated in the conception, development, and writing of this manuscript. All authors agree to be accountable for the content of the work. All authors contributed to the article and approved the submitted version.
Author JW is VP of Clinical Research for Vapotherm, Inc–a manufacturer of high flow oxygen systems. Author KW has been employed within the past 12 months as a scientific consultant. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.