2 AJTCCM VOL. 30 NO. 1 2024
EDITORIAL
High-ow nasal oxygen (HFNO) therapy is the provision of a heated
and humidied air/oxygen mixture at high ow rates via a large-
bore nasal cannula.[1] By heating and humidifying the air/oxygen gas
mixture, much higher ow rates of up to 60 L/min, as opposed to 15
L/min with conventional oxygen face masks, can be provided. e
physiological benets of HFNO are numerous and include washing
out carbon dioxide from the naso- and oropharynx, decreasing the
work of breathing, and improving mucociliary clearance. HFNO can
provide a fraction of inspired oxygen (FiO2) of up to 1.0 and generate
a low level of positive end-expiratory pressure (PEEP) because of
the high ow rates that are applied. From a patient point of view, the
nasal interface is comfortable, which makes it acceptable even for
claustrophobic patients to use for prolonged periods of time, compared
with the tight-tting face masks required with continuous positive
airway pressure, bilevel positive airway pressure or non-invasive
ventilation, which are oen impeded by air leaks and skin injury. e
clinical conditions and settings in which HFNO has been applied
are diverse and include hypercapnic and hypoxaemic respiratory
failure, pre-oxygenation before intubation and respiratory support
aer extubation, acute heart failure, bronchoscopic procedures, and
the palliative management of patients with respiratory failure, where
escalation to invasive mechanical ventilation is deemed futile.[2] A
major benet to healthcare institutions is the ease of use and scalability
of HFNO, since minimal training is required to be procient in its use
and it can be provided anywhere in the hospital, even outside intensive
care units (ICUs).
One of the conditions in which mechanical ventilation is still the
mainstay of treatment, as opposed to HFNO, is acute respiratory distress
syndrome (ARDS). ARDS is characterised by severe inammation
of the alveolar epithelial-capillary endothelial barrier caused by
direct or indirect pulmonary injury, resulting in diffuse protein-
rich interstitial and alveolar oedema, hyaline membrane formation,
surfactant dysfunction and pulmonary microvascular thrombosis.
[3] These pathophysiological changes lead to severe ventilation/
perfusion mismatching, increased shunt fraction, increased dead-
space ventilation, poor lung compliance and severe hypoxaemia.
As per the Berlin denition,[4] ARDS is clinically recognised by new
or worsening respiratory symptoms, bilateral pulmonary opacities,
respiratory failure that is not fully explained by cardiac failure or uid
overload, and a partial pressure of arterial oxygen (PaO2)/FiO2 ratio
≤300 while providing a PEEP level of at least 5 cm H2O. In resource-
poor as well as non-ICU settings, the Kigali modication of the Berlin
denition,[5] which uses a peripheral oxygen saturation/FiO2 ratio
≤315 with no requirement for PEEP as a dening criterion for severe
hypoxaemic respiratory failure, may be more practical. In view of
the pathophysiological changes resulting in diuse alveolar ooding,
ARDS was traditionally considered to be a condition of poor lung
compliance in which HFNO, which does not provide high levels of
PEEP, would have a minor role.
Non-invasive means of providing oxygen increased substantially
during the COVID-19 pandemic, when ICU resources were
completely overwhelmed by patients with severe acute hypoxaemic
respiratory failure (AHRF). HFNO was extensively used outside
the ICU in South Africa (SA). A previous study from Western Cape
Province in SA reported on the utility and feasibility of HFNO therapy
in patients with severe COVID-19.[6] In the current issue of AJTCCM,
Audley et al.[7] add to the body of knowledge by reporting on the
outcomes in 744 patients with severe COVID-19 who were managed
with HFNO during the rst and third waves of the pandemic. ese
were patients with severe AHRF, with median PaO2/FiO2 ratios of 57.9
and 64.3 mmHg during the rst and third waves, respectively, who
were managed in high-care wards. HFNO failed in 58.5% and 49.7% of
the patients died, with no dierences in outcomes observed between
the rst and third waves. e authors conclude that despite signicant
dierences in patient age, comorbidities and healthcare personnel
experience with HFNO, there were no differences in outcomes
between the waves. New insights into subgroups of ARDS may partly
explain why HFNO is more benecial in some patients with severe
AHRF than in others. Studies using chest computed tomography
(CT) images of patients with ARDS during the COVID-19 pandemic
assisted in categorising patients into different phenotypes: those
with focal patchy areas of consolidation with high lung compliance
and limited recruitable lung, and those with bilateral dependent
pulmonary consolidation, low lung compliance and potentially more
recruitable lung.[8] From a clinical point of view, it is oen dicult to
recognise these phenotypes at the bedside without resorting to special
investigations such as CT or electrical impedance tomography, but
the dierent phenotypes may partly explain the ecacy of HFNO in
approximately half of patients with severe COVID-19 and ARDS.
A remaining question is why patients who failed HFNO died despite
escalation to mechanical ventilation. ere may be several reasons, but
one possibility could be that positive-pressure ventilation in an already
inamed lung worsens lung damage by means of ventilator-induced
lung injury, despite applying lung-protective ventilation strategies,
thereby resulting in poor outcomes in ventilated patients. Another
possibility is that a delay in timeously recognising failure of HFNO to
decrease the work of breathing within the rst few hours of application
may worsen alveolar inammation by increased negative pleural and
thereby transpulmonary pressures, thus contributing to patient self-
inicted lung injury. Failing to recognise and act on a lack in clinical
improvement timeously makes HFNO a double-edged sword. The
expanding array of conditions for which HFNO has been found to be
benecial opens the possibility of managing more and more patients
with severe hypoxaemic respiratory failure outside the ICU, such as
in high-care or even general wards. e challenge, however, is that
failure to monitor patients on HFNO adequately may result in a delay
in timeous intubation and mechanical ventilation, thereby worsening
outcomes. It is important for clinicians practising in settings with scarce
ICU resources to be well versed and comfortable in using non-invasive
means such as HFNO for managing AHRF. We should, however,
remain vigilant and beware of becoming complacent in our monitoring
of patients while they are on HFNO, since a delay in escalating care
can have detrimental outcomes for patients and give HFNO a bad
reputation. A trial of HFNO in patients with severe AHRF to assess
High-ow nasal oxygen therapy outside the intensive care unit
AJTCCM VOL. 30 NO. 1 2024 3
EDITORIAL
for a response to treatment makes sense; however, a very low threshold
for intubation and mechanical ventilation should be maintained for
patients who fail to respond to HFNO within the rst few hours.
S Maasdorp, MB ChB, MMed (Int Med), FCP, Cert Pulmonology
(SA) Phys
Head: Pulmonology, Department of Internal Medicine, Faculty of
Health Sciences, University of the Free State, Bloenfontein, South Africa
maasdorpsd1@ufs.ac.za
1. Nishimura M. High-ow nasal cannula oxygen therapy in adults. J Intensive Care
2015;3(1):15. https://doi.org/10.1186/s40560-015-0084-5
2. Nishimura M. High-flow nasal cannula oxygen therapy in adults: Physiological
benets, indication, clinical benets, and adverse eects. Respir Care 2016;61(4):529-
541. https://doi.org/10.4187/respcare.04577
3. Bos LDJ, Ware LB. Acute respiratory distress syndrome: Causes, pathophysiology,
and phenotypes. Lancet 2022;400(10358):1145-1156. https://doi.org/10.1016/S0140-
6736(22)01485-4
4. Ferguson ND, Fan E, Camporota L, et al. The Berlin definition of ARDS: An
expanded rationale, justication, and supplementary material. Intensive Care Med
2012;38(10):1753-1582. https://doi.org/10.1007/s00134-012-2682-1
5. Riviello ED, Kiviri W, Twagirumugabe T, et al. Hospital incidence and outcomes of
the acute respiratory distress syndrome using the Kigali modication of the Berlin
denition. Am J Respir Crit Care Med 2016;193(1):52-59. https://doi.org/10.1164/
rccm.201503-0584OC
6. Calligaro GL, Lalla U, Audley G, et al. e utility of high-ow nasal oxygen for severe
COVID-19 pneumonia in a resource-constrained setting: A multi-centre prospective
observational study. EClinicalMedicine 2020;28:100570. https://doi.org/10.1016/j.
eclinm.2020.100570
7. Audley G, Raubenheimer P, Symons G, et al. High-ow nasal oxygen in resource-
constrained, non-intensive, high-care wards for COVID-19 acute hypoxaemic
respiratory failure: Comparing outcomes of the rst v. third waves in South Africa.
Afr J orac Crit Care Med 2023;30(1):e1151. https://doi.org/10.7196/AJTCCM.2023.
v30i1.1151
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2020;24(1):154. https://doi.org/10.1186/s13054-020-02880-z
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