SYMPOSIUM: INTENSIVE CARE
The A-B-C of high-flow
nasal oxygen therapy use
in a sick child
Toranj H Wadia
Ramnarayan Padmanabhan
Abstract
Heated humidified high flow nasal cannula therapy (HFNC) is a rela-
tively new method of oxygen delivery that came into vogue only a
decade ago. The additional physiological benefits it provides make
HFNC more than just a fancy oxygen delivery device. Theoretically,
Continuous Positive Airway Pressure (CPAP) continues to be the
gold standard therapy for moderate to severe respiratory disease.
Practically, there are limitations to its use especially in older children
outside of an intensive care setting. Initially, thought of as a step-
down or step-up from or towards CPAP i.e. halfway between CPAP
and nasal oxygen, HFNC has now overtaken CPAP as the respiratory
support mechanism of choice. Paediatricians go straight from failure
of HFNC to intubation without a trial of CPAP, or extubate children
straight onto HFNC. Today, more than a decade later, high quality ev-
idence (FIRST-ABC and Tramontane Trials) is finally available to guide
its use. The article summarises the evidence base behind the clinical
safety, efficacy, cost-effectiveness and practical use of HFNC in man-
aging sick children on high dependency and intensive care units. We
outline what HFNC therapy is, the respiratory physiology underlying
its use, currently available devices, practicalities of how to select the
flow rate and its role in current paediatric practice with clinical
examples.
Keywords Acute respiratory illness; bronchiolitis; continuous posi-
tive airway pressure; CPAP; heated humidified high flow nasal cannula
therapy; HFNC; high flow nasal cannula therapy; paediatric respiratory
support
Introduction
Heated humidified high flow nasal cannula therapy (HFNC) is a
relatively new method of oxygen delivery that came into vogue
only a decade ago. HFNC is different from routine high flow
oxygen devices and provides therapeutic benefits that extend
beyond simply delivering oxygen. Studies indicate introduction
of HFNC has resulted in significant decline in intubations for
bronchiolitis.
Toranj H Wadia MBBS MD FRCPCH Paediatric Intensive Care Fellow,
Paediatric Intensive Care Unit, Imperial Healthcare NHS Trust,
London, UK. Conflicts of interest: none declared.
Ramnarayan Padmanabhan MBBS FRCPCH MD FFICM Paediatric
Intensive Care Consultant, Paediatric Intensive Care Unit, Imperial
Healthcare NHS Trust, London, UK. Conflicts of interest: Dr
Padmanabhan is the lead investigator for FIRST-ABC Trials
referenced extensively in this review.
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The aim of this article is to summarize the current role of
HFNC in managing sick children on high dependency units and
PICUs. We will outline what HFNC therapy is, the respiratory
physiology underlying its use, currently available devices, prac-
ticalities of how to select the flow rate and its role in current
paediatric practice with clinical examples.
What is heated humidified high flow nasal cannula oxygen
therapy (HFNC)?
It is a therapy delivering adjustable and relatively constant high-
flow (2e60 L/minute) of air with desired oxygen concentrations
(21e100%), temperature (34e39
C) and relative humidity (up
to 100%) through nasal prongs.
Currently available devices for paediatric HFNC delivery
HFNC technology (see Figure 1) involves a source of
oxygen  source of air, air-oxygen blender, humidifying and
heating system, heated ventilator tubing and large (occupying
50% of the nares) but soft silicone nasal prongs.
There are two types of HFNC delivery devices:
1. Devices needing a wall mounted air and oxygen source: Pre-
cision FlowÔ by Vapotherm (delivering a maximum of 40 LPM
flow rate) and OptiflowÔ by Fisher & Paykel Healthcare Ltd
(delivering a maximum of 60 LPM flow rate).
2. Devices needing only wall mounted oxygen source: HVT 2.0Ô
(Vapotherm-5-45 LPM) and the AIRVO2Ô (Fisher & Paykel)
devices mix in room air using a turbine.
How does it work?
Box 1 lists the proposed mechanisms of action and physiological
effects of HFNC. Video 1 demonstrates HFNC set-up using a
AIRVO2Ô (Fisher & Paykel) device (the video can be found at
https://doi.org/10.1016/j.paed.2023.02.002)
How do I decide what flow to use?
Oxygen delivery devices are classified into low flow (simple
mask, nasal prongs) and high flow systems (venturi masks).
While instinctively, one might think a low flow device is one
that delivers a gas flow below a certain number for example,
less than 2e4 Litres Per Minute (LPM) in reality the level of
gas flow needed to draw the distinction is not an absolute
number. Instead, it is relative to the patient’s Peak Inspiratory
Flow Rate (PIFR) which is the flow of air needed to deliver a
set tidal volume within a set inspiratory time. PIFR is deter-
mined by the respiratory rate, inspiratory time and inspired
tidal volume, expressed as ml/second or L/minute. A high
flow device is one that can match the patient’s PIFR irre-
spective of the actual gas flow. Thus, the same device run at
the same gas flow can be a high flow device for a younger
child and a low-flow device for an older child. Similarly, the
same flow may provide high flow for a child at rest with no
respiratory distress and low flow for the same child when in
respiratory distress. The PIFR increases as respiratory rate
increases assuming the tidal volume and inspiratory: expira-
tory (I:E) ratio stay the same. Table 1 explains some basic
calculations to derive PIFR in children at different ages with
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 SYMPOSIUM: INTENSIVE CARE

Figure 1 Devices delivering HFNC therapy. Reprinted with permission from Nolasco S et al. High-flow nasal cannula oxygen therapy: physiological
mechanisms and clinical applications in children. Front Med (Lausanne) 2022:3(9):920549 under Creative Commons CC BY 4.0 licence.

and without respiratory distress used to estimate the dose for
the HFNC therapy.
An international survey of variation in practice (2020) by
Kawaguchi and colleagues showed majority of PICU physicians
start HFNC at 2 liters/kg/minute flow rate in infants and a fixed
flow rate in older children between 15 and 60 LPM. About half of
them escalate treatment to a higher flow going up to 3 liters/kg/
minute in case of failure to respond.
Studies (Franklin and colleagues) showed HFNC at 2 liters/
kg/minute significantly improved the chance of treatment suc-
cess compared to standard oxygen therapy (SOT) in bronchioli-
tis. Whilst 1 liter/kg/minute flow rate can achieve the same rate
of treatment success as 2 liters/kg/minute (Yurtseven and col-
leagues; 1 liter/kg/minute (n ¼ 88): 11.4%; 2 liters/kg/minute (n
¼ 80): 10%) it does not provide the benefit of lowering oxygen
consumption (Kepreotes and colleagues) seen with use of 2 li-
ters/kg/minute (K. Maitland and colleagues, 2021).
Although tempting, increasing the flow rate to 3 liters/kg/
minute provides no additional benefit with some risk of harm.
The TRAMONTANE 2 Trial, a large multicentre RCT, concluded
3 liters/kg/minute (n ¼ 144) did not reduce the risk of treatment
failure compared to 2 liters/kg/minute (n ¼ 142) in infants
(38.9% (3 liters) vs. 38.7% (2 liters); p ¼ 0.98). The intubation
rate [2.8% (2 liters) vs. 6.9% (3 liters), p ¼ 0.17], duration of
invasive [0.2 (2 liters) vs. 0.5 (3 liters) days, p ¼ 0.10] and
noninvasive [1.4 (2 liters) vs. 1.6 (3 liters) days, p ¼ 0.97]
ventilation was the same. Discomfort was more frequent (43%
vs. 16%, p ¼ 0.002) and PICU stays were longer (6.4 vs. 5.3 days,
p ¼ 0.048) with 3 liters/kg/minute. No patient had air leak
syndrome or died.
The flow rate you choose must match the PIFR of your patient
between 1 and 2 L/kg/minute. A good guide is Table 2 used in
the First line support for Assistance in Breathing in Children
(FIRST-ABC) trial.1,2
liters/minute), HFNC or nasal continuous positive airway pres-
sure (nCPAP). Factors influencing this decision are clinical out-
comes, cost-effectiveness, and availability/tolerance of therapies.
The FIRST-ABC step-up trial1 results represent the amount of
High dependency unit (HDU) and Paediatric intensive Care Unit
(PICU) resources currently needed for managing acute paediatric
respiratory illnesses in a developed country. The median dura-
tion of respiratory support in the study was 2e3 days with 75%
children being free of all support by day 4e5 and more than 90%
being free by day 10. 15% patients on respiratory support needed
intubation. Average length of hospital stay was as high as
20 days. The mortality was low at 1e2%. The clinical outcomes
that can be improved in current practice include length of res-
piratory support, risk of intubation and length of hospital stay.
Case 1
A 4-month-old is seen in the emergency department with a 24-hour
history of coryza and cough. On examination, he has moderate
subcostal recession and a respiratory rate of 80 bpm with no
grunting. His oxygen saturation in room air is 80% and improves to
89% in a non-rebreathing mask. CXR shows bilateral infiltrates.
Bronchiolitis is the commonest paediatric respiratory illness
indicating use of respiratory support in developed countries.
Current practice3 is SOT as first line for hypoxic children with
mild-moderate respiratory distress aiming to achieve saturations
more than 92% with up to 2 LPM nasal prong oxygen. Treatment
is either escalated to HFNC in case of respiratory deterioration/
desaturation on SOT or started as first line in children with
moderate to severe respiratory distress. A small subset of very
sick infants are started on nCPAP as first line.
This infant has moderate-severe bronchiolitis and is started on
HFNC as first line. Let us see if this choice is evidence-based,
clinically safe, cost-effective, and practical in terms of availabil-
ity and treatment compliance.

What is its place in current paediatric clinical practice?

Clinical outcomes
When faced with a hypoxic child, clinicians have to choose from Randomized controlled trials (RCT) in hypoxic children with
amongst standard (nasal prong) oxygen therapy (SOT, up to 4 bronchiolitis have successfully proved ‘treatment failure’ is

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 SYMPOSIUM: INTENSIVE CARE
Physiological mechanisms of action of high flow nasal
cannula technology
1. Reliably provides a specified concentration of oxygen
HFNC enables delivery of 100% fractional inspired oxygen (FIO2)
reliably. The only other device that can currently deliver 90e100%
FiO2 is a non-rebreathing mask with a reservoir running at 15 L/
minute if snugly fit around the face. This snug fit is rarely possible in
an awake child. HFNC is an open system and does not need a snug
nasal cannula fit. It achieves target FiO2 by matching the patient’s
peak inspiratory flow rate (PIFR). The level of respiratory distress
determines the flow rate-greater the respiratory distress more is the
patient’s PIFR. The bigger the gap between the patient’s own PIFR
and the HFNC flow rate, greater the entrainment of air around the
prongs which reduces the ability to deliver a set FiO2.
2. Pharyngeal (anatomical) dead space washout and reduction in the
work of breathing
The nasopharyngeal airway above the vocal cords has no gas ex-
change capacity i.e. it forms part of the anatomical dead space. It
warms and humidifies inspired air before it enters the lungs. Heating
and humidification by the HFNC device eliminates the need for this
space. Its presence adds to the work of breathing by increasing the
distance the air has to travel to reach the gas exchanging part of the
lungs. HFNC with its high inspired flow rate overcomes the resistance
of the nasopharynx by application of Pascal’s law: Flow ¼ Pressure
difference/Resistance (greater the flow lower the resistance)
Dead space contains the reservoir of air that is the first to be inhaled
into the alveoli for gas exchange and contains expired air with a
higher carbon dioxide (CO2) concentration. Rebreathing of this air
can increase blood CO2. Constant high inspired flow of air through
high flow replaces the anatomical dead space air (which is pushed
out from around the nasal prongs) with fresh oxygenated air. It
avoids rebreathing and improves CO2 clearance.
3. Provides flow dependant Peak end expiratory pressure (PEEP)
The constant flow of air compared to intermittent inspiratory flow
provides a level of peak end expiratory pressure (PEEP). In the
experimental setting, positive lung-distending pressure increased as
the flow increased from 0 to 12 L/minute. Limited pressure delivery of
2e4 cm H2O was measured in the pharynx and esophagus in children
and adults with HFNC. It is colloquially referred to as ‘CPAP light’.
High flow was initially advertised solely as a means of delivering
oxygen flow at a higher rate to enable giving a specific concentration
of inspired oxygen going upto 100%. But by Pascal’s law when one
provides a flow of air through small breathing tubes that provide
resistance, that flow of air generates a pressure difference which is
directly proportional to the flow and the resistance of the airways.
Pascal’s law: Pressure difference ¼ resistance  flow
The mechanism of action of high flow is not simply attributed to its
unique ability to deliver fixed oxygen concentrations but to its ability
to also deliver PEEP especially important in children less than one
year of age. Paediatric lungs have a low functional residual capacity
(FRC). When the FRC reduces because of lung collapse or consoli-
dation, it falls below the closing capacity of the lung leading to a
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complete collapse of alveoli with each breath. It then takes extra
work of breathing (WOB) to re-open a collapsed alveolus. This
increased WOB is manifested as chest recessions followed by
grunting i.e. forced expiration against a closed glottis, the body’s
mechanism of maintaining PEEP. Adding respiratory support which
delivers PEEP at this stage can relieve the child of extra work.
4. Carbon-dioxide clearance in obstructive respiratory illnesses like
asthma/viral induced wheeze
HFNC provides a peak inspiratory flow rate that overcomes airway
resistance. As seen in the calculations in Table 1, the peak inspiratory
flow rate of 2 L/kg/minute is more than that generated by the child in
severe respiratory distress assuming an I:E ratio of 1:3. In obstructive
airway diseases, the prolonged expiration may reduce the I:E ratio to
1:4 or 1:5 in which case a higher peak inspiratory flow rate will
ensure an adequate tidal volume is still delivered to the alveoli
within the constrained I-time. This improves CO2 clearance.
5. Protects the mucociliary membrane with warm humidified air
Increasing the flow brings with it the need to warm and humidify the
air. Cold dry air inhaled at high flow even over a short period is
uncomfortable and causes mucociliary damage. High flow oxygen
delivery devices delivering oxygen without heating and humidifica-
tion cause harm (nasal pain, dryness, bleeding, bronchospasm,
thickening of secretions) if used long-term. HFNC reduces the risk of
bronchospasm and prevents drying and thickening of respiratory
secretions. It also reduces respiratory metabolic expenditure-the
body does not have to spend energy heating and humidifying the
inhaled air.
Box 1
highest with SOT (Franklin and colleagues) followed by HFNC
and least likely with CPAP (TRAMONTANE trial). Patients who
‘failed treatment’ in these studies had timely and protocolized
escalation to alternate modes of respiratory support. This meant
treatment failure did not correlate with an increase in risk of
intubations, PICU admissions, PICU or hospital length of stay and
mortality (systematic reviews by Luo et al. (2019) and Lin et al.
(2019). SOT would not be clinically effective in this child but
could have been tried if the child had a milder degree of respi-
ratory distress and was maintaining saturations of more than
92% on mask oxygen.
Nasal CPAP/BiPAP was the gold standard respiratory support
for moderate to severe bronchiolitis before HFNC came into
vogue around 2009. How does HFNC compare to CPAP for
moderate to severe bronchiolitis in terms of treatment effective-
ness and outcomes?
In the multicentre randomized TRAMONTANE trial,4 Milesi
and colleagues focussed on ‘treatment failure’. They compared
HFNC 2 liters/kg/minute with CPAP 7 cm H2O specifically for
bronchiolitis children less than 6 months of age (n ¼ 142). They
found the failure rate on HFNC was more than 15% of the failure
rate on CPAP after 24 hours of treatment [31% failure on nCPAP
and 50.7% on HFNC, a difference of -19% (95% CI -35 to -3%)].
Trial results showed significantly higher treatment success
(Relative Risk RR 1.6, p ¼ 0.001) with CPAP compared to HFNC
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 SYMPOSIUM: INTENSIVE CARE

Calculations explaining peak inspiratory flow rate (PIFR) in children with normal breathing, moderate and severe
respiratory distress
Normal breathing Moderate respiratory distress Severe respiratory distress

Calculation of PIFR in a 6 month old weighing 6 kg

RR/minute 30 60 90
I:E ratio 1:3 1:3 1:3
I time 0.77 s 0.44 s 0.22 s
Required TV (assumed approx. 6 ml/kg) 40 ml 40 ml 40 ml
Peak Inspiratory Flow rate 40 ml/0.77 s 40 ml/0.44 s 40 ml/0.22 s
¼ 52 ml/second ¼ 91 ml/second ¼181 ml/second
¼ 3 L/minute ¼ 5.4 L/minute ¼11 L/minute
¼ 0.5 L/kg/minute ¼ 1 L/kg/minute ¼ 1.8 L/kg/minute
Calculation of PIFR in a 5 year old weighing 20 kg
RR/minute 20 40 60
I:E ratio 1:3 1:3 1:3
I time 0.99 s 0.49 s 0.33 s
Required TV (assumed approx. 6e8 ml/kg) 120e160 ml 120e160 ml 120e160 ml
Peak Inspiratory Flow rate 120e160 ml/second 120e160 ml/0.5 s 120 ml/0.33 s
¼ 7e9 L/minute ¼ 244 ml/second ¼363 ml/second
¼ 0.36e0.48 L/kg/minute ¼ 14e18 L/minute ¼21e27 L/minute
¼ 0.7e0.9 L/kg/minute ¼ 1e1.5 L/kg/minute
Calculation of PIFR in a 15 year old weighing 70 kg
RR/minute 15 20 30
I:E ratio 1:3 1:3 1:3
I time 1.3 1 0.5
Required TV (assumed approx. 500 ml) 500 ml 500 ml 500 ml
Peak Inspiratory Flow rate 500 ml/1.32 s 500 ml/second 500 ml/0.5 s
378 ml/second 30 L/minute 1000 ml/minute
22 L/minute 60 L/minute

PIFR does not increase in a linear fashion with age and weight. The PIFR in severe respiratory distress is 2 L/kg/minute in a 6 month old, 1e1.5 L/kg/minute in a 5 year old
and 60e80 L/minute in a teenager.

Table 1

FIRST ABC trial: flow rates used in the trial The First line support for Assistance in Breathing in Children
(FIRST-ABC) Step-up Trial2 compared use of HFNC 2 liters/kg/
Weight Dose of HFNO flow Flow range minute with nCPAP 7e8 cm H2O focussing on the outcome of
‘time to liberation from respiratory support’ rather than ‘treat-
First 12 kg 2 L/kg/minute 2e24 L/minute
ment failure’. It was not limited to a homogenous group with
13e15 kg 30 L/minute 25e30 L/minute
bronchiolitis, though bronchiolitis represented half the trial
16e30 kg 35 L/minute 30e40 L/minute
population. The median time to liberation from respiratory sup-
31e50 kg 40 L/minute 40e60 L/minute
port in the HFNC group was only 5 hours longer. They concluded
50 kg 50 L/minute
HFNC did not significantly prolong time on respiratory support
including specifically in the subgroups with bronchiolitis and
Table 2
younger infants aged less than 12 months. The rate of intubation
within 48 hours was not significantly different between the
for moderate to severe bronchiolitis. The study was not powered groups. Length of PICU stay was significantly shorter in the
to conclude nCPAP decreased need for intubation or length of HFNC group (5 days vs 7.4 days for CPAP).
stay. The failure criteria (1-point increase in mWCAS (modified The trial results helpfully demonstrated through pre-specified
Woods clinical asthma score) or discomfort EDIN (Echelle de subgroup analysis that first line use of HFNC produced the same
Douleur et d’Inconfort du Nouveau-ne) score, Respiratory rate outcome even in children presenting with severe respiratory
(RR) rise more than 10/minute with RR more than 60/minute) distress. There is however a small subset of patients in the FIRST-
were overly sensitive resulting in an overall failure rate of 40% ABC step-up trial with severe respiratory distress who were
which was much higher than their initial predicted failure rate of started on respiratory support prior to randomization. Subgroup
15% from previous studies. This could have amplified the dif- analysis (FIRST-ABC Step-up Trial) showed these children were
ference between the two therapies. sicker (more tachycardic, tachypneic, lower saturations). In

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 SYMPOSIUM: INTENSIVE CARE
these children at the very severe end of the disease spectrum,
initial use of HFNC was disadvantageous (it prolonged the length
of respiratory support by more than 18 hours) compared to
CPAP. This is indirect evidence, children presenting very sick,
could benefit from first line nCPAP instead of HFNC.
TRAMONTANE and FIRST-ABC (step-up) trials showed chil-
dren ‘failed’ HFNC more commonly because of worsening respi-
ratory distress rather than discomfort. Currently, clinician
preference in a District General Hospital (DGH) HDU with no
attached PICU support is to proceed straight from failure of HFNC/
nCPAP to intubation. Evidence suggests swapping therapies in a
timely manner using objective monitoring criteria to define
treatment failure can reduce intubation risk. Among the bron-
chiolitis cohort in TRAMONTANE, 18/22 infants who ‘failed’
CPAP were rescued by HFNC (82%), while 26/36 infants who
‘failed’ HFNC were rescued by CPAP (72%). The rate of intuba-
tion in both arms was small (3/71 infants randomized to CPAP
and 5/71 infants randomized to HFNC, p ¼ 0.72) because cross-
over between treatment arms was allowed. The FIRST-ABC trial
also showed 70e80% patients responded to swapped therapies.
Cost-effectiveness
HFNC is costlier than SOT not simply because of the cost of the
HFNC machine and consumables (humidifier, heated ventilator
circuit, special nasal prongs) but because of the increased level of
monitoring needed. Currently, HFNC is classed as a level 1 basic
critical care intervention (‘High Dependency Care for Children -
Time To Move On’) to be delivered on level 1 high dependency
units with higher nursing to patient ratios compared to SOT.
Studies in mild-moderate bronchiolitis comparing HFNC with
SOT failed to show this cost could be offset by reducing length of
oxygen supplementation (Kepreotes and colleagues), preventing
intubations and PICU admissions (Franklin and colleagues, sys-
tematic reviews by Luo et al. (2019) and Lin et al. (2019)).
60e70% children in both the Kepreotes and Franklin studies
needed no more than nasal oxygen (number needed to treat
(NNT) reported as 7 from a recent (2021) meta-analysis; n ¼
1867 children less than 2 years of age). Starting all these children
on HFNC would add significantly to the cost with no clinical
benefit from long term patient-centred outcomes. A safe time
interval for observation of these children before escalation of
therapy can be taken from the Franklin trial where escalation
after 0.67  0.83 days (around 16 hours) resulted in no observed
differences in overall outcomes.
On the other hand, High dependency units (HDU’s) need
adequate funding to ensure trial outcomes are replicated in real-
life practice despite the higher risk of treatment failure with
HFNC use in moderate to severe disease. Whilst current evidence
supports using HFNC as a substitute for CPAP for moderate to
severe disease, HFNC (labelled ‘level 1’ critical care intervention)
is still provided less funding compared to CPAP (level 2 critical
care intervention). Moderate-severe disease carries with it the
responsibility of additional monitoring, nursing input and cost
irrespective of therapy choice.
Availability and tolerance
Nasal CPAP is currently easily available for infants less than 5 kg
(on average less than 6e8 months of age) but specialized
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equipment (for example, ventilators, NIPPYÔ/ResmedÔ) to
deliver CPAP in older bronchiolitis or viral wheeze children is
not available in all settings. By contrast HFNC is now widely
available.
In the FIRST -ABC step-up trial, 50% of patients on HFNC
continued HFNC at 24 hours compared to only 30% on CPAP
indicating better tolerance of HFNC. In addition to not being
easily available, CPAP is poorly tolerated in infants aged more
than 3 months often needing sedation. Sedation use was signif-
icantly lower with HFNC (27.7% vs 37.0% for CPAP).
In conclusion, HFNC has a higher risk of treatment failure
compared to CPAP in moderate-severe bronchiolitis but does not
increase overall time on respiratory support, does not increase
risk of intubation, has better compliance, needs less sedation,
and shortens PICU length of stay. Current evidence supports
HFNC use as first line therapy in moderate to severe bronchiolitis
in infants aged less than 12 months.
Case 2
A 5-year-old boy is admitted to the paediatric HDU bed with fever,
cough and respiratory distress. On examination, he has moderate
recessions and a respiratory rate of 45 bpm. His oxygen saturation
in room air is 80%. Saturations improve to 94% on a non-
rebreathing mask. CXR shows a right basal consolidation.
This child has a lower respiratory tract infection (LRTI) and
moderate respiratory distress. Current practice is to start SOT in
hypoxic children with mild respiratory distress targeting satura-
tions more than 92%. HFNC is used as second-line therapy if
respiratory distress worsens in mild cases or as first-line in
children with moderate to severe LRTI.
Let us look at the factors governing this choice.
Clinical outcomes
In contrast to moderate bronchiolitis, both HFNC and CPAP have a
significant disease modifying effect when started in the first 48
hours in moderate LRTI. The COAST trial by K. Maitland and col-
leagues (2021) comparing HFNC with SOT and the RCT by Chisti
et al. comparing CPAP with SOT both showed higher treatment
failure coupled with higher mortality with use of SOT in moderate-
severe pneumonia independent of oxygenation (i.e. even when
patients on SOT maintained saturations more than 92%).
A comparison of clinical outcomes with HFNC vs. CPAP for
moderate-severe LRTI shows similar risks of treatment failure,
intubation, and mortality (Luo 2019, Chisti 2015).
More recently, the FIRST-ABC step-up trial (2022) showed no
significant benefit from CPAP vs. HFNC in preventing in-
tubations, reducing PICU length of stay and mortality in the small
(20%) percentage of trial population with LRTI. But a large
proportion of patients switched from CPAP to HFNC by 24 hours
making the two groups similar. This could have attenuated a
potential difference between CPAP and HFNC outcomes.
The very sick children presenting with severe respiratory
distress would once again benefit from CPAP over HFNC as
discussed above.
Cost-effectiveness
The COAST trial (K. Maitland, 2021) showed HFNC resulted in
less overall oxygen exposure to the patient and less overall
129 Ó 2023 Elsevier Ltd. All rights reserved.
 SYMPOSIUM: INTENSIVE CARE
oxygen consumption compared to SOT. In the moderate hypox-
emia stratum (80e89% saturations) only 55% needed oxygen
titrated in to keep saturations more than 92%. The oxygen used
was significantly less in HFNC (2731 liters/child) than LFO (3591
liters/child). This put patients at reduced risk of oxygen toxicity
and ensured a cost saving on the amount of oxygen consumed.
Availability and tolerance
CPAP was poorly tolerated in older children in the step-up trial as
described above. The proportion of patients switching from
HFNC to CPAP was 20% (mainly for clinical deterioration) whilst
the proportion switching from CPAP to HFNC was 31% (mainly
for patient discomfort).
Limited availability of suitable CPAP delivery devices and
interfaces for older children more than 5 kg/6e8 months and
lack of trained staff limit the practical use of CPAP in older
children with LRTI. CPAP delivery devices (for example, venti-
lators, NIPPYÔ/ResmedÔ) and different CPAP mask sizes and
types are not currently available on all HDUs nor are general
paediatric staff universally trained in their use.
This logistic problem means the older child in this case will be
started on HFNC first in many UK centres. If respiratory distress
worsens, the option of escalating to CPAP is only available in
hospitals with appropriately trained staff (mostly hospitals with
an attached PICU). In many District General Hospital (DGH)
HDUs, the only practical option after HFNC treatment failure is to
intubate this child for safe transfer to PICU at another hospital. It
is unsafe to transfer a deteriorating child at risk of needing
intubation on CPAP/HFNC in an ambulance even with a
specialized PICU transport team. PICU beds being a scarce and
expensive resource, HFNC provided on the HDU remains the
preferred cost-effective first-line therapy even in severe
pneumonia.
Case 3
A 1-year-old is extubated after 7 days of ventilation for a pneu-
monia. 12 hours post-extubation, he develops moderate respira-
tory distress with saturations of 90% in 2 LPM nasal prong
oxygen. Would you start HFNC/CPAP in this patient?
There was no evidence base to guide clinicians in this choice
until recently. Clinicians would choose HFNC or nCPAP based on
personal experience, severity of respiratory distress, age, ease of
application and perceived tolerance.
The International Clinical Practice Guidelines for Paediatric
Ventilator Liberation now recommend nCPAP for children less
than 1 year of age who are being started on non-invasive respi-
ratory support (either planned or rescue) after extubation. The
evidence behind this recent change in practice comes from the
step-down arm of the FIRST-ABC RCT.2
Clinical outcomes
The step-down FIRST-ABC RCT2 compared HFNC vs. CPAP for
children 0e15 years of age (n ¼ 553; HFNC, 281; CPAP, 272)
needing non-invasive respiratory support after extubation. ‘Time
to liberation from respiratory support’ was significantly longer
with HFNC compared to CPAP. Subgroup analysis did not
highlight any specific subgroups (ventilated 5 days, severely
hypoxemic and cardiac patients) benefitting from nCPAP but
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75% trial population was less than 1 year of age. This is why the
practice change directive by the Paediatric Ventilator Liberation
guidelines group is limited to children less than 1 year of age.
The rate of reintubation within 48 hours was not significantly
different between the groups (HFNC, 13.3%; CPAP, 11.5%;
adjusted OR, 1.17 [95% CI, 0.7e2.0]) but time to reintubation
was longer for patients receiving HFNC (25 hours vs. 11 hours)
indicating a delay in escalation. There was no difference in
mortality at PICU discharge but mortality at 180 days was
significantly higher in the HFNC group (5.6% vs 2.4% for CPAP;
adjusted OR, 3.07 [95% CI, 1.1e8.8]. This has to be interpreted
cautiously. Despite randomization, there were more newborns
and cardiac patients in the HFNC group potentially with associ-
ated chronic respiratory changes, which may have prolonged
time to liberation and increased mortality at 6 months.
Cost-effectiveness
The cost-effectiveness outcome of the trial has not been pub-
lished yet. Use of CPAP is cost-effective by reducing the length of
time for which respiratory support is needed. But this benefit
may be offset by its inability to significantly reduce the reintu-
bation rate, mean PICU length of stay (6 days) and mean hospital
length of stay (20 days).
Availability and tolerance
There was no difference in the complication rate (including
pneumothorax and nasal/facial trauma), possibly due to the
short duration of respiratory support.
37% of HFNC switched to CPAP mainly for clinical deterio-
ration and 33% CPAP switched to HFNC mainly for discomfort
indicating a better overall tolerance of CPAP compared to the
step-up trial. This could be related to a level of weakness from
being critically ill or presence of residual sedation/ongoing
sedation to reduce withdrawal side-effects. Either way tolerance/
compliance with CPAP no longer seemed a limiting factor in this
cohort.
CPAP is easily available on all PICUs, so availability does not
influence the decision making. Though the fact that HFNC can be
provided on the ward has the potential to enable faster patient
flow if the patient is being transferred to an in-hospital ward
especially when bed pressures are high in winter.
Monitoring on HFNC
This involves two aspects: monitoring for treatment failure and
complications.
Treatment failure
Evidence suggests treatment failure on HFNC is related to clinical
deterioration rather than patient discomfort.
Clinical deterioration: This is measured through objective
criteria such as those in Table 3 used in the TRAMONTANE4 and
FIRST-ABC1,2 trials.
In clinical practice, worsening objective criteria, growing sub-
jective (parental and staff) concerns of respiratory fatigue and a
rising carbon dioxide on the blood gas with worsening respiratory
acidosis prompt treatment escalation. The aim is to avoid an un-
planned respiratory arrest with emergency intubation.
130 Ó 2023 Elsevier Ltd. All rights reserved.
 SYMPOSIUM: INTENSIVE CARE

patient discomfort on HFNC for example, the EDIN score used in

Objective failure criteria used in TRAMONTANE and the TRAMONTANE trial and the COMFORT-B (Behaviour) score
FIRST-ABC trials used in FIRST-ABC Trials.
TRAMONTANE trial criteria FIRST-ABC trial criteria
Monitoring complications
Modified Woods Clinical Asthma FIO2 requirement 0.60 to There are few adverse events (AE) in the use of HFNC. The
Score (composite of cyanosis, maintain saturations 92%. adverse events monitored in the FIRST-ABC trial included:
air entry, accessory muscle use, 1. Nasal trauma (Commonest AE; Incidence: 2% FIRST-ABC step-
wheezing and cerebral function) up, 2.6% TRAMONTANE)
RR rise >10/minute with Severe respiratory distress 2. Facial/neck trauma
RR >60/minute (defined as use of all accessory 3. Abdominal distension
muscles, severe indrawing of 4. Pneumothorax (Risk of air leak is mentioned but is too small to
subcostal and intercostal quantify in most studies)/Pneumomediastinum/Subcutaneous
muscles, severe tachypnoea, emphysema
regular grunting) 5. Facial thermal injury
Apnea frequency and severity: >2 Pooled data analysed in a systematic review (Lin 2019)
apneas in 1 hour showed no significant increase in adverse events with HFNC use
compared to SOT (RR 0.99, 95%CI 0.32 to 3.07, p ¼ 0.99). HFNC
Table 3 has less adverse events compared to CPAP (FIRST-ABC step up
results: 8% vs. 14% (p ¼ 0.03)). Nasal trauma is the commonest
adverse effect seen with both therapies and is more common
There is a general belief amongst paediatricians, the under-
with CPAP; 6.5% vs 2.0% with HFNC.
lying lung pathology and therefore respiratory distress, is worst
around day 3e5 of the bronchiolitis illness. This is not univer-
Weaning HFNC
sally true, and treatment should be individualized.
There are no RCTs comparing weaning strategies for HFNC, and
Patient discomfort: HFNC is relatively well tolerated. Less than a clinical practice is not protocolized. A global survey of practice
third need sedation to tolerate a flow of 2 liters/kg/minute or involving 1000 PICU professionals (Kawaguchi and colleagues)
less. There are objective scores (Figure 2) adapted to assess highlighted three main weaning strategies:

Figure 2 Scores to assess comfort, compliance and tolerability of High Flow Nasal Cannula (HFNC) Therapy. Scoring method: nurses observe the
infant for several hours during and between caring and feeding, and test the efficacy of consoling. They then score each item and calculate the
total score as the sum of the items out of 35 for COMFORT-B and 15 for EDIN score. Reproduced from (left) Ambuel B et al. Assessing distress in
pediatric intensive care environments: the COMFORT scale. J Pediatr Psychol 1992; 17(1):95e109 with permission from Oxford University Press
and (right) Debillon T et al. Development and initial validation of the EDIN scale, a new tool for assessing prolonged pain in preterm infants. Arch Dis
Child Fetal Neonatal Ed 2001; 85:F36eF41 with permission from BMJ Publishing Group Ltd.

PAEDIATRICS AND CHILD HEALTH 33:5 131 Ó 2023 Elsevier Ltd. All rights reserved.

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on June 09, 2023. For personal use only. No other uses without permission. Copyright ©2023. Elsevier Inc. All rights reserved.
 SYMPOSIUM: INTENSIVE CARE

Figure 3 FIRST-line support for assistance in breathing in children (FIRST-ABC) Algorithm for delivery and weaning of HFNC. *Titrate FiO2 while on
HFNC to maintain peripheral oxygen saturations (SpO2) s92% (or patient-specific target). yRespiratory distress defined as: mild (one accessory
muscle used, mild indrawing of subcostal and intercostal muscles, mild tachypnoea, no grunting), moderate (two accessory muscles used,
moderate indrawing of subcostal and intercostal muscles, moderate tachypnoea, occasional grunting); or severe (use of all accessory muscles,
severe indrawing of subcostal and intercostal muscles, severe tachypnoea, regular grunting). Reproduced from Richards-Belle A et al. FIRST-line
support for assistance in breathing in children (FIRST-ABC): a master protocol of two randomized trials to evaluate the non-inferiority of high-flow
nasal cannula (HFNC) versus continuous positive airway pressure (CPAP) for non-invasive respiratory support in paediatric critical care. BMJ Open
2020; 10:e038002 under Creative Commons CC BY 4.0 licence.

PAEDIATRICS AND CHILD HEALTH 33:5 132 Ó 2023 Elsevier Ltd. All rights reserved.

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 SYMPOSIUM: INTENSIVE CARE
1. 68% weaned the FiO2 first to a threshold value (e.g., 40%) and
then weaned the flow rate gradually,
2. 11% weaned the FiO2 first to a threshold value (e.g. 40%) and
then stopped HFNC, and
3. 4% weaned the flow rate alone without weaning the FiO2.
Evidence (Wiser and colleagues) suggests protocolized
weaning reduces time on respiratory support and intensive care
length of stay. The FIRST-ABC trial protocol (Figure 3) reflects
the most popular weaning strategy.
Conclusion
HFNC therapy offers multiple physiological advantages in addition
to oxygen delivery. It is quick and easy to set up at the bedside
including in clinical areas without a wall mounted air supply
(paediatric wards). It is costlier than standard nasal prong oxygen
therapy and therefore is not used first line in mild-moderate
bronchiolitis and in mild LRTI/pneumonia. Its use in moderate
to severe bronchiolitis and LRTI is evidence based, clinically safe,
cost-effective, and well-tolerated. Limitations in its use include
children aged less than 12 months needing non-invasive respira-
tory support after extubation and a small subset of ‘very sick’ pa-
tients with acute respiratory illness. These patients benefit from
first-line use of nCPAP. The clinical danger, logistic limitations,
and resource implications of transferring children more than 5 kg
or aged more than 6e8 months to a PICU for nCPAP delivery limits
the practical use of nCPAP despite its lower risk of treatment failure
in severe bronchiolitis and pneumonia in older children. Clinicians
should be conscious the advantages of HFNC lead to lower
thresholds in initiation and complacency in discontinuation; both
practices being detrimental to resource limited settings. Proto-
colized escalation and weaning along with appropriate resource
allocation will ensure trial results are replicated in clinical
practice. A
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nasal cannula therapy vs continuous positive airway pressure
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2 Ramnarayan P, Richards-Belle A, Drikite L, et al. FIRST-ABC step-
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study group. Effect of high-flow nasal cannula therapy vs contin-
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from respiratory support in critically ill children: a randomized
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(HFNC) versus nasal continuous positive airway pressure (nCPAP)
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FURTHER READING
Kawaguchi A, Garros D, Joffe A, et al. Variation in practice related to
the use of high flow nasal cannula in critically ill children. Pediatr
Crit Care Med 2020 May; 21: e228e35. https://doi.org/10.1097/
PCC.0000000000002258. PMID: 32106187.
Luo J, Duke T, Chisti MJ, et al. Efficacy of high-flow nasal cannula vs
standard oxygen therapy or nasal continuous positive airway
pressure in children with respiratory distress: a meta-analysis.
J Pediatr 2019 Dec; 215: 199e2088. https://doi.org/10.1016/j.
jpeds.2019.07.059. Epub 2019 Sep 27. PMID: 31570155.
si Christophe, Essouri S, Pouyau R, et al. A multicenter random-
Mile
ized controlled trial of a 3-L/kg/min versus 2-L/kg/min high-flow
nasal cannula flow rate in young infants with severe viral
bronchiolitis (TRAMONTANE 2). Intensive care med 2018; 44:
1870e8. Web.
Tortosa F, Izcovich A, Carrasco G, et al. High-flow oxygen nasal
cannula for treating acute bronchiolitis in infants: a systematic re-
view and meta-analysis. Medwave 2021 May 12; 21: e8190.
Spanish, English. https://doi.org/10.5867/medwave.2021.04.8190.
PMID: 34086669.
Wiser RK, Smith AC, Khallouq BB, et al. A paediatric high-flow nasal
cannula protocol standardizes initial flow and expedites weaning.
Pediatr Pulmonol 2021 May; 56: 1189e97. https://doi.org/10.1002/
ppul.25214. Epub 2021 Jan 11. PMID: 33295690.
Practice points
C HFNC flow rate should match the patients expected Peak Inspi-
ratory Flow Rate to be effective. This is approximately 2 liters/kg/
minute in infants and a fixed flow rate in older children between
15d60 LPM
C In mild-moderate bronchiolitis and mild pneumonia/LRTI, it is
clinically safe and cost-effective to start standard oxygen therapy
as first-line targeting saturations more than 92% and escalate to
HFNC at 2 liters/kg/minute if there is no improvement
C In moderate-severe respiratory disease of any cause, it is clinically
safe, beneficial, cost-effective, and practical to start HFNC as first-
line over gold standard CPAP especially in older children outside
of intensive care settings. Escalating to CPAP in case of treatment
failure, if practically possible, reduces the risk of intubation
C The International Clinical Practice Guidelines for Paediatric
Ventilator Liberation now recommend CPAP for children less than
1 year of age who are being started on non-invasive respiratory
support (either planned or rescue) after extubation
C Protocolizing escalation and weaning improves the cost-
effectiveness and clinical efficacy of HFNC in a resource limited
setting
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