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High flow nasal prongs

For the patient whose inspiratory flow rate exceeds even Created on Mon, 09/28/2015 -
the generous threshold of Venturi masks, high flow nasal 19:05
oxygen is an excellent option. ough the first paper to Last updated Wed,
03/13/2019 - 04:04
describe these devices (Dewan & Bell, 1994) gave us this
Topic
terminology, subsequent authors have occasionally Respiratory Medicine and
referred to these devices as "high flow nasal cannulae" or Mechanical Ventilation
"high flow nasal oxygen", because presumably the word
Previous chapter: Non-
"prongs" is somehow uncivilized or intrinsically comical. invasive mechanical
All CICM trainees will be familiar with the device - it is ventilation

a single-limb circuit which connects a gas blender to a Next chapter: Weaning

heater/humidifier, and then funnels a mixture of oxygen from mechanical ventilation

and air into the patient, essentially using their All SAQs related to this topic
respiratory system as a PEEP valve.
All vivas related to this topic
estion 2 from the first  paper of 2013 asked for
indications, contraindications and complications of high
flow nasal prong therapy. To cover all bases, this chapter
was wrien to answer estion 2 as if it were a "critically evaluate" style SAQ. en, in
the first paper of 2017 estion 3 asked the candidates to critically evaluate high flow
nasal prongs. LITFL notes on this topic cover the subject in enough detail to answer it.
ere is also a  great article by J-D Ricard (2012)  which dissects this oxygen delivery
system. e more recent review by Papazian et al (2016) offers a decent overview of the
evidence to support all the indications for HFNP. To say that these resources have been
condensed into the summary below would be unfair to the definition of condensation.
However, the time-poor exam candidate will be spared the job of filtering through self-
indulgent drivel by the brief summary offered in the grey box below:
 Physiological rationale for Scenarios where HFNP is a favoured
using HFNP indication

Improved oxygenation by Where NIV is poorly tolerated or

reservoir effect and reduced
dilution of inspired O2
Improved tolerance by
heating and humidification
Improved tolerance of
secretions
Improved CO2
clearance and respiratory
effort efficiency
by pharyngeal dead space
washout
Limitations and
contraindications
Unprotected airway;  need
for intubation
Nasal, facial, base of skull
injuries
Need for a predictable level
of PEEP.
inappropriate (eg. oesophageal surgery)
Where intubation is not appropriate
Apnoeic oxygenation pre-intubation
Evidence for the use of HFNP:
Parke et al (2011): n= 60; HFNP vs. high-
flow face mask.  HFNP group did much
beer (10% rate of NIV vs. 30% for the
standard mask)
FLORALI trial (2015): n=310, HFNP vs.
NIV,  no difference in intubation rate, but
an improvement in 90 day mortality
associated with HFNP.
PREOXYFLOW (2015): n=124. HFNP
vs. high-flow face mask for pre-
oxygenation during intubation. ere was
no difference (well, a difference of 1%
SpO2).
THRIVE (2014): observational case series,
n=25 (difficult airways).

Complications  of HFNP Apnoeic oxygenation times were around

Barotrauma and
pneumothorax
Nasal mucosal damage and
pressure areas, irritation,
epistaxis
Aspiration, including of
contaminated circuit rain-
out, epistaxis, saliva, teeth,
food
Delay of intubation (i.e.
time-wasting behaviour,
prevents definitive
management)
14 minutes (half of these patients were
obese and a third had stridor).
S68 Hi-Flo study (2014): n= 72 babies under
18mth with bronchiolitis; no difference
BiPOP (2015): n= 830 post-CABG
patients; HFNP vs. NIV. HFNP was non-
inferior but otherwise,  no difference in
ICU mortality.
Meta-analysis: benefit in mortality among
immunocompromised patients, but not
among immunocompetent ones.

Rationale for the use of high flow nasal prongs (HFNP)

Pharyngeal dead space washout

e upper airways are "rinsed" with humidified oxygen; this is called the "pharyngeal
dead space washout". According to the original studies by Fowler (1948) that space is
about 150ml, which makes about 25% of the  tidal volume. As such, under normal
circumstances that volume ends up being filled with expired air, which might be
highly CO2-rich if the patient is significantly hypercapneic. e  next breath drags this
stagnant swamp gas back into the lungs. e high-flow jet reaches deep into this
anatomical dead space and flushes out the expired air with nice humidified oxygen-rich
(CO2-poor) gas, which is not something that can be accomplished by other non-invasive
devices or even high--flow face masks. Probably, the tracheobronchial gas remains
untouched - but at least some nasopharyngeal gas ends up being replaced in this way.

is can have two main effects. One is to produce an improvement in the elimination of
CO2. If the expired air is re-inhaled the mixture will contain expired CO2 and this will
decrease the gradient for the removal of CO2 from the alveolar blood. HFNP should
theoretically improve CO2  clearance by increasing that gradient.

It's actually not clear whether this really happens. According to Dysart et al (2009), this
effect is an extrapolation of the enhanced CO2 clearance which is seen with tracheal
fresh gas insufflation in ARDS, for example. Puing a tracheal catheter into the airway of
a severe ARDS patient is one of the (relatively exotic) ways to mitigate the inevitable
"permissive hypercapnea" associated with low tidal volume ventilation, so that it does
not have to be quite so permissive. Results from Dewan & Bell (1994) suggest that the
dead space washout effect is about the same for the nasal prongs and the tracheal
catheters, so the extrapolation is probably valid. Also, Fricke et al (2016) convinced a 62
year old COPD patient to have an endotracheal catheter through his tracheostomy for
the purposes of measuring the concentration of gas in their anatomic dead space while
on high flow nasal prongs, and found that yes - it does wash out something like 50% of
rebreathed CO2. e authors implied that if sustained, this CO2 removal effect would be
comparable with what is achieved by NIV; they were able to drop the arterial PCO2 by
7.4% over 15 minutes. 

e othermore boring  effect of dead space washout is an improvement in oxygenation.

According to Chatila et al (2004), this is mainly because the dead space volume is
replaced by oxygen, essentially turning it into a reservoir. is is based on an abstract
presented by Tiep and Barne, who built an airway model and recorded videos of
ultrasonic flow studies.  Chatila et al took this information, mixed it with their own
findings (improved arterial oxygenation) and made several inferences on this basis,
among which one was that this "reservoir effect" contributes substantially to the
oxygenation improvement. e debate as to exactly how substantially it contributes
trespasses into the territory of academic pointlessness. 

e ultimate upshot of all these factors is that pharyngeal dead space washout improves
the efficiency of the respiratory effort. Per unit effort (however you measure it), more
CO2 is expired, and more oxygen is inspired. e pharyngeal washout effect is probably
the most important way the HFNP device improves respiratory function over the short
and medium-term ventilation timeframes.
Improved oxygenation by PEEP effect
People rave about the PEEP effect of high flow nasal prongs, and protocols are built on
the basis of it. e effect is probably a fairly minor contributor to the overall benefit from
high-flow nasal prongs. It seems to only be about 3cm H2O with 60L/min flow, when the
mouth is open. Tobin and Grove (2007) demonstrated this by convincing some of the
staff of St Vincent's Hospital in Melbourne to have their airways topicalised and then
passing 10Fr suction catheters into them to transduce the pressure. With their mouths
closed, the volunteers had an average PEEP of about 7.5 cm H2O while the HFNP was set
to 60L  (the maximum was 9.7, in the female subjects). 

Why was the PEEP higher in females than in males? Nostril size. By fiing too loosely in
large masculine nares, the nasal prongs had sufficient leak around them to depressurise
the airway. In contrast, nasal prongs fit more snugly into dainty ladylike nares, the leak
is less, and therefore the pressure is higher. is is a purely speculative statement from
the Tobin and Grove study, as the authors failed to report important details such as nare
diameter (though they did observe that PEEP increased proportionally to decreasing staff
member height, suggesting that nare diameter and height are somehow related). is
probably has only comedic value to the intensivist, with the exception of those who
routinely practice on neonates (as neonatal high flow nasal prongs can easily fit too
snugly, produce too much pressure and generate a pneumothorax).

If this PEEPish effect works, then it has all the benefits of "proper" PEEP - recruitment of
atelectatic lungs, decreased work of breathing, and so forth. On top of that, it is supposed
to overcome the "nasopharyngeal resistance" of obese OSA patients.  In fact the benefits
seem to be most pronounced in the obese patients- and the degree of improvement in gas
exchange tends to be related to the degree of increase in end-expiratory lung volume,
which suggests that there is a real alveolar recruitment effect happening here (Corley et
al, 2011).

Improved oxygenation by oxygen dilution reduction

e patient in respiratory failure typically struggles for breath, and has a high
inspiratory flow rate, in tens of litres per minute. To use some meaningful comparison,
the peak inspiratory flow rate of moderately athletic humans under the load of light
exercise was approximately 30L/min according to Anderson et al (2006). If such a human
is receiving oxygen by conventional means, that oxygen is being delivered at a sluggish
flow rate, say 2-6 litres per minute. us, the panicking respiratory failure patient will
inhale a gas mixure which will have an inordinately large proportion of room air, and
very lile of their supplemental oxygen.  High flow nasal prongs ensure that no maer
how high the patients' inspiratory flow, the inhaled gas mixture will contain a large
amount of oxygen. Most high flow nasal gas delivery systems max out at 60L/min flow,
which probably represents something close to the realistic maximum of a hypoxic
 patient with respiratory failure.  One can make the assumption that they are probably
hypoxic because of some sort of problem with their respiratory system, and therefore
their diseased respiratory system is insufficiently powerful to generate flows higher than
that.

Benefits of humidification: prevention of heat loss and improved

secretion clearance
Humidified oxygen is theoretically beer than raw untreated wall oxygen. Wall oxygen
comes form a tank where the super-low temperature excludes the contribution of any
added water: there may be residual water ice inside the tank, but it remains frozen solid
at the temperature at which the liquid oxygen turns to gas. e wall oxygen is therefore
is very cold and completely dry. e effect of breathing cold dry gas is the loss of both
moisture and heat. Heating and humidification therefore theoretically prevents heat loss
and moisture loss. Prevention of moisture loss is particularly important to prevent the
inspissation of secretions (a topic discussed in some detail in the chapter on heat and
moisture exchangers). Mucociliary function is beer preserved when the mucus is moist,
and with heating and humidification, it is possible to blast high flow oxygen into a
patient for 30 days without serious consequences (Boyer et al, 2011). Having said this, we
have no direct evidence that HFNP increase the rate or volume of secretion clearance; all
this is extrapolated from the (decades-old) findings that in the absence of good quality
humidification, ventilator circuits reduce secretion clearance. Nobody has ever measured
the airway mucus of HFNP patients and remarked on how much less viscous it was. 

Increased comfort
Increased in relation to what, one might ask. To intubation? Asphyxia? Apparently,
when comfort comes into the equation, high flow nasal oxygen is compared to CPAP.
e main reason for this is the fact that the mouth is le alone, unlike most forms of
CPAP. Additionally, the humidification of oxygen tends to decrease the nasty side effects
of oxygen therapy, such as raw stripped mucosa.  Because there is no need for a tight
mask, there is no claustrophobia. e patient is able to eat, drink and communicate
without the NIV mask in the way. With improved tolerance, there is less need for
chemical behaviour control in the delirious or demented population. Tellingly, trials of
HFNP like Sztrymf et al (2011) practically  always report that none of the patients asked
for the HFNP to be discontinued because of intolerance. 

HFNP may be appropriate in circumstances where NIV is not

Specific situations favouring the use of HFNP may include oropharyngeal surgery and
oesophageal surgery such as oesophagectomy. estion 22 from the first paper of 2014 is
a fine example of such a situation. Nasopharyngeal surgery however might be off-limits.
 You wouldn't want 60L/min of gas pneumodissecting its way into your sella turcica
aer transspenoidal pituitary surgery.

Apnoeic oxygenation peri-intubation

HFNP may be used for apnoeic oxygenation as an alternative to the standard
mask. However, this does not seem to be an improvement over the normal methods - in
the PREOXY-FLOW trial the HFNP group did not experience any fewer desaturaton
events as compared to the standard bag-valve mask  (Vourc'h et al, 2015). It is  not clear
what the effect of this on the airway manipulator would be as they stand to face the
patient - 60L/min of gas can throw a whole lot of aerosolised pathogens at you (eg. if the
patient has active tuberculosis), whereas at least the bag-valve mask poses something of
a physical barrier. 

Limitations of HFNP and contraindications to their use

e patient must be able to protect their airway

e nose must be intact (i.e. its not obstructed, fractured, or
e base of skull should be intact (in base of skull fracture you might induce a
pneumocephalus and god knows what else)
ere should be no epistaxis (or the blood will end up being aspirated)
If there has been recent nasal surgery, HFNP may do damage the operative site
If there has been recent oesophageal surgery, use of HFNP must be weighed
against the risk of anastomotic breakdown (though it could still be used, and is
probably safer than NIV)
ere is some PEEP, but it is not measured, and is completely unpredictable
If the patient requires intubation and intubation is delayed because of people
wasting time experimenting with HFNP, the outcome may be worse.
is topic of using HFNP following upper airway and GI surgery remains contentious. In
short, most reasonable people who understand the function of HFNP will agree that
there is minimal risk from their use, as the PEEP-like pressure exerted by these devices is
trivial. Other equally reasonable people will instead point to the fact that these devices
have never been demonstrated to improve any important parameters (oxygenation etc)
in upper GI surgical patients, and that the risk of compromising an oesophageal
anastomosis - though theoretical - is not zero. 

Where does the truth lie? Likely, there is some middle ground, but the situation is not
very well studied. e evidence regarding the use of HFNP in these questionable
scenarios is mixed, and can be used to promote either viewpoint. Observe:
 On one hand, if you wanted to protect your precious anastomosis at any cost, you could
argue against the use of HFNP using the following information:

ere does not appear to be any benefit, in terms of outcomes.  Futier et al

(2016) included a wide range of abdominal surgical patients in a randomised trial
and found no improvement in oxygenation (or any other secondary outcomes like
pneumonia or reintubation) when comparing HFNP to conventional oxygen
delivery methods. 
HFNP is known to produce PEEP, and so any contraindications to the use of PEEP
should logically apply to HFNP (Natham et al, 2019)
On the other hand, if you really wanted to use HFNP, you could point to the following:

If PEEP is your main concern, then NIV should be even more unsafe in these
scenarios, and yet multiple authors have demonstrated the safety of NIV with
pressures as high as 16cm H2O (Joris et al, 1997; Kingden-Milles et al, 2005; Pessoa
et al, 2010). Applying PEEP is clearly not such a big problem.
e UpToDate authors or other review writers (eg. Wilcox et al , 2018, or
Nishimura et al, 2016) do not usually list upper GI surgery as one of the
contraindications for the use of HFNP.
Futier et al (2016) included numerous upper GI patients in their study (35 post
Whipples,  4 post gastrectomy and 7 post oesophagectomy). ey blasted these
people with 50-60L/min without any dramatic increase in the need for re-operation
within seven days. Clearly, none of those anastomoses ended up leaking.

Potential adverse effects associated with the use of HFNP

Trawling though the evidence, one can find relatively few articles where the
complications of HFNP are discussed in any sort of great detail. ey are generally from
the paediatric literature (eg, Baudin et al,  2016)

Pressure and flow-related complications

Overdistension of the alveoli, and barotrauma

in fact, in neonates this may lead to pneumothorax
Nasal mucosal damage due to high flow
Pressure areas due to the device
Aspiration of food

If the patient is trying to eat and the pressure of this devise has not bean dialled
down, bad things may happen. In the best case scenario the high flow gas will blow
the food out of their mouth, and make an embarrassing mess. In the worst case
 scenario, the jet of gas will blow the food into their airway. e same goes for
vomit that has been regurgitated by a semiconscious patient, or secretions from
their nose.
Discomfort of the device

e nasal prongs need to be fastened at all times; the cannulae may be irritating to
the nostrils; and the devise produces a constant loud hiss, which can be so
irritating as to drive you mad.
Other complications:

Failure to achieve the desired effect because of mouth-breathing

Overabundance of secretions (Velasco et al, 2014) - though some might view this as
a desired effect
Epistaxis
Time-wasting (delaying the inevitable intubation)
Aspiration of circuit condensation water (there's no evidence that this causes
pneumonia, but people complained about it in a survey of paediatric ICUs
conducted by Manley et al, 2012). e perception of infection risk from warm
circuit water seems to be greater than the actual risk, but some literature out there
does exist to support at least the theoretical possibility of this; for example Pierce
& Sanford (1973) present some evidence that Pseudomonas can be spread through
the humidification systems of infant incubators, and quote contemporary studies
where the horrified authors cultured all sorts of microorganisms from the water
baths of humidifiers. e authors wisely recommend that a good standard for
humidification equipment would be make sure that the deliver air is no more
contaminated than the room air of the hospital (a relatively low bar).

Clinical applications of high flow nasal prongs

As a stand-alone therapy for hypoxic respiratory failure, in which case it could be

used in any sort of respiratory failure (LITFL list a handful of different types, such
as asthma, APO, pneumonia, etc etc)
Instead of NIV:
When positive pressure is contraindicated, eg. oesophagectomy
When the patient is intolerant of NIV (eg. delirium)
When clearance of secretions must be maintained, but the patient is too
hypoxic for conventional oxygen delivery devices (eg. in pneumonia)
Instead of intubation:
In patients whom it is inappropriate to intubate (i.e. as a palliative measure)
 In patients for whom intubation is associated with a worse outcome, eg.
febrile neutropenic patients and those recovering from bone marrow
transplant.
Prior to intubation:
HFNP may significantly improve preoxygenation and reduce episodes of
hypoxia (Miguel-Montanes et al, 2015).
is seems to be something that benefits difficult airway patients (THRIVE) 
rather than all-comers (PREOXY-FLOW)

Evidence in support of the use of HFNP

Parke et al (2011):  one of the first studies comparing HFNP and standard high-flow face
mask

60 patients randomised to either normal mask or HFNP

Main outcome measure was having to resort to NIV
HFNP group did much beer (10% rate of NIV vs. 30% for the standard mask)
FLORALI trial (2015): multicenter open-label trial, 310 patients

Only hypoxic patients were selected (P/F ratio <300) - hypercapnea was excluded
Primary outcome was intubation rate, secondary outcome was mortality
HNFP was compared to standard oxygen and NIV
ere was no difference in intubation rate, but somehow there was a improvement
in 90 day mortality associated with the use of high-flow oxygen.
e NIV group had 9ml/kg tidal volumes, which may have influenced their
mortality by exacerbating their lung injury
Of the intubated and NIV patients, more died of shock rather than respiratory
failure.
PREOXYFLOW (2015): multicenter open-label trial,124 patients

Randomised to either high flow oxygen mask (removed at the end of intubation) or
high flow nasal prongs (kept on during the whole process).
e main point was to see whether an apnoeic patient would benefit from high
flow oxygen blowing into their airway; theoretically they should desaturate more
slowly during the intubation aempt because pure oxygen from the HFNP-
irrigated upper airways will be entrained into the lung by mass transfer.
No such effect was seen (a statistically insignificant difference of 1% SpO2 was
found).
THRIVE (2014): observational case series of 25 patients with difficult airways
 HFNP was commenced prior to the induction of anaesthesia
While maintaining jaw thrust, HFNP delivered oxygen to the apnoeic patient
(apnoea time was counted from the administration of muscle relaxant)
Median apnoea time was 14 minutes (ranging from 9 to 19 minutes) and the
patients did not desaturate beyond 90%.
Given that half of these patients were obese and a third had stridor, this is an
outstanding result. Amazed authors concluded that this technique "has the
potential to transform the practice of anaesthesia".
S68 Hi-Flo study (2014): Randomised controlled trial of 72 babies under 18 months of age

Bronchiolitis was the specific pathology under investigation

Comparison of 2L vs 8L O2
ere was a minor improvement of clinical parameters (a modified Tal score), but
no real difference otherwise
BiPOP (2015): Multicenter, randomized trial in 830 post-op cardiothoracic patients

Inclusion criteria were respiratory failure aer surgery, or those who were
"deemed at risk" of this following extubation
e patients were then randomised to either HFNP or NIV
HFNP was non-inferior: the rate of reintubation was the same in both groups
ere was also no difference in ICU mortality.
NIV produced more skin pressure areas, but was otherwise equivalent.
Meta-analysis (Nedel et al, 2016) -  critically ill patients with respiratory failure, or at risk
of it

9 studies met inclusion criteria

No mortality difference was found when the data were pureed in the meta-analysis
blender, because the studies were severely heterogeneous and each insisted on
measuring the improvement in oxygenation in some different way
Many of the trials excluded hypercapneic COPD patients, unfairly (as HFNP could
be of substantial benefit to these patients)
Meta-analysis (Monro-Somerville, et al; 2017)

14 studies met inclusion criteria (n= 2,507)

No mortality benefit
However, the mortality was quite low (6% with HFNP, vs. 8.1% with usual care)
Presumably selecting sicker patients will allow benefits to beer manifest, might
say the HFNP enthusiast
Meta-analysis (Huang et al, 2018) - immunocompromised patients with respiratory
fialure
 n = 667
Significant reduction in short-term mortality and intubation rate
Unchanged ICU length of stay
Meta-analysis (Conte et al, 2018) - pre-term neonates

n = 1227 
When nasal CPAP was used, failure rate (i.e. progression to intubation) was lower. 
i.e. HFNP failed more frequently, and in those situations the NCPAP occasionally
prevent the need for intubation

Previous chapter: Non-invasive

mechanical ventilation

Next chapter: Weaning from mechanical

ventilation

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