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E X PE RT O P I N I O N
High flow nasal oxygen in acute respiratory failure
J.-D. RICARD
1, 2, 3
1Assistance
Publique, Hôpitaux de Paris, Hôpital Louis Mourier, Service de Réanimation Médico-Chirurgicale,
Colombes, France; 2Université Paris Diderot, Sorbonne Paris Cité, Paris, France; 3INSERM, UMRS-722, Paris,
France
ABSTRACT
Use of high flow nasal cannula oxygen (HFNC) is increasingly popular in adult ICUs for patients with acute hypoxemic respiratory failure. This is the result of the successful long-term use of HFNC in the neonatal field and
recent clinical data in adults indicating beneficial effects of HFNC over conventional facemask oxygen therapy.
HFNC rapidly alleviates symptoms of respiratory distress and improves oxygenation by several mechanisms, including deadspace washout, reduction in oxygen dilution and in inspiratory nasopharyngeal resistance, a moderate positive airway pressure effect that may generate alveolar recruitment and an overall greater tolerance and comfort with
the interface and the heated and humidified inspired gases. Indications of HFNC are broad, encompassing most if
not all causes of acute hypoxemic respiratory failure. HFNC can also provide oxygen during invasive procedures,
and be used to prevent or treat postextubation respiratory failure. HFNC may also alleviate respiratory distress in
patients at a palliative stage. Although observational studies suggest that HFNC might reduce the need for intubation in acute hypoxemic respiratory failure; such a reduction has not yet been demonstrated. Beyond this potential
additional effect on outcome, the evidence already published argues in favor of the large use of HFNC as first line
therapy for acute respiratory failure. (Minerva Anestesiol 2012;78:836-41)
Key words: Respiratory therapy - Anoxia - Intubation - Ventilation.
O
xygen supply constitutes the first line therapy for patients with acute respiratory failure.1 It is generally provided either via facemasks,
nasal cannula or nasals prongs. Several drawbacks
are however associated with these interfaces. In
numerous instances, these drawbacks are easily
outweighed because the amount of oxygen delivered is sufficient to correct hypoxemia. In others,
they may limit efficacy and tolerance of oxygen
delivery. First of all, oxygen flow through these
devices is limited and generally no greater than
15 L/min with a facemask. A certain amount of
oxygen dilution (delivered oxygen is diluted with
room air) may occur due to the difference between oxygen flow delivered by the device and the
patient’s inspiratory flow 1 and, for this reason,
the greater the inspiratory flow, the greater the
dilution.2 If this phenomenon may not impact
836
too much on patients with mild hypoxemia, the
situation may be different in patients with more
pronounced respiratory failure with inspiratory
flow rates varying between 30 and above 120 L/
min.3 To resume, not only is FiO2 not constant
during conventional oxygen therapy, but the true
delivered FiO2 is often much lower than expected
and it is not monitored. Finally, tolerance may be
poor because of insufficient heat and humidity.4
An alternative to conventional oxygen therapy
has received growing attention: heated, humidified high flow nasal cannula oxygen (HFNC) is
a technique that can deliver up to 100% heated
and humidified oxygen at a maximum flow of 60
L/mn of gas via nasal prongs or cannula. Most of
the available data with this technique has been
published in the neonatal field 5 where it is increasingly used. Here, we review the existing lit-
MINERVA ANESTESIOLOGICA
July 2012
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High flow nasal oxygen in acute respiratory failure
erature in adults and discuss issues that need to
be addressed in future studies.
Principles of high
flow nasal cannula oxygen
The device operates as follows: an air-oxygen
blender (allowing from 21% to 100% FiO2)
generates up to 60 L/min flow rates, the gas is
heated and humidified through an active heated
humidifier, comparable to the ones used during
mechanical ventilation, and delivered via a single limb heated inspiratory circuit (to avoid heat
loss and condensation) to the patient through
nasal cannulas with large diameter.
Physiological effects of high
flow nasal cannula oxygen
Pharyngeal dead space washout
One of the main effects of delivering high
gas flows directly in the nasopharynx is to wash
CO2 whereby reducing CO2 rebreathing and
providing a reservoir of fresh gas. This reduces
dead space and increases the alveolar ventilation over minute ventilation ratio.6 Dewan et
al. have showed the clinical impact of this effect in a study on exercise tolerance in patients
with chronic obstructive pulmonary disease
(COPD),7 where exercise tolerance was compared in patients receiving either high or low
flow oxygen via either transtracheal catheter or
nasal cannula. High flow enabled greater exercise tolerance, regardless of the route of administration.7 Interestingly, transtracheal oxygen did
not increase maximum exercise tolerance with
less dyspnea as compared with oxygen via nasal cannula at equivalent SaO2. This dead space
washout also exerts beneficial effects in terms
of oxygenation as observed by Chatila et al. in
COPD patients in whom high flow nasal oxygen
enabled to maintain greater arterial oxygen tension, exercise longer and with less dyspnea than
low flow oxygen despite matched FiO2.8
Nasopharyngeal resistance
During inspiration, negative airway pressure
limits inspiratory airflow because of nasopha-
Vol. 78 - No. 7
RICARD
ryngeal collapse, a phenomenon aggravated in
patients with obstructive sleep apnea.9 Applying
positive pressure has been shown to counteract
this phenomenon by decreasing supraglottic resistance directly through mechanical splinting
of the airway.10 Because high flow devices can
generate flows that match or exceed patients’
peak inspiratory demand, it is thought that high
flow nasal oxygen minimizes the nasopharyngeal
resistance whereby decreasing resistive work of
breathing.6
PEEP effect
In the same line of reasoning, it was speculated that the use of high flows generated a certain
amount of positive airway pressure. A flow-dependent generation of positive expiratory pressure was measured in healthy volunteers, with
a median pressure of 7.4 cmH2O at 60 L/min
mouth closed.11 These results were confirmed
in patients recovering from cardiac surgery in
whom a mean positive airway pressure of 2.7
cmH2O was measured at 35 L/min with the
mouth closed. A large interpatient variability
was noted, probably in relation with the different ratios of the size of the cannula to the nare
size.12 Although it may be interesting in adults to
minimize leaks around the cannula (by choosing
the largest) so as to increase the PEEP effect, this
aspect deserves particular attention in neonates,
because of the risk of inadvertently generating
considerable PEEP and distending pressure.13
The net effect on oxygenation of these modest
levels of PEEP is unknown. One may hypothesise that this effect will depend on the amount
of alveolar recruitment obtained.
Increase in end-inspiratory lung volume
To address the question of high flow-induced
alveolar recruitment, a recent study assessed
twenty patients under low-flow oxygen then
under HFNC.14 Electrical lung impedance tomography was used to assess changes in lung
volume. Authors measured a significant correlation between end-expiratory lung impedance
and airway pressure.14 Compared with low-flow,
HFNC significantly increased end-expiratory
MINERVA ANESTESIOLOGICA
837
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RICARD
High flow nasal oxygen in acute respiratory failure
lung impedance and airway pressure. Tidal impedance was also increased with HFNC. These
improvements translated into better oxygenation and decreased respiratory rate and dyspnea.
Interestingly, authors also found that these results were most beneficial in patients with higher
body mass indexes.14 This study is important
because it clearly and elegantly shows that part
at least of the improvement in oxygenation observed in patients with acute respiratory failure
15-17 is due to alveolar recruitment.
Humidification and tolerance
The need to heat and humidify supplemental
oxygen during spontaneous breathing has been
a long debate.2 A recent study showed that bubble humidifiers delivered poor levels of humidity
and were associated with significant discomfort.4
Use of a heated humidifier noticeably alleviated
discomfort and delivered much higher levels of
humidity.4 Because very high flows of oxygen
are used during HFNC and because increased
airway resistance has been described with cold
and dry air nasal inhalation,18 addition of heat
and humidity are compulsory with HFNC. One
may hypothesize that the remarkable tolerance
of HFNC systematically reported with HFNC
during acute hypoxemic respiratory failure 15-17
is attributable at least in part, to the heat and
humidity supplied by the device. Of note, a case
of prolonged use of HFNC for over 30 days was
recently reported.19
Clinical evaluation
Physiological studies
Roca et al. compared respiratory parameters
of patients with moderate respiratory distress
during two 30-min periods, one with convenTable I.—Physiological effects of HFNC.
Deadspace washout
Nasopharyngeal resistance reduction
Positive pharyngeal pressure
Alveolar recruitment
Oxygen dilution reduction
Enhanced mucociliary function
838
tional oxygen therapy with a facemask and the
other with HFNC. They showed that HFNC
enabled a significant improvement in all parameters in comparison with the facemask. Comfort
was also greater with HFNC (Table I).17
Outcome studies
These beneficial effects led investigators to assess the effects of HFNC during a longer period.
We recently reported our very first experience
with HFNC in 20 patients with acute hypoxemic
respiratory failure.16 These patients had moderate
to severe respiratory failure, with a median respiratory rate of 28 bpm and a median pulse oxymetry of 93.5% under a median of 15 L/mn oxygen
with a facemask. After patients where placed under HFNC, we were able to show that respiratory
distress was rapidly alleviated with a significant
decrease in respiratory rate to a median of 24.5
(P=0.006) and a concomitant significant increase
in pulse oxymetry to 98.5 (P=0.0003). Of note,
HFNC was well tolerated during a median duration of 26.5 h and a maximum of 156 h. In this
small series of patients, 6/20 patients ultimately
required intubation, providing a 70% success
rate of the technique. In the following study,15
we wished to confirm our initial observations in
a larger cohort of patients, and identify early predictors for HFNC failure. We confirmed: 1) the
rapid alleviation of respiratory distress in more
severe patients; 2) the remarkable tolerance of the
device for a much longer duration of use (2.8 d
and a maximum of 7 d); and 3) the success rate
of this technique (76%). Persistence of tachypnea
and thoraco-abdominal asynchrony, and lower
pulse oxymetry were significantly more frequent
in patients ultimately requiring intubation.15 In
less severe patients with mild to moderate failure, HFNC was compared to facemask oxygen
therapy in a preliminary randomized controlled
trial, with success with the allocated therapy and
subsequent need for non-invasive ventilation as
principal outcomes.20 In this study, significantly
more HFNC patients succeeded with their allocated therapy and rate of NIV was 3/29 with
HFNC and 8/27 with facemask oxygen (P=0.1).
Patients with HFNC had significantly fewer desaturation.20
MINERVA ANESTESIOLOGICA
July 2012
High flow nasal oxygen in acute respiratory failure
PaO2
200
175
28
24
125
20
100
16
75
25
0
12
Corley et al, 2011
Sztrymf et al, 2011b
Roca et al, 2010
Sztrymf et al, 2011a
50
Conv 02
HFNC
Conv 02
8
4
HFNC
HFNC can also ensure adequate oxygenation during bronchoalveolar lavage, as reported
recently.23 Our routine practice is also to use
HFNC for other invasive procedures such as
transoesophageal echocardiography or digestive
tract endoscopy when performed in hypoxemic,
spontaneously breathing patients.
0
Figure 1.—Differences in PaO2 (and PaO2/FiO2 in one case)
and respiratory rate (RR) in four studies conducted in adults
with acute respiratory failure, between conventional facemask
oxygen therapy (Conv O2) and high flow nasal cannula oxygen
(HFNC).
Ours are to date the only outcome studies in
severe acute hypoxemic ICU patients.15, 16 However, their observational design precludes any
definite answer only a controlled trial can provide, as to whether HFNC reduces intubation in
these patients or not (Figure 1).
Other uses of HFNC
Postextubation
Because HFNC rapidly alleviates signs of respiratory distress,15-17 it is appealing to investigate
the use of HFNC either to prevent or to treat
postextubation respiratory failure. Two studies have undertaken such an evaluation. In an
Italian study,21 109 patients were randomized
to receive either facemask Venturi oxygen or
HFNC. All parameters were in favor of the use
of HFNC (respiratory rate, oxygenation, device
displacement, comfort). Of note, reintubation
was significantly less frequent in the HFNC
group (3.5%) than in the Venturi mask group
(21%) although one may argue that this latter
figure seems unusually high. Nonetheless, this
study clearly shows the potential benefit for this
technique to improve comfort and enhance oxygenation in the postextubation period. Results
from an earlier study comparing HFNC and
facemask oxygen after extubation and showing
greater tolerance with HFNC,22 are consistent
with the study detailed above.
Vol. 78 - No. 7
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Oxygen support during invasive procedures
36
32
PaO2 /FiO2
150
PaO2 (mmHg)
RR
Respiratory rate (bpm)
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or other proprietary information of the Publisher.
COPYRIGHT© 2012 EDIZIONI MINERVA MEDICA
Preintubation oxygenation
Intubation in the ICU is often performed in
hypoxemic, unstable patients and is associated
with signifcant complications.24 Non-invasive
ventilation can be used to enhance oxygenation
before tracheal intubation,25 but the mask has to
be removed during the laryngoscopy which deprives the patient from oxygen during the procedure. Because the nasal cannulas do not interfere with the laryngoscopy, HFNC could be
used to deliver oxygen during the apneic period
of tracheal intubation. A recent animal study
elegantly showed that direct pharyngeal administration of 10 L/min oxygen during intubation
of hypoxemic piglets significantly delayed occurrence of severe desaturation during apnea.26
The potential benefit of HFNC during intubation of ICU patients should be further evaluated
in a clinical study. However, the design of the
study may not be, for ethical reasons, that of a
randomized controlled trial. Indeed, given the
amount of published data clearly showing the
superiority of HFNC over conventional facemask in terms of oxygenation (Table II),14-17,
20, 27 equipoise no longer exists between these
two devices. As of consequence, as advocated by
Freedman, it would not be ethical to perform
a randomized controlled study comparing these
two devices.28
Palliative care
Do-not-intubate patients could potentially
benefit from HFNC. As stated above, a case of
successful prolonged-use of HFNC in a patient
with respiratory failure, for whom a do-not-intubate order had been given, has been reported.19
Because of the very good tolerance of the device,
MINERVA ANESTESIOLOGICA
839
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means which may allow access to the Article. The use of all or any part of the Article for any Commercial Use is not permitted. The creation of derivative works from the Article is not permitted. The production of reprints for personal or commercial use is
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RICARD
High flow nasal oxygen in acute respiratory failure
Unresolved issues
Table II.—Potential indications for HFNC.
Acute hypoxemic respiratory failure
References
Community-acquired pneumonia
[15-17, 27]
Viral pneumonia (H1N1)
[15]
Acute asthma
[15, 17]
Cardiogenic pulmonary edema
[15-17, 27]
Pulmonary embolism
[15, 16]
Interstitial pneumonia
[15, 16]
Carbon monoxide poisoning
[27]
Postextubation respiratory distress
[16, 21, 22]
Do-not-intubate
[19, 27]
Postcardiac surgery
[12, 14]
Oxygen supply during invasive
[23]
procedures
Bronchoalveolar lavage
[23]
Transoesophageal echocardiography Unpublished personal data
Gastro-eosophageal endoscopy
Unpublished personal data
Intubation
Unpublished personal data
and because speech and oral intake are unaltered
with HFNC, even with the highest flows, this
technique provides adequate conditions to manage respiratory failure in palliative patients.27
HFNC outside the ICU
Given the ease of use of this new device,
HFNC could also be applied to patients outside the ICU, and namely in the emergency
department (ED). Dyspnea and hypoxemia are
indeed very frequent motives for ED consultations. Rapid relief of dyspnea and correction of
hypoxemia are not always achieved by conventional oxygen. The potential benefit and feasibility of HFNC in the ED was therefore recently
evaluated.27 Patients with hypoxemic respiratory distress were treated with HFNC after having received conventional oxygen therapy via a
facemask. HFNC’s efficacy assessment focused
on a dyspnea relief with the use of Borg’s scale,
improvement in clinical respiratory parameters
and in a subset of patients, arterial blood gas.
Compared to conventional oxygen therapy,
HFNC enabled a rapid and significant improvement of dyspnea score and other respiratory
parameters, suggesting the potential usefulness
of this technique in the ED.27 Further studies
are required to show whether or not early application of HFNC avoids ICU admission in
patients presenting to the ED with respiratory
failure.
840
The main question that remains without definite answer is whether or not HFNC reduces the
need for intubation in patients with hypoxemic
acute respiratory failure. Although some clinicians may have the impression that in some instances, use of HFNC has avoided intubation,
this has not yet been shown in a controlled trial.
There are nonetheless some indications in the
literature that this may be the fact. Our study
that evaluated the clinical impact of HFNC in
patients with severe respiratory failure found a
success rate of 68%:15 i.e., only 32% of patients
treated with HFNC required subsequent mechanical ventilation (invasive or non-invasive).
How the other patients would have evolved in
the absence of HFNC remains purely speculative, but clinicians, when asked the question,
considered that 42% would have required intubation, whereas only 24% actually did.15 Once
again, this is no demonstration, and one will have
to wait for the results of the FLORALI study, a
randomized controlled trial that compares three
arms: conventional oxygen therapy, HFNC and
HFNC with non-invasive ventilation.
Conclusions
HFNC has been extensively and successfully
used in neonates and seems to achieve the same
popularity in adults. It offers a rapid and sustained improvement in respiratory parameters in
patients with hypoxemic acute respiratory failure, while ensuring patient comfort. Although
suspected, a further effect on intubation rate reduction has not yet been shown. Nonetheless,
beyond this last effect, results already achieved
argue for the widespread use of HFNC as first
line therapy for patients with acute hypoxemic
respiratory failure.
Key messages
—— High flow nasal cannula (HFNC) oxygen may provide up to 60 L/min heated and
humidified oxygen.
MINERVA ANESTESIOLOGICA
July 2012
This document is protected by international copyright laws. No additional reproduction is authorized. It is permitted for personal use to download and save only one file and print only one copy of this Article. It is not permitted to make additional copies
(either sporadically or systematically, either printed or electronic) of the Article for any purpose. It is not permitted to distribute the electronic copy of the article through online internet and/or intranet file sharing systems, electronic mailing or any other
means which may allow access to the Article. The use of all or any part of the Article for any Commercial Use is not permitted. The creation of derivative works from the Article is not permitted. The production of reprints for personal or commercial use is
not permitted. It is not permitted to remove, cover, overlay, obscure, block, or change any copyright notices or terms of use which the Publisher may post on the Article. It is not permitted to frame or use framing techniques to enclose any trademark, logo,
or other proprietary information of the Publisher.
COPYRIGHT© 2012 EDIZIONI MINERVA MEDICA
High flow nasal oxygen in acute respiratory failure
—— Drawbacks to conventional facemask
oxygen are overcome with HFNC.
—— HFNC rapidly alleviates respiratory
distress in patients with acute hypoxemic respiratory failure and improves oxygenation.
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Received on February 28, 2012. - Accepted for publication on April 18, 2012.
Corresponding author: J.-D. Ricard, Service de Réanimation Médico-Chirurgicale, Hôpital Louis Mourier, 178 rue des Renouillers,
F-92700 Colombes, France. E-mail: [email protected]
This article is freely available at www.minervamedica.it
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