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The high flow nasal oxygen in acute respiratory failure

Jean-Damien Ricard
Minerva Anestesiol. 2012 April 24. [Epub ahead of print]
Minerva Anestesiologica
A Journal on Anesthesiology, Resuscitation, Analgesia and Intensive Care
Official Journal of the Italian Society of Anesthesiology, Analgesia, Resuscitation and Intensive Care
pISSN 0375-9393 - eISSN 1827-1596
Article type : Experts' opinion
The online version of this article is located at http://www.minervamedica.it
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MINERVA MEDICA
The high flow nasal oxygen in acute respiratory failure

Jean-Damien Ricard
Assistance Publique – Hôpitaux de Paris, Hôpital Louis Mourier, Service de Réanimation Médico-chirurgicale,
Colombes, France
UFR de Médecine, Université Paris Diderot – Paris 7, PRES Sorbonne Paris Cité, Paris, France
Unité INSERM U722, Site de Bichat, 75018 Paris
Corresponding author :
Prof Jean-Damien Ricard
Service de Réanimation Médico-chirurgicale
Hôpital Louis Mourier
178, rue des Renouillers, F-92700 Colombes, France
Phone : + 33147606195 ; Fax : +33147606192 ; email : jean-damien.ricard@lmr.aphp.fr
Conflicts of interest: none

Key words: humidification, respiratory failure, hypoxemia, intubation, ventilation, oxygen delivery
Word count: 2371
Tables: 2
Figures: 1
References: 28
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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 post-extubation 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.
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Introduction
Oxygen 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 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 literature
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
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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 nasopharyngeal 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 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
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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 conventional 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 [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 twenty 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 15L/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 hrs and a
maximum of 156 hrs. 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
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longer duration of use (2.8 d and a maximum of 7d) 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].
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.
Other uses of HFNC

Post-extubation
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 post-extubation 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 post-
extubation 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.
Oxygen support during invasive procedures
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.
Pre-intubation 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
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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 [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, 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.
Unresolved issues
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
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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.
Conclusion
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.
Drawbacks to conventional facemask oxygen are overcome with HFNC.
HFNC rapidly alleviates respiratory distress in patients with acute hypoxemic respiratory failure and improves
oxygenation.
MINERVA MEDICA
References
1. Kallstrom TJ. AARC Clinical Practice Guideline: oxygen therapy for adults in the acute care facility--2002
revision & update. Respir Care. 2002;47:717-20.
2. Ricard JD, Boyer A. Humidification during oxygen therapy and non-invasive ventilation: do we need some and
how much? Intensive Care Med 2009;35:963-5.
3. L'Her E, Deye N, Lellouche F, Taille S, Demoule A, Fraticelli A, Mancebo J, Brochard L. Physiologic effects of
noninvasive ventilation during acute lung injury. Am J Respir Crit Care Med 2005;172:1112-1118.
4. Chanques G, Constantin JM, Sauter M, Jung B, Sebbane M, Verzilli D, Lefrant JY, Jaber S. Discomfort
associated with underhumidified high-flow oxygen therapy in critically ill patients. Intensive Care Med. 2009;35:996-
1003.
5. Dani C, Pratesi S, Migliori C, Bertini G. High flow nasal cannula therapy as respiratory support in the preterm
infant. Pediatr Pulmonol. 2009;44:629-34.
6. Dysart K, Miller TL, Wolfson MR, Shaffer TH. Research in high flow therapy: mechanisms of action. Respir
Med 2009;103:1400-1405.
7. Dewan NA, Bell CW. Effect of low flow and high flow oxygen delivery on exercise tolerance and sensation of
dyspnea. A study comparing the transtracheal catheter and nasal prongs. Chest. 1994;105:1061-5.
8. Chatila W, Nugent T, Vance G, Gaughan J, Criner GJ. The effects of high-flow vs low-flow oxygen on exercise
in advanced obstructive airways disease. Chest. 2004;126:1108-15.
9. Shepard JW, Jr., Burger CD. Nasal and oral flow-volume loops in normal subjects and patients with obstructive
sleep apnea. Am Rev Respir Dis. 1990;142:1288-93.
10. Miller MJ, DiFiore JM, Strohl KP, Martin RJ. Effects of nasal CPAP on supraglottic and total pulmonary
resistance in preterm infants. J Appl Physiol. 1990;68:141-6.
11. Groves N, Tobin A. High flow nasal oxygen generates positive airway pressure in adult volunteers. Aust Crit
Care 2007;20:126-131.
12. Parke R, McGuinness S, Eccleston M. Nasal high-flow therapy delivers low level positive airway pressure. Br J
Anaesth 2009;103:886-90.
13. Locke RG, Wolfson MR, Shaffer TH, Rubenstein SD, Greenspan JS. Inadvertent administration of positive end-
distending pressure during nasal cannula flow. Pediatrics. 1993;91:135-8.
14. Corley A, Caruana LR, Barnett AG, Tronstad O, Fraser JF. Oxygen delivery through high-flow nasal cannulae
increase end-expiratory lung volume and reduce respiratory rate in post-cardiac surgical patients. Br J Anaesth
2011;107:998-1004.
15. Sztrymf B, Messika J, Bertrand F, Hurel D, Leon R, Dreyfuss D, Ricard JD. Beneficial effects of humidified high
flow nasal oxygen in critical care patients: a prospective pilot study. Intensive Care Med 2011;37:1780-6.
16. Sztrymf B, Messika J, Mayot T, Lenglet H, Dreyfuss D, Ricard JD. Impact of high-flow nasal cannula oxygen
therapy on intensive care unit patients with acute respiratory failure: A prospective observational study. J Crit Care
2011;Sep 27. [Epub ahead of print].
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17. Roca O, Riera J, Torres F, Masclans JR. High-flow oxygen therapy in acute respiratory failure. Respir Care
2010;55:408-13.
18. Fontanari P, Burnet H, Zattara-Hartmann MC, Jammes Y. Changes in airway resistance induced by nasal
inhalation of cold dry, dry, or moist air in normal individuals. J Appl Physiol. 1996;81:1739-43.
19. Boyer A, Vargas F, Delacre M, Saint-Leger M, Clouzeau B, Hilbert G, Gruson D. Prognostic impact of high-flow
nasal cannula oxygen supply in an ICU patient with pulmonary fibrosis complicated by acute respiratory failure. Intensive
Care Med 2010;37:558-9.
20. Parke RL, McGuinness SP, Eccleston ML. A preliminary randomized controlled trial to assess effectiveness of
nasal high-flow oxygen in intensive care patients. Respir Care 2011;56:265-70.
21. Moccaldo A, Vaschetto R, Bernini V, Antonicelli F, Festa R, Idone F, Boggero A, Antonelli M, Navalesi P,
Maggiore S. Ossigenoterapia dopo estubazione: confronto tra sistema ad alti flussi (Optiflow) e maschera venturi
[abstract P299]. Minerva Anestesiol 2011;77(10 suppl 2):169.
22. Tiruvoipati R, Lewis D, Haji K, Botha J. High-flow nasal oxygen vs high-flow face mask: A randomized
crossover trial in extubated patients. J Crit Care 2010;25:463-8.
23. Lomas C, Roca O, Ãlvarez A, Masclans JR. Fibroscopy in patients with hypoxemic respiratory insufficiency:
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24. Jaber S, Amraoui J, Lefrant JY, Arich C, Cohendy R, Landreau L, Calvet Y, Capdevila X, Mahamat A, Eledjam
JJ. Clinical practice and risk factors for immediate complications of endotracheal intubation in the intensive care unit: a
prospective, multiple-center study. Crit Care Med. 2006;34:2355-61.
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Noninvasive ventilation improves preoxygenation before intubation of hypoxic patients. Am J Respir Crit Care Med
2006;174:171-7.
26. Engstrom J, Hedenstierna G, Larsson A. Pharyngeal oxygen administration increases the time to serious
desaturation at intubation in acute lung injury: an experimental study. Crit Care 2010;14:R93.
27. Lenglet H, Sztrymf B, Leroy C, Brun P, Dreyfuss D, Ricard J-D. Humidified high flow nasal oxygen during
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28. Freedman B. Equipoise and the ethics of clinical research. N Engl J Med 1987;317:141-145.
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Table 1:
Physiological effects of HFNC
Deadspace washout
Nasopharyngeal resistance reduction
Positive pharyngeal pressure
Alveolar recruitment
Oxygen dilution reduction
Enhanced mucociliary function
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Table 2: Potential indications for HFNC
Acute hypoxemic respiratory failure References

[15-17, 27]
Community-acquired pneumonia
[15]
Viral pneumonia (H1N1)
[15, 17]
Acute asthma
[15-17, 27]
Cardiogenic pulmonary edema
[15, 16]
Pulmonary embolism
[15, 16]
Interstitial pneumonia
[27]
Carbon monoxide poisoning
[16, 21, 22]
Post-extubation respiratory distress
[19, 27]
Do-not-intubate
[12, 14]
Post-cardiac surgery
Oxygen supply during invasive procedures
Bronchoalveolar lavage [23]

Transoesophageal echocardiography Unpublished personal data
Gastro-eosophageal endoscopy Unpublished personal data
Intubation Unpublished personal data
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Figure 1
Figure legend:
Changes 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).

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MINERVA ANESTESIOLOGICA

EDIZIONI MINERVA MEDICA

The high flow nasal oxygen in acute respiratory failure

Minerva Anestesiol. 2012 April 24. [Epub ahead of print]

A Journal on Anesthesiology, Resuscitation, Analgesia and Intensive Care

pISSN 0375-9393 - eISSN 1827-1596

Article type : Experts' opinion

The online version of this article is located at http://www.minervamedica.it

Subscription: Information about subscribing to Minerva Medica journals is online at:

COPYRIGHT© 2012 EDIZIONI MINERVA MEDICA

The high flow nasal oxygen in acute respiratory failure

Conflicts of interest: none

Principles of high flow nasal cannula oxygen

Physiological effects of high flow nasal cannula oxygen

Pharyngeal dead space washout

Other uses of HFNC

HFNC outside the ICU

Table 2: Potential indications for HFNC

Acute hypoxemic respiratory failure References

Oxygen supply during invasive procedures

Bronchoalveolar lavage [23]

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