High flow nasal oxygen in acute respiratory failure J.-D. RICARD 1, 2, 3

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1 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 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 E X P E R T O P I N I O N High flow nasal oxygen in acute respiratory failure J.-D. 1Assistance Publique, Hôpitaux de Paris, Hôpital Louis Mourier, Service de Réanimation Médico-Chirurgicale, Colombes, France; 2 Université Paris Diderot, Sorbonne Paris Cité, Paris, France; 3 INSERM, UMRS-722, Paris, France 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 FiO 2 not constant during conventional oxygen therapy, but the true delivered FiO 2 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- 836 MINERVA ANESTESIOLOGICA July , 2, 3 A B S T R A C T 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.

2 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% FiO 2 ) 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 CO 2 whereby reducing CO 2 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 SaO 2. 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 FiO 2. 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 cmh 2 O 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 cmh 2 O 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 Vol No. 7 MINERVA ANESTESIOLOGICA 837

3 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 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 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 Physiological studies Clinical evaluation Roca et al. compared respiratory parameters of patients with moderate respiratory distress during two 30-min periods, one with conven- Table I. Physiological effects of HFNC. Deadspace washout Nasopharyngeal resistance reduction Positive pharyngeal pressure Alveolar recruitment Oxygen dilution reduction Enhanced mucociliary function HIGH FLOw NASAL OxyGEN IN ACUTE RESPIRATORy FAILURE 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 MINERVA ANESTESIOLOGICA July 2012

4 High flow NASAL OxyGEN IN ACUTE RESPIRATORy FAILURE PaO 2 (mmhg) 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). Postextubation Conv 02 PaO 2 PaO 2 /FiO 2 Corley et al, 2011 Sztrymf et al, 2011b Roca et al, 2010 Sztrymf et al, 2011a Other uses of HFNC Because HFNC rapidly alleviates signs of respiratory distress, 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, 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. RR HFNC Conv 02 HFNC Figure 1. Differences in PaO 2 (and PaO 2 /FiO 2 in one case) and respiratory rate (RR) in four studies conducted in adults with acute respiratory failure, between conventional facemask oxygen therapy (Conv O 2 ) and high flow nasal cannula oxygen (HFNC). 0 Respiratory rate (bpm) 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. 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, Vol No. 7 MINERVA ANESTESIOLOGICA 839

5 Table II. Potential indications for HFNC. Acute hypoxemic respiratory failure Community-acquired pneumonia Viral pneumonia (H1N1) Acute asthma Cardiogenic pulmonary edema Pulmonary embolism Interstitial pneumonia Carbon monoxide poisoning Postextubation respiratory distress Do-not-intubate Postcardiac surgery Oxygen supply during invasive procedures Bronchoalveolar lavage Transoesophageal echocardiography Gastro-eosophageal endoscopy Intubation 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 References [15-17, 27] [15] [15, 17] [15-17, 27] [15, 16] [15, 16] [27] [16, 21, 22] [19, 27] [12, 14] [23] [23] Unpublished personal data Unpublished personal data Unpublished personal data 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. HIGH FLOw NASAL OxyGEN IN ACUTE 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 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. 840 MINERVA ANESTESIOLOGICA July 2012

6 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. References 1. Kallstrom TJ. AARC Clinical Practice Guideline: oxygen therapy for adults in the acute care facility revision & update. Respir Care 2002;47: Ricard JD, Boyer A. Humidification during oxygen therapy and non-invasive ventilation: do we need some and how much? Intensive Care Med 2009;35: L Her E, Deye N, Lellouche F, Taille S, Demoule A, Fraticelli A et al. Physiologic effects of noninvasive ventilation during acute lung injury. Am J Respir Crit Care Med 2005;172: Chanques G, Constantin JM, Sauter M, Jung B, Sebbane M, Verzilli D et al. Discomfort associated with underhumidified high-flow oxygen therapy in critically ill patients. Intensive Care Med 2009;35: Dani C, Pratesi S, Migliori C, Bertini G. High flow nasal cannula therapy as respiratory support in the preterm infant. Pediatr Pulmonol 2009;44: Dysart K, Miller TL, Wolfson MR, Shaffer TH. Research in high flow therapy: mechanisms of action. Respir Med 2009;103: 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: 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: 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: 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: Groves N, Tobin A. High flow nasal oxygen generates positive airway pressure in adult volunteers. Aust Crit Care 2007;20: Parke R, McGuinness S, Eccleston M. Nasal high-flow therapy delivers low level positive airway pressure. Br J Anaesth 2009;103: Locke RG, Wolfson MR, Shaffer TH, Rubenstein SD, Greenspan JS. Inadvertent administration of positive enddistending pressure during nasal cannula flow. Pediatrics 1993;91: 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: 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: 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 [Epub ahead of print]. 17. Roca O, Riera J, Torres F, Masclans JR. High-flow oxygen therapy in acute respiratory failure. Respir Care 2010;55: 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: 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: 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: Moccaldo A, Vaschetto R, Bernini V, Antonicelli F, Festa R, Idone F et al. Ossigenoterapia dopo estubazione: confronto tra sistema ad alti flussi (Optiflow) e maschera venturi [abstract P299]. Minerva Anestesiol 2011;77(10 Suppl. 2): 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: Lomas C, Roca O, Ãlvarez A, Masclans JR. Fibroscopy in patients with hypoxemic respiratory insufficiency: Utility of the high-flow nasal cannula. Respir Med 2009;2: Jaber S, Amraoui J, Lefrant JY, Arich C, Cohendy R, Landreau L et al. 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: Baillard C, Fosse JP, Sebbane M, Chanques G, Vincent F, Courouble P et al. Noninvasive ventilation improves preoxygenation before intubation of hypoxic patients. Am J Respir Crit Care Med 2006;174: 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:R Lenglet H, Sztrymf B, Leroy C, Brun P, Dreyfuss D, Ricard J-D. Humidified high flow nasal oxygen during respiratory failure in the emergency department: feasibility and efficacy. Respir Care 2012 [Epub ahead of print]. 28. Freedman B. Equipoise and the ethics of clinical research. N Engl J Med 1987;317: Received on February 28, Accepted for publication on April 18, Corresponding author: J.-D. Ricard, Service de Réanimation Médico-Chirurgicale, Hôpital Louis Mourier, 178 rue des Renouillers, F Colombes, France. jean-damien.ricard@lmr.aphp.fr This article is freely available at Vol No. 7 MINERVA ANESTESIOLOGICA 841

Use of High-Flow Nasal Cannula for Acute Dyspnea and Hypoxemia in the Emergency Department

Use of High-Flow Nasal Cannula for Acute Dyspnea and Hypoxemia in the Emergency Department Nuttapol Rittayamai MD, Jamsak Tscheikuna MD, Nattakarn Praphruetkit MD, and Sunthorn Kijpinyochai MD BACKGROUND: