0
Contemporary Reviews in Critical Care Medicine |

Heated Humidified High-Flow Nasal Oxygen in AdultsHigh-Flow Nasal Oxygen: Mechanisms of Action and Clinical Implications FREE TO VIEW

Giulia Spoletini, MD; Mona Alotaibi, MD; Francesco Blasi, MD; Nicholas S. Hill, MD, FCCP
Author and Funding Information

From the Department of Pathophysiology and Transplantation (Drs Spoletini and Blasi), Università degli Studi di Milano, IRCCS Fondazione Ospedale Maggiore Policlinico Cà Granda, Milan, Italy; Department of Internal Medicine (Dr Alotaibi), University Hospital Case Medical Center, Cleveland, OH; and Division of Pulmonary, Critical Care and Sleep Medicine (Dr Hill), Tufts Medical Center, Boston, MA.

CORRESPONDENCE TO: Nicholas S. Hill, MD, FCCP, Division of Pulmonary, Critical Care and Sleep Medicine, Tufts Medical Center, 800 Washington St, #257, Boston, MA 02111; e-mail: nhill@tuftsmedicalcenter.org


Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2015;148(1):253-261. doi:10.1378/chest.14-2871
Text Size: A A A
Published online

Traditionally, nasal oxygen therapy has been delivered at low flows through nasal cannulae. In recent years, nasal cannulae designed to administer heated and humidified air/oxygen mixtures at high flows (up to 60 L/min) have been gaining popularity. These high-flow nasal cannula (HFNC) systems enhance patient comfort and tolerance compared with traditional high-flow oxygenation systems, such as nasal masks and nonrebreathing systems. By delivering higher flow rates, HFNC systems are less apt than traditional oxygenation systems to permit entrainment of room air during patient inspiration. Combined with the flushing of expired air from the upper airway during expiration, these mechanisms assure more reliable delivery of high Fio2 levels. The flushing of upper airway dead space also improves ventilatory efficiency and reduces the work of breathing. HFNC also generates a positive end-expiratory pressure (PEEP), which may counterbalance auto-PEEP, further reducing ventilator work; improve oxygenation; and provide back pressure to enhance airway patency during expiration, permitting more complete emptying. HFNC has been tried for multiple indications, including secretion retention, hypoxemic respiratory failure, and cardiogenic pulmonary edema, to counterbalance auto-PEEP in patients with COPD and as prophylactic therapy or treatment of respiratory failure postsurgery and postextubation. As of yet, very few high-quality studies have been published evaluating these indications, so recommendations regarding clinical applications of HFNC remain tentative.

Figures in this Article

Oxygen therapy is the first line of treatment in patients with hypoxemia and may be delivered using low-flow devices (up to 15 L/min), such as nasal cannulae, nonrebreathing masks, and masks with reservoir bags. These deliver varying levels of Fio2 depending on the patient’s breathing pattern, peak inspiratory flow rate, delivery system, and mask characteristics.1,2 Maximal flow rates with these devices are limited partly by their inability to effectively heat and humidify gas at high flow rates. Conventional high-flow systems, such as Venturi masks, use a constant flow of oxygen through precisely sized ports and, through steady entrainment of room air using the Bernoulli effect, provide a more constant Fio2 than conventional nasal systems.1-3 However, these systems are less well tolerated than nasal cannulae due to obtrusiveness of the masks and insufficient heating and humidification of the inspired gas.1-3 Additionally, at high patient inspiratory flow rates, entrained room air dilutes the oxygen and lowers Fio2.

Over the past 2 decades, systems to deliver heated and humidified oxygen at high flows through nasal cannulae have been developed as an alternative to standard oxygen delivery systems. A high-flow nasal cannula (HFNC) delivers a flow rate up to 8 L/min in infants and 60 L/min in adults. The device consists of an air/oxygen blender connected through an active heated humidifier to the nasal cannula and allows adjustment of the Fio2 independently from the flow rate.

HFNC was first used in preterm neonates and pediatric care. In this population, its role has been and is still being extensively studied as a first-line treatment in respiratory distress syndrome, in apnea of prematurity, and in the postextubation period to prevent extubation failure. Some authors have proposed the use of HFNC in neonates as an alternative to CPAP because as opposed to standard oxygen therapy, it can also generate positive end-expiratory pressure (PEEP) and is better tolerated as a result of the heating and humidification.4

More recently, anecdotal case reports, case series, and some preliminary controlled trials have drawn attention to the potential role of HFNC in adults owing to its ability to set and deliver a desired Fio2, its better tolerance compared with standard face masks, and its avoidance of desiccation, which enhances comfort and secretion mobilization. In this narrative review, we critically examine the current literature focusing on the proposed mechanisms of action, clinical benefits, and potential applications of HFNC in adults receiving acute care; compare this approach to conventional oxygen supplementation and noninvasive ventilation (NIV); and highlight the many knowledge gaps requiring further study.

We searched for publications and abstracts on PubMed, the Cochrane Database of Systematic Reviews, and Scopus using the search terms “high flow” OR “humidified” OR “heated” AND “oxygen therapy” OR “nasal oxygen.” We limited the search to English-language publications but did not limit the search based on publication type. We searched for both bench studies and adult human studies. We considered only studies defining nasal high flow as a flow rate ≥ 20 L/min.

HFNC consists of high-flow gas with an Fio2 ranging from 0.21 to nearly 1.0 adjusted by an oxygen blender, brought to body temperature, and saturated with water through an in-line humidifier. The gas mixture is then provided to the nares through loose-fitting nasal prongs that are slightly larger but softer than those used for standard nasal oxygen therapy. The mechanisms by which HFNC may offer advantages to patients with dyspnea and hypoxemia are shown in Table 1.

Table Graphic Jump Location
TABLE 1 ]  Potential Mechanisms of Clinical Benefit During HFNC Use

HFNC = high-flow nasal cannula; PEEP = positive end-expiratory pressure.

Favorable Effects of Heated and Humidified Gas
Effects on Comfort and Tolerance:

Traditional methods of oxygen delivery provide nonhumidified or underhumidified gas that dries the upper airway, interferes with mucociliary clearance, facilitates atelectasis, and ultimately reduces patient comfort and tolerance. Little evidence is available on the beneficial effects of humidification when low-flow oxygen is supplemented, but with conventional higher-flow oxygen (up to 15 L/min) through face masks, tolerance is reduced by inhalation of cold, dry gas, even when a bubble humidifier is used.3,25 In a crossover study in 20 patients with acute respiratory failure mainly due to pneumonia, Roca et al5 found that compared with face mask oxygenation using a bubble humidifier, HFNC was associated with greater overall comfort, lower dyspnea scores, and reduced mouth dryness.

In other studies of patients postextubation, a favorable trend in comfort and tolerance was observed in patients on HFNC compared with conventional oxygen therapy.6,7 In contrast, Parke et al26 found that HFNC was less well tolerated than conventional oxygen therapy in the postextubation period after cardiac surgery. However, the study population was more stable than in the other studies and may not have had conditions likely to benefit from HFNC. On the whole, the available evidence suggests that HFNC enhances comfort and tolerance in patients with respiratory distress, but more work is needed to determine how to best select candidates and make adjustments (airflow, levels of heat and humidity) to optimize comfort.

Effects on Secretion Characteristics and Mobilization:

Patients with respiratory distress and failure commonly have increased airway secretions and expend considerable effort expelling them. This effort could contribute to respiratory muscle fatigue and progression of respiratory failure, especially when secretions become thick and difficult to mobilize. This is not an uncommon occurrence during NIV when instances of mucus retention have been reported.27

Water content of mucus affects viscosity and plays an important role in the transport of secretions. Physiologic humidification of secretions depends on proper functioning of airway epithelial cells through Na+ absorption and Cl secretion. Breathing dry gas is dessicating, damaging epithelial cells and altering the characteristics of mucus.8 Proper humidification is, therefore, needed to preserve and optimize mucosal functions, including facilitating gas exchange, limiting the metabolic cost of breathing, and maintaining host defenses.28

Warming inspired gas to the level of core temperature (37°C) and humidifying it to saturation help to maintain adequate mucosal function and preserve the rheology and volume of secretions, maximizing mucociliary clearance without risk of thermal injury or overhumidification.8 Deviation from these optimal conditions interferes with ciliary function and mucus transport, as shown by reductions of both ciliary beat frequency and mucus transport velocity after exposure to lower temperatures (34°C and 30°C).29,30

By virtue of its ability to hydrate airways, HFNC was first envisioned as a modality to facilitate secretion removal in patients with bronchiectasis.9 Thus, in conditions characterized by the need for adequate secretion removal (ie, pneumonia, COPD, cystic fibrosis, acute and chronic bronchitis, bronchiectasis), HFNC could be quite helpful.

Reduction in the Metabolic Cost of Breathing:

The delivery of warmed and humidified gas not only enhances comfort for the patient but also avoids desiccation of the nose and upper airways and therefore may help to avoid the bronchoconstricting effect of cold, dry gas.10 The metabolic cost necessary to warm and increase the relative humidity of inspired gas is not negligible, especially in patients with tachypnea and acute respiratory failure.11 Reducing this metabolic component of the work of breathing could potentially be beneficial for patients. Furthermore, by maintaining the integrity of mucociliary function and rendering secretions easier to mobilize, HFNC might also reduce the energy expended with expectoration. However, these “energy-saving” effects of HFNC and their impacts on outcomes in patients with respiratory failure are largely speculative and remain to be better understood.

High Flow Rate Minimizes Entrainment of Room Air

Patients in respiratory distress often have high inspiratory flow rates that substantially exceed the flow rates of standard oxygen delivery systems.1 Entrained room air dilutes the supplemental oxygen, often substantially reducing delivered Fio2. HFNC generates a higher flow rate compared with other oxygen delivery systems, exceeding the patient’s peak inspiratory flow rate in most cases. As a consequence, less mixing with room air occurs, and the desired Fio2 is more reliably delivered.12-14

However, open-mouth breathing during HFNC lowers delivered Fio2 compared with closed-mouth nasal breathing due to mixing of the high-flow nasal oxygen with room air inhaled through the mouth.13 Additionally, peak inspiratory flow rate may rise to > 90 L/min during exercise, exceeding the flow capabilities even of HFNC, so that entrained room air may substantially lower delivered Fio2.13 Nonetheless, HFNC is likely to perform better under these circumstances than traditional oxygen supplementation.

Increase in Ventilatory Efficiency
Washout of Nasopharyngeal Dead Space:

The ability to continually flush out CO2 from the upper airway is another potential benefit of HFNC.15-17 Similar to tracheal gas insufflation,31 this would eliminate dead space attributable to the flushed-out volume, permitting a higher fraction of minute ventilation to participate in gas exchange.32 Using a bench model of the nasal cavity to assess the fluid dynamics of gas during both simulated spontaneous breathing and use of HFNC, Spence et al33 demonstrated that the flow pattern of gas in the nasopharynx was significantly altered by HFNC. In particular, gas recirculation flushes CO2 from the nasopharynx during HFNC use, reducing the fraction of inspired CO2 and raising Fio2.18 Frizzola et al34 reported the same effect in a piglet model of acute lung injury, showing that the washout of anatomic dead space was related more to the incremental flow than to the incremental pressure. These effects would be expected to improve the efficiency of ventilation and efficacy of oxygen delivery compared with standard oxygen delivery systems. The evidence suggests greater effects at higher flow rates, but precisely how much dead space can be flushed out at high nasal flow rates in patients with respiratory failure remains to be determined.

PEEP Effect:

Multiple studies on infants and neonates have shown that HFNC significantly elevates nasopharyngeal or esophageal pressure, approximating levels seen with nasal CPAP. Because of air leakage though, the pressure levels are quite variable.19-22 In 2007, Groves and Tobin23 were the first to demonstrate that HFNC systems also generate positive expiratory pharyngeal pressure in adults. The airway pressure recorded during spontaneous breathing with HFNC correlates linearly with the administered flow rate and is significantly higher when subjects breathe with their mouths closed.23 These results have been confirmed in healthy volunteers12,23 and in patients with stable COPD and idiopathic pulmonary fibrosis24 and postcardiac surgery.35-37 Parke et al37 observed that for each increase of 10 L/min in flow rate, mean airway pressure increased by 0.69 cm H2O (P < .01) when subjects breathed with their mouths closed and by 0.35 cm H2O (P < .03) when they breathed with their mouths open. Another study by the same group showed that pressure generated by HFNC peaks at end expiration (Fig 1).38

Figure Jump LinkFigure 1 –  Nasopharyngeal pressure generated by high-flow nasal cannula oxygen during the respiratory cycle at various flow rates in one patient postcardiac surgery. (Reprinted with permission from Parke and McGinness.38)Grahic Jump Location

Low-level positive airway pressure is also generated by HFNC during inspiration, unrelated to the amount of mouth closure during breathing.23,37 Even though this finding suggests a role of HFNC in reducing the work of breathing by providing a small amount of inspiratory assistance and counterbalancing auto-PEEP through the aforementioned end-expiratory pressure effect, especially in patients with COPD, no direct measurements of the effects of HFNC on respiratory muscle function have yet been reported. Therefore, conclusions about the effect of HFNC on the work of breathing, especially in patients with various etiologies for respiratory failure, must await more definitive investigations.

Effects on Breathing Pattern:

In healthy volunteers, HFNC alters the breathing pattern through an increase in tidal volume and reduction in respiratory rate, with minute volume remaining steady.39,40 Using electrical impedance tomography, Corley et al36 observed the same increase in tidal volume in postcardiac surgery patients. Tidal volume and end-expiratory lung volume increased the most in patients with a higher BMI. Such alterations in breathing pattern and lung volumes could reproduce the favorable effects of CPAP in patients with acute pulmonary edema, opening of flooded alveoli with improved oxygenation, and lung compliance as well as reduced left ventricular afterload.41-43 But whether the pressure elevations with HFNC are sufficient to realize these benefits has not yet been established.

Hypoxemic Respiratory Failure

HFNC has been tried in a number of different types of hypoxemic respiratory failure (Table 2). Initially, a few anecdotal cases were reported on the comfort and oxygenation advantages of HFNC in respiratory failure and during procedures such as bronchoscopy in patients with hypoxemia.44,49-51 Two retrospective analyses showed significant improvement in oxygenation and reduction in respiratory rate in adult burn patients52 and in a surgical high-dependency unit.53

Table Graphic Jump Location
TABLE 2 ]  Potential Clinical Applications of High-Flow Nasal Oxygen

In 2010, Roca et al5 reported the first prospective crossover intervention study in acute respiratory failure comparing HFNC to conventional oxygen delivery through high-flow face mask (HFFM) combined with nasal cannula (sum of face mask and nasal cannula flow, 20 L/min). In 20 patients, comfort, tolerance, and oxygenation were all better with HFNC than with HFFM at the same targeted Fio2 of 50% (Pao2, 127 mm Hg vs 77 mm Hg; P = .002), with no significant difference in pH or Paco2. Sztrymf et al16 confirmed the favorable effects of HFNC on oxygenation as well as significantly lower respiratory (24.5/min vs 28/min, P < .006) and heart rates at 1 h compared with HFFM. These authors identified failure of respiratory rate to drop, lower oxygen saturation, and persisting thoracoabdominal asynchrony as predictors of HFNC failure (nine of the 38 subjects needed intubation and mechanical ventilation).15

Most studies on HFNC in patients with hypoxemia have been conducted in an ICU or high-dependency unit. Lenglet et al17 examined HFNC use in patients with hypoxemia in the ED. After 15 min, HFNC improved oxygen saturation as measured by pulse oximetry (Spo2) (96% vs 90%, P < .01), respiratory rate (25/min vs 28/min), and dyspnea scores (both Borg and a 10-point visual analog scale) compared with baseline values. An accompanying survey of ED providers found that 75% preferred HFNC over standard oxygen therapy.17

In a recent prospective but uncontrolled trial in 28 patients with hypoxemic respiratory failure, excluding those with acute cardiogenic pulmonary edema (ACPE), Frat et al45 applied HFNC sequentially with NIV (2 h alternating with 1 h, respectively) and found that HFNC improved oxygenation compared with standard oxygen therapy but not as much as NIV. HFNC also reduced respiratory rate compared with standard oxygen therapy and was better tolerated than NIV. Ten patients (36%) required intubation, and a respiratory rate ≥ 30/min after initiation of HFNC predicted the need for intubation. Despite these promising results, we await the completion of several large, multicenter randomized trials currently under way to adequately assess oxygenation capabilities compared with standard oxygen therapy and NIV and to determine the types and severities of hypoxemic respiratory failure most likely to benefit from HFNC.

Acute Cardiogenic Pulmonary Edema

By virtue of its ability to oxygenate effectively and provide low levels of PEEP, HFNC has been proposed as a therapy for ACPE. Like CPAP, HFNC is hypothesized to open flooded alveoli, improving lung compliance and oxygenation while enhancing cardiac function through the afterload-reducing effect of the end-expiratory pressure. In a cohort of five patients with persisting hypoxemia and dyspnea on conventional oxygen therapy after treatment of ACPE with NIV, HFNC significantly improved arterial blood gases (Po2 and pH) and reduced dyspnea.54 Randomized controlled trials on the use of HFNC as a treatment in patients with ACPE are needed.

Postoperative Patients
Postcardiothoracic and Vascular Surgery:

In a preliminary randomized trial of 60 patients with mild to moderate acute hypoxemic respiratory failure following cardiothoracic or vascular surgery, Parke et al46 found that patients treated with HFNC had a lower failure rate (defined as escalation to NIV) than those receiving HFFM (P = .006) and had fewer oxygen desaturations. Use of NIV in the two groups was not significantly different, but five of the failures in the face mask group were crossed over to HFNC, of whom only one required NIV. Although the results favored HFNC, the small sample size, use of HFNC as an escalation therapy from face mask, and lack of protocolized criteria for escalation in an unblinded study limited the conclusions.

A more recent prospective study in 40 patients with hypoxemic respiratory failure, most of whom were postoperative, showed improved thoracoabdominal synchrony with HFNC compared with low-flow-mask oxygen delivery (up to 8 L/min).47 Oxygenation was not better in the HFNC group than the low-flow oxygen group, but the study was small, and most patients had only mild respiratory failure and may not have been sufficiently hypoxemic to manifest a significant benefit.47

Postcardiac Surgery:

Corley et al36 found in a cohort of 20 patients with respiratory dysfunction that HFNC reduced respiratory rate and Borg dyspnea score and improved oxygenation compared with baseline measures. In addition, HFNC increased airway pressure and end-expiratory lung volume as determined by electrical impedance tomography, especially in patients with a higher BMI. The authors speculated that HFNC could play a useful role in postcardiac surgery in patients who are obese or intolerant of NIV.36

Parke et al26 randomized 340 patients undergoing elective cardiac surgery, including sternotomy and cardiopulmonary bypass, to postoperative prophylactic use of HFNC or standard oxygen therapy. They found no significant difference in Spo2 or Fio2 on days 1 to 3 after surgery. Furthermore, HFNC did not reduce atelectasis or ICU length of stay. HFNC did lower the need for escalation to NIV or intubation (27.8% vs 45% of patients, P < .001). Further trials are needed to assess the possible role of HFNC to avoid pulmonary complications or escalation of therapy in postcardiac surgical and other postoperative settings, especially in higher-risk populations.

Postextubation

Patients recently extubated are prone to oxygen desaturations and often require standard high-flow oxygen therapy; therefore, it is reasonable to hypothesize that HFNC is useful for these patients. Two randomized crossover trials compared short-term interventions (30-min HFNC vs 30-min HFFM) in patients extubated after passing a spontaneous breathing trial (SBT).6,7 Both studies showed a trend toward better comfort with HFNC and no significant difference in gas exchange. However, the results of the two trials were conflicting, with one6 reporting no differences between treatments and the other7 finding reductions in dyspnea score (1.6 vs 2.9, P = .04), respiratory rate (19.8/min vs 23.1/min, P = .009), and heart rate (89.5/min vs 95.4/min, P = .006) with HFNC compared with HFFM. This discrepancy could be explained by the different protocols used in the two studies. In the former, subjects were randomized to the first intervention 30 min after extubation, and the HFFM flow rate was ≥ 30 L/min. In the latter, the randomization happened immediately after extubation, and the HFFM flow rate was only 6 to 8 L/min.

A more recent randomized trial55 compared HFNC to Venturi masks in 105 patients intubated for at least 24 h and extubated after passing an SBT but having a Pao2/Fio2 ≤ 300 at the end of the SBT. If patients had failed more than three SBTs, were hypercapnic (Paco2 > 45 mm Hg), or had a respiratory rate > 25/min just before the SBT, they received NIV and did not undergo randomization. The HFNC group had a significantly better oxygen saturation and Pao2/Fio2 and a lower respiratory rate than those randomized to the Venturi mask. The Pco2 and discomfort related to the interface and dryness were also lower in the HFNC group. Furthermore, HFNC was associated with fewer episodes of interface displacement and oxygen desaturation and less need for escalation to NIV or reintubation. These promising results seem to justify the use of HFNC in the postextubation setting, but how to select patients most likely to benefit and when to apply it in relation to conventional oxygen techniques and NIV deserve further study.

Do-Not-Intubate Patients and Palliative Care

Another possible indication for HFNC is as a palliative treatment of hypoxemia and respiratory distress in do-not-intubate (DNI) patients. In this population, HFNC is an alternative to standard NIV, which would otherwise add to discomfort and interfere with speaking and eating.56 In a retrospective analysis of HFNC in DNI patients with cancer and respiratory distress, Epstein et al48 found that 85% of 183 patients treated with HFNC improved or remained stable. Another retrospective study involving DNI patients mainly with idiopathic pulmonary fibrosis, pneumonia, or COPD showed that HFNC improved oxygenation and respiratory mechanics, but 18% of patients still needed escalation of therapy to NIV.57 Minimal information is available on this application of HFNC, however, and the role of HFNC among the multiple options for palliation remains to be determined.

Based on the multiple physiologic and subjective benefits of HFNC compared with standard oxygen therapy, HFNC is assuming a role in the management of hypoxemia and respiratory failure. The greatest benefit appears to be in patients who have severe hypoxemia and would ordinarily receive standard high-flow oxygen therapy by mask. For these patients, HFNC offers enhanced comfort, more-reliable delivery of Fio2, and more-efficient ventilation. HFNC is unlikely to benefit patients with more mild hypoxemia doing well on low-flow nasal oxygen. Additionally, although it is better tolerated than NIV and might be used in place of NIV in some patients or sequentially with NIV to provide better oxygenation and comfort during breaks from NIV, caution should be exercised in patients with high breathing workloads whose ventilatory failure is worsening. Because it generates only slight elevations of airway pressure at end expiration, HFNC is unlikely to reduce the work of breathing as effectively as NIV. Thus, HFNC is perhaps best situated in the middle of the spectrum of therapies to treat hypoxemia and respiratory failure. It supplies more oxygenation and gas flow than is necessary for patients with mild hypoxemia and not enough positive pressure or ventilator assistance for patients more severely afflicted. The advantages of HFNC over standard oxygen delivery systems are significant, and we will likely see increasing use in acute and critical care settings as more data emerge and its role becomes better defined.

Because of the limited clinical data available for adult applications of HFNC, it is difficult to make firm recommendations on practical aspects of HFNC use. Physiologic studies have demonstrated that the beneficial effects of HFNC are related to flow rate, so we prefer to initiate therapy by adjusting this parameter first and then to titrate the Fio2 to maintain target oxygenation. Flow rates on commercially available devices range from 5 to 60 L/min. Studies in the literature have started with flow rates of 20,5 35,26 and 5057 L/min. We usually start with a flow rate of 35 L/min, which provides some PEEP and is well tolerated by most patients. Flow rate is then adjusted upward in 5 to 10 L/min increments if the respiratory rate fails to drop or breathing remains labored and downward if not tolerated. Either increasing Fio2 or the flow rate would be expected to improve oxygenation, the latter because of reduced entrainment of room air during inspiration. Uptitration of flow rate is usually preferred to raising Fio2 as an initial strategy to increase Spo2, but if Spo2 falls substantially below the target level (usually > 90% to 92%), increases in Fio2 can raise Spo2 more rapidly. Further increases in flow rate can then be used to maintain targeted Spo2 while Fio2 is lowered to nontoxic levels (≤ 60%). Patients can tolerate HFNC continuously for prolonged periods (many days) and can be weaned to standard oxygen supplementation techniques if they are oxygenated adequately on a flow rate ≤ 20 L/min and Fio2 ≤ 50%. Until the safety of HFNC can be established in various settings, we recommend that HFNC use be limited to ICUs or intermediate care units where patients can be closely monitored; its use on regular wards should be discouraged, especially in patients with severe hypoxemia who are prone to severe oxygen desaturations if disconnected.

Devices that deliver high-flow heated and humidified oxygen through nasal cannulae (HFNCs) have become a standard of care in several clinical situations for infants, children, and preterm neonates. By virtue of a number of physiologic benefits over conventional oxygen therapy, including greater comfort and tolerance, more-effective oxygenation in some circumstances, and improved breathing pattern with increased tidal volume and decreased respiratory rate and dyspnea, we are now seeing increasing use for adults. HFNC has been used to treat hypoxemic respiratory failure and cardiogenic pulmonary edema as well as postoperatively and postextubation as both prophylaxis against pulmonary complications and treatment of frank respiratory failure. However, most of the studies addressing these applications are of low quality, limiting the ability to draw conclusions or make recommendations. Further physiologic and randomized controlled studies are needed to confirm the clinical advantages of HFNC over other methods in specific adult populations, to evaluate longer-term effects, and to determine the optimal use of HFNC in relation to other modalities, such as standard oxygen therapy and NIV.

Financial/nonfinancial disclosures: The authors have reported to CHEST the following conflicts: Dr Hill has served on the Medical Advisory Board and received consulting fees from Fisher Paykel and has also received consulting fees from Vapotherm. Drs Spoletini, Alotaibi, and Blasi have reported that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

ACPE

acute cardiogenic pulmonary edema

DNI

do not intubate

HFFM

high-flow face mask

HFNC

high-flow nasal cannula

NIV

noninvasive ventilation

PEEP

positive end-expiratory pressure

SBT

spontaneous breathing trial

Spo2

oxygen saturation as measured by pulse oximetry

Kallstrom TJ; American Association for Respiratory Care (AARC). AARC clinical practice guideline: oxygen therapy for adults in the acute care facility—2002 revision & update. Respir Care. 2002;47(6):717-720. [PubMed]
 
Shapiro BA, Kacmarek RM, Cane RD, Hauptman D. Clinical Application of Respiratory Care.,4th ed. St Louis, MO: Mosby; 1990.
 
Chanques G, Constantin JM, Sauter M, et al. Discomfort associated with underhumidified high-flow oxygen therapy in critically ill patients. Intensive Care Med. 2009;35(6):996-1003. [CrossRef] [PubMed]
 
Manley BJ, Dold SK, Davis PG, Roehr CC. High-flow nasal cannulae for respiratory support of preterm infants: a review of the evidence. Neonatology. 2012;102(4):300-308. [CrossRef] [PubMed]
 
Roca O, Riera J, Torres F, Masclans JR. High-flow oxygen therapy in acute respiratory failure. Respir Care. 2010;55(4):408-413. [PubMed]
 
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(3):463-468. [CrossRef] [PubMed]
 
Rittayamai N, Tscheikuna J, Rujiwit P. High-flow nasal oxygen versus conventional oxygen therapy after endotracheal extubation: a randomized crossover physiologic study. Respir Care. 2014;59(4):485-490. [CrossRef] [PubMed]
 
Williams R, Rankin N, Smith T, Galler D, Seakins P. Relationship between the humidity and temperature of inspired gas and the function of the airway mucosa. Crit Care Med. 1996;24(11):1920-1929. [CrossRef] [PubMed]
 
Hasani A, Chapman TH, McCool D, Smith RE, Dilworth JP, Agnew JE. Domiciliary humidification improves lung mucociliary clearance in patients with bronchiectasis. Chron Respir Dis. 2008;5(2):81-86. [CrossRef] [PubMed]
 
Richards GN, Cistulli PA, Ungar RG, Berthon-Jones M, Sullivan CE. Mouth leak with nasal continuous positive airway pressure increases nasal airway resistance. Am J Respir Crit Care Med. 1996;154(1):182-186. [CrossRef] [PubMed]
 
Dysart K, Miller TL, Wolfson MR, Shaffer TH. Research in high flow therapy: mechanisms of action. Respir Med. 2009;103(10):1400-1405. [CrossRef] [PubMed]
 
Sim MAB, Dean P, Kinsella J, Black R, Carter R, Hughes M. Performance of oxygen delivery devices when the breathing pattern of respiratory failure is simulated. Anaesthesia. 2008;63(9):938-940. [CrossRef] [PubMed]
 
Ritchie JE, Williams AB, Gerard C, Hockey H. Evaluation of humidified nasal high-flow oxygen system, using oxygraphy, capnography and measurement of upper airways pressure. Anesth Intensive Care. 2011:39(6):1103-1110.
 
Wagstaff TAJ, Soni N. Performance of six types of oxygen delivery devices at varying respiratory rates. Anaesthesia. 2007;62(5):492-503. [CrossRef] [PubMed]
 
Sztrymf B, Messika J, Bertrand F, et al. Beneficial effects of humidified high flow nasal oxygen in critical care patients: a prospective pilot study. Intensive Care Med. 2011;37(11):1780-1786. [CrossRef] [PubMed]
 
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. 2012;27(3):e9-e13. [CrossRef] [PubMed]
 
Lenglet H, Sztrymf B, Leroy C, Brun P, Dreyfuss D, Ricard JD. Humidified high flow nasal oxygen during respiratory failure in the emergency department: feasibility and efficacy. Respir Care. 2012;57(11):1873-1878. [CrossRef] [PubMed]
 
Spence CJT, Buchmann NA, Jermy MC. Unsteady flow in the nasal cavity with high flow therapy measured by stereoscopic PIV. Exp Fluids. 2011;52(3):569-579. [CrossRef]
 
Saslow JG, Aghai ZH, Nakhla TA, et al. Work of breathing using high-flow nasal cannula in preterm infants. J Perinatol. 2006;26(8):476-480. [CrossRef] [PubMed]
 
Spence KL, Murphy D, Kilian C, McGonigle R, Kilani RA. High-flow nasal cannula as a device to provide continuous positive airway pressure in infants. J Perinatol. 2007;27(12):772-775. [CrossRef] [PubMed]
 
Kubicka ZJ, Limauro J, Darnall RA. Heated, humidified high-flow nasal cannula therapy: yet another way to deliver continuous positive airway pressure? Pediatrics. 2008;121(1):82-88. [CrossRef] [PubMed]
 
Hasan RA, Habib RH. Effects of flow rate and airleak at the nares and mouth opening on positive distending pressure delivery using commercially available high-flow nasal cannula systems: a lung model study. Pediatr Crit Care Med. 2011;12(1):e29-e33. [CrossRef] [PubMed]
 
Groves N, Tobin A. High flow nasal oxygen generates positive airway pressure in adult volunteers. Aust Crit Care. 2007;20(4):126-131. [CrossRef] [PubMed]
 
Bräunlich J, Beyer D, Mai D, Hammerschmidt S, Seyfarth HJ, Wirtz H. Effects of nasal high flow on ventilation in volunteers, COPD and idiopathic pulmonary fibrosis patients. Respiration. 2012;85(4):319-325. [CrossRef] [PubMed]
 
Cuquemelle E, Pham T, Papon JF, Louis B, Danin PE, Brochard L. Heated and humidified high-flow oxygen therapy reduces discomfort during hypoxemic respiratory failure. Respir Care. 2012;57(10):1571-1577. [CrossRef] [PubMed]
 
Parke R, McGuinness S, Dixon R, Jull A. Open-label, phase II study of routine high-flow nasal oxygen therapy in cardiac surgical patients. Br J Anaesth. 2013;111(6):925-931. [CrossRef] [PubMed]
 
Wood KE, Flaten AL, Backes WJ. Inspissated secretions: a life-threatening complication of prolonged noninvasive ventilation. Respir Care. 2000;45(5):491-493. [PubMed]
 
Esquinas Rodriguez AM, Scala R, Soroksky A, et al. Clinical review: humidifiers during non-invasive ventilation—key topics and practical implications. Crit Care. 2012;16(1):203-209. [CrossRef] [PubMed]
 
Kilgour E, Rankin N, Ryan S, Pack R. Mucociliary function deteriorates in the clinical range of inspired air temperature and humidity. Intensive Care Med. 2004;30(7):1491-1494. [CrossRef] [PubMed]
 
Chidekel A, Zhu Y, Wang J, Mosko JJ, Rodriguez E, Shaffer TH. The effects of gas humidification with high-flow nasal cannula on cultured human airway epithelial cells. Pulm Med. 2012;2012:380686. [CrossRef] [PubMed]
 
Nakos G, Lachana A, Prekates A, et al. Respiratory effects of tracheal gas insufflation in spontaneously breathing COPD patients. Intensive Care Med. 1995;21(11):904-912. [CrossRef] [PubMed]
 
Ravenscraft SA, Shapiro RS, Nahum A, et al. Tracheal gas insufflation: catheter effectiveness determined by expiratory flush volume. Am J Respir Crit Care Med. 1996;153(6):1817-1824. [CrossRef] [PubMed]
 
Spence CJT, Buchmann NA, Jermy MC, Moore SM. Stereoscopic PIV measurement of flow in the nasal cavity with high flow therapy. Exp Fluids. 2010;50(4):1005-1007. [CrossRef]
 
Frizzola M, Miller TL, Rodriguez ME, et al. High-flow nasal cannula: impact on oxygenation and ventilation in an acute lung injury model. Pediatr Pulmonol. 2011;46(1):67-74. [CrossRef] [PubMed]
 
Parke R, McGuinness S, Eccleston M. Nasal high-flow therapy delivers low level positive airway pressure. Br J Anaesth. 2009;103(6):886-890. [CrossRef] [PubMed]
 
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(6):998-1004. [CrossRef] [PubMed]
 
Parke RL, Eccleston ML, McGuinness SP. The effects of flow on airway pressure during nasal high-flow oxygen therapy. Respir Care. 2011;56(8):1151-1155. [CrossRef] [PubMed]
 
Parke RL, McGuinness SP. Pressures delivered by nasal high flow oxygen during all phases of the respiratory cycle. Respir Care. 2013;58(10):1621-1624. [CrossRef] [PubMed]
 
Mündel T, Feng S, Tatkov S, Schneider H. Mechanisms of nasal high flow on ventilation during wakefulness and sleep. J Appl Physiol (1985). 2013;114(8):1058-1065. [CrossRef] [PubMed]
 
Riera J, Pérez P, Cortés J, Roca O, Masclans JR, Rello J. Effect of high-flow nasal cannula and body position on end-expiratory lung volume: a cohort study using electrical impedance tomography. Respir Care. 2013;58(4):589-596. [CrossRef] [PubMed]
 
Katz JA, Marks JD. Inspiratory work with and without continuous positive airway pressure in patients with acute respiratory failure. Anesthesiology. 1985;63(6):598-607. [CrossRef] [PubMed]
 
Fessler HE, Brower RG, Wise RA, Permutt S. Effects of systolic and diastolic positive pleural pressure pulses with altered cardiac contractility. J Appl Physiol (1985). 1992;73(2):498-505. [PubMed]
 
Lenique F, Habis M, Lofaso F, Dubois-Randé JL, Harf A, Brochard L. Ventilatory and hemodynamic effects of continuous positive airway pressure in left heart failure. Am J Respir Crit Care Med. 1997;155(2):500-505. [CrossRef] [PubMed]
 
Lomas C, Roca O, Alvarez A, Masclans JR. Fibroscopy in patients with hypoxemic respiratory insufficiency: utility of the high-flow nasal cannula. Respir Med CME. 2009;2(3):121-124. [CrossRef]
 
Frat J-P, Brugiere B, Ragot S, et al. Sequential application of oxygen therapy via high-flow nasal cannula and noninvasive ventilation in acute respiratory failure: an observational pilot study. Respir Care. 2015;60(2):170-178. [CrossRef] [PubMed]
 
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(3):265-270. [CrossRef] [PubMed]
 
Itagaki T, Okuda N, Tsunano Y, et al. Effect of high-flow nasal cannula on thoraco-abdominal synchrony in adult critically ill patients. Respir Care. 2014;59(1):70-74. [CrossRef] [PubMed]
 
Epstein AS, Hartridge-Lambert SK, Ramaker JS, Voigt LP, Portlock CS. Humidified high-flow nasal oxygen utilization in patients with cancer at Memorial Sloan-Kettering Cancer Center. J Palliat Med. 2011;14(7):835-839. [CrossRef] [PubMed]
 
Calvano TP, Sill JM, Kemp KR, Chung KK. Use of a high-flow oxygen delivery system in a critically ill patient with dementia. Respir Care. 2008;53(12):1739-1743. [PubMed]
 
Boyer A, Vargas F, Delacre M, et al. Prognostic impact of high-flow nasal cannula oxygen supply in an ICU patient with pulmonary fibrosis complicated by acute respiratory failure. Intensive Care Med. 2011;37(3):558-559. [CrossRef] [PubMed]
 
Lacroix G, Pons F, D’Aranda E, Legodec J, Romanat PE, Goutorbe P. High-flow oxygen, a therapeutic bridge while awaiting thrombolysis in pulmonary embolism? Am J Emerg Med. 2013:31(2):463.e1-463.e2. [CrossRef]
 
Chung KK, McLaughlin DF, Horvath EE, et al. Nasal cannula O2 delivery system improves oxygenation and ventilation in adult burn patients [abstract]. Chest. 2005:130(4_MeetingAbstract):276S.
 
Makowski A, Mistzal B, Plowright C, Safranow K. Effectiveness of Vapotherm therapy for patients with respiratory failure at surgical high dependency unit [abstract]. Intensive Care Med. 2007;33(suppl 2):S86.
 
Carratalá Perales JM, Llorens P, Brouzet B, et al. High-flow therapy via nasal cannula in acute heart failure. Rev Esp Cardiol. 2011;64(8):723-725. [CrossRef] [PubMed]
 
Maggiore SM, Idone FA, Vaschetto R, et al. Nasal high-flow versus Venturi mask oxygen therapy after extubation. Effects on oxygenation, comfort, and clinical outcome. Am J Respir Crit Care Med. 2014;190(3):282-288. [CrossRef] [PubMed]
 
Lacroix G, Legodec J, D’Aranda E, Esnault P, Romanat PE, Goutorbe P. Is non-invasive ventilation the best ventilatory support for ‘do not intubate’ patients? Crit Care. 2012;16(4):442. [CrossRef] [PubMed]
 
Peters SG, Holets SR, Gay PC. High-flow nasal cannula therapy in do-not-intubate patients with hypoxemic respiratory distress. Respir Care. 2013;58(4):597-600. [PubMed]
 

Figures

Figure Jump LinkFigure 1 –  Nasopharyngeal pressure generated by high-flow nasal cannula oxygen during the respiratory cycle at various flow rates in one patient postcardiac surgery. (Reprinted with permission from Parke and McGinness.38)Grahic Jump Location

Tables

Table Graphic Jump Location
TABLE 1 ]  Potential Mechanisms of Clinical Benefit During HFNC Use

HFNC = high-flow nasal cannula; PEEP = positive end-expiratory pressure.

Table Graphic Jump Location
TABLE 2 ]  Potential Clinical Applications of High-Flow Nasal Oxygen

References

Kallstrom TJ; American Association for Respiratory Care (AARC). AARC clinical practice guideline: oxygen therapy for adults in the acute care facility—2002 revision & update. Respir Care. 2002;47(6):717-720. [PubMed]
 
Shapiro BA, Kacmarek RM, Cane RD, Hauptman D. Clinical Application of Respiratory Care.,4th ed. St Louis, MO: Mosby; 1990.
 
Chanques G, Constantin JM, Sauter M, et al. Discomfort associated with underhumidified high-flow oxygen therapy in critically ill patients. Intensive Care Med. 2009;35(6):996-1003. [CrossRef] [PubMed]
 
Manley BJ, Dold SK, Davis PG, Roehr CC. High-flow nasal cannulae for respiratory support of preterm infants: a review of the evidence. Neonatology. 2012;102(4):300-308. [CrossRef] [PubMed]
 
Roca O, Riera J, Torres F, Masclans JR. High-flow oxygen therapy in acute respiratory failure. Respir Care. 2010;55(4):408-413. [PubMed]
 
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(3):463-468. [CrossRef] [PubMed]
 
Rittayamai N, Tscheikuna J, Rujiwit P. High-flow nasal oxygen versus conventional oxygen therapy after endotracheal extubation: a randomized crossover physiologic study. Respir Care. 2014;59(4):485-490. [CrossRef] [PubMed]
 
Williams R, Rankin N, Smith T, Galler D, Seakins P. Relationship between the humidity and temperature of inspired gas and the function of the airway mucosa. Crit Care Med. 1996;24(11):1920-1929. [CrossRef] [PubMed]
 
Hasani A, Chapman TH, McCool D, Smith RE, Dilworth JP, Agnew JE. Domiciliary humidification improves lung mucociliary clearance in patients with bronchiectasis. Chron Respir Dis. 2008;5(2):81-86. [CrossRef] [PubMed]
 
Richards GN, Cistulli PA, Ungar RG, Berthon-Jones M, Sullivan CE. Mouth leak with nasal continuous positive airway pressure increases nasal airway resistance. Am J Respir Crit Care Med. 1996;154(1):182-186. [CrossRef] [PubMed]
 
Dysart K, Miller TL, Wolfson MR, Shaffer TH. Research in high flow therapy: mechanisms of action. Respir Med. 2009;103(10):1400-1405. [CrossRef] [PubMed]
 
Sim MAB, Dean P, Kinsella J, Black R, Carter R, Hughes M. Performance of oxygen delivery devices when the breathing pattern of respiratory failure is simulated. Anaesthesia. 2008;63(9):938-940. [CrossRef] [PubMed]
 
Ritchie JE, Williams AB, Gerard C, Hockey H. Evaluation of humidified nasal high-flow oxygen system, using oxygraphy, capnography and measurement of upper airways pressure. Anesth Intensive Care. 2011:39(6):1103-1110.
 
Wagstaff TAJ, Soni N. Performance of six types of oxygen delivery devices at varying respiratory rates. Anaesthesia. 2007;62(5):492-503. [CrossRef] [PubMed]
 
Sztrymf B, Messika J, Bertrand F, et al. Beneficial effects of humidified high flow nasal oxygen in critical care patients: a prospective pilot study. Intensive Care Med. 2011;37(11):1780-1786. [CrossRef] [PubMed]
 
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. 2012;27(3):e9-e13. [CrossRef] [PubMed]
 
Lenglet H, Sztrymf B, Leroy C, Brun P, Dreyfuss D, Ricard JD. Humidified high flow nasal oxygen during respiratory failure in the emergency department: feasibility and efficacy. Respir Care. 2012;57(11):1873-1878. [CrossRef] [PubMed]
 
Spence CJT, Buchmann NA, Jermy MC. Unsteady flow in the nasal cavity with high flow therapy measured by stereoscopic PIV. Exp Fluids. 2011;52(3):569-579. [CrossRef]
 
Saslow JG, Aghai ZH, Nakhla TA, et al. Work of breathing using high-flow nasal cannula in preterm infants. J Perinatol. 2006;26(8):476-480. [CrossRef] [PubMed]
 
Spence KL, Murphy D, Kilian C, McGonigle R, Kilani RA. High-flow nasal cannula as a device to provide continuous positive airway pressure in infants. J Perinatol. 2007;27(12):772-775. [CrossRef] [PubMed]
 
Kubicka ZJ, Limauro J, Darnall RA. Heated, humidified high-flow nasal cannula therapy: yet another way to deliver continuous positive airway pressure? Pediatrics. 2008;121(1):82-88. [CrossRef] [PubMed]
 
Hasan RA, Habib RH. Effects of flow rate and airleak at the nares and mouth opening on positive distending pressure delivery using commercially available high-flow nasal cannula systems: a lung model study. Pediatr Crit Care Med. 2011;12(1):e29-e33. [CrossRef] [PubMed]
 
Groves N, Tobin A. High flow nasal oxygen generates positive airway pressure in adult volunteers. Aust Crit Care. 2007;20(4):126-131. [CrossRef] [PubMed]
 
Bräunlich J, Beyer D, Mai D, Hammerschmidt S, Seyfarth HJ, Wirtz H. Effects of nasal high flow on ventilation in volunteers, COPD and idiopathic pulmonary fibrosis patients. Respiration. 2012;85(4):319-325. [CrossRef] [PubMed]
 
Cuquemelle E, Pham T, Papon JF, Louis B, Danin PE, Brochard L. Heated and humidified high-flow oxygen therapy reduces discomfort during hypoxemic respiratory failure. Respir Care. 2012;57(10):1571-1577. [CrossRef] [PubMed]
 
Parke R, McGuinness S, Dixon R, Jull A. Open-label, phase II study of routine high-flow nasal oxygen therapy in cardiac surgical patients. Br J Anaesth. 2013;111(6):925-931. [CrossRef] [PubMed]
 
Wood KE, Flaten AL, Backes WJ. Inspissated secretions: a life-threatening complication of prolonged noninvasive ventilation. Respir Care. 2000;45(5):491-493. [PubMed]
 
Esquinas Rodriguez AM, Scala R, Soroksky A, et al. Clinical review: humidifiers during non-invasive ventilation—key topics and practical implications. Crit Care. 2012;16(1):203-209. [CrossRef] [PubMed]
 
Kilgour E, Rankin N, Ryan S, Pack R. Mucociliary function deteriorates in the clinical range of inspired air temperature and humidity. Intensive Care Med. 2004;30(7):1491-1494. [CrossRef] [PubMed]
 
Chidekel A, Zhu Y, Wang J, Mosko JJ, Rodriguez E, Shaffer TH. The effects of gas humidification with high-flow nasal cannula on cultured human airway epithelial cells. Pulm Med. 2012;2012:380686. [CrossRef] [PubMed]
 
Nakos G, Lachana A, Prekates A, et al. Respiratory effects of tracheal gas insufflation in spontaneously breathing COPD patients. Intensive Care Med. 1995;21(11):904-912. [CrossRef] [PubMed]
 
Ravenscraft SA, Shapiro RS, Nahum A, et al. Tracheal gas insufflation: catheter effectiveness determined by expiratory flush volume. Am J Respir Crit Care Med. 1996;153(6):1817-1824. [CrossRef] [PubMed]
 
Spence CJT, Buchmann NA, Jermy MC, Moore SM. Stereoscopic PIV measurement of flow in the nasal cavity with high flow therapy. Exp Fluids. 2010;50(4):1005-1007. [CrossRef]
 
Frizzola M, Miller TL, Rodriguez ME, et al. High-flow nasal cannula: impact on oxygenation and ventilation in an acute lung injury model. Pediatr Pulmonol. 2011;46(1):67-74. [CrossRef] [PubMed]
 
Parke R, McGuinness S, Eccleston M. Nasal high-flow therapy delivers low level positive airway pressure. Br J Anaesth. 2009;103(6):886-890. [CrossRef] [PubMed]
 
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(6):998-1004. [CrossRef] [PubMed]
 
Parke RL, Eccleston ML, McGuinness SP. The effects of flow on airway pressure during nasal high-flow oxygen therapy. Respir Care. 2011;56(8):1151-1155. [CrossRef] [PubMed]
 
Parke RL, McGuinness SP. Pressures delivered by nasal high flow oxygen during all phases of the respiratory cycle. Respir Care. 2013;58(10):1621-1624. [CrossRef] [PubMed]
 
Mündel T, Feng S, Tatkov S, Schneider H. Mechanisms of nasal high flow on ventilation during wakefulness and sleep. J Appl Physiol (1985). 2013;114(8):1058-1065. [CrossRef] [PubMed]
 
Riera J, Pérez P, Cortés J, Roca O, Masclans JR, Rello J. Effect of high-flow nasal cannula and body position on end-expiratory lung volume: a cohort study using electrical impedance tomography. Respir Care. 2013;58(4):589-596. [CrossRef] [PubMed]
 
Katz JA, Marks JD. Inspiratory work with and without continuous positive airway pressure in patients with acute respiratory failure. Anesthesiology. 1985;63(6):598-607. [CrossRef] [PubMed]
 
Fessler HE, Brower RG, Wise RA, Permutt S. Effects of systolic and diastolic positive pleural pressure pulses with altered cardiac contractility. J Appl Physiol (1985). 1992;73(2):498-505. [PubMed]
 
Lenique F, Habis M, Lofaso F, Dubois-Randé JL, Harf A, Brochard L. Ventilatory and hemodynamic effects of continuous positive airway pressure in left heart failure. Am J Respir Crit Care Med. 1997;155(2):500-505. [CrossRef] [PubMed]
 
Lomas C, Roca O, Alvarez A, Masclans JR. Fibroscopy in patients with hypoxemic respiratory insufficiency: utility of the high-flow nasal cannula. Respir Med CME. 2009;2(3):121-124. [CrossRef]
 
Frat J-P, Brugiere B, Ragot S, et al. Sequential application of oxygen therapy via high-flow nasal cannula and noninvasive ventilation in acute respiratory failure: an observational pilot study. Respir Care. 2015;60(2):170-178. [CrossRef] [PubMed]
 
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(3):265-270. [CrossRef] [PubMed]
 
Itagaki T, Okuda N, Tsunano Y, et al. Effect of high-flow nasal cannula on thoraco-abdominal synchrony in adult critically ill patients. Respir Care. 2014;59(1):70-74. [CrossRef] [PubMed]
 
Epstein AS, Hartridge-Lambert SK, Ramaker JS, Voigt LP, Portlock CS. Humidified high-flow nasal oxygen utilization in patients with cancer at Memorial Sloan-Kettering Cancer Center. J Palliat Med. 2011;14(7):835-839. [CrossRef] [PubMed]
 
Calvano TP, Sill JM, Kemp KR, Chung KK. Use of a high-flow oxygen delivery system in a critically ill patient with dementia. Respir Care. 2008;53(12):1739-1743. [PubMed]
 
Boyer A, Vargas F, Delacre M, et al. Prognostic impact of high-flow nasal cannula oxygen supply in an ICU patient with pulmonary fibrosis complicated by acute respiratory failure. Intensive Care Med. 2011;37(3):558-559. [CrossRef] [PubMed]
 
Lacroix G, Pons F, D’Aranda E, Legodec J, Romanat PE, Goutorbe P. High-flow oxygen, a therapeutic bridge while awaiting thrombolysis in pulmonary embolism? Am J Emerg Med. 2013:31(2):463.e1-463.e2. [CrossRef]
 
Chung KK, McLaughlin DF, Horvath EE, et al. Nasal cannula O2 delivery system improves oxygenation and ventilation in adult burn patients [abstract]. Chest. 2005:130(4_MeetingAbstract):276S.
 
Makowski A, Mistzal B, Plowright C, Safranow K. Effectiveness of Vapotherm therapy for patients with respiratory failure at surgical high dependency unit [abstract]. Intensive Care Med. 2007;33(suppl 2):S86.
 
Carratalá Perales JM, Llorens P, Brouzet B, et al. High-flow therapy via nasal cannula in acute heart failure. Rev Esp Cardiol. 2011;64(8):723-725. [CrossRef] [PubMed]
 
Maggiore SM, Idone FA, Vaschetto R, et al. Nasal high-flow versus Venturi mask oxygen therapy after extubation. Effects on oxygenation, comfort, and clinical outcome. Am J Respir Crit Care Med. 2014;190(3):282-288. [CrossRef] [PubMed]
 
Lacroix G, Legodec J, D’Aranda E, Esnault P, Romanat PE, Goutorbe P. Is non-invasive ventilation the best ventilatory support for ‘do not intubate’ patients? Crit Care. 2012;16(4):442. [CrossRef] [PubMed]
 
Peters SG, Holets SR, Gay PC. High-flow nasal cannula therapy in do-not-intubate patients with hypoxemic respiratory distress. Respir Care. 2013;58(4):597-600. [PubMed]
 
NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).

Some tools below are only available to our subscribers or users with an online account.

Related Content

Customize your page view by dragging & repositioning the boxes below.

Find Similar Articles
CHEST Journal Articles
PubMed Articles
  • CHEST Journal
    Print ISSN: 0012-3692
    Online ISSN: 1931-3543