By J. Brady Scott, MSc, RRT-ACCS, AE-C, FAARC, FCCP

Associate Professor, Director of Clinical Education, Respiratory Care Program, Rush University, Chicago

Mr. Scott reports that he receives research/grant support from Teleflex, Inc., and serves as a consultant for Ventec Life Systems.

A relatively new modality, high-flow nasal cannula (HFNC) oxygen therapy is used commonly to treat acute respiratory failure. HFNC oxygen therapy enables clinicians to deliver warmed, humidified gas at flow rates that meet or exceed the inspiratory flow demands of the patient.1,2 For the sake of this article, HFNC will refer to devices that deliver flow rates between 25 L/min and 60 L/min. High-flow cannulas with a flow range of 6 L/min to 15 L/min will not be discussed.

The Interface

Noninvasive ventilation (NIV) has been studied extensively for acute hypercapnic and hypoxemic respiratory failure. In many studies, NIV has been shown to be quite successful. That said, a known cause of NIV failure is intolerance of the interface. One of the perceived benefits of HFNC oxygen therapy is comfort and tolerability. The cannula interface has been shown to be generally well tolerated, which improves patient compliance with the modality.3-5 Improved compliance, balanced with an improvement in oxygenation and ventilation, makes HFNC an attractive treatment option.1 The cannula interface varies by manufacturer and is a distinguishing characteristic between commercially available devices. The high-velocity nasal insufflation device (Hi-VNI) uses a cannula that has a narrow internal diameter, which produces the higher flow velocity (flow range from 5 L/min to 40 L/min). In contrast, the Airvo 2 system uses a large-bore circuit and cannula interface (flow range from 2 L/min to 60 L/min). At this time, it is not clear if either offers an advantage over the other. Clinicians charged with applying HFNC should be familiar with interface sizing options and recommendations to maximize performance and comfort.

Physiologic Effects of High-Flow Nasal Cannula

In addition to comfort, HFNC has important physiologic benefits, including positive airway pressure, adequate heating and humidification of inspired gases, washout of anatomic dead space, and a more stable delivery of fraction of inspired oxygen (FiO2).

Positive Pressure

An often-cited advantage of HFNC is the ability to generate some degree of positive pressure.1,6 Although HFNC is an open system, some studies have shown an increase in pharyngeal pressures and end-expiratory lung volumes (EELV).7-9 The increase in EELV is interesting, since it may reflect an increase in functional residual capacity and, thus, some degree of alveolar recruitment. The increase in alveolar recruitment from the positive pressure generated by HFNC may improve gas exchange. The positive pressure effect of HFNC is complicated by the reality that patients often breathe with their mouths open. Substantial variability in pharyngeal pressures have been demonstrated in studies evaluating the effects of having the mouth closed or open.1,6-10 Body mass index, lung heterogeneity, and device flow rate also may play a role in the variability of lung recruitment from HFNC.1,6

Adequate Heating and Humidification of Inspired Gases

Commercially available HFNC devices are capable of delivering well-conditioned (heated and humidified) gases to patients, as long as HFNC flow is higher than patient inspiratory flow. If device flow is lower than patient inspiratory flow, the patient will inspire drier room air. Properly warmed and humidified gases improve mucociliary function, facilitate secretion clearance, minimize airway constriction, and limit the metabolic cost of breathing.1,6,11,12

A ‘More Stable’ Delivery of FiOby Meeting or Exceeding Inspiratory Demand

When device flow is greater than a patient’s peak inspiratory flow, HFNC is capable of delivering a stable FiO2, since patients mainly breathe in gas delivered by the device. This minimizes room air entrainment that can dilute the delivered FiO2. Since patients control their own inspiratory flow rate and tidal volume, there may be some variability in the actual FiO2 delivered to the patient.13,14

Washout of Anatomic Dead Space

Carbon dioxide (CO2) is washed out of the anatomic dead space during HFNC therapy. This creates an efficiency in terms of gas exchange, because a higher fraction of minute volume is involved.14 According to Delorme et al,15 this is considered a key mechanism in patients with respiratory failure in terms of reducing respiratory effort and improving comfort.

Recent Evidence

At least 20 randomized controlled trials (RCTs) and 10 meta-analyses on HFNC for adults have been published in the past two years.2 Many of these studies have evaluated critical care conditions treated with HFNC, such as acute hypoxemic respiratory failure (AHRF), post-extubation, pre-oxygenation before intubation, and chronic obstructive pulmonary disease (COPD).

For patients with AHRF, several older studies demonstrated that HFNC was superior to conventional oxygen therapy and non-inferior to NIV for clinical improvements in oxygenation and avoidance of intubation. However, a paper published in 2018 on HFNC use in immunocompromised patients showed no differences in intubation and mortality between the HFNC and oxygen therapy groups.16 Subsequently, Rochwerg et al17 published a systematic review and meta-analysis in 2019 that showed the rate of intubation was lower in patients treated with HFNC when compared to those treated with conventional oxygen therapy. However, there was no difference in intensive care unit (ICU) length of stay, hospital length of stay, and mortality between the two groups.2,17 That review excluded studies that included post-extubation respiratory failure. Also in 2019, Shen et al18 found that patients with a PaO2/FiO2 of > 200 mmHg had the greatest benefit from HFNC. Interestingly, post-extubation patients had a particularly positive benefit from HFNC in their study. In an analysis of studies completed in an emergency department setting, Tinelli et al19 found no benefit of using HFNC over conventional oxygen therapy in subjects with AHRF.

Regarding the role of HFNC for patients after extubation, Zhu et al20 published a systematic review and meta-analysis of patients undergoing a planned extubation. They found that HFNC reduced respiratory failure after extubation or risk of re-intubation in some studies. In their study, the authors noted only about one-third of patients in both the HFNC and conventional therapy groups were re-intubated, which may underscore the importance of care escalation from one modality to the other in an attempt to mitigate the need for reintubation.2 Other RCTs subsequently published demonstrated a benefit of HFNC when compared to conventional oxygen therapy. For post-cardiac surgery patients, HFNC use prophylactically after extubation reduced the need for NIV. HFNC also was shown to decrease hospital length of stay and ICU readmission in this group.21,22 For postoperative obese patients, HFNC use after extubation demonstrated some benefit regarding oxygenation levels after three hours and a reduction in postoperative pulmonary complications.23 It is important to interpret these results cautiously, since they are contradictory to other studies with similar populations.24,25

For patients deemed high-risk at extubation, the data are a bit unclear regarding whether HFNC is non-inferior to NIV. A paper published in 2016 found no significant differences in re-intubation rates between patients with risk factors for extubation failure who were treated with HFNC or NIV. The authors did note a higher incidence of post-extubation failure in the NIV group.26 However, in 2019, Thille et al found conflicting results.27 In their RCT, they noted a lower re-intubation rate and incidence of post-extubation failure in the NIV group compared to the HFNC group. The contradictory results probably can be explained by the way NIV was used in both studies. Thille et al used NIV for longer periods of time, and also used HFNC during breaks from NIV.27

A 2019 study demonstrated that compared to oxygen therapy, HFNC prior to intubation in adult patients with hypoxemia reduced intubation-related complications.28 When compared to NIV, however, HFNC resulted in more desaturation events. Whether using HFNC has any advantages over a manual resuscitator (with a positive end-expiratory pressure [PEEP] valve) or a critical care ventilator (with a mask) remains to be seen. It is not yet known if placing a previously unused HFNC for the purposes of preoxygenation prior to intubation is necessary because of cost and resource availability concerns.2

There has been considerable interest in the role of HFNC for the treatment of COPD exacerbations because of the effects of dead space washout on CO2 and overall patient improvement.29 Lee et al published an RCT in 2018 that found no differences between the NIV group and the HFNC group in terms of intubation rate and 30-day hospital mortality.30 This study should be interpreted with caution, however, because the study design was a bit vague. That said, the findings were similar to an observational cohort study published in 2019 (evaluating HFNC vs. NIV in hypercapnic respiratory failure), which found that treatment failure was similar between the modalities.31 Other studies also suggest that HFNC may be useful as an alternative to NIV in mild to moderate COPD patients, but more high-quality studies are needed.29,32

As of 2020, it appears that HFNC can reduce the intubation rate in patients with AHRF. This may be particularly true in patients with milder hypoxemia. Regarding post-extubation, HFNC reduces the risk of developing post-extubation failure, but may not reduce re-intubation rates. For pre-intubation use, HFNC appears to be superior to oxygen therapy, but not better than NIV in terms of desaturation events. Finally, HFNC might be useful as a substitute to NIV in mild to moderate COPD.

Regardless of the many published studies to date, a great deal of uncertainty remains. It is difficult to interpret HFNC literature because of the variations in devices (high flow vs. high velocity), disease conditions, settings (flow, FiO2), duration of treatment, and comparators. HFNC certainly plays an important role in the critical care setting, but the timing, duration, management, and weaning from HFNC needs further study. Additionally, a theoretical advantage of HFNC over NIV is that it allows patients to eat and drink while on the device. This is concerning, as the impact of HFNC oxygen therapy on swallow function has not been investigated thoroughly. This deserves more study so that clinicians can have confidence when deciding to allow patients to eat or drink. Finally, the best way to initiate, manage, and titrate HFNC is not known, so clinical practice varies widely. It is reasonable to apply the highest flow tolerable to the patient in an effort to maximize the physiologic effects of HFNC. At least in theory, this would allow for the FiO2 to be titrated to meet oxygenation goals, although this, too, deserves more study.

HFNC and COVID-19

For patients with COVID-19, HFNC oxygen therapy may be a suitable way to improve oxygenation and reduce the need for endotracheal intubation.34-40 While the data are relatively limited at this time, available evidence suggests HFNC is used commonly in patients with COVID-19-related respiratory distress.40 In a retrospective observational study of HFNC use in two hospitals in China, Wang et al noted that HFNC was used more commonly than NIV and invasive mechanical ventilation as a first-line therapy.40 Not surprisingly, they found a higher HFNC failure rate (7/11, [63%]) in patients with lower PaO2/FiO2 ratios (≤ 200 mmHg) compared to the failure rate (0/6, [0%]) in those with a higher PaO2/FiO2 ratio (> 200 mmHg).40

An interesting use of HFNC is combining it with the effects of prone positioning on oxygenation. Slessarev et al reported in an editorial their experiences with this combination therapy to treat a patient with COVID-19.35 They found an overall positive result of having their patient self-prone (approximately 16-18 hours/day), which included avoidance of intubation. Elharrar et al found in their prospective, single-center, before-after study of awake, non-intubated patients that 63% of patients were able to tolerate prone positioning for more than three hours.41 However, it should be noted that oxygenation did not increase in all patients after prone positioning. In fact, only six of 24 patients were considered responders to prone positioning, defined by a partial pressure of arterial oxygen (PaO2) increase ≥ 20% between before and during prone positioning.

Currently, an RCT is underway comparing HFNC alone to HFNC plus prone positioning for patients with COVID-19-induced moderate to severe acute respiratory distress syndrome (ARDS) (ClinicalTrials.gov Identifier: NCT04325906). It is hoped that this trial and others will provide clarity on whether HFNC alone is sufficient or should be combined with prone positioning as tolerated for patients with COVID-19.

There is reasonable concern about using HFNC during the COVID-19 pandemic because of bio-aerosol dispersion and virus transmission. According to Li et al, studies show that when compared to oxygen therapy delivered via a mask interface, HFNC does not increase environmental microbacterial contamination.42-44 However, efforts to mitigate risk to healthcare providers should be taken (e.g., wearing adequate personal protective equipment, using negative pressure rooms if available, using portable high-efficiency particulate air filters if negative pressure rooms are unavailable) when HFNC oxygen therapy is used for a patient with COVID-19.37

Summary

HFNC is an effective therapeutic modality used to treat acute respiratory failure. It combines comfort and tolerability with multiple physiologic effects, making it a reasonable first-line or alternative modality for a variety of conditions.

Although the evidence to support HFNC oxygen therapy is evolving, many questions remain. Future studies are needed to better understand how to initiate, manage, and titrate HFNC properly for various clinical conditions.

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