Supplemental oxygen is conventionally delivered through nasal prongs or various types of masks. Although these devices increase the inspired oxygen concentration, they have significant limitations. The inability to generate adequate flows in patients who are dyspneic is a major drawback. Respiratory failure is characterized by high peak inspiratory flow rates ranging from 30–120 L/min (1). However, most conventional devices are limited to a maximum flow of 15 L/min, resulting in a significant mismatch between the peak inspiratory and delivered flows. The flow mismatch results in variable entrainment of atmospheric air and failure to deliver a constant FiO2.
Bubble humidifiers are commonly used to humidify the inspired gas. However, the humidification imparted by bubble humidifiers is negligible (2). Dry inspired gas, delivered at room temperature, results in reduced water content of the airway mucus. Lack of humidification and low temperature of supplemental oxygen impairs ciliary activity and inhibits mucus clearance (3). To make matters worse, many patients in respiratory failure are unable to cough forcefully, leading to retention of secretions. There has been increasing interest in the use of high flow nasal cannula (HFNC) to deliver optimally warmed and humified oxygen at high flows following an initial report by Dewan et al (4). Several commercially available devices are currently in use that can deliver fully conditioned gas at flows of up to 60 L/min, at a fixed FiO2. (Figure 1). These systems use a built-in flow generator and an air-oxygen blender that generates inspired gas flows at a pre-set FiO2. A heated passover type of humidifier is utilized to ensure adequate humification. The pre-warmed, humidified gas mixture flows through a heated wire embedded, single limb corrugated tubing. The heated tubing prevents condensation of water and any significant drop in temperature of the inspired gas as it reaches the patient end. A soft, wide-bored nasal cannula is used to deliver the inspired gas.
Figure 1. A typical high-flow device with nasal cannula
How does HFNC deliver a constant FiO2?
The flow rates delivered by HFNC exceed the peak inspiratory flow rate of patients who are dyspneic. This minimizes atmospheric air entrainment and enables a constant, predictable FiO2. Most devices allow a maximal gas flow of 60L/min, at a fixed FiO2 ranging between 0.21 to nearly 1.0.
Does HFNC enable CO2 washout?
High gas flows result in flushing out of CO2 from the nasopharynx with less rebreathing of dead space gas and improved alveolar ventilation (5). A lower partial pressure of carbon dioxide in the inspired gas mixture results in an increase in the FiO2 (6). As the alveolar ventilation improves, a lower respiratory rate and a greater sense of comfort ensue (7).
Does HFNC offer positive end-expiratory pressure?
HFNC generates positive pressure in the airways, directly proportional to the flow rate. In postoperative patients, the airway pressure increased with increasing inspiratory flow. Mean airway pressures with the mouth closed ranged from 1.52 ± 0.7, 2.21 ± 0.8, and 3.1 ± 1.2 cm H2O at flow rates of 40, 50, and 60 L/min respectively in postoperative patients (8). The low level of PEEP generated by HFNC may facilitate alveolar recruitment and an increase in the end-expiratory lung volume.
HFNC and airway resistance
The nasopharynx is a narrow part of the supraglottic airway that offers resistance to airflow. The application of positive pressure may splint and widen the airways during inspiration and reduce airway resistance. Furthermore, inspiratory gas flows that closely match the peak inspiratory flow may contribute to decreased inspiratory resistance. Both these mechanisms may contribute to a decrease in the resistive work of breathing (9).
The beneficial effects of humidification
Warming and humidification of the inspired gas involve an energy expenditure of 156 calories/min for a tidal volume of 500 ml at a respiratory rate of 12/min. Delivery of pre-conditioned gas conserves the energy thus expended and may reduce the metabolic cost of breathing. Furthermore, warming and humidification results in an improved sense of comfort and reduces resistance to breathing. Besides, optimal humidification adds to the aqueous content of the mucosal layer, thus improving ciliary activity and secretion clearance (10).
The aforementioned physiological effects of HFNC are clearly advantageous. However, do they translate to improved clinical outcomes in the real world?
Does HFNC help in patients with acute hypoxemic respiratory failure?
Early studies with the use of HFNC in patients with acute hypoxemic respiratory failure have shown improvement in physiological endpoints including oxygenation and respiratory rate, besides increasing the level of comfort (5,11). The FLORALI study evaluated HFNC therapy in patients with acute hypoxic respiratory failure (12). In this three-armed randomized controlled study, HFNC was compared with non-invasive ventilation (NIV) and oxygen administered through a non-rebreather mask. There was no significant reduction in the requirement for endotracheal intubation and invasive ventilation with HFNC use. The overall intubation rate was lower than that assumed for power calculation; this may have led to a type II error. In patients who required intubation and mechanical ventilation, HFNC use resulted in more ventilator-free days and improved 90-day survival after adjusting for simplified acute physiology score II (SAPS II) scores. On post hoc analysis, a significantly lower rate of endotracheal intubation was noted in with PaO2/FiO2 ratios of less than 200. This finding suggests that severely hypoxic patients may benefit with HFNC; however, this hypothesis needs validation. The 90-d mortality was lower in the HFNC group; however, being a secondary endpoint, the study was not powered to demonstrate a difference.
In a randomized controlled study (RCT) of postoperative patients who underwent cardiac surgery under cardiopulmonary bypass, HFNC was compared with standard oxygen therapy through a face mask or nasal prongs. There was no significant difference in the SpO2/FiO2 ratios between groups on day 3 after enrolment. However, NHFC resulted in fewer episodes of desaturation. The number of patients requiring escalation of respiratory support was significantly lower in the HFNC group (13).
HFNC was used in patients with severe ARDS in a single center, 1-y observational study. The intubation rate was 40% in this study; failure of HFNC was associated with higher SAPS II scores, the presence of extra-pulmonary organ failures, a lower PaO2/FiO2 ratio, and a higher respiratory rate (14).
Concerns have been raised regarding persistence with HFNC for too long with delayed intubation leading to adverse outcomes. In a propensity-matched, retrospective study, patients who required endotracheal intubation after failure of HFNC were analyzed. Delayed intubation after 48 hours of HFNC use was associated with significantly higher mortality compared to intubation within 48 hours (15).
Is HFNC beneficial as postextubation therapy?
Earlier studies showed improvement in physiological endpoints including heart rate, respiratory rate, and dyspnoea scores with postextubation use of HFNC (16). HFNC was compared with ventimask in a randomized controlled trial of patients with a PaO2/FiO2 ratio of less than 300 prior to extubation (17). There were fewer episodes of desaturation with HFNC use. The need for NIV support and endotracheal intubation was also significantly less in patients who received HFNC. In patients who were at high risk of reintubation following cardiothoracic surgery, HFNC was compared to NIV delivered as bilevel positive airway pressure following extubation. There was no difference in treatment failure (reintubation, switch to the other treatment modality, or premature discontinuation of the study intervention) or intensive care mortality(18). HFNC was compared with standard oxygen therapy using nasal prongs or facemask after extubation in patients who underwent major abdominal surgery (19). The incidence of hypoxemia 1 h after extubation and after discontinuation of treatment was not different between groups. Pulmonary complications at 1 week after surgery were also similar. In a large, multicentre randomized controlled study, HFNC was compared with standard oxygen therapy following extubation among patients who were at low risk for reintubation (20). Reintubation within 72 h of extubation was significantly lower with HFNC (4.9% vs 12.2%, p = 0.004). Postextubation respiratory failure was also less common with HFNC.
HFNC may be the preferred mode of support in terminally ill patients in whom endotracheal intubation and invasive ventilation may be inappropriate. In addition to an increased sense of comfort, HFNC perseveres the ability to communicate and allows oral intake. HFNC may be the ideal modality of continuous oxygen administration during attempts at intubation with better maintenance of oxygen saturation. It may also be useful to prevent desaturation in awake, spontaneously breathing patients who undergo bronchoscopy.
The bottom line
- HFNC delivers warmed and humified gases. As the delivered flow is higher than peak inspiratory flow rates, a constant FiO2 is achieved
- The high flow rate enables maintenance of positive airway pressure in the nasopharynx with augmentation of the end-expiratory lung volume
- The positive airway pressure distends the airways and reduces airway resistance
- Improved physiological parameters have been consistently demonstrated with HFNC
- HFNC may reduce the requirement for intubation and invasive mechanical ventilation in patients with low PaO2/FiO2 ratios
- Improvement in oxygenation, reduced requirement for NIV use and reintubation are possible advantages with postextubation HFNC use
- As with any other form of respiratory support, persistence with HFNC in non-responders and delayed intubation may lead to adverse outcomes
- 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 Nov 1;172(9):1112–8.
- Chanques G, Constantin J-M, 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 Jun;35(6):996–1003.
- 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 Jul;30(7):1491–4.
- 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 Apr;105(4):1061–5.
- Sztrymf B, Messika J, Bertrand F, Hurel D, Leon R, Dreyfuss D, et al. Beneficial effects of humidified high flow nasal oxygen in critical care patients: a prospective pilot study. Intensive Care Med. 2011 Nov;37(11):1780–6.
- Spence CJT, Buchmann NA, Jermy MC. Unsteady flow in the nasal cavity with high flow therapy measured by stereoscopic PIV. Exp Fluids. 2012;52(3):569–579.
- Schmidt M, Banzett RB, Raux M, Morélot-Panzini C, Dangers L, Similowski T, et al. Unrecognized suffering in the ICU: addressing dyspnea in mechanically ventilated patients. Intensive Care Med. 2014 Jan;40(1):1–10.
- Ritchie JE, Williams AB, Gerard C, Hockey H. Evaluation of a humidified nasal high-flow oxygen system, using oxygraphy, capnography and measurement of upper airway pressures. Anaesth Intensive Care. 2011 Nov;39(6):1103–10.
- Ricard J-D. High flow nasal oxygen in acute respiratory failure. Minerva Anestesiol. 2012 Jul;78(7):836–41.
- Sim M a. B, 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 Sep;63(9):938–40.
- Roca O, Riera J, Torres F, Masclans JR. High-flow oxygen therapy in acute respiratory failure. Respir Care. 2010 Apr;55(4):408–13.
- Frat J-P, Thille AW, Mercat A, Girault C, Ragot S, Perbet S, et al. High-Flow Oxygen through Nasal Cannula in Acute Hypoxemic Respiratory Failure. N Engl J Med. 2015 Jun 4;372(23):2185–96.
- 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 Aug 6;aet262.
- Messika J, Ben Ahmed K, Gaudry S, Miguel-Montanes R, Rafat C, Sztrymf B, et al. Use of High-Flow Nasal Cannula Oxygen Therapy in Subjects With ARDS: A 1-Year Observational Study. Respir Care. 2015 Feb;60(2):162–9.
- Kang BJ, Koh Y, Lim C-M, Huh JW, Baek S, Han M, et al. Failure of high-flow nasal cannula therapy may delay intubation and increase mortality. Intensive Care Med. 2015 Apr;41(4):623–32.
- Rittayamai N, Tscheikuna J, Rujiwit P. High-flow nasal cannula versus conventional oxygen therapy after endotracheal extubation: a randomized crossover physiologic study. Respir Care. 2014 Apr;59(4):485–90.
- Maggiore SM, Idone FA, Vaschetto R, Festa R, Cataldo A, Antonicelli F, 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 Aug;190(3):282–8.
- Stéphan F, Barrucand B, Petit P, Rézaiguia-Delclaux S, Médard A, Delannoy B, et al. High-Flow Nasal Oxygen vs Noninvasive Positive Airway Pressure in Hypoxemic Patients After Cardiothoracic Surgery: A Randomized Clinical Trial. JAMA. 2015 Jun 16;313(23):2331–9.
- Futier E, Paugam-Burtz C, Godet T, Khoy-Ear L, Rozencwajg S, Delay J-M, et al. Effect of early postextubation high-flow nasal cannula vs conventional oxygen therapy on hypoxaemia in patients after major abdominal surgery: a French multicentre randomised controlled trial (OPERA). Intensive Care Med. 2016 Dec;42(12):1888–98.
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