Non-invasive respiratory support using a high-flow nasal cannula (HFNC) is an emerging modality of therapy in patients with acute hypoxemic respiratory failure. Although widely established to be efficacious in respiratory illnesses of varying etiology leading to hypoxia, there is limited information regarding its usefulness in COVID-19 pneumonia. Concerns have been raised regarding aerosolization and transmission of infection to healthcare personnel; besides, undue delays in intubation and invasive mechanical ventilation may occur with injudicious, prolonged use of HFNC therapy. However, HFNC therapy may be a realistic and feasible option in resource-limited settings experiencing widespread outbreaks of COVID-19.
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. 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 enables optimal humification. The pre-warmed, humidified gas mixture flows through a heated, wire-embedded, single limb corrugated tubing. The heated tubing prevents the condensation of water and any significant drop in temperature of the inspired gas before it reaches the patient end. A soft, wide-bored nasal cannula is used to deliver the inspired gas.
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.
Carbon dioxide washout with HFNC
High gas flows result in flushing out of CO2 from the nasopharynx with less rebreathing of dead space gas and improved alveolar ventilation.1 A lower partial pressure of carbon dioxide in the inspired gas mixture results in an increase in FiO2. As the alveolar ventilation improves, a lower respiratory rate and a greater sense of comfort ensue.2
HFNC and PEEP effect
HFNC generates a 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.3 The low level of PEEP generated by HFNC may facilitate alveolar recruitment and an increase in the end-expiratory lung volume.
Airway resistance and work of breathing
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.4
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.5
Aerosol spread with HFNC compared with other devices
Hui et al. evaluated the extent of aerosol generation with the use of high-flow nasal cannula on a high-fidelity human patient simulator. The mean exhaled air dispersion distance was 17.2 cm at flows of 60 l/min with normal lungs and 4.8 cm in severely diseased lungs. This study suggests that the risk of exposure of healthcare workers to aerosol generation during HFNC therapy is minimal. However, the authors cautioned that misconnection between the nasal cannula and the interface tube could result in a more extensive lateral dispersion.6 The extent of aerosol dispersion during HFNC use is lower compared to the use of nasal prongs, a simple face mask, venturi mask, and non-invasive positive pressure ventilation (Figure 1).7 A standard surgical mask worn over the HFNC device has been recommended to reduce dispersion and may protect healthcare workers from the transmission of infection.8
HFNC in acute hypoxemic respiratory failure
Frat et al. compared the use of HFNC with face mask oxygen therapy and NIV in patients with acute hypoxemic respiratory failure and a PaO2/FiO2 ratio of less than 300 mm Hg. In this study, the use of HFNC resulted in significantly more ventilator-free days at 28 days; furthermore, the hazard ratio for death at 90 days was also significantly lower with HFNC use.9 In a single-center, before-after study, the introduction of HFNC resulted in fewer patients requiring NIV or invasive ventilation; besides, there was a significant reduction in the number of ventilator days and an increase in ventilator-free days.10
How efficacious is HFNC therapy in patients with viral pneumonia?
Rello et al. performed a post hoc analysis of a single-center study involving a cohort of critically ill patients admitted with severe acute respiratory illness (SARI) due to 2009 Influenza or H1N1 infection. Among the 35 patients studied, 20 had persistently low oxygen saturation below 92% and were administered HFNO therapy. Mechanical ventilation could be avoided in nine of these patients, all of whom survived. There was no incidence of nosocomial pneumonia with the use of HFNC. Besides, no transmission of infection was reported among healthcare workers involved in the care of these patients.11
In a meta-analysis of patients with acute hypoxemic respiratory failure, 2093 subjects were included from 9 randomized controlled trials. There was no difference in mortality with the use of HFNC compared to conventional oxygen therapy. However, there was a significant reduction in the requirement for invasive ventilation or escalation of respiratory support in patients who received HFNC. Although complications were reported variably, there was no discernible harm with the use of HFNC.12
Evidence of efficacy in COVID-19
HFNC use in COVID-19 appears to be highly variable across different geographic locations, ranging from 4.8–42%.13,14 In an early study from China, 27/318 (8.4%) patients developed severe acute respiratory failure. Seventeen (63%) patients received HFNC as initial therapy. Overall, 7/17 (41%) patients required escalation of respiratory support. The failure rate with HFNC use was 63% among patients with a PaO2/FiO2 ratio ≤ 200 mm Hg. HFNC therapy was successful in all patients with a PaO2/FiO2 ratio of > 200 mm Hg. The respiratory rate decreased significantly among patients in whom HFNC use was successful compared with those who failed therapy.
Patel et al. retrospectively studied 104 COVID-19 patients with moderate to severe respiratory failure who received oxygen therapy through HFNC. Among this cohort, invasive or non-invasive mechanical ventilation could be avoided in 67 (64.4%) patients. Patients who were continued on HFNC experienced a significant improvement in oxygenation with a lower incidence of hospital-acquired pneumonia compared to those who required escalation of respiratory support. Hospital mortality was significantly lower in patients who remained on HFNC compared to those who required invasive mechanical ventilation (2.9% vs. 34.4%). This study suggests that the use of HFNC is safe and efficacious as the initial mode of respiratory support in patients with COVID-19 associated acute respiratory failure.
An Italian study of 670 patients diagnosed with COVID-19 aimed to evaluate safety of healthcare workers and outcomes of non-invasive respiratory support provided outside the intensive care unit. The overall 30-day mortality was 26.9%; the mortality associated with HFNC use was 16% compared to 30% each with patients who received CPAP and NIV. The requirement for endotracheal intubation was 29% in patients who received HFNC compared to 25% in patients who received CPAP and 28% in those who received NIV. After adjustment for confounders, the probability of death was unrelated to the use of non-invasive modalities of respiratory support. An increase in mortality was observed with increasing age and the presence of comorbidities. The infection rate among healthcare workers was 11.4%; however, only three among them required hospitalization.15
Could the failure of HFNC therapy followed by invasive mechanical ventilation lead to an increase in mortality? A retrospective, multicenter, cohort study from Atlanta, Georgia, evaluated the effect of HFNC use and time to intubation on clinical outcomes in patients with COVID-19. HFNC was used in 109/231 (47.2%) patients as the initial modality of treatment. Among these, 78 (71.6%) patients failed HFNC therapy and required invasive mechanical ventilation. However, the failure of HFNC followed by invasive mechanical ventilation did not lead to an increase in mortality compared to patients who were invasively ventilated without a trial of HFNC therapy.16
Early recognition of HFNC failure
There are no established criteria to identify patients who are likely to fail HFNC therapy and progress to escalation of support. Bedside vigilance, close monitoring, and clinical judgment are crucial in the early recognition of patients who are likely to require invasive mechanical ventilation. Continued, injudicious use of non-invasive supportive modalities and inordinate delays in intubation are likely to lead to adverse clinical outcomes. Patients in whom relief of tachypnea and thoracoabdominal asynchrony do not occur rapidly are likely to fail HFNC therapy.1
Patel et al. evaluated the predictive value of the ROX index, represented by the SpO2/FiO2 to respiratory rate ratio, to determine HFNC outcomes and the requirement for invasive mechanical ventilation among patients with COVID-19. These subjects experienced moderate to severe respiratory failure. Among the 129 patients studied, 40 (31%) required intubation. A ROX index of < 5 at the time of initiation of HFNC therapy was predictive of failure and subsequent requirement for invasive mechanical ventilation. An unchanged ROX index or any decrease within the first 24 hours of initiation of HFNC therapy was also predictive of failure and requirement for intubation. A decrease of the ROX index by 1 over 24 hours was strongly predictive of the need for intubation, regardless of the baseline value.17
A two-center study from Cape Town, South Africa, enrolled 293 patients with COVID-19 who were treated with HFNC. The median baseline PaO2/FiO2 ratio was 68 (54–92) mm Hg. Among these patients who were severely hypoxic at the initiation of therapy, 137 (47%) were successfully weaned from HFNC. Among these 137 patients, 128 (93%) were discharged home at the time of reporting. A 6-hour ROX score of ≥ 3.7 was 80% predictive of successful weaning; a score of ≤ 2.2 was 74% predictive of failure. A higher ROX score at 6 hours compared to baseline value predicted successful weaning from HFNC therapy. This study suggests that HFNC is effective therapy in resource-limited settings among COVID-19 patients who are severely hypoxic at baseline.18
- HFNC is extensively used in patients with COVID-19 in resource-limited settings
- Although there is a paucity of robust evidence, HFNC appears to be a feasible option and may reduce the requirement for invasive ventilation among patients with COVID 19
- Close bedside monitoring of patients on HFNC therapy is of crucial importance to recognize the need for escalation of respiratory support, including intubation
- Patients who fail to improve within a reasonable period of time may need escalation of support
- The ROX score at 6 hours after initiation of HFNC therapy may be a good indicator of the likelihood of success
- The likelihood of transmission of infection to healthcare workers is low with the use of HFNC and comparable to the risks associated with the use of a standard face mask. The risk of transmission with HFNC therapy is lower compared to non-invasive ventilation using an oro-nasal mask
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