By Richard Kallet, MS, RRT, FAARC, FCCM
Director of Quality Assurance, Respiratory Care Services, San Francisco General Hospital
Mr. Kallet reports no financial relationships relevant to this field of study.
SYNOPSIS: Managing acute hypoxemic respiratory failure with high-flow nasal cannula (HFNC) significantly reduced intubation rates compared to standard oxygen (O2) mask delivery and non-invasive ventilation among patients whose arterial O2 tension to inspired O2 fraction ratio (PaO2/FiO2) was < 200. Among all study patients, hospital mortality was lower in the HFNC group.
SOURCE: Frat JP, et al. High-flow oxygen through nasal cannula in acute hypoxemic respiratory failure. N Engl J Med 2015;372:2185-2196.
This multicenter, randomized, controlled trial posited that heated, humidified high-flow nasal cannula (HFNC) standard oxygen (O2) at 40-60 L/min provides a high stable FiO2, reduces upper airway dead space, and creates continuous positive airway pressure (CPAP). This would reduce minute ventilation demand and work of breathing, thereby reducing the need for invasive mechanical ventilation (MV).
The study enrolled 313 patients who met these criteria: 1) PaO2/FiO2 < 300 breathing face mask O2 > 10 L/min, 2) respiratory rate > 25 breaths/min, and 3) arterial carbon dioxide tension < 45 mmHg. Patients with chronic lung disease, cardiogenic pulmonary edema, neurologic injury, severe neutropenia, hemodynamic instability, or limited care were excluded. Patients were randomized to HFNC at 40-60 L/min, face mask O2 at > 10 L/min, or NIV with inspiratory pressure titrated to achieve a tidal volume of 7-10 mL/kg with a CPAP of 5 cm H2O for at least 8 hours/day. For all treatment arms, FiO2 was titrated to keep O2 saturation > 92%. Baseline physiology, demographics, and comorbidities were not different between the treatment arms.
Overall, the primary outcome of need for invasive MV was not significantly different between the treatment groups. However, in a post hoc analysis of those with an initial PaO2/FiO2 < 200, there was a significant difference in the need for invasive MV in favor of the HFNC group (35% for HFNC vs 53% for standard O2 therapy and 58% for NIV; P = 0.009). Neither the time interval to intubation nor the underlying cause necessitating invasive MV were different between therapies. The HFNC cohort had a significantly higher number of ventilator-free days (24 ± 8 days) compared to those receiving standard O2 therapy (22 ± 10 days), and those on NIV (19 ± 12 days) (P = 0.02). The hazard ratio (HR) for death at day 90 was significantly higher in the standard O2 and NIV groups compared to the HFNC group (HR, 2.01; 95% confidence interval [CI], 1.01-3.99; HR, 2.50; 95% CI, 1.31-4.78, respectively; P = 0.02). Those treated with HFNC also experienced greater improvement in dyspnea compared to those receiving standard O2 and NIV (76% vs 42% vs 58%, respectively; P < 0.001).
The FLORALI (High-Flow Oxygen Therapy for the Resuscitation of Acute Lung Injury) study suggests we reconsider our initial management approach in select patients with acute hypoxemic respiratory failure. The concern, however, is that misapplication of HFNC O2 therapy may lead to delayed intubation that paradoxically worsens outcomes. It is essential to target appropriate candidates while clearly specifying early discontinuation.
FLORALI and other studies provide practical guidelines for appropriate patient selection.1 HFNC is contraindicated in those with acute hypercapnia because it signifies either respiratory muscle fatigue or depressed respiratory drive, both of which necessitate invasive MV. Likewise, profound tachypnea and accessory muscle use not readily reversed with HFNC (e.g., within < 30 min) requires invasive MV. In addition, HFNC is not indicated for patients who are either hemodynamically unstable or manifest signs of acute neurologic deterioration.
HFNC therapy should be terminated quickly in favor of invasive MV when exclusion criteria develop after therapy commences: a sustained respiratory rate > 35 breaths/min, lack of improvement in respiratory distress/dyspnea, sustained O2 saturation < 90%, arterial pH < 7.35, decreased systolic (< 90 mmHg) or mean (< 65 mmHg) arterial blood pressure despite fluid boluses and/or vasopressors, or when either definitive airway control is indicated or with the presence of copious pulmonary secretions.1
In considering HFNC, NIV can provide some guidance. The principle indications for NIV also apply to HFNC, namely situations where the cause of respiratory failure can be readily reversed. In contrast, clinical conditions such as acute respiratory distress syndrome (ARDS) are not ideal for NIV and, likewise, HFNC. This condition often resolves more slowly, frequently requiring several weeks of MV. Moreover, ARDS is associated with an elevated minute ventilation and severely impaired pulmonary mechanics, both of which greatly increase WOB.2 As a result, NIV failure rates in ARDS typically exceed 50% and delayed intubation is associated with heightened mortality risk.3 Similarly, in those failing HFNC O2 therapy, ICU mortality was markedly lower (39% vs 67%) when invasive MV was instituted within 48 hours (median of 10 hours).1
The apparent success of HFNC over NIV requires comment. NIV was used only 8 hours/day, which likely limited its efficacy. Also, in patients with pneumonia (the primary diagnosis among FLORALI subjects), HFNC was as effective as CPAP of 5 cm H2O in reducing inspiratory effort.4 Although HFNC reduced the work of breathing in these pneumonia patients, the baseline spontaneous work of breathing was not markedly elevated compared to the spontaneous work of breathing measured in patients with ARDS.2 Moreover, the mortality in the NIV group is consistent with the NIV literature and likely signifies complications associated with invasive MV rather than pre-intubation management, per se. The FLORALI study did not explicitly state whether protocol managed invasive MV. Therefore, the significance of mortality differences reported in the FLORALI study remains uncertain.
In summary, current high-level evidence supports using HFNC as the primary O2 delivery method for patients in acute respiratory failure from pneumonia without hypercapnia and who exhibit hemodynamic and neurologic stability.
Kang BJ, et al. Failure of high-flow nasal cannula therapy may delay intubation and increase mortality. Intensive Care Med 2015;41:623-632.
Kallet RH, et al. The spontaneous breathing pattern and work of breathing in patients with acute respiratory distress syndrome and acute lung injury. Respir Care 2007;52:989-995.
Antonelli M, et al. Predictors of failure of noninvasive pressure support ventilation in patients with acute hypoxemic respiratory failure: A multi-center study. Intensive Care Med 2001;27:1718-1728.
Vargas F, et al. Physiologic effects of high-flow nasal cannula oxygen in critical care subjects. Respir Care 2015 May 5 [Epub ahead of print].