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Summary: High-flow oxygen through nasal cannula in acute hypoxemic respiratory failure.
Topic: Primary Support
Frat JP, Thille AW, Mercat A, et al. High-flow oxygen through nasal cannula in acute hypoxemic respiratory failure. N Engl J Med. 2015;372(23):2185-2196.
Frat and colleagues conducted a multicenter, randomized trial to determine if nasal high flow oxygen therapy or noninvasive ventilation therapy could reduce the rate of endotracheal intubation in patients with acute hypoxemic respiratory failure, as compared to standard oxygen therapy. The treatment with high flow oxygen improved the survival rate among patients with acute hypoxemic respiratory failure, even though no difference in the primary outcome of intubation rate was observed with high flow oxygen therapy, as compared with standard oxygen therapy or noninvasive ventilation.
The study was conducted in 23 ICUs in France and Belgium. Patients 18 years of age or older were enrolled if they met all four of the following criteria: a respiratory rate of more than 25 breaths per minute, a ratio of the partial pressure of arterial oxygen (PaO2) to the FiO2 of 300 mm Hg or less while the patient was breathing oxygen at a flow rate of 10 liters per minute or more for at least 15 minutes, a partial pressure of arterial carbon dioxide (PCO2) not higher than 45 mm Hg, and an absence of clinical history of underlying chronic respiratory failure.
The primary outcome was the proportion of patients intubated at day 28; secondary outcomes included all-cause mortality in the intensive care unit at 90 days and the number of ventilator-free days at day 28.
A total of 310 patients were included in the analysis. 94 patients were assigned to standard oxygen therapy, 106 to high flow oxygen therapy, and 110 to noninvasive ventilation. In the standard oxygen group, oxygen therapy was applied continuously through a nonrebreather face mask at a flow rate of 10 liters per minute or more. In the high flow oxygen group, oxygen was passed through a heated humidifier (MR850, Fisher and Paykel Healthcare) and applied continuously through large-bore binasal prongs, with a gas flow rate of 50 liters per minute and an FiO2 of 1.0 at initiation (Optiflow, Fisher and Paykel Healthcare). In the noninvasive ventilation group, noninvasive ventilation was delivered to the patient through a face mask (Fisher and Paykel Healthcare) that was connected to an ICU ventilator, with pressure support applied in a noninvasive ventilation mode. The pressure-support level was adjusted with the aim of obtaining an expired tidal volume of 7 to 10 ml per kilogram of predicted body weight, with an initial positive end expiratory pressure (PEEP) between 2 and 10 cm of water. Oxygen delivery was adjusted to maintain an SpO2 of 92% or more for all interventions.
The intubation rate at day 28 was 38% in the high-flow oxygen group, 47% in the standard group, and 50% in the noninvasive ventilation group (P = 0.18 for all comparisons); not statistically significant. The number of ventilator-free days at day 28 was significantly higher in the high flow oxygen group (24±8 days, vs. 22±10 in the standard oxygen group and 19±12 in the noninvasive ventilation group; P = 0.02 for all comparisons).
The in-ICU mortality and 90-day mortality differed significantly among the three groups. The hazard ratio for death at 90 days was 2.01 (95% confidence interval [CI], 1.01 to 3.99) in the standard oxygen group as compared with the high flow oxygen group (P = 0.046) and 2.50 (95% CI, 1.31 to 4.78) in the noninvasive ventilation group as compared with the high flow oxygen group (P = 0.006). The risk of death at 90 days remained significantly lower in the high flow oxygen group after adjustment for the baseline Simplified Acute Physiology Score II and history of cardiac insufficiency.
The main limitation of the study was the low power to detect a significant between-group difference
in the intubation rate in the overall population. In addition, the authors note that noninvasive ventilation administered to patients with severe lung injury in this study could have increased the incidence of ventilator-induced lung injury by increasing tidal volumes that exceeded 9 ml/kg of predicted body weight.
The authors concluded that treatment with high flow oxygen in this multicenter trial improved the survival rate among patients with acute hypoxemic respiratory failure, even though no difference in the primary outcome of intubation was observed with high flow oxygen therapy, as compared with standard oxygen therapy or noninvasive ventilation.
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