High flow nasal cannula therapy. The complete solution

BACKGROUND

Whether noninvasive ventilation should be administered in patients with acute hypoxemic respiratory failure is debated. Therapy with high-flow oxygen through a nasal cannula may offer an alternative in patients with hypoxemia.

METHODS

We performed a multicenter, open-label trial in which we randomly assigned patients without hypercapnia who had acute hypoxemic respiratory failure and a ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen of 300 mm Hg or less to high-flow oxygen therapy, standard oxygen therapy delivered through a face mask, or noninvasive positive-pressure ventilation. The primary outcome was the proportion of patients intubated at day 28; secondary outcomes included all-cause mortality in the intensive care unit and at 90 days and the number of ventilator-free days at day 28.

RESULTS

A total of 310 patients were included in the analyses. The intubation rate (primary outcome) was 38% (40 of 106 patients) in the high-flow-oxygen group, 47% (44 of 94) in the standard group, and 50% (55 of 110) in the noninvasive-ventilation group (P=0.18 for all comparisons). 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 hazard ratio for death at 90 days was 2.01 (95% confidence interval [CI], 1.01 to 3.99) with standard oxygen versus high-flow oxygen (P=0.046) and 2.50 (95% CI, 1.31 to 4.78) with noninvasive ventilation versus high-flow oxygen (P=0.006).

CONCLUSIONS

In patients with nonhypercapnic acute hypoxemic respiratory failure, treatment with high-flow oxygen, standard oxygen, or noninvasive ventilation did not result in significantly different intubation rates. There was a significant difference in favor of high-flow oxygen in 90-day mortality. (Funded by the Programme Hospitalier de Recherche Clinique Interrégional 2010 of the French Ministry of Health; FLORALI ClinicalTrials.gov number, NCT01320384.).

OBJECTIVES

High-flow nasal cannula is increasingly used in the management of respiratory failure. However, little is known about its impact on respiratory effort, which could explain part of the benefits in terms of comfort and efficiency. This study was designed to assess the effects of high-flow nasal cannula on indexes of respiratory effort (i.e., esophageal pressure variations, esophageal pressure-time product/min, and work of breathing/min) in adults.

DESIGN

A randomized controlled crossover study was conducted in 12 patients with moderate respiratory distress (i.e., after partial recovery from an acute episode, allowing physiologic measurements).

SETTING

Institut Universitaire de Cardiologie et de Pneumologie de Québec, QC, Canada.

SUBJECTS

Twelve adult patients with respiratory distress symptoms were enrolled in this study.

INTERVENTIONS

Four experimental conditions were evaluated: baseline with conventional oxygen therapy and high-flow nasal cannula at 20, 40, and 60 L/min. The primary outcomes were the indexes of respiratory effort (i.e., esophageal pressure variations, esophageal pressure-time product/min, and work of breathing/min). Secondary outcomes included tidal volume, respiratory rate, minute volume, dynamic lung compliance, inspiratory resistance, and blood gases.

MEASUREMENTS AND MAIN RESULTS

Esophageal pressure variations decreased from 9.8 (5.8-14.6) cm H2O at baseline to 4.9 (2.1-9.1) cm H2O at 60 L/min (p = 0.035). Esophageal pressure-time product/min decreased from 165 (126-179) to 72 (54-137) cm H2O • s/min, respectively (p = 0.033). Work of breathing/min decreased from 4.3 (3.5-6.3) to 2.1 (1.5-5.0) J/min, respectively (p = 0.031). Respiratory pattern variables and capillary blood gases were not significantly modified between experimental conditions. Dynamic lung compliance increased from 38 (24-64) mL/cm H2O at baseline to 59 (43-175) mL/cm H2O at 60 L/min (p = 0.007), and inspiratory resistance decreased from 9.6 (5.5-13.4) to 5.0 (1.0-9.1) cm H2O/L/s, respectively (p = 0.07).

CONCLUSIONS

High-flow nasal cannula, when set at 60 L/min, significantly reduces the indexes of respiratory effort in adult patients recovering from acute respiratory failure. This effect is associated with an improvement in respiratory mechanics.

BACKGROUND

The use of non-invasive ventilation is controversial in immunocompromised patients with acute respiratory failure, whereas the use of high-flow nasal cannula oxygen therapy is growing as an alternative to standard oxygen. We aimed to compare outcomes of immunocompromised patients with acute respiratory failure treated with standard oxygen with those treated with high-flow nasal cannula oxygen alone or high-flow nasal cannula oxygen associated with non-invasive ventilation.

METHODS

We did a post-hoc subgroup analysis in a subset of immunocompromised patients with non-hypercapnic acute respiratory failure from a multicentre, randomised, controlled trial. In the trial, patients from 23 intensive care units in France and Belgium were randomly assigned (1:1:1) to receive either standard oxygen, high-flow nasal cannula alone, or non-invasive ventilation interspaced with high-flow nasal cannula between non-invasive ventilation sessions (non-invasive ventilation group). Patients with profound neutropenia, acute-on-chronic respiratory failure, cardiogenic pulmonary oedema, shock, or altered consciousness were excluded. The primary outcome was the proportion of patients who required endotracheal intubation within 28 days after randomisation.

FINDINGS

Of the 82 immunocompromised patients, 30 were treated with standard oxygen, 26 with high-flow nasal cannula alone, and 26 with non-invasive ventilation plus interspaced high-flow nasal cannula. 8 (31%) of 26 patients treated with high-flow nasal cannula alone, 13 (43%) of 30 patients treated with standard oxygen, and 17 (65%) of 26 patients treated with non-invasive ventilation required intubation at 28 days (p=0·04). Odds ratios (ORs) for intubation were higher in patients treated with non-invasive ventilation than in those treated with high-flow nasal cannula: OR 4·25 (95% CI 1·33-13·56). ORs were not significantly different between patients treated with high-flow nasal cannula alone and standard oxygen: OR 1·72 (0·57-5·18). After multivariable logistic regression, the two factors independently associated with endotracheal intubation and mortality were age and use of non-invasive ventilation as first-line therapy.

INTERPRETATION

Non-invasive ventilation might be associated with an increased risk of intubation and mortality and should be used cautiously in immunocompromised patients with acute hypoxaemic respiratory failure.

FUNDING

French Ministry of Health, the French societies of intensive care (Société de Réanimation de Langue Française, SRLF) and pneumology (Société de Pneumologie de Langue Française, SPLF), La Mutuelle de Poitiers, AADAIRC (Association pour l'Assistance à Domicile Aux Insuffisants Respiratoires Chroniques), and Fisher&Paykel Healthcare.