Acute Hypoxemic Respiratory Failure in the ICU: What is the best method to reduce endotracheal intubation and improve outcomes?

Noninvasive positive-pressure ventilation (NPPV) reduces the need for endotracheal intubation and mortality due to acute hypoxemic respiratory failure.1 Noninvasive positive-pressure ventilation provides ventilatory support with oxygen and pressurized airflow using a face or nasal mask with a tight seal but without endotracheal intubation. There have been numerous trials reporting the benefits of NPPV for patients with acute respiratory failure due to COPD exacerbations. In one meta-analysis of eight studies, NPPV was associated with lower mortality, lower intubation rates, shorter hospital stays, and greater improvements in serum pH in 1 hour compared with treatment with usual care alone.2 The need for mechanical ventilation is associated with higher mortality rates, thus it is imperative to prevent intubation in order to improve outcomes.1

Title: High-Flow Oxygen through Nasal Cannula in Acute Hypoxemic Respiratory Failure3
Design Prospective, multicenter, randomized, controlled trial; N = 310
Objective To determine whether high-flow oxygen therapy or noninvasive ventilation therapy, as compared with standard oxygen therapy alone, could reduce the rate of endotracheal intubation and improve outcomes
Study Groups High-flow oxygen therapy, standard oxygen therapy, or noninvasive ventilation
Methods Standard-oxygen group (n=94): Oxygen therapy given continuously via non-rebreather face mask at ≥ 10 L/min, adjusted to maintain O2 sat ≥ 92%, measured by pulse oximetry (SpO2), until the patient recovered or was intubated.

High-flow–oxygen group (n=106): Oxygen passed through a heated humidifier and applied continuously via large-bore binasal prongs, at 50 L/min and fraction of inspired O2 (FIO2) of 1.0 at initiation and adjusted to maintain SpO2 ≥ 92%. Given ≥ two calendar days; after two days the patient can be switched to standard oxygen therapy.

Noninvasive-ventilation group (n=110): NPPV delivered via facemask connected to an ICU ventilator in noninvasive-ventilation mode. Pressure-support level was adjusted to obtain expired tidal volume of 7 to 10 ml/kg predicted body weight, with an initial positive end-expiratory pressure (PEEP) between 2 – 10 cm of water. The FIO2 ± PEEP level were then adjusted to maintain SpO2 ≥ 92%. The minimum duration of noninvasive ventilation was eight hours/day for ≥ two days. Noninvasive ventilation was applied during sessions of at least one hour and resumed if respiratory rate > 25 breaths per minute or SpO2 < 92%. Between sessions, patients received high-flow oxygen (see above).

Duration February 2011 through April 2013
Primary Outcome Measure Proportion of patients who required endotracheal intubation within 28 days after randomization
Baseline Characteristics The characteristics of the patients at enrollment were similar in the three groups.
The main cause of acute respiratory failure was community-acquired pneumonia, which was the diagnosis in 197 patients (64%). Bilateral pulmonary infiltrates were present in 244 patients (79%), and 238 patients (77%) had a PaO2:FIO2 of 200 mm Hg or less at the time of enrollment. The mean baseline FIO2 in 286 patients was 0.65±0.13.
Results The intubation rate at day 28 was 38% in the high-flow–oxygen group, 47% in the standard-oxygen group, and 50% in the noninvasive-ventilation group (P=0.18; P=0.17)
The intervals between enrollment and intubation did not differ significantly among the three groups (P = 0.18).

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 (P = 0.02).

Adverse Events Common Adverse Events: N/A
Serious Adverse Events: 18 episodes of cardiac arrest: three occurred before intubation [(one in the standard-oxygen group (5%) and two in the high-flow–oxygen group (8%)]. Two patients died during the process of intubation (0.06%).
Percentage that Discontinued due to Adverse Events: N/A
Study Author Conclusions Treatment with high-flow oxygen improved 90-day survival rate among patients with acute hypoxemic respiratory failure (secondary outcome), even though there was no statistically significant difference in intubation rate observed with high-flow oxygen therapy (primary outcome).

The primary outcome measure was the reduction of the need for endotracheal intubation in patients exhibiting acute hypoxemic respiratory failure in the ICU. The secondary outcome measures were all-cause mortality in the ICU and at 90 days, and the number of ventilator-free days at day 28. 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; however, there was a significant difference in favor of high-flow oxygen in 90-day mortality.3


1. Brochard L, Mancebo J, Wysocki M, et al. Noninvasive Ventilation for Acute Exacerbations of Chronic Obstructive Pulmonary Disease. N Engle J Med 1995;333:817-822
2. Bourdet SV, Williams DM. Chapter 16. Chronic Obstructive Pulmonary Disease. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L. eds. Pharmacotherapy: A Pathophysiologic Approach, 9e. New York, NY: McGraw-Hill; 2014. Accessed May 20, 2015.
3. Frat JP, Thille AW, Mercat A, et al. High-Flow Oxygen through Nasal Cannula in Acute Hypoxemic Respiratory Failure. N Engl J Med. 2015;
DOI: 10.1056/NEJMoa1503326


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