By Betty Tran, MD, MSc

Assistant Professor of Medicine, Pulmonary and Critical Care Medicine, Rush University Medical Center, Chicago

Dr. Tran reports no financial relationships relevant to this field of study.

SYNOPSIS: In this multicenter, randomized, clinical trial of critically ill adults at high risk for reintubation, high-flow conditioned oxygen therapy was not inferior to noninvasive mechanical ventilation with regard to preventing reintubation and postextubation respiratory failure within 72 hours of extubation.

SOURCE: Hernandez G, Vaquero C, Colinas L, et al. Effect of postextubation high-flow nasal cannula vs noninvasive ventilation on reintubation and postextubation respiratory failure in high-risk patients: A randomized clinical trial. JAMA 2016;316:1565-1574.

This was a multicenter, randomized, noninferiority trial in Spain between 2012-2014 in which patients from three ICUs were screened for inclusion in the study if they were ready for extubation with at least one risk factor that deemed them high risk for reintubation: age > 65 years, heart failure as the primary indication for mechanical ventilation, moderate-severe COPD, an Acute Physiology and Chronic Health Evaluation II (APACHE II) score > 12 on extubation day, body mass index > 30 kg/m2, airway patency problems (e.g., high risk of developing laryngeal edema), inability to deal with respiratory secretions, difficult/prolonged weaning, failing first attempt at extubation, more than two comorbidities, and mechanical ventilation for more than seven days. Patients who passed their spontaneous breathing trial and underwent extubation were randomized to receive noninvasive ventilation (NIV) or high-flow conditioned oxygen to begin immediately after extubation for a duration of 24 hours before switching to conventional oxygen therapy, if needed. NIV was delivered via full face mask with settings adjusted to target a respiratory rate of 25 breaths/minute and adequate gas exchange (arterial oxygen saturation [SpO2] of 92%, pH 7.35). Notably, sedation to help increase tolerance to NIV was not allowed. High-flow oxygen was initiated with a flow of 10 L/minute and titrated up by 5 L/minute steps until patients experienced discomfort; FiO2 was adjusted to maintain an SpO2 of 92%. The primary outcomes were reintubation after extubation and postextubation respiratory failure within 72 hours defined by any of the following: pH < 7.35 with PaCO2 > 45 mmHg, SpO2 < 90% or PaO2 < 60 mmHg at FiO2 > 0.4, respiratory rate > 35 breaths/minute, decreased level of consciousness, agitation, or clinical signs of respiratory fatigue or increased work of breathing. Secondary outcomes included respiratory infection, sepsis, or multiple organ failure, ICU and hospital length of stay, and mortality, and the reason for failure of the assigned treatment, if applicable (e.g., patient discomfort requiring withdrawal of the therapy for more than six hours, nasal septum, or skin trauma). Noninferiority was established if the between-group difference in treatment failure rates was < 10%.

After screening 1,211 adults on mechanical ventilation for > 12 hours, 604 were randomized: 290 to high-flow oxygen and 314 to NIV. There were only two dropouts in each group. Both groups were similar except for a lower incidence of heart failure in the high-flow oxygen group and a higher incidence of surgical diagnoses in the NIV group. High-flow oxygen was noninferior to NIV, with reintubation occurring in 60 patients (19.1%) in the NIV group compared to 66 patients (22.8%) in the high-flow oxygen group (risk difference, -3.7%; 95% confidence interval [CI], -9.1% to infinity). More patients in the NIV group experienced postextubation respiratory failure within 72 hours than in the high-flow oxygen group (39.8% vs. 26.9%; risk difference, 12.9%; 95% CI, 6.6% to infinity). Median time to reintubation was not significantly different in the two groups. In terms of secondary outcomes, median ICU length of stay was lower in the high-flow oxygen group compared to the NIV group (3 days vs. 4 days; IQR, 2-9; P = 0.048), but other secondary outcomes were similar between the two groups.


This study adds to the growing literature on the role of noninvasive approaches to reducing the need for reintubation in respiratory failure. The benefits of avoiding reintubation if possible include shorter ICU stays and reduced morbidity and mortality, mainly attributable to nosocomial infection.1 The role of NIV in postextubation respiratory failure has been debated, with some studies showing no benefit or even harm with regard to delaying reintubation and others reporting improved outcomes in patients specifically with COPD and hypercapnia.2-4 A more recent study by Jaber et al found that NIV use reduced the seven-day reintubation rate compared to standard oxygen therapy in a population of patients undergoing major abdominal surgery, although the NIV group contained more COPD patients, which may have skewed the findings.5 With regard to high-flow oxygen therapy, the same group led by Hernandez et al previously reported that compared to standard treatment with oxygen, high-flow nasal cannula reduced the risk of reintubation within 72 hours among a group of patients at low risk for reintubation.6

The question of whether to use one modality over the other, however, remains unanswered. In addition to the current study, Stephan et al reported that high-flow nasal cannula was not inferior to NIV in a population of postoperative cardiac surgery patients in reducing the rate of reintubation, crossover to the other study therapy, or early discontinuation of treatment.7 It seems intuitive that high-flow nasal cannula may be the easier alternative with regard to patient comfort, tolerability, and longer-term continuous use (to avoid facial skin breakdown and allow for oral intake), although whether it can be used with similar effect with NIV will need to be evaluated in different patient populations.

There are several other issues to keep in mind. First, these studies are randomized, but it is impossible to blind them; specific, predefined clinical criteria with regard to postextubation failure does help reduce bias. Second, these studies are conducted in experienced centers, and the results may not be reproducible in the community at large. Finally, based on the data we have, we still do not know the optimal settings and durations of use for NIV and high-flow oxygen in the postextubation setting. The two groups in this study contained patients on these therapies for no more than 24 hours, and in the NIV group, the total time under NIV was only 14 hours (IQR, 8-23). As the authors noted, although longer usage of these modalities may improve extubation success, it may run the risk of delaying reintubation when necessary. At this time, it is difficult to make specific recommendations or guidelines for the use of either high-flow oxygen or NIV as a part of the management of postextubation respiratory failure given these uncertainties.


  1. Epstein SK, Ciubotaru RL, Wong JB. Effect of failed extubation on the outcome of mechanical ventilation. Chest 1997;112:186-192.
  2. Keenan SP, Powers C, McCormack DG, Block G. Noninvasive positive-pressure ventilation for postextubation respiratory distress: A randomized controlled trial. JAMA 2002;287:3238-3244.
  3. Esteban A, Frutos-Vivar F, Ferguson ND, et al. Noninvasive positive-pressure ventilation for respiratory failure after extubation. N Engl J Med 2004;350:2452-2460.
  4. Ferrer M, Esquinas A, Arancibia F, et al. Noninvasive ventilation during persistent weaning failure: A randomized controlled trial. Am J Respir Crit Care Med 2003;168:70-76.
  5. Jaber S, Lescot T, Futier E, et al. Effect of noninvasive ventilation on tracheal reintubation among patients with hypoxemic respiratory failure following abdominal surgery. JAMA 2016;315:1345-1353.
  6. Hernandez G, Vaquero C, Gonzalez P, et al. Effect of postextubation high-flow nasal cannula vs conventional oxygen therapy on reintubation in low-risk patients: A randomized clinical trial. JAMA 2016;315:1354-1361.
  7. Stephan F, Barrucand B, Petit P, et al. High-flow nasal oxygen vs noninvasive positive airway pressure in hypoxemic patients after cardiothoracic surgery: A randomized clinical trial. JAMA 2015;313:2331-2339.