Hernández G, et al. Effect of post-extubation noninvasive ventilation with active humidification vs high-flow nasal cannula on reintubation in patients at very high risk for extubation failure: a randomized trial. Intensive Care Med. 2022 Dec;48(12):1751–9.
Both non-invasive ventilation (NIV) and high-flow nasal cannula (HFNC) have been used solely and in combination as respiratory support following extubation. Reintubation rates and post extubation respiratory failure were compared among patients with at least one of 10 pre-specified risk factors in a previous randomized controlled trial (RCT) (1). In this RCT, HFNC was shown to be non-inferior to NIV in the prevention of reintubation and post-extubation respiratory failure. However, patients with multiple (>4) risk factors may have improved outcomes with NIV compared with HFNC according to a post-hoc analysis of a previous RCT (2).
Humidification of the inspired gas during NIV use might improve patient comfort and allow prolonged use. The authors hypothesized that patients with >4 risk factors might have improved outcomes using NIV with active humidification compared to HFNC (3).
Population and design
This RCT was conducted in two ICUs in Spain. The study evaluated the efficacy of NIV with active humidification compared with HFNC on reintubation rates in adult patients on mechanical ventilation for 24 hours or more, who were at high risk of extubation failure. Patients were considered to be at high risk of extubation failure if they met 4 or more of the following criteria.
- Age >65 years
- Mechanical ventilation for more 7 or more days or hypercapnia >45 mm Hg
- Mechanical ventilation was required primarily for cardiac failure
- Moderate to severe chronic obstructive airways diseases (COPD)
- APACHE II score of ≥12 on the day of extubation
- Body Mass Index >30
- Problems expected with airway maintenance
- Poor cough reflex
- Prolonged or difficult weaning – one or more episode of weaning failure
- Two or more co-morbidities
Patients who had do-not-resuscitate orders, or contraindications for NIV use, including recent surgery of the head and neck, active upper gastrointestinal bleeding, and excessive secretions were excluded.
Patients underwent daily screening for the evaluation of readiness for weaning. Those who were considered ready underwent a spontaneous breathing trial (SBT) with pressure support of 7 cm H2O and zero PEEP for 30 minutes. Those who tolerated the SBT were reinstituted on the previous level of ventilator support for 1 hour to enable rest and further evaluation prior to extubation. Following extubation, patients were randomized into two groups.
NIV with active humidification group
After extubation, patients in this group were initiated on NIV with active humification using a heated humidifier. The inspiratory and expiratory pressures were set to deliver a tidal volume of 6–8 ml/kg, maintain a respiratory rate of less than 26/min, SpO2 ≥92%, and a pH of 7.35.
In this group, the HFNC was applied just before extubation. The initial flow was set at 10 l/min and increased in steps of 5 l/min up to a maximum flow of 60 l/min depending on patient comfort. The temperature was initially set at 37 °C.
The FiO2 was titrated to an SpO2 level ≥92% in both groups. Both modalities of support were continued for 48 hours, following which, patients were switched to conventional oxygen therapy as required. Rescue NIV was not allowed in the HFNC group. All other aspects of care were left to clinician judgment. Reintubation was based on predefined criteria.
The sample size was calculated based on the primary outcome of reintubation due to any cause within 7 days of extubation. The authors assumed a 45% reintubation rate at baseline. A sample size of 88 patients in each arm was calculated assuming an absolute reduction in the reintubation rate by 21%. This sample size provided the study with 80% power at an alpha level of 0.05.
The study randomized 182 patients – 92 to humidified NIV and 90 to HFNC. Patients with acute heart failure, COPD, and hypercapnia at the end of the SBT were more common in the NIV group.
Reintubation due to any cause at 7 days was significantly less in the humidified NIV group compared with the HFNC group (23.3% vs. 38.8%, absolute risk difference −15.5%, 95% CI −28.3 to −1.0, p = 0.019). The number of patients who needed to be treated with NIV to avoid one reintubation was 6.2 patients. Among patients with risk factors known to benefit with NIV (acute heart failure, COPD, and hypercapnia at the end of the SBT), reintubation rates, as expected, was lower with NIV compared to HFNC.
The median time to reintubation was 27 hours in both groups.
The incidence of post-extubation respiratory failure (based on pre-defined criteria) was similar in the NIV and HFNC groups (43.5% vs. 44.4%). ICU mortality (13% vs. 4.4%) and hospital mortality (15.2 vs. 6.7%) were higher in the NIV group, although the difference was not statistically significant.
The median ICU length of stay was shorter with NIV compared with HFNC [9.5 (4–15) days vs. 12.5 (6.7–19) days, p = 0.047]. The hospital length of stay was also shorter in the NIV group, although the difference was not statistically significant.
Discomfort associated with therapy was more common with NIV – including nasal discomfort and skin ulceration, necessitating temporary discontinuation of therapy.
After day 5, only patients in the HFNC group were reintubated. The reintubation rate within the first 3 days of extubation was not different between the NIV (21.7%) and HFNC (28.9%) groups. The reintubation rate within 5 days was also similar (22.8% vs. 28.9%). Time to reintubation was significantly longer with HFNC (27 h vs. 10 h), in patients who were reintubated within 5 days. Reintubation was associated with increased mortality.
- NIV was tolerated better than previously reported, allowing prolonged use for more than 20 hours per day in the first 48 hours
- Skin ulceration was less common (4.3%) compared to previous reports
- The inspiratory pressures were set low (<5 cm H2O) which may have increased the level of comfort with NIV
- No NIV patient was reintubated after day 5; in the HFNC group, 9/35 failures occurred after 5 days. This suggests that the benefits of NIV therapy may sustain longer compared to HFNC
- At 3 and 5 days, reintubation rates were similar in both groups. Hence, the difference was entirely due to the increased reintubation rate in the HFNC group after 5 days (9/35 vs. 0/21)
- The authors suggest that humidification may increase patient comfort, improve tolerance, and may delay reintubation
- There were more patients with risk factors known to benefit from NIV (hypercapnia, and lung or heart disease) in the NIV group
- The study could not be blinded. Lack of blinding could have biased the decision to intubate, although reintubation was based on predefined criteria
- The reintubation rate of 45% used for sample size calculation may be too high, leading to a small sample size
- NIV and HFNC were continued only for 48 hours – many ICUs may continue for a longer duration
- The study was confined to two ICUs in Spain – hence, it may not be generalizable to other populations
- Post extubation respiratory failure was similar in both groups – however, reintubation was higher with HFNC – how would you explain this difference?
This study by Hernández et al. aimed to evaluate the efficacy of NIV with active humidification compared to HFNC in preventing reintubation rates in adult patients at high risk of extubation failure. The study was conducted in two ICUs in Spain. Patients were considered to be at high risk of extubation failure if they met four or more of ten pre-specified criteria. The primary outcome, reintubation due to any cause at seven days, was significantly less in the humidified NIV group compared with the HFNC group, and the number of patients who needed to be treated with NIV to avoid one reintubation was 6.2 patients. Among patients with risk factors known to benefit with NIV, reintubation rates were lower with NIV compared to HFNC. The study found that NIV with active humidification was more effective than HFNC in preventing reintubation in high-risk patients.
1. Hernández G, Vaquero C, Colinas L, Cuena R, González P, Canabal A, 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 Oct 18;316(15):1565.
2. Thille AW, Coudroy R, Nay MA, Gacouin A, Decavèle M, Sonneville R, et al. Beneficial Effects of Noninvasive Ventilation after Extubation in Obese or Overweight Patients: A Post Hoc Analysis of a Randomized Clinical Trial. Am J Respir Crit Care Med. 2022 Feb 15;205(4):440–9.
3. Hernández G, Paredes I, Moran F, Buj M, Colinas L, Rodríguez ML, et al. Effect of postextubation noninvasive ventilation with active humidification vs high-flow nasal cannula on reintubation in patients at very high risk for extubation failure: a randomized trial. Intensive Care Med. 2022 Dec;48(12):1751–9.