HIGH-WEAN Trial: Extubation to High-Flow Nasal Oxygen + Noninvasive Ventilation vs High-Flow Nasal Oxygen Alone

high wean trial visual summary

Objective

The goal of the HIGH-WEAN trial was to evaluate if high-flow nasal oxygen with noninvasive ventilation, compared with high-flow nasal oxygen alone, decreased the rate of reintubation within the first 7 days after extubation in the ICU.

Study Design

  • Multicenter
  • Randomized,
  • Open-label

Study Groups

Patients were randomly assigned in a 1:1 ratio to receive high-flow nasal oxygen alone (control group) or along with noninvasive ventilation (intervention group) immediately after extubation.

The median duration of mechanical ventilation prior to extubation was 5 days. At the time of extubation, 111 patients (17%) had hypercapnia (Paco2 >45 mm Hg).

High-flow nasal oxygen alone group

Patients were continuously treated by high-flow nasal oxygen alone for a mean of 42 hours within the first 48 hours with a flow of 50 L/min and fraction of inspired oxygen (0.41 FiO2) adjusted to obtain adequate oxygenation, with an oxygen saturation as measured by pulse oximetry (SpO2) of ≥ 92%.

High-flow + NIV group

Patients assigned to the intervention group (O2 + NIV) were treated with high-flow nasal oxygen alternating with noninvasive ventilation. Noninvasive ventilation was initiated immediately after extubation with a first session of ≥ 4 hours. The minimal duration was of 12 hours. Continuous application of noninvasive ventilation was promoted throughout the entire night period. FiO2 was adjusted to obtain adequate oxygenation (Spo2 ≥92%). Between noninvasive ventilation sessions, high-flow nasal oxygen was delivered.

Study Population of the HIGH-WEAN Trial

  • Total number of enrollees: 3121
  • Patients included in the analysis: 641
  • Patients assigned to control group (only high-flow nasal oxygen): 302
  • Patients assigned to intervention group (high-flow nasal oxygen with non-invasive ventilation): 339
  • Difficult or prolonged weaning: 32%
  • Mean patient age: 70
  • Percentage female: 34%

 Inclusion criteria:

  • Patients at high risk of reintubation: ≥65 years or with an underlying cardiac or respiratory disease
  • Extubation after at least 24h of mechanical ventilation

 Exclusion criteria:

  • At low risk of extubation failure
  • Intubated <24 h
  • Underlying chronic neuromuscular disease (myopathy or myasthenia gravis)
  • Under law protection or non affiliated to health system
  • Do-not-reintubate order at the time of extubation
  • Long-term treatment with noninvasive ventilation or continuous positive airway pressure at home
  • Unplanned extubation (accidental or self-extubation)
  • Contraindication to noninvasive ventilation
  • Traumatic brain injury
  • Minors

Principal Findings of the HIGH-WEAN Trial:

Outcomes:

Comparisons are high-flow nasal oxygen alone vs. high-flow nasal oxygen with noninvasive ventilation

Primary outcomes

Reintubation rates at day 7:

18% vs. 12% – Absolute difference −6.4% (95% CI, −12.0 to −0.9; P=.02)

Secondary outcomes

Postextubation respiratory failure at day 7:

29% vs. 21%  Absolute difference −8.5% (95% CI,  −15.2 to −1.8 ; P=.01)

Reintubation:

  • At 48 h:  12% vs. 7%
    Absolute difference −4.8% (95% CI, −9.6 to −0.3; P= .04)
  • At 72 h: 16% vs. 9%
    Absolute difference −6.7% (95% CI,  −11.9 to −1.7; P= .009)
  • Up until ICU discharge:  20% vs 12%  
    Absolute difference −7.4% (95% CI, −13.2 to −1.8; P=.009)

Length of stay, median (IQR), days:

  • In ICU: 11 vs. 12
    Absolute difference 0.5% (95% CI, −1.6 to 2.6; P= .55)
  • In hospital: 23 vs. 25
    Absolute difference 2.3%(95% CI, −1.4 to 6.1; P=.31)

Mortality:

  • In ICU:  26% vs. 21
    Absolute difference −2.4%(95% CI, −6.7 to 1.7; P=.25)
  • In hospital:  46% vs. 54%
    Absolute difference 0.7% (95% CI, −5.0 to 6.3; P=.80)
  • At day28: 33% vs. 39%
    Absolute difference 0.6% (95% CI, −4.4 to 5.5; P=.82)
  • At day 90: 65% vs. 62%
    Absolute difference −3.2% (95% CI, −9.5 to 2.9; P=0.30)

Exploratory Outcomes

Patients meeting reintubation criteria:

  • During ICU stay: 65% vs. 49%
    Absolute difference −7.1% (95% CI, −13.1 to −1.1; P=.02)
  • Mortality or reintubation in ICU: 64% vs. 51%
    Absolute difference −6.2% (95% CI, −12.2 to −0.2; P= .04)
  • Mortality of reintubated patients: 36% vs. 27%
    Absolute difference −8.8% (95% CI,  −25.7 to 9.9; P= .35)

The reason for reintubation was severe respiratory failure in 88 patients, neurological failure in 37 patients, hemodynamic failure in 16 patients, and respiratory or cardiac arrest in 10 patients.

Results:

One hour after treatment initiation, Pao2:FiO2 was higher with noninvasive ventilation than with high-flow nasal oxygen alone. An absolute difference of 8% in the rate of reintubation was seen in favor of NIV + O2. Mortality in the ICU, in the hospital, and at day 90 were not significantly different between groups.

Conclusion:

In mechanically ventilated patients at high risk of extubation failure, the use of high-flow nasal oxygen with noninvasive ventilation immediately after extubation significantly decreased the risk of reintubation compared with high-flow nasal oxygen alone.

HIGH-WEAN Trial Via JAMA