High Wean Trial Dr Swapnil Pawar
Liberating high-risk patients from mechanical ventilation poses a unique challenge to all intensive care physicians. The use of high flow has increased over the last decade, however, the combination of high flow nasal oxygen and NIV has not been tested so far. The present study published in JAMA tries to answer this dilemma.
Effect of Postextubation High-Flow Nasal Oxygen With Noninvasive Ventilation vs High-Flow Nasal Oxygen Alone on Reintubation Among Patients at High Risk of Extubation Failure: A Randomized Clinical Trial
The decision regarding when to liberate patients from mechanical ventilation faces intensive care unit (ICU) clinicians regularly. While this decision is typically based on a variety of data, there is often considerable uncertainty about the success of extubation.
The data from a study by Thille et al published in Am J Resp Crit care in 2013 suggested that approximately 10% to 15% of patients ready to be separated from a ventilator experience extubation failure leading to reintubation. This figure is controversial itself as in my ICU we have less than 3 % reintubation rates. Also, it partly because how do you define the reintubation. However, we all agree and the evidence supports that reintubation is associated with particularly high mortality.
What’s known so far –
Nava et al. enrolled 97 patients who were randomised 1 h after extubation, following a successful SBT, to receive either NIV (minimum 8 h·day–1 for 2 days) or standard treatment (oxygen therapy). NIV reduced the rate of re-intubation, which resulted in reduced ICU mortality. Ferrer et al. randomised 162 patients considered to be at risk for extubation failure to either NIV (near-continuously for 24 h) or oxygen therapy only. NIV decreased the number of patients developing post-extubation respiratory failure and ICU mortality; however, the rate of re-intubation, ICU and hospital length of stay, and hospital mortality were not significantly different between the two groups. A post hoc analysis showed that NIV improved hospital and 90-day survival in the subgroup of patients who developed hypercapnia during the SBT prior to extubation. Subsequent to these observations, the same authors enrolled a select group of 106 patients with chronic respiratory disorders developing hypercapnia during the SBT to investigate the benefits of NIV, as opposed to oxygen therapy alone, after extubation. The rate of respiratory failure after extubation was lower in the NIV group than in the controls. While ICU and hospital mortality were not different between the treatment and control groups, the 90-day survival rate was significantly improved in the NIV group, as opposed to controls.
Two small single-centre trials (40 patients each) also randomised patients to NIV or standard treatment after planned extubation. Kihlnani et al. enrolled COPD patients and found no differences in intubation rate or ICU and hospital lengths of stay. In a small group of patients for whom the only inclusion criterion was mechanical ventilation for >72 h because of ARF, predominantly secondary to COPD exacerbations, Ornico et al. found a reduction in re-intubation and death in the NIV group.
ATS/ERS guidelines 2017 –
We suggest that NIV be used to prevent post-extubation respiratory failure in high-risk patients post-extubation. (Conditional recommendation, low certainty of evidence.)
Among mechanically ventilated patients at high risk of extubation failure, does the use of high-flow nasal oxygen with noninvasive ventilation after extubation reduce the risk of reintubation compared with high-flow nasal oxygen alone?
Design: Multicentric study including thirty ICUs in France. Patients were randomly assigned to receive high- flow nasal oxygen alone or HFNO combined with noninvasive ventilation after extubation. Computerized randomization in permuted blocks of four. Stratification based on the center and the PaCO2 levels at the end of a SBT of ≤45 or >45 mm Hg).
Population: Inclusion: Adult patients ventilated for more than 24 hours, undergone a successful SBT and were ready for extubation. Patients were enrolled if they were at high risk of extubation failure defined as:
Excluded: Home NIV, contraindication to non-invasive ventilation, chronic neuromuscular disease, traumatic brain injury, patients who suffered accidental extubation, do-not-reintubate status at extubation
Intervention: NIV commenced immediately after extubation with an initial period of at least 4 hours. The minimum duration of NIV of at least 12 hours a day during the first 48 hours after extubation. Uninterrupted NIV was encouraged during the night. Pressure support mode with a minimal pressure-support level of 5 cm H2O with a target tidal volume of 6–8 ml/kg of predicted body weight. PEEP between 5–10 cm H2O, FiO2 titrated to >92%. HFNO was applied during the periods of time when NIV was interrupted. This type of therapy was continued for 48 hours.
Control: HFNO at 50 L/min and a fraction of inspired oxygen (FIO2) titrated to pulse oximetry (SpO2) of at 92% or more. Humidifier temperature set at 37°C. This was continued for 48 hours after extubation as well.
Standard oxygen therapy after 48 hours in both groups
Severe respiratory failure
How did they calculate the sample size? The investigators assumed an 8% reduction in the rate of reintubation with combination therapy from 18% to 10%. 590 patients for a power of 80% at a 2-sided α level of 0.05.
During the approximately one-year study period, 3121 patients were extubated.
Out of this, 1460 were excluded; 927 (majority) were at low risk of extubation failure (who were obviously not included in the study) 414 were ventilated for <24 h.
Among 1661 who were extubated after 24 h of ventilation 692 were excluded for various reasons, including 274 do-not-reintubate status, 182 were on long-term NIV at home, 119 accidental extubations, 41 had a contraindication to NIV, 30 had a chronic neuromuscular disease, 37 had TBI.
969 patients were assessed for eligibility; 321 not included (270 No staff available or logistic issues 51 declined participation). Finally out of 648 patients, 306 randomized to receive HFNO (302 received the allocated intervention); 342 to NIV plus HFNO (339 received the allocated intervention).
Primary outcome: Reintubation within 7 days of extubation: was significantly lower 11.8% (95% CI, 8.4%- 15.2%) vs. 18.2% (95% CI, 13.9%- 22.6%) (difference, −6.4% [95% CI, −12.0 to −0.9]; P = .02)
Reintubation at 48 hours: Significantly higher with HFNC alone
Reintubation at 72 hours: Significantly higher with HFNC alone
Reintubation until ICU discharge: Significantly higher with HFNC alone
Post-extubation respiratory failure within 7 days following extubation
Higher with HFNC alone
Not different were the ICU and hospital length of stay
ICU mortality: Not different
Hospital mortality: Not different
28-d mortality: Not different
90-d mortality: Not different
Arterial blood gases 1 hour after treatment initiation: higher with NIV
Time to reintubation: Not different
The proportion of patients who met criteria for reintubation: Higher with HFNC alone
Indication for reintubation
Severe respiratory failure: 88 patients
Neurological failure: 37 patients
Hemodynamic failure: 16 patients
Respiratory or cardiac arrest: 10 patients
Use of NIV as rescue therapy: 20 patients in the HFNC group received rescue NIV; 10 were reintubated
Mortality or reintubation in ICU: More with HFNC
Mortality of reintubated patients: Not different
Among patients with a PaCO2 of 45 mm Hg or less, re-intubation rates at day 7 were not significantly different between groups (13% with noninvasive ventilation vs 18% with high-flow nasal oxygen alone; difference, −5.0% [95% CI, −11.2% to 1.1%]; P = .10). After adjustment for PaCO2 level at enrollment (≤45 or >45 mm Hg) and underlying chronic lung disease, the odds ratio for reintubation at day 7 remained significantly lower with noninvasive ventilation than with high-flow nasal oxygen alone.
The post hoc analysis showed a lower reintubation rate with noninvasive ventilation after adjustment for the hospital random effect
the combination of high-flow nasal oxygen with noninvasive ventilation had not been previously assessed after extubation in the ICU
Largest RCT on this topic
Reintubation rates almost exactly the expected rates in the 2 groups (18.2% and 11.8%), reinforcing the external validity of the study.
Multicentre with a standardised protocol, baseline similarity, a sick cohort of patients and objective criteria for reintubation.
Combination of NIV and High flow nasal oxygen is beneficial in high-risk patients to prevent re-intubation
Appropriate selection of patients for the combined strategy is warranted.