Extubation to Non-invasive Ventilation for Weaning Reduces Mortality, Morbidity, and Length of Stay

Abstract & Commentary

By David J. Pierson, MD, Editor, Professor, Pulmonary and Critical Care Medicine, Harborview Medical Center, University of Washington, Seattle, is Editor for Critical Care Alert.

Synopsis: This meta-analysis of 12 clinical trials in adult patients with acute respiratory failure showed that extubation directly to non-invasive ventilation before weaning would normally have been attempted decreases mortality, ventilator-associated pneumonia, and length of stay — especially for patients with COPD.

Source: Burns KE, et al. Use of non-invasive ventilation to wean critically ill adults off invasive ventilation: Meta-analysis and systematic review. BMJ 2009 May 21;338:b1574; doi: 10.1136/bmj.b1574.

In 2003, Burns and colleagues published a cochrane review1 of available studies examining the effects of early direct extubation to non-invasive ventilation (NIV) in adult patients receiving invasive mechanical ventilation for acute respiratory failure. That review showed significant benefit of the non-invasive approach in terms of mortality, the incidence of ventilator-associated pneumonia (VAP), total duration of mechanical ventilation, and length of hospital stay — although the authors emphasized the small number of available studies on this topic. These same investigators, along with other colleagues in Hamilton, Toronto, and Vancouver, Canada, have now updated their assessment, incorporating the findings of several more recent studies that substantially improve the quality of the evidence base in this important area.

Burns et al conducted an exhaustive search for all studies of NIV in weaning. They conducted duplicate independent citation screening in Medline and several other indexing sources, reviewed abstracts presented at relevant meetings, and contacted investigators of potentially relevant trials to clarify the methods used. They included randomized trials (plus a few carefully screened quasi-randomized trials) of extubation to immediate NIV vs weaning from invasive mechanical ventilation, in adult patients requiring > 24 hours of invasive mechanical ventilation for acute respiratory failure. The primary outcome variable was mortality; secondary outcomes examined were the incidence of VAP, duration of mechanical ventilation both with and without NIV, and length of stay in both ICU and hospital. The authors carried out extensive analysis for publication bias, heterogeneity among the included studies, and other factors that might influence the results.

Twelve studies met all the inclusion criteria, including 7 subsequent to the 5 in the authors' original meta-analysis. Of the 12 studies (530 patients), 4 were published in Chinese, 2 were published in abstract form, and 1 was an unpublished dissertation. Eight trials included only patients with COPD, and the other 4 included patients with other diagnoses as well as COPD. They used a variety of criteria for patient inclusion as well as for invasive and non-invasive ventilation and weaning; however, the authors judged them similar enough in design to include in the meta-analysis of pooled data.

Use of NIV as an adjunct to weaning was associated with reduced overall mortality (relative risk, 0.55; 95% confidence interval [CI], 0.38-0.79; P = 0.001). The incidence of VAP was also substantially reduced, with a relative risk of 0.29 (95% CI, 0.19-0.45; P < 0.001). As would have been expected, the duration of intubation was much less in patients managed with NIV for weaning: weighted mean difference, -7.8 days (95% CI, -11 to -4 days; P < 0.001). However, total duration of ventilation (invasive + NIV) was also less with NIV (-5.6 days; 95% CI, -9.5 to -1.8 days; P = 0.004). Length of stay was shorter with NIV, both in the ICU (-6.2 days; 95% CI, -8.8 to -3.8 days; P < 0.001) and overall in the hospital (-7.2 days; 95% CI, -10.8 to -3.6 days; P < 0.001). On the basis of these findings, which agree with and strengthen those of their earlier study, the authors conclude that NIV is indeed efficacious in improving all the examined outcomes, and that it should be used preferentially in patients with COPD.


The evidence base on the use of NIV in acute care has expanded dramatically in the last decade.2-4 This modality is now standard of care for severe COPD exacerbations and acute cardiogenic pulmonary edema, and its use in certain forms of acute hypoxemic respiratory failure is also supported by considerable evidence. The results of the study by Burns et al clearly indicate that NIV as a bridge to weaning from ventilatory support should be added to this list of "proven indications."

Although the results of this meta-analysis are clear and clinically relevant, it should be emphasized (as it was by the authors) that the available clinical evidence in this area is still not particularly robust. The included studies varied widely in their reported rates of mortality (ranging from 11% to 60%) and VAP (6% to 59%). Because of low event rates, none of the individual clinical trials included in the meta-analysis was adequately powered to demonstrate a difference between the compared weaning strategies. Nonetheless, Burns et al found no evidence of publication bias in the examined studies, and the absence of individual trials with contrary results seems noteworthy.

The figure provides a conceptual illustration of how NIV should be used — in appropriately selected patients — as discussed here. A multitude of studies now demonstrate that intubation can be avoided in many instances of acute respiratory failure, especially when it occurs in patients with underlying COPD. Staying hands that have become accustomed to reaching for the endotracheal tube in this situation has required a substantial practice change for many clinicians. Moreover, the reality is that intensivists often first become involved in the patient's care after intubation has already taken place, whether in the pre-hospital setting, in the emergency department, or at the hands of another clinician in the hospital. Given the strong evidence that patients with acute respiratory failure complicating COPD can usually be managed without intubation,2-4 such patients are the ideal candidates for early extubation to NIV. The clinician should not be locked into continuing invasive ventilation in patients in whom it might well have been avoided in the first place. In hypoxemic acute respiratory failure (for example, in severe pneumonia or the acute respiratory distress syndrome), the decision is admittedly a bit less clear.

Based on the Burns meta-analysis and the other available evidence,5 the following guidelines appear reasonable:

Good candidates for early extubation to NIV:

  • COPD exacerbation as the reason for acute respiratory failure;
  • No major coexistent acute medical conditions;
  • Awake, alert, cooperative patient; and
  • Minimal or easily manageable airway secretions.

Poor candidates for early extubation to NIV:

  • Hypoxemic respiratory failure requiring high FIO2 and/or PEEP;
  • Hemodynamically unstable (e.g., requiring more than minimal pressors);
  • Presence of serious coexisting conditions (e.g., multiple organ dysfunction, cardiac ischemia, unstable arrhythmias, or acute brain injury);
  • Obtundation or persistent agitation, inability to cooperate, requirement for restraints;
  • Copious respiratory secretions;
  • Weak or absent cough; and
  • Facial or upper airway problems.

In all cases, the patient needs to be cared for in a closely monitored situation, with adequate staffing until NIV is discontinued and clinical stability has been achieved.


  1. Burns KE, et al. Noninvasive positive pressure ventilation as a weaning strategy for intubated patients with respiratory failure. Cochrane Database Syst Rev 2003;(4):CD004127.
  2. Garpestad E, et al. Noninvasive ventilation for critical care. Chest 2007;132:711-720.
  3. Peñuelas O, et al. Noninvasive positive-pressure ventilation in acute respiratory failure. CMAJ 2007;177:1211-1218.
  4. Keenan SP, Mehta S. Noninvasive ventilation for patients presenting with acute respiratory failure: The randomized controlled trials. Respir Care 2009;54:116-126.
  5. Epstein SK. Noninvasive ventilation to shorten the duration of mechanical ventilation. Respir Care 2009;54:198-208.