Use of rescue noninvasive ventilation for post-extubation respiratory failure

Abstract

Background: Robust evidence supports the use of preemptive non-invasive ventilation (NIV) after extubation in selected high-risk patient cohorts. In contrast, current guidelines discourage the use of NIV as a rescue therapy for respiratory failure that develops later after extubation, based on earlier studies indicating a potential increase in hospital mortality due to delayed reintubation. Nonetheless, NIV continues to be employed in this setting. We conducted a post-hoc analysis of a randomized trial to assess the clinical outcomes of rescue NIV for post-extubation respiratory failure.

Methods: In this post-hoc analysis of a randomized trial comparing high-flow with Venturi mask oxygen in hypoxemic patients after extubation, we included those who developed post-extubation respiratory failure according to prespecified criteria; patients who received rescue NIV per physician's decision were compared to those who received direct re-intubation. Criteria for re-intubation during NIV were prespecified. Odds ratio after inverse probability of treatment weighting and posterior probabilities by Bayesian regression are reported.

Results: Among 494 extubated patients, 147 developed respiratory failure while receiving oxygen therapy, occurring at a median of 37 h [IQR 13-85] after extubation: 83 (57%) were treated with rescue NIV and 64 (43%) received immediate re-intubation. The rate of NIV failure was 58%, without differences between patients with hypoxemic respiratory failure and those with hypercapnia and/or respiratory distress (60% vs. 56%, p = 0.82). In the weighted cohort, the use of rescue NIV, compared to direct re-intubation, was associated with lower intensive care unit mortality (adjusted odds ratio = 0.31 [95%CI: 0.12-0.82], p = 0.019) and similar hospital mortality (adjusted odds ratio = 1.01 [95%CI: 0.43-2.33], p = 0.99). The posterior probability that NIV reduced intensive care unit mortality was > 90% across all priors. The posterior probability that NIV did not increase hospital mortality was 44% under a noninformative prior, 47% under a skeptical prior, and 39% under a pessimistic prior.

Conclusion: Rescue NIV for post-extubation respiratory failure is associated with high failure rates; however, when applied with well-defined criteria for reintubation, it does not appear to be clearly associated with increases in hospital mortality. A randomized trial to re-evaluate the efficacy of rescue NIV for post-extubation respiratory failure is warranted.

Clinical trial registration: Registered at clinicaltrials.gov (NCT02107183) on April 8th, 2014.

Keywords: Noninvasive ventilation; Post-extubation respiratory failure; Weaning.

Fig. 1

Study flow diagram

Fig. 2

Kaplan Meier tables depicting the cumulative proportion of patients experiencing rescue NIV failure in the intensive care unit

Fig. 3

Kaplan Meier tables depicting the cumulative proportion of patients discharged alive from the intensive care unit (left) and patients’ survival to hospital discharge (right)

Fig. 4

Forest plots of hospital and intensive care unit mortality across predefined subgroups. Each point represents the odds ratio for mortality (hospital, left panel; intensive care unit, right panel) associated with rescue NIV versus direct reintubation, with 95% confidence intervals. Results were consistent across all subgroups, with all interaction p-values > 0.05. Shaded background colors indicate clinical domains: blue for patient-related baseline characteristics, green for post-extubation management strategy, and red for clinical features of post-extubation respiratory failure

Fig. 5

Probability distributions for the expected effect of rescue NIV for ICU and hospital mortality under noninformative (mean log odds 0, standard deviation 2.5), skeptical (mean log odds 0, standard deviation 1), and pessimistic (mean log odds 0.7, standard deviation 1) priors. The pessimistic prior was selected based on a previous study by Esteban et al., which suggested harm on hospital mortality by rescue NIV (a relative risk of 1.78, corresponding to an odds ratio of approximately 2 and log odds of 0.7) [14]