Effects of early extubation followed by noninvasive ventilation versus standard extubation on the duration of invasive mechanical ventilation in hypoxemic non-hypercapnic patients: a systematic review and individual patient data meta-analysis of randomized controlled trials

Abstract

Background: Usefulness of noninvasive ventilation (NIV) in weaning patients with non-hypercapnic hypoxemic acute respiratory failure (hARF) is unclear. The study aims to assess in patients with non-hypercapnic hARF, the efficacy of NIV after early extubation, compared to standard weaning.

Methods: In this individual patient data meta-analysis, we searched EMBASE, Medline and Cochrane Central Register of Controlled Trials to identify potentially eligible randomized controlled trials published from database inception to October 2020. To be eligible, studies had to include patients treated with NIV after early extubation and compared to conventional weaning in adult non-hypercapnic hARF patients. Anonymized individual patient data from eligible studies were provided by study investigators. Using one-step and two-step meta-analysis models we tested the difference in total days spent on invasive ventilation.

Results: We screened 1605 records. Six studies were included in quantitative synthesis. Overall, 459 participants (mean [SD] age, 62 [15] years; 269 [59%] males) recovering from hARF were included in the analysis (233 in the intervention group and 226 controls). Participants receiving NIV had a shorter duration of invasive mechanical ventilation compared to control group (mean difference, - 3.43; 95% CI - 5.17 to - 1.69 days, p < 0.001), a shorter duration of total days spent on mechanical ventilation (mean difference, - 2.04; 95% CI - 3.82 to - 0.27 days, p = 0.024), a reduced risk of ventilatory associated pneumonia (odds ratio, 0.24; 95% CI 0.08 to 0.71, p = 0.014), a reduction of time spent in ICU (time ratio, 0.81; 95% CI 0.68 to 0.96, p = 0.015) and in-hospital (time ratio, 0.81; 95% CI 0.69 to 0.95, p = 0.010), with no difference in ICU mortality.

Conclusions: Although primary studies are limited, using an individual patient data metanalysis approach, NIV after early extubation appears useful in reducing total days spent on invasive mechanical ventilation.

Trial registration: The protocol was registered to PROSPERO database on 12/06/2019 and available at PROSPERO website inserting the study code i.e., CRD42019133837.

Keywords: Hypoxemic acute respiratory failure; Noninvasive ventilation; Weaning.

Conflict of interest statement

PN reports, outside the submitted work, non-financial support from Draeger and Intersurgical SpA, personal fees from, Resmed, Philips, Novartis, MSD, Getinge and, Draeger. In addition, PN has a patent 102020000008305 pending to Università di Padova, and a patent 102016000114357 with royalties paid from Intersurgical S.p.A. GDP is supported as a NIHR Senior Investigator and by NIHR Applied Research Collaboration (ARC) West Midlands. FL contributed to the development of a new device (European Patent number EP3320941). RV, AP, DM, GC, MF, RPA, MC, FM, HQ, FDC, FBA declare no competing interests.

Figures

Fig. 1

PRISMA-IPD flow diagram. The following flow diagram summarizes the selection process of the randomized control trials included in the systematic review, from the identification to the final phase of data analysis. IPD individual patient data, PICO patient intervention comparison outcome

Fig. 2

Results of 2-stage IPD-MA. a Mean i-MV time (p value = 0.006); b mean total ventilation time (p value = 0.13); c occurrence of VAP (p value = 0.03); d time to ICU discharge (p value = 0.09); e time to ICU death (p value = 0.222), f time to hospital discharge (p value = 0.009). CI confidence interval, ICU intensive care unit, i-MV invasive mechanical ventilation, IPD-MA individual patient data meta-analysis, VAP ventilator associated pneumonia