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Noninvasive Ventilation and Survival in Acute Care Settings: A Comprehensive Systematic Review and Metaanalysis of Randomized Controlled Trials*

Cabrini, Luca MD; Landoni, Giovanni MD; Oriani, Alessandro MD; Plumari, Valentina P. MD; Nobile, Leda MD; Greco, Massimiliano MD; Pasin, Laura MD; Beretta, Luigi MD; Zangrillo, Alberto MD

doi: 10.1097/CCM.0000000000000819
Review Articles

Objective: Noninvasive ventilation is increasingly applied to prevent or treat acute respiratory failure, but its benefit on survival is still controversial for many indications. We performed a metaanalysis of randomized controlled trials focused on the effect of noninvasive ventilation on mortality.

Data Sources: BioMedCentral, PubMed, Embase, and the Cochrane Central Register of clinical trials (updated December 31, 2013) were searched.

Study Selection: We included all the randomized controlled trials published in the last 20 years performed in adults, reporting mortality, comparing noninvasive ventilation to any other treatment for prevention or treatment of acute respiratory failure or as a tool allowing an earlier extubation. Studies with unclear methodology, comparing two noninvasive ventilation modalities, or in palliative settings were excluded.

Data Extraction: We extracted data on mortality, study design, population, clinical setting, comparator, and follow-up duration.

Data Synthesis: Seventy-eight studies were analyzed. Noninvasive ventilation was associated with a reduction in mortality (12.6% in the noninvasive ventilation group vs 17.8% in the control arm; risk ratio = 0.73 [0.66–0.81]; p < 0.001; number needed to treat = 19 with 7,365 patients included) at the longest available follow-up. Mortality was reduced when noninvasive ventilation was used to treat (14.2% vs 20.6%; risk ratio = 0.72; p < 0.001; number needed to treat = 16, with survival improved in pulmonary edema, chronic obstructive pulmonary disease exacerbation, acute respiratory failure of mixed etiologies, and postoperative acute respiratory failure) or to prevent acute respiratory failure (5.3% vs 8.3%; risk ratio = 0.64 [0.46–0.90]; number needed to treat = 34, with survival improved in postextubation ICU patients), but not when used to facilitate an earlier extubation. Overall results were confirmed for hospital mortality. Patients randomized to noninvasive ventilation maintained the survival benefit even in studies allowing crossover of controls to noninvasive ventilation as rescue treatment.

Conclusions: This comprehensive metaanalysis suggests that noninvasive ventilation improves survival in acute care settings. The benefit could be lost in some subgroups of patients if noninvasive ventilation is applied late as a rescue treatment. Whenever noninvasive ventilation is indicated, an early adoption should be promoted.

Supplemental Digital Content is available in the text.

Department of Anesthesia and Intensive Care, IRCCS San Raffaele Hospital, Vita-Salute University, Milan, Italy.

* See also p. 927.

All authors developed the concept of this study. Drs. Landoni, Pasin, Beretta, and Zangrillo developed the search strategy. Drs. Cabrini, Oriani, Plumari, and Nobile retrieved the studies and extracted the data. Drs. Landoni and Greco did the statistical analyses. The first draft of the article was written by Drs. Cabrini and Pasin and was thoroughly revised by Drs. Beretta and Zangrillo.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (

Supported, in part, by departmental funds. The Department of Anesthesia and Intensive Care had no role in study design, data collection, data analysis, data interpretation, or writing of the report.

Dr. Cabrini consulted for Medival (received honoraria for consultancy) and disclosed a patent (applied for patent in a noninvasive ventilation [NIV] device). Dr. Landoni has disclosed a patent (applied for patent in a NIV device). The remaining authors have disclosed that they do not have any potential conflicts of interest.

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