BACKGROUND: Acute hypoxaemia de novo or on a background of chronic hypoxaemia is a common reason for admission to intensive care and for provision of mechanical ventilation. Various refinements of mechanical ventilation or adjuncts are employed to improve patient outcomes. Mortality from acute respiratory distress syndrome, one of the main contributors to the need for mechanical ventilation for hypoxaemia, remains approximately 40%. Ventilation in the prone position may improve lung mechanics and gas exchange and could improve outcomes.

OBJECTIVES: The objectives of this review are (1) to ascertain whether prone ventilation offers a mortality advantage when compared with traditional supine or semi recumbent ventilation in patients with severe acute respiratory failure requiring conventional invasive artificial ventilation, and (2) to supplement previous systematic reviews on prone ventilation for hypoxaemic respiratory failure in an adult population.

SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2014, Issue 1), Ovid MEDLINE (1950 to 31 January 2014), EMBASE (1980 to 31 January 2014), the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1982 to 31 January 2014) and Latin American Caribbean Health Sciences Literature (LILACS) (1992 to 31 January 2014) in Ovid MEDLINE for eligible randomized controlled trials. We also searched for studies by handsearching reference lists of relevant articles, by contacting colleagues and by handsearching published proceedings of relevant journals. We applied no language constraints, and we reran the searches in CENTRAL, MEDLINE, EMBASE, CINAHL and LILACS in June 2015. We added five new studies of potential interest to the list of "Studies awaiting classification" and will incorporate them into formal review findings during the review update.

SELECTION CRITERIA: We included randomized controlled trials (RCTs) that examined the effects of prone position versus supine/semi recumbent position during conventional mechanical ventilation in adult participants with acute hypoxaemia.

DATA COLLECTION AND ANALYSIS: Two review authors independently reviewed all trials identified by the search and assessed them for suitability, methods and quality. Two review authors extracted data, and three review authors reviewed the data extracted. We analysed data using Review Manager software and pooled included studies to determine the risk ratio (RR) for mortality and the risk ratio or mean difference (MD) for secondary outcomes; we also performed subgroup analyses and sensitivity analyses.

MAIN RESULTS: We identified nine relevant RCTs, which enrolled a total of 2165 participants (10 publications). All recruited participants suffered from disorders of lung function causing moderate to severe hypoxaemia and requiring mechanical ventilation, so they were fairly comparable, given the heterogeneity of specific disease diagnoses in intensive care. Risk of bias, although acceptable in the view of the review authors, was inevitable: Blinding of participants and carers to treatment allocation was not possible (face-up vs face-down).Primary analyses of short- and longer-term mortality pooled from six trials demonstrated an RR of 0.84 to 0.86 in favour of the prone position (PP), but findings were not statistically significant: In the short term, mortality for those ventilated prone was 33.4% (363/1086) and supine 38.3% (395/1031). This resulted in an RR of 0.84 (95% confidence interval (CI) 0.69 to 1.02) marginally in favour of PP. For longer-term mortality, results showed 41.7% (462/1107) for prone and 47.1% (490/1041) for supine positions, with an RR of 0.86 (95% CI 0.72 to 1.03). The quality of the evidence for both outcomes was rated as low as a result of important potential bias and serious inconsistency.Subgroup analyses for mortality identified three groups consistently favouring PP: those recruited within 48 hours of meeting entry criteria (five trials; 1024 participants showed an RR of 0.75 (95% CI 0.59 to 94)); those treated in the PP for 16 or more hours per day (five trials; 1005 participants showed an RR of 0.77 (95% CI 0.61 to 0.99)); and participants with more severe hypoxaemia at trial entry (six trials; 1108 participants showed an RR of 0.77 (95% CI 0.65 to 0.92)). The quality of the evidence for these outcomes was rated as moderate as a result of potentially important bias.Prone positioning appeared to influence adverse effects: Pressure sores (three trials; 366 participants) with an RR of 1.37 (95% CI 1.05 to 1.79) and tracheal tube obstruction with an RR of 1.78 (95% CI 1.22 to 2.60) were increased with prone ventilation. Reporting of arrhythmias was reduced with PP, with an RR of 0.64 (95% CI 0.47 to 0.87).

AUTHORS' CONCLUSIONS: We found no convincing evidence of benefit nor harm from universal application of PP in adults with hypoxaemia mechanically ventilated in intensive care units (ICUs). Three subgroups (early implementation of PP, prolonged adoption of PP and severe hypoxaemia at study entry) suggested that prone positioning may confer a statistically significant mortality advantage. Additional adequately powered studies would be required to confirm or refute these possibilities of subgroup benefit but are unlikely, given results of the most recent study and recommendations derived from several published subgroup analyses. Meta-analysis of individual patient data could be useful for further data exploration in this regard. Complications such as tracheal obstruction are increased with use of prone ventilation. Long-term mortality data (12 months and beyond), as well as functional, neuro-psychological and quality of life data, are required if future studies are to better inform the role of PP in the management of hypoxaemic respiratory failure in the ICU.

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