Meta Analysis Prone positioning reduces mortality from acute respiratory distress syndrome in low tidal volume era: a meta-analysis
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Summary
Posted By:	Pip Heighes
E-Mail:	pheighes@med.usyd.edu.au
Posted Date:	25/11/14
Title:	Prone positioning reduces mortality from acute respiratory distress syndrome in low tidal volume era: a meta-analysis
Authors:	Beitler J.R, Shaefi S, Montesi S.B, Devlin A, Loring S.H, Talmor D, Malhotra A.
Reference:	Intensive Care Med 2014 Mar; 40(3): 332-41. DOI 10.1007/s00134-013-3194-3.
Link:	Click here for a direct link to the paper. A password may be required for access to fulltext.
Abstract:	PURPOSE: Prone positioning for ARDS has been performed for decades without definitive evidence of clinical benefit. A recent multicenter trial demonstrated for the first time significantly reduced mortality with prone positioning. This meta-analysis was performed to integrate these findings with existing literature and test whether differences in tidal volume explain conflicting results among randomized trials. METHODS: Studies were identified using MEDLINE, EMBASE, Cochrane Register of Controlled Trials, LILACS, and citation review. Included were randomized trials evaluating the effect on mortality of prone versus supine positioning during conventional ventilation for ARDS. The primary outcome was risk ratio of death at 60 days meta-analyzed using random effects models. Analysis stratified by high (>8 ml/kg predicted body weight) or low (¡Ü 8 ml/kg PBW) mean baseline tidal volume was planned a priori. RESULTS: Seven trials were identified including 2,119 patients, of whom 1,088 received prone positioning. Overall, prone positioning was not significantly associated with the risk ratio of death (RR 0.83; 95% CI 0.68-1.02; p = 0.073; I (2) = 64%). When stratified by high or low tidal volume, prone positioning was associated with a significant decrease in RR of death only among studies with low baseline tidal volume (RR 0.66; 95% CI 0.50-0.86; p = 0.002; I (2) = 25%). Stratification by tidal volume explained over half the between-study heterogeneity observed in the unstratified analysis. CONCLUSIONS: Prone positioning is associated with significantly reduced mortality from ARDS in the low tidal volume era. Substantial heterogeneity across studies can be explained by differences in tidal volume.
Are the Results Valid?
1. Did the overview address a focused clinical question?
	Yes. Following the publication of a recent RCT by Guerin et al (N Engl J Med. 2013 May 20) that found prone positioning reduced risk of death by half, the authors hypothesised that the benefits of prone positioning in ARDS are only present when damaging high tidal volumes are avoided.
2. Were the criteria used to select articles for inclusion appropriate?
	Yes, the authors included only RCTs in adult patients meeting the Berlin definition for ARDS in which prone positioning was compared to supine positioning during conventional mechanical ventilation. Studies that did not report mortality were excluded.
3. Is it unlikely that important, relevant studies were missed?
	It is unlikely important relevant studies were missed. A thorough computerised literature search using appropriate MeSH terms and keywords of major databases was conducted (Medline, EMBASE, LILACS, Cochrane Central Register of Controlled Trials). It is not stated whether language restrictions were applied.
4. Was the validity of the included studies appraised?
	Study quality was evaluated by considering allocation concealment, completeness of follow-up, blinded analysis, crossover between study arms, post-hoc exclusions, and early trial discontinuation.
5. Were assessments of studies reproducible?
	Yes, the findings of the quality assessments are reported in results section of manuscript.
6. Were the results similar from study to study?
	There was minimal heterogeneity (I2 = 25%) for the primary hypotheses tested as specified a priori by the authors that prone positioning only reduces mortality when injurious high tidal volumes are avoided.
What are the Results?
1. What are the overall results of the overview?
	After stratification, prone positioning was associated with a significant decrease in risk ratio of death for studies that used low tidal volume ventilation (RR=0.66; 95% CI 0.50-0.86; p=0.002).
2. How precise were the results?
	The 95% confidence interval based around the results for the primary outcome was precise (see results above).
Will the Results Help Me In Caring For My Patients?
1. Can the results be applied to my patient care
	Yes, prone positioning can be implemented in the majority of ICU's. No special equipment is required to turn patients prone. If staff are not experienced in proning a useful training video is available at www.nejm.org/doi/full/10.1056/NEJMoa1214103.
2. Were all clinically important outcomes considered?
	The authors investigated other potential sources of heterogenity amongst RCTs of proning such as duration (hours) of prone positioning and illness severity. Clinical outcomes that are of interest such as rates of accidental tube removal, incidence of pressure areas etc were not investigated in this meta-analysis.
3. Are the benefits worth the harms and costs?
	The authors do not investigate harms and costs in their review, however considering the potential reduction in mortality versus the minimal costs associated with proning, it is definitely worth considering as an intervention in ARDS patients with low tidal volume ventilation.
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