JOURNAL ARTICLE
META-ANALYSIS
REVIEW
SYSTEMATIC REVIEW
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High versus low positive end-expiratory pressure (PEEP) levels for mechanically ventilated adult patients with acute lung injury and acute respiratory distress syndrome.

BACKGROUND: Mortality in patients with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) remains high. These patients require mechanical ventilation, but this modality has been associated with ventilator-induced lung injury. High levels of positive end-expiratory pressure (PEEP) could reduce this condition and improve patient survival.

OBJECTIVES: To assess the benefits and harms of high versus low levels of PEEP in patients with ALI and ARDS.

SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, 2013, Issue 4), MEDLINE (1950 to May 2013), EMBASE (1982 to May 2013), LILACS (1982 to May 2013) and SCI (Science Citation Index). We used the Science Citation Index to find references that have cited the identified trials. We did not specifically conduct manual searches of abstracts of conference proceedings for this review. We also searched for ongoing trials (www.trialscentral.org; www.clinicaltrial.gov and www.controlled-trials.com).    

SELECTION CRITERIA: We included randomized controlled trials that compared the effects of two levels of PEEP in ALI and ARDS participants who were intubated and mechanically ventilated in intensive care for at least 24 hours.

DATA COLLECTION AND ANALYSIS: Two review authors assessed the trial quality and extracted data independently. We contacted investigators to identify additional published and unpublished studies. 

MAIN RESULTS: We included seven studies that compared high versus low levels of PEEP (2565 participants). In five of the studies (2417 participants), a comparison was made between high and low levels of PEEP with the same tidal volume in both groups, but in the remaining two studies (148 participants), the tidal volume was different between high- and low-level groups. We saw evidence of risk of bias in three studies, and the remaining studies fulfilled all criteria for adequate trial quality.In the main analysis, we assessed mortality occurring before hospital discharge only in those studies that compared high versus low PEEP with the same tidal volume in both groups. With the three studies that were included, the meta-analysis revealed no statistically significant differences between the two groups (relative risk (RR) 0.90, 95% confidence interval (CI) 0.81 to 1.01), nor was any statistically significant difference seen in the risk of barotrauma (RR 0.97, 95% CI 0.66 to 1.42). Oxygenation was improved in the high-PEEP group, although data derived from the studies showed a considerable degree of statistical heterogeneity. The number of ventilator-free days showed no significant difference between the two groups. Available data were insufficient to allow pooling of length of stay in the intensive care unit (ICU). The subgroup of participants with ARDS showed decreased mortality in the ICU, although it must be noted that in two of the three included studies, the authors used a protective ventilatory strategy involving a low tidal volume and high levels of PEEP.

AUTHORS' CONCLUSIONS: Available evidence indicates that high levels of PEEP, as compared with low levels, did not reduce mortality before hospital discharge. The data also show that high levels of PEEP produced no significant difference in the risk of barotrauma, but rather improved participants' oxygenation to the first, third, and seventh days. This review indicates that the included studies were characterized by clinical heterogeneity.  

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