Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are acute and severe conditions affecting the structure and function of the lungs that are caused by increased permeability of the alveolar-capillary barrier leading to an inflammatory injury. The mortality rate of ALI and ARDS has decreased over time and is currently reported at 43%. Patients with ALI and ARDS require mechanical ventilation, but this intervention can cause ventilator-induced lung injury. For this reason, the therapeutic target for these patients is based on lung-protective ventilation. The use of high levels of positive end-expiratory pressure (PEEP) is part of the strategy aimed at reducing ventilator-induced lung injury. PEEP is a mechanical manoeuvre that exerts a positive pressure in the lung and is used primarily to correct the hypoxaemia caused by alveolar hypoventilation. In this Cochrane review, we assess the benefits and harms of high versus low levels of PEEP in patients with ALI and ARDS. The undertaking of this review was both relevant and necessary because the optimal level of PEEP in these patients is still controversial, and available evidence indicates no difference in mortality. We included seven studies involving a total of 2565 participants and found that high levels of PEEP, as compared with low levels, did not produce a reduction in hospital mortality, although we did see a trend towards decreased mortality. We also found evidence of clinical heterogeneity among the included studies (clinical heterogeneity concerns differences in participants, interventions, and outcomes that might have an impact on results from the use of PEEP). The studies included were of moderate to good quality. We did not find a significant difference with respect to barotrauma—defined as the presence of pneumothorax on chest radiography or a chest tube insertion for known or suspected pneumothorax. We furthermore ascertained that high levels of PEEP improved participants' oxygenation up to the first, third, and seventh days. The number of ventilator-free days showed no significant difference between the two groups (the term ventilator-free days refers to the number of days between successful weaning from mechanical ventilation and day 28 after study enrolment), and available data were insufficient to allow pooling of lengths of stay in the intensive care unit. Additional trials will be required to determine which patients should receive high PEEP levels and the best means of applying this intervention.
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.
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.
To assess the benefits and harms of high versus low levels of PEEP in patients with ALI and ARDS.
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).
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.
Two review authors assessed the trial quality and extracted data independently. We contacted investigators to identify additional published and unpublished studies.
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.