We wanted to find evidence from randomised controlled trials on the benefits and harms of high versus low levels of lung positive end-expiratory pressure (PEEP). We wanted to focus on adult patients with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). These patients have low oxygen levels in the blood and therefore reduced tissue oxygenation.
PEEP is pressure in the lungs (alveolar pressure) at the end of each breath (expiration). In mechanically ventilated patients, PEEP works against passive emptying of the lung and collapse of air sacs (alveoli). Collapse of air sacs can lead to incomplete inflation of the lung on the next breath and reduced oxygenation. PEEP is used to improve oxygenation.
ALI and ARDS are caused by leakage of fluid in the lung and local inflammation that can cause widespread alveolar damage and a build-up of fluid in the lungs. The build-up of fluid can be seen on chest X-rays. Alveolar damage can lead to later scarring (fibrosis). Common causes are pneumonia infection and more general (systemic) infection, as with sepsis.
ALI and ARDS patients are placed on mechanical ventilation (delivery of positive pressure to the lungs, usually via a breathing tube). Mechanical ventilation is a method of artificial support for respiration that introduces gas into the patient's airway through an external mechanical system. Use of PEEP is one of the lung protection strategies aimed at improving oxygenation of patients and survival.
The benefits and risks of PEEP are unclear, as it could increase the risk of lung damage called barotrauma. This occurs when air leaks into the space between the lung and the chest wall (pneumothorax). This air pushes on the outside of the lung and causes it to collapse.
Evidence is current to May 2020. This review has no funding sources. We included 10 studies with 3851 participants (6 from the previous review and 4 from our updated search of the literature). In eight studies (3703 participants), a comparison was made between high and low levels of PEEP, with the same amount of air delivered to the lungs and breathed out (exhaled) with each breath (tidal volume) in each group. The other two studies used different tidal volumes for the two groups and could not be included in all of the review results.
We noted the following findings.
• Higher levels of PEEP (compared to lower levels) may make little to no difference in the number of patients who die before hospital discharge (7 studies, 3642 participants; moderate-certainty evidence).
• Blood oxygenation was improved with higher PEEP on the first, third (6 studies, over 2300 participants, both low-certainty evidence), and seventh days (5 studies, 1611 participants; moderate-certainty evidence) of studies.
• Higher levels of PEEP were not associated with barotrauma (9 studies, 3790 participants; low-certainty evidence).
• High PEEP levels did not increase the number of ventilator-free days over a 28-day time period (3 studies, 1654 participants; low-certainty evidence).
Finally, available data were insufficient to evaluate the impact of PEEP on length of stay in the intensive care unit, which is required with mechanical ventilation.
Certainty of the evidence
The highest level of certainty of evidence was moderate, and some outcomes were supported by low-certainty evidence. Patients in the different studies varied in severity of ALI or ARDS and in other clinical factors (causing heterogeneity). Different approaches were used to set and adjust PEEP levels.
Moderate-certainty evidence shows that high levels compared to low levels of PEEP do not reduce mortality before hospital discharge. Low-certainty evidence suggests that high levels of PEEP result in little to no difference in the risk of barotrauma. Low-certainty evidence also suggests that high levels of PEEP improve oxygenation up to the first and third days of mechanical ventilation, and moderate-certainty evidence indicates that high levels of PEEP improve oxygenation up to the seventh day of mechanical ventilation. As in our previous review, we found clinical heterogeneity - mainly within participant characteristics and methods of titrating PEEP - that does not allow us to draw definitive conclusions regarding the use of high levels of PEEP in patients with ALI and ARDS. Further studies should aim to determine the appropriate method of using high levels of PEEP and the advantages and disadvantages associated with high levels of PEEP in different ARDS and ALI patient populations.
In patients with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), mortality remains high. These patients require mechanical ventilation, which has been associated with ventilator-induced lung injury. High levels of positive end-expiratory pressure (PEEP) could reduce this condition and improve patient survival. This is an updated version of the review first published in 2013.
To assess the benefits and harms of high versus low levels of PEEP in adults with ALI and ARDS.
For our previous review, we searched databases from inception until 2013. For this updated review, we searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, LILACS, and the Web of Science from inception until May 2020. We also searched for ongoing trials (www.trialscentral.org; www.clinicaltrial.gov; www.controlled-trials.com), and we screened the reference lists of included studies.
We included randomised controlled trials that compared high versus low 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 risk of bias and extracted data independently. We contacted investigators to identify additional published and unpublished studies. We used standard methodological procedures expected by Cochrane.
We included four new studies (1343 participants) in this review update. In total, we included 10 studies (3851 participants). We found evidence of risk of bias in six studies, and the remaining studies fulfilled all criteria for low risk of bias. In eight studies (3703 participants), a comparison was made between high and low levels of PEEP, with the same tidal volume in both groups. In the remaining two studies (148 participants), the tidal volume was different between high- and low-level groups.
In the main analysis, we assessed mortality occurring before hospital discharge only in studies that compared high versus low PEEP, with the same tidal volume in both groups. Evidence suggests that high PEEP may result in little to no difference in mortality compared to low PEEP (risk ratio (RR) 0.97, 95% confidence interval (CI) 0.90 to 1.04; I² = 15%; 7 studies, 3640 participants; moderate-certainty evidence).
In addition, high PEEP may result in little to no difference in barotrauma (RR 1.00, 95% CI 0.64 to 1.57; I² = 63%; 9 studies, 3791 participants; low-certainty evidence). High PEEP may improve oxygenation in patients up to the first and third days of mechanical ventilation (first day: mean difference (MD) 51.03, 95% CI 35.86 to 66.20; I² = 85%; 6 studies, 2594 participants; low-certainty evidence; third day: MD 50.32, 95% CI 34.92 to 65.72; I² = 83%; 6 studies, 2309 participants; low-certainty evidence) and probably improves oxygenation up to the seventh day (MD 28.52, 95% CI 20.82 to 36.21; I² = 0%; 5 studies, 1611 participants; moderate-certainty evidence). Evidence suggests that high PEEP results in little to no difference in the number of ventilator-free days (MD 0.45, 95% CI -2.02 to 2.92; I² = 81%; 3 studies, 1654 participants; low-certainty evidence). Available data were insufficient to pool the evidence for length of stay in the intensive care unit.