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Meta-Analysis
. 2021 Mar 30;3(3):CD009098.
doi: 10.1002/14651858.CD009098.pub3.

High versus low positive end-expiratory pressure (PEEP) levels for mechanically ventilated adult patients with acute lung injury and acute respiratory distress syndrome

Roberto Santa Cruz  1   2 , Fernando Villarejo  3 , Celica Irrazabal  4 , Agustín Ciapponi  5
Affiliations
Meta-Analysis

High versus low positive end-expiratory pressure (PEEP) levels for mechanically ventilated adult patients with acute lung injury and acute respiratory distress syndrome

Roberto Santa Cruz et al. Cochrane Database Syst Rev. .

Abstract

Background: 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.

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

Search methods: 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.

Selection criteria: 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.

Data collection and analysis: 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 We contacted investigators to identify additional published and unpublished studies.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.

Main results: 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.

Authors' conclusions: 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.

Trial registration: ClinicalTrials.gov NCT04012073 NCT03589482.

PubMed Disclaimer

Conflict of interest statement

Roberto Santa Cruz: none known.

Fernando Villarejo: none known.

Celica Irrazabal: none known.

Agustin Ciapponi: none known.

Figures

1
1
Flow diagram of selection of trials included in the meta‐analysis.
2
2
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
3
3
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
4
4
Forest plot of comparison: 1 High versus low levels of PEEP, outcome: 1.1 Mortality before hospital discharge (main analysis).
1.1
1.1. Analysis
Comparison 1: High versus low levels of PEEP, Outcome 1: Mortality before hospital discharge
1.2
1.2. Analysis
Comparison 1: High versus low levels of PEEP, Outcome 2: Oxygen efficiency (PaO₂/FIO₂) Day 1
1.3
1.3. Analysis
Comparison 1: High versus low levels of PEEP, Outcome 3: Oxygen efficiency (PaO₂/FIO₂) Day 3
1.4
1.4. Analysis
Comparison 1: High versus low levels of PEEP, Outcome 4: Oxygen efficiency (PaO₂/FIO₂) Day 7
1.5
1.5. Analysis
Comparison 1: High versus low levels of PEEP, Outcome 5: Oxygen efficiency (PaO₂/FIO₂) Day 1. Subgroup: patients with ARDS
1.6
1.6. Analysis
Comparison 1: High versus low levels of PEEP, Outcome 6: Oxygen efficiency (PaO₂/FIO₂) Day 3. Subgroup: patients with ARDS
1.7
1.7. Analysis
Comparison 1: High versus low levels of PEEP, Outcome 7: Barotrauma
1.8
1.8. Analysis
Comparison 1: High versus low levels of PEEP, Outcome 8: Barotrauma. Subgroup: patients with ARDS
1.9
1.9. Analysis
Comparison 1: High versus low levels of PEEP, Outcome 9: Ventilator‐free days (only studies reporting means)
1.10
1.10. Analysis
Comparison 1: High versus low levels of PEEP, Outcome 10: Ventilator‐free days. Subgroup: patients with ARDS
1.11
1.11. Analysis
Comparison 1: High versus low levels of PEEP, Outcome 11: Mortality before hospital discharge (studies comparing high vs low levels of PEEP with or without other interventions)
1.12
1.12. Analysis
Comparison 1: High versus low levels of PEEP, Outcome 12: Mortality within 28 days of randomisation
1.13
1.13. Analysis
Comparison 1: High versus low levels of PEEP, Outcome 13: Mortality before hospital discharge. Subgroup: patients with ARDS
1.14
1.14. Analysis
Comparison 1: High versus low levels of PEEP, Outcome 14: Mortality before hospital discharge. Subgroup: PEEP administered according to mechanical characteristics of the lung
1.15
1.15. Analysis
Comparison 1: High versus low levels of PEEP, Outcome 15: Mortality before hospital discharge. Subgroup: PEEP administered according to FIO₂ and PaO₂
1.16
1.16. Analysis
Comparison 1: High versus low levels of PEEP, Outcome 16: Mortality before hospital discharge. Subgroup: high PEEP and low tidal volume vs low PEEP and high tidal volume
1.17
1.17. Analysis
Comparison 1: High versus low levels of PEEP, Outcome 17: Mortality before hospital discharge. Subgroup (post‐hoc): high PEEP with previous recruitment manoeuvre
1.18
1.18. Analysis
Comparison 1: High versus low levels of PEEP, Outcome 18: Mortality before hospital discharge. Subgroup (post‐hoc): decremental PEEP with previous recruitment manoeuvre
1.19
1.19. Analysis
Comparison 1: High versus low levels of PEEP, Outcome 19: Mortality before hospital discharge. Sensitivity analysis: exclusion of studies at unclear and high risk of bias
1.20
1.20. Analysis
Comparison 1: High versus low levels of PEEP, Outcome 20: Mortality before hospital discharge. Sensitivity analysis: exclusion of studies with large effect sizes
See this image and copyright information in PMC

Update of

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