Efficacy of Higher Positive End-Expiratory Pressure Ventilation Strategy in Patients With Acute Respiratory Distress Syndrome: A Systematic Review and Meta-Analysis

Abstract

Previous systematic reviews and meta-analyses assessing the pooled effects of higher positive end-expiratory pressure (PEEP) failed to show significantly reduced mortality in patients with acute respiratory distress syndrome (ARDS). Some new randomized controlled trials (RCTs) have been reported and an updated systematic review is needed to evaluate the use of higher PEEP in patients with ARDS. We searched MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Igaku-Chuo-Zasshi, ICTRP, the National Institute of Health Clinical Trials Register, and the reference list of recent guidelines. We included RCTs to compare the higher PEEP ventilation strategy with the lower strategy in patients with ARDS. Two authors independently assessed the eligibility of the studies and extracted the data. The primary outcomes were 28-day mortality. The GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) methodology was used to evaluate the certainty of the evidence. Among the 6530 screened records, 16 randomized trials involving 4150 patients were included in our meta-analysis. When comparing higher PEEP versus lower PEEP, the pooled risk ratio (RR) for 28-day mortality was 0.85 (15 studies, n=4108, 95% CI 0.72 to 1.00, I²=58%, low certainty of evidence). Subgroup analysis by study participants with a low tidal volume (LTV) strategy showed an interaction (P for interaction, 0.001). Our study showed that in patients with ARDS, the use of higher PEEP did not significantly reduce 28-day mortality compared to the use of lower PEEP.

Keywords: acute respiratory distress syndrome [ards]; ards (acute respiratory distress syndrome); invasive mechanical ventilation; peep; peep - positive end expiratory pressure; severe ards; systematic review and meta analysis; ventilator induced lung injury.

Figure 1. PRISMA flow diagram

^* One record did not describe post-intervention PEEP levels, and one record was of unclear design. ^† Two records were interim analyses reports, one record was the first report of Amato 1998 [8]. PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-Analyses; CENTRAL: Cochrane Central Register of Controlled Trials; CINAHL: Cumulative Index to Nursing and Allied Health Literature; ICTRP: International Clinical Trials Registry Platform; PEEP: positive end-expiratory pressure; ECMO: extracorporeal membrane oxygenation

Figure 2. Risk of bias summary

Figure 3. Funnel plot for mortality

SE (log [RR]): standard error (log [risk ratio]); RR: risk ratio A: 28-day mortality; B: Longest follow-up mortality

Figure 4. Forest plot of the comparison of higher PEEP ventilation versus lower PEEP ventilation for mortality

PEEP: positive end-expiratory pressure; CI: confidence interval; M–H: Mantel-Haenszel method (A) 28-day mortality. Data extracted from the Kaplan-Meier curve at 28 days; Brower 2004 [3], and Villar 2006 [9], in-hospital mortality; Hodgson 2011 [24], and 28-day mortality; the other studies. (B) The longest follow-up mortality. Data extracted from the Kaplan-Meier curve at 28 days; Villar 2006 [9], 28-day mortality; Ranieri 1999 [21], Long 2006 [22], Li 2017 [27], Nguyen 2019 [13], and Salem 2020 [14], 60-day mortality; Brower 2004 [3], Mercat 2008 [5], and Kacmareg 2016 [25], six-month mortality; Talmor 2008 [23], ART 2017 [26], and Hodgson 2019 [24], and in-hospital mortality; other studies.

Figure 5. Forest plot of the comparison of higher PEEP ventilation versus lower PEEP ventilation for P/F ratio at day1 and VFD up to 28 days.

CI, confidence interval; IV, inverse variance; PEEP: positive end-expiratory pressure. (A): PaO₂/FiO₂ ratio on day 1; (B) Ventilator-free days up to 28 days.

Figure 6. Forest plot of the comparison of higher PEEP ventilation versus lower PEEP ventilation for the length of hospital stay and barotrauma

PEEP: positive end-expiratory pressure; CI: confidence interval; IV: inverse variance; M–H: Mantel–Haenszel method. (A) Length of hospital stay; (B) Barotrauma.