OLA strategy for ARDS: Its effect on mortality depends on achieved recruitment (PaO2/FiO2) and mechanical power. Systematic review and meta-analysis with meta-regression

Abstract

Objective: The "Open Lung Approach" (OLA), that includes high levels of positive end-expiratory pressure coupled with limited tidal volumes, is considered optimal for adult patients with ARDS. However, many previous meta-analyses have shown only marginal benefits of OLA on mortality but with statistical heterogeneity. It is crucial to identify the most likely moderators of this effect. To determine the effect of OLA strategy on mortality of ventilated ARDS patients. We hypothesized that the degree of recruitment achieved in the control group (PaO₂/FiO₂ ratio on day 3 of ventilation), and the difference in Mechanical Power (MP) or Driving Pressure (DP) between experimental and control groups will be the most likely sources of heterogeneity.

Design: A Systematic Review and Meta-analysis was performed according to PRISMA statement and registered in PROSPERO database. We searched only for randomized controlled trials (RCTs). GRADE guidelines were used for rating the quality of evidence. Publication bias was assessed. For the Meta-analysis, we used a Random Effects Model. Sources of heterogeneity were explored with Meta-Regression, using a priori proposed set of possible moderators. For model comparison, Akaike's Information Criterion with the finite sample correction (AICc) was used.

Setting: Not applicable.

Patients: Fourteen RCTs were included in the study.

Interventions: Not applicable.

Main variables of interest: Not applicable.

Results: Evidence of publication bias was detected, and quality of evidence was downgraded. Pooled analysis did not show a significant difference in the 28-day mortality between OLA strategy and control groups. Overall risk of bias was low. The analysis detected statistical heterogeneity. The two "best" explicative meta-regression models were those that used control PaO₂/FiO₂ on day 3 and difference in MP between experimental and control groups. The DP and MP models were highly correlated.

Conclusions: There is no clear benefit of OLA strategy on mortality of ARDS patients, with significant heterogeneity among RCTs. Mortality effect of OLA is mediated by lung recruitment and mechanical power.

Keywords: Acute Respiratory Distress Syndrome; Estrategia open-lung; Lung recruitment; Mechanical power; Open lung; Positive end-expiratory pressure; Potencia mecánica; Presión positiva teleespiratoria; Reclutamiento pulmonar; Síndrome de distrés respiratorio agudo.