Meta-analysis of controlled trials of ventilator therapy in acute lung injury and acute respiratory distress syndrome: an alternative perspective

Abstract

Objective: The role of protective ventilation in acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) is controversial. Evidence was sought from published randomised trials for a consistent treatment effect of protective ventilation and any covariate modification. Design: Meta-analysis of protective ventilation trials in ALI/ ARDS and meta-regression of covariates on treatment effect (log odds ratio), with respect to 28-day mortality. Heterogeneity impact on the meta-analysis was assessed by the H statistic (substantial impact, >1.5) and graphical analysis. Five trials with a total of 1,202 patients were considered. Measurements and results: Average 28-day mortality was 0.40 in the treatment group (protective ventilation, n=605) vs. 0.46 in the control group (control ventilation, n=597). The treatment effect (odds ratio) was: fixed-effects, 0.71 (95% CI 0.56–0.91, p=0.006; heterogeneity, p=0.06) and random effects: 0.80 (95% CI 0.49–1.31, p=0.37). Heterogeneity impact (H statistic=1.50) was adjudged as modest. The treatment effect was significant and (a) favoured protective ventilation for a tidal volume less than 7.7 ml/kg predicted (treatment group) and a mean plateau pressure of 30 cmH2O or higher (control group) but was not influenced by plateau pressure 21– 30 cmH2O (treatment group) and (b) depended upon plateau pressure difference greater than 5–7 cmH2O between protective ventilation and standard ventilation. Conclusions: Overall treatment effect estimate favoured protective ventilation but did not achieve statistical significance. Protective ventilation depended upon threshold levels of tidal volume, plateau pressure, and plateau pressure difference.