Low tidal volume versus non–volume-limited strategies for patients with acute respiratory distress syndrome: A systematic review and meta-analysis

Rationale: Trials investigating use of lower tidal volumes and inspiratory pressures for patients with acute respiratory distress syndrome (ARDS) have shown mixed results. Objectives: To compare clinical outcomes of mechanical ventilation strategies that limit tidal volumes and inspiratory pressures (LTV) to strategies with tidal volumes of 10 to 15 ml/kg among patients with ARDS. Methods: This is a systematic review and meta-analysis of clinical trials investigating LTV mechanical ventilation strategies. We used random effects models to evaluate the effect of LTV on 28-day mortality, organ failure, ventilator-free days, barotrauma, oxygenation, and ventilation. Our primary analysis excluded trials for which the LTV strategy was combined with the additional strategy of higher positive end-expiratory pressure (PEEP), but these trials were included in a stratified sensitivity analysis. We performed metaregression of tidal volume gradient achieved between intervention and control groups on mortality effect estimates. We used Grading of Recommendations Assessment, Development, and Evaluation methodology to determine the quality of evidence. Results: Seven randomized trials involving 1,481 patients met eligibility criteria for this review. Mortality was not significantly lower for patients receiving an LTV strategy (33.6%) as compared with control strategies (40.4%) (relative risk [RR], 0.87; 95% confidence interval [CI], 0.70–1.08; heterogeneity statistic I ² = 46%), nor did an LTV strategy significantly decrease barotrauma or ventilator-free days when compared with a lower PEEP strategy. Quality of evidence for clinical outcomes was downgraded for imprecision. Metaregression showed a significant inverse association between larger tidal volume gradient between LTV and control groups and log odds ratios for mortality (β, 20.1587; P = 0.0022). Sensitivity analysis including trials that protocolized an LTV/high PEEP cointervention showed lower mortality associated with LTV (nine trials and 1,629 patients; RR, 0.80; 95% CI, 0.66–0.98; I ² = 46%). Compared with trials not using a high PEEP cointervention, trials using a strategy of LTV combined with high PEEP showed a greater mortality benefit (RR, 0.58; 95% CI, 0.41–0.82; P for interaction = 0.05). Conclusions: The trend toward lower mortality with LTV ventilation in the primary analysis and the significant relationship between the degree of tidal volume reduction and the mortality effect together suggest, but do not prove, that LTV ventilation improves mortality among critically ill adults with ARDS.