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 10-15 mL/kg among patients with ARDS. METHODS: Systematic review and meta-analysis of clinical trials investigating LTV mechanical ventilation strategies. We used random effects models to evaluate 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 meta-regression of tidal volume gradient achieved between intervention and control groups on mortality effect estimates. We used GRADE methodology to determine the quality of evidence. RESULTS: Seven randomized trials involving 1481 patients met eligibility criteria for this review. Mortality was not significantly lower for patients receiving a LTV strategy (33.6%) as compared to control strategies (40.4%) [RR 0.87 (95% CI 0.70-1.08), I2 = 46%], nor did an LTV strategy significantly decrease barotrauma or ventilator-free days when compared to a lower PEEP strategy. Quality of evidence for clinical outcomes was downgraded for imprecision. Meta-regression showed a significant inverse association between larger tidal volume gradient between LTV and control groups and log odds ratios for mortality (β -0.1587, p=0.0022). Sensitivity analysis including trials that protocolized a LTV/high PEEP co-intervention showed lower mortality associated with LTV [9 trials and 1629 patients; RR 0.80, (95% CI 0.66-0.98), I2 =46%]. Compared with trials not using a high PEEP co-intervention, 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.