Ventilation with lower tidal volumes as compared to conventional tidal volumes for patients without acute lung injury - a preventive randomized controlled trial

ABSTRACT: INTRODUCTION: Recent cohort studies have identified use of large tidal volumes as a major risk factor for development of lung injury in mechanically ventilated patients without acute lung injury (ALI). We compared the effect of conventional versus lower tidal volumes on pulmonary inflammation and development of lung injury in critically ill patients without ALI at onset of mechanical ventilation. METHODS: Randomized controlled non-blinded preventive trial comparing mechanical ventilation with tidal volumes of 10 ml versus 6 ml per kilogram of predicted body weight in critically ill patients without ALI at the onset of mechanical ventilation. The primary endpoint was cytokine levels in bronchoalveolar lavage fluid and plasma during mechanical ventilation. The secondary endpoint was development of lung injury, as determined by consensus criteria for ALI, duration of mechanical ventilation, and mortality. RESULTS: One hundred fifty patients (74 conventional vs. 76 lower tidal volume) were enrolled and analyzed. No differences were observed in lavage fluid cytokine levels at baseline between randomization groups. Plasma interleukin-6 (IL-6) levels decreased significantly stronger in the lower tidal volume group (from 51 [20 - 182] ng/ml to 11 [5 - 20] ng/ml vs. 50 [21 - 122] ng/ml to 21 [20 - 77] ng/ml; P = 0.01). The trial was stopped prematurely for safety reasons because development of lung injury was higher in the conventional tidal volume group as compared to the lower tidal volume group (13.5% vs. 2.6%, P = 0.01). Univariate analysis showed statistical relations between baseline lung injury score, randomization group, level of positive end-expiratory pressure (PEEP), number of transfused blood products, presence of a risk factor for ALI and baseline IL-6 lavage fluid levels and development of lung injury. Multivariate analysis revealed randomization group and level of PEEP as independent predictors of the development of lung injury. CONCLUSIONS: Mechanical ventilation with conventional tidal volumes is associated with sustained cytokine production as measured in plasma. Our data suggest mechanical ventilation with conventional tidal volumes contributes to development of lung injury in patients without ALI at onset of mechanical ventilation. Trial registration: ISRCTN8253388