RATIONALE:

Low tidal volume ventilation (LTVV, 6 mL/kg) benefits patients with acute respiratory distress syndrome (ARDS) and may aid those with other causes of respiratory failure. Current early ventilation practices are poorly defined. OBJECTIVES:

We observed patients with acute respiratory failure to assess feasibility of a pragmatic trial of LTVV and to guide experimental design. METHODS:

We prospectively enrolled consecutive patients with acute respiratory failure admitted to intensive care units expected to participate in the proposed trial. We collected clinical data, initial and daily ventilator settings, and inpatient mortality. We estimated benefit of LTVV using predictive linear and non-linear models. We simulated models to estimate power and feasibility of a cluster-randomized trial of LTVV vs. usual care in acute respiratory failure. RESULTS:

We included 2484 newly mechanically ventilated patients (31% with ARDS) from 49 hospitals. Hospital mortality was 28%. Mean initial tidal volume was 7.1 mL/kg predicted body weight (PBW) (95% CI 7.1-7.2) with 78% of patients receiving tidal volumes ≤ 8 mL/kg. Our models estimated a mortality benefit of 0-2% from LTVV compared to usual care. Simulation of a stepped-wedged cluster trial suggested that enrollment of 106,361 patients was necessary to achieve >90% power. CONCLUSIONS:

Use of initial tidal volumes less than 8 ml/kg PBW is common at hospitals participating in the NHLBI PETAL Network. After considering the size and budgetary requirement for a cluster-randomized trial of LTVV vs. usual care in acute respiratory failure, the PETAL network deemed the proposed trial infeasible. A rapid observational study and simulations to model anticipated power may help better design trials.