ObjectiveTo evaluate the feasibility of airway pressure release ventilation (APRV) in providing ventilatory support to patients with acute lung injury of diverse etiology and mild-to-moderate severity.DesignProspective, multicenter, nonrandomized crossover trial.SettingICUs in six major referral hospitals.PatientsFifty adult patients with respiratory failure requiring mechanical ventilation and positive end-expiratory airway pressure.InterventionsAfter optimization of continuous positive airway pressure (CPAP), conventional ventilation and APRV were administered sequentially for 30 mins. During APRV, the CPAP level and airway pressure release level were adjusted to prevent hypoxemia, while the degree of ventilatory support was adjusted by altering the frequency of pressure release.Measurements and Main ResultsCirculatory and ventilatory pressures, arterial blood gases and pH, heart rate, and respiratory rate were measured. Alveolar ventilation was augmented adequately in 47 of 50 patients by APRV. Adjustment of APRV required an increase in mean CPAP from 13 ± 3 (SD) to 21 ± 9 cm H2O and a release pressure of 6 ± 5 cm H2O. This airway pressure pattern produced a mean airway pressure comparable to that pressure achieved during conventional ventilation. Failure of APRV in three patients could be attributed to an inadequate level of CPAP or an inadequate APRV rate. While maintaining oxygenation of arterial blood and circulatory function, APRV allowed a substantial (55 ± 17%;p< .0001) reduction in peak airway pressure compared with conventional positive pressure ventilation adjusted to deliver a comparable or lower level of ventilatory support.ConclusionsAPRV is a feasible alternative to conventional mechanical ventilation for augmentation of alveolar ventilation in patients with acute lung injury of mild-to-moderate severity.