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Airway pressure release ventilation (APRV) is a mode of mechanical ventilation, which has demonstrated potential benefits in trauma patients. We therefore sought to compare relevant pulmonary data and safety outcomes of this modality to the recommendations of the Adult Respiratory Distress Syndrome Network.Patients admitted after traumatic injury requiring mechanical ventilation were randomized under a 72-hour waiver of consent to a respiratory protocol for APRV or low tidal volume ventilation (LOVT). Data were collected regarding demographics, Injury Severity Score, oxygenation, ventilation, airway pressure, failure of modality, tracheostomy, ventilator-associated pneumonia, ventilator days, length of stay (LOS), pneumothorax, and mortality.Sixty-three patients were enrolled during a 21-month period ending in February 2006. Thirty-one patients were assigned to APRV and 32 to LOVT. Patients were well matched for demographic variables with no differences between groups. Mean Acute Physiology and Chronic Health Evaluation II score was higher for APRV than LOVT (20.5 ± 5.35 vs. 16.9 ± 7.17) with a p value = 0.027. Outcome variables showed no differences between APRV and LOVT for ventilator days (10.49 days ± 7.23 days vs. 8.00 days ± 4.01 days), ICU LOS (16.47 days ± 12.83 days vs. 14.18 days ± 13.26 days), pneumothorax (0% vs. 3.1%), ventilator-associated pneumonia per patient (1.00 ± 0.86 vs. 0.56 ± 0.67), percent receiving tracheostomy (61.3% vs. 65.6%), percent failure of modality (12.9% vs. 15.6%), or percent mortality (6.45% vs. 6.25%).For patients sustaining significant trauma requiring mechanical ventilation for greater than 72 hours, APRV seems to have a similar safety profile as the LOVT. Trends for APRV patients to have increased ventilator days, ICU LOS, and ventilator-associated pneumonia may be explained by initial worse physiologic derangement demonstrated by higher Acute Physiology and Chronic Health Evaluation II scores.