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To investigate the effectiveness of the constant-flow, pressure-volume curve (PVC) to prescribe positive end-expiratory pressure (PEEP) in acute lung injury (ALI) and risk of cardiopulmonary deterioration during the PVC process.A retrospective, cohort study.A surgical intensive care unit (ICU) of a tertiary, university hospital.Fifty consecutive ventilated patients diagnosed with ALI undergoing the PVC maneuver from 1999 to 2003.Titration of PEEP based on the lower inflection point of the constant-flow, pressure-volume curve.Patients were divided into 2 groups based on PVC-guided PEEP changes of <3 cm H2O (PVC-NC or “no change”) or ≥3 cm H2O (PVC-CHG or “change”) from the initial empiric prescription. There was a greater increase in partial pressure of arterial oxygen (PaO2)/fractional concentration of inspired oxygen (FIO2) in the PVC-CHG group, with a mean change of 80 ± 50 (95% confidence interval [CI] 61, 98) versus 42 ± 54 (95% CI 17, 67) in the PVC-NC group. Eighty-two percent of patients (41/50) showed an increase in ratio of partial pressure of arterial oxygen to fraction of inspired oxygen (PaO2/FIO2) by 20% within 6 to 24 hours after the PVC test—greater in the PVC-CHG group (OR 1.44, 95% CI 1.02, 2.01). Thirteen percent (4/ 30) within the PVC-CHG group and none within the PVC-NC group (0/20) required a 25% increase in vasoactive infusion rates (P = .089) in relation to the procedure. Univariate logistic regression showed that PVC-CHG was significantly associated with a 20% change in PaO2/FIO2 (OR 7.54, 95% CI 1.37, 41.41). Multivariate logistic modeling showed that PVC-guided PEEP changes of ≥3 cm H2O, age ≤65 years, and pre-PVC FIO2 ≥.85 were significantly associated with a 20% increase in PaO2/FIO2 (receiver operator area under the curve = .86).In the setting of acute lung injury, use of the constant-flow, pressure-volume curve to prescribe PEEP appears associated with improvement in oxygenation with limited risk of acute, process-related, cardiopulmonary deterioration.