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To evaluate the tolerance and the efficacy of noninvasive continuous positive airway pressure (CPAP) in severe acute respiratory failure occurring in intensive care unit (ICU) neutropenic patients with hematologic malignancies, and to establish predictive variables of efficacy of this method.Prospective study over a 5-yr period.Hematologic and medical intensive care unit of a teaching hospital.Among 129 neutropenic patients admitted to the ICU, 64 patients presented with febrile acute hypoxemic normocapnic respiratory failure (Pao2/Fio2 ratio <200) and were enrolled. In addition to standard therapy, patients received CPAP with a facial mask. The initial settings of the CPAP were 6 cm H2O positive end-expiratory pressure and Fio2 0.8 (80%). Physiologic measurements were performed at the end of 45 mins of ventilation with first adjustments. CPAP was used with a sequential mode (45 mins/3 hrs). CPAP was efficient if intubation was avoided.The setting of CPAP, after adjustments, was as follows: positive end-expiratory pressure 7 ± 1 cm H2O and Fio2 0.7 ± 0.1 (70% ± 10%). For the 64 patients, CPAP was administered for a total of 6 ± 2 hrs during the first 24 hrs. The mean duration of CPAP was 7 ± 3 days. A reduction in respiratory rate to less than 25 breaths/min was achieved in 53% of patients. Pao2/Fio2 ratio increased from 128 ± 32 to 218 ± 28. CPAP was successful in avoiding endotracheal intubation in 16/64 patients. A total of 16 responders and four nonresponders survived. Hepatic failure was a criterion indicating the failure of1/16 vs. 26/48 (p = .001). In multivariate analysis, two variables were predictive of failure ofSimplified Acute Physiology Score II (58 ± 14 vs. 41 ± 11) and a hepatic failure at the entry into the study.CPAP was efficient in 25% of cases. All the responders survived. This noninvasive method was used as a way to avoid mechanical ventilation, which is well correlated with a poor prognosis in neutropenic ICU patients. Further controlled studies are needed to confirm the efficacy of noninvasive CPAP and to evaluate the most appropriate selection of immunocompromised patients.