EFFECTS OF HFOV & INO IN TREATMENT OF ACUTE HYPOXEMIC RESPIRATORY FAILURE

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Acute hypoxemic respiratory failure complicates and contributes significantly to the morbidity and mortality of critically ill children with diverse underlying diseases. Despite aggressive treatment, mortality associated with Acute Hypoxemic Respiratory Failure (AHRF) remains between 40 - 60% (1, 2). High mortality is associated with progressive and sustained impairment in oxygenation in children with ARDS. Although multiorgan failure and the primary diagnosis associated with AHRF contribute to mortality, progressive deterioration of lung disease complicates the clinical course of patients with AHRF. Ventilatory strategies which result in alveolar over-distention and cyclic reopening of collapsed alveoli may contribute to progressive lung injury (6, 7). Adjunctive therapies that improve oxygenation and protect the lung from progressive injury may contribute to lower morbidity and improved clinical courses (8, 9, 10, 11). Inhaled nitric oxide therapy has been shown to acutely lower PAP and improve gas exchange in neonates, children, and adults with AHRF (12, 13, 14). The proposed study is a prospective, multi-center, randomized, placebo-controlled trial comparing the effects of nitric oxide for inhalation in the treatment of AHRF in pediatric patients admitted to the PICU requiring intubation. Nitric oxide will be delivered at 5 ppm continuously into the inspiratory limb of the ventilator circuit in mechanically ventilated patients using a blinded version of the INOvent delivery system. The hypothesis to be tested is that the combination of a protective ventilator strategy to recruit the lung and iNO can slow the progression of lung disease in AHRF. Study endpoints are discharge from the PICU, day 28, or death. The primary outcome measures are length of ventilation and PICU stay. 330 subjects will be enrolled.