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

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 急性低氧性呼吸衰竭使患有各种基础疾病的危重儿童的发病率和死亡率显著增加，并极大地增加了其发病率和死亡率。尽管积极治疗，与急性低氧性呼吸衰竭(AHRF)相关的死亡率仍保持在40%-60%(1，2)之间。ARDS儿童的高死亡率与进行性和持续性的氧合损伤有关。虽然与AHRF相关的多器官衰竭和初步诊断导致死亡率，但肺部疾病的进行性恶化使AHRF患者的临床过程复杂化。导致肺泡过度扩张和塌陷的肺泡周期性重新开放的呼吸策略可能导致进行性肺损伤[6，7]。改善氧合和保护肺免受进行性损伤的辅助治疗可能有助于降低发病率和改善临床病程(8、9、10、11)。吸入一氧化氮疗法已被证明能显著降低患有AHRF的新生儿、儿童和成人的PAP并改善气体交换(12，13，14)。这项拟议的研究是一项前瞻性、多中心、随机、安慰剂对照试验，比较了吸入一氧化氮对需要插管的PICU患儿AHRF的治疗效果。在使用盲版INOVENT输送系统的机械通气患者中，一氧化氮将以5ppm的速度持续输送到呼吸机回路的吸气肢体中。需要检验的假设是，联合使用保护性呼吸机策略来招募肺和iNO可以减缓AHRF中肺部疾病的进展。研究终点是从PICU出院、第28天或死亡。主要的结果衡量指标是呼吸机持续时间和PICU住院时间。将招收330个科目。

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.