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

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。急性低氧性呼吸衰竭是多种基础疾病的危重儿童的并发症和死亡率的重要因素。尽管积极治疗，与急性低氧性呼吸衰竭（AHRF）相关的死亡率仍在40 - 60%之间（1,2）。ARDS患儿的高死亡率与进行性和持续性氧合障碍有关。虽然与AHRF相关的多器官衰竭和初步诊断会导致死亡率，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肺泡循环重开的通气策略可能导致进行性肺损伤（6,7）。辅助治疗可改善氧合并保护肺部免受进行性损伤，可能有助于降低发病率和改善临床病程（8,9,10,11）。吸入性一氧化氮治疗已被证明可急剧降低PAP并改善患有AHRF的新生儿、儿童和成人的气体交换（12,13,14）。该研究是一项前瞻性、多中心、随机、安慰剂对照试验，比较吸入一氧化氮在PICU需要插管的儿科患者AHRF治疗中的效果。使用INOvent盲法给药系统，将一氧化氮以5ppm的浓度连续输送到机械通气患者的呼吸机回路的吸气端。待验证的假设是，将保护性呼吸机策略与一氧化氮结合使用可减缓AHRF中肺部疾病的进展。研究终点为从PICU出院，第28天或死亡。主要观察指标为通气时间和PICU停留时间。将招募330名受试者。

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.