Non-Invasive Inhaled NO in Premature Newborns

吸入一氧化氮（iNO）治疗已被证明是一种安全有效的治疗足月新生儿， PPHN和低氧性呼吸衰竭。最近的研究集中在iNO在细胞凋亡中的潜在作用。 预防支气管肺发育不良（BPD），然而，它对肺循环的影响， 早产儿受到的关注较少。早产儿特别容易受到 氧中毒和肺部炎症的不良反应，导致肺实质、气道和 肺血管损伤，所有这些都有助于BPD和肺动脉高压的发展。 BPD仍然是早产儿发病和死亡的主要原因，其特征在于： 慢性结构和功能性肺血管异常。iNO在气管插管患者中的临床试验 到目前为止，患有低氧血症性呼吸衰竭的早产儿产生了相互矛盾的结果。我们 在早产儿中进行的iNO多中心试验（N=793）即将完成，将有助于阐明iNO的作用 然而，在需要机械通气治疗低氧性呼吸衰竭婴儿人群中， 外科医生越来越多地避免常规插管和机械通气， 早产儿，而不是选择使用早期，无创持续气道正压通气（早期 CPAP、eCPAP），预期这种呼吸支持模式将减少急性肺损伤， 波士顿警局不幸的是，初步观察并没有表明这种方法明显减少了 BPD的发展。虽然eCPAP降低了VILI的风险，但它可能不会改变VILI引起的损伤。 未成熟肺中的氧中毒和肺部炎症。我们假设低剂量iNO eCPAP期间的非侵入性将降低不需要BPD的早产儿的BPD发生率 在生命的最初24小时内进行机械通气，并将减少早期和晚期的肺部检查结果。 以BPD为特征高血压。为了验证这一假设，我们设计了一个单中心随机， 非侵入性iNO治疗的对照、盲法初步试验。本研究的具体目的是：1）确定是否 iNO可降低早产儿（出生体重500-1250克）的BPD/死亡率联合终点 在生命的前24小时内不需要插管的患者; 2）确定非侵入性iNO治疗是否 减少该人群的早期和晚期肺血管异常。

Inhaled nitric oxide (iNO) therapy has proven to be a safe and effective treatment for term newborns with PPHN and hypoxemic respiratory failure. Recent studies have focused on the potential role of iNO in the prevention of bronchopulmonary dysplasia (BPD), however, its effect on the pulmonary circulation in premature newborns has received less attention. Premature infants are particularly susceptible to the adverse effects of oxygen toxicity and lung inflammation which cause pulmonary parenchymal, airway, and pulmonary vascular injury, all of which contribute to the development of BPD and pulmonary hypertension. BPD remains a major cause of morbidity and mortality in premature newborns, and is characterized by chronic structural and functional pulmonary vascular abnormalities. Clinical trials of iNO in intubated premature newborns with hypoxemic respiratory failure have yielded conflicting results to date. Our multicenter trial of iNO in premature newborns (N=793) is near completion and will help clarify the role of iNO in this population of infants who require mechanical ventilation for hypoxemic respiratory failure, however, neonatologists are increasingly avoiding routine intubation and mechanical ventilation for even the most premature infants, opting instead to employ early, non-invasive continuous positive airway pressure (early CPAP, eCPAP) with the expectation that this mode of respiratory support will reduce acute lung injury and BPD. Unfortunately, preliminary observations have not demonstrated that this approach markedly reduces the development of BPD. Although eCPAP reduces the risk from VILI, it may not modify the injury caused by oxygen toxicity and lung inflammation in the immature lung. We hypothesize that low-dose iNO delivered non-invasively during eCPAP will reduce the incidence of BPD in premature newborns who do not require mechanical ventilation in the first 24 hours of life, and will reduce the early and late findings of pulmonary hypertension that characterize BPD. To test this hypothesis, we have designed a single-center randomized, controlled, masked pilot trial of non-invasive iNO treatment. Specific aims of this study are: 1)to determine if iNO reduces the combined endpoint of BPD/mortality in premature newborns (500-1250 grams birth weight) who do not require intubation in the first 24 hours of life; and 2) to determine if non-invasive iNO treatment decreases early and late pulmonary vascular abnormalities in this population.