Non-Invasive Inhaled NO in Premature Newborns

早产儿无创吸入一氧化氮

• 批准号: 8214143
• 负责人: John Patrick Kinsella
• 金额: $ 6.49万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-01-01 至 2012-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8214143
• 关键词: Acute Lung Injury; Address; Adverse effects; Affect; Animal Experiments; Attention; Biological Markers; Birth Weight; Blood Vessels; Breathing; Bronchopulmonary Dysplasia; Categories; Chi-Square Tests; Child; Chronic; Clinical; Clinical Research; Clinical Trials; Colorado; Confidence Intervals; Conflict (Psychology); Consent; Continuous Positive Airway Pressure; Data; Development; Disease; Dose; Early treatment; Employee Strikes; Enrollment; Environmental air flow; Evaluation; Event; Exclusion Criteria; Functional disorder; Funding; Gestational Age; Grant; Growth; Guidelines; Hour; Hypoxemia; Incidence; Infant; Injury; Intervention; Intracranial Hemorrhages; Intubation; Life; Light; Long-Term Effects; Lung; Lung Inflammation; Masks; Mechanical ventilation; Morbidity - disease rate; Multicenter Trials; National Heart, Lung, and Blood Institute; Neonatal; Neonatal Screening; Newborn Infant; Nose; Oxygen; Patients; Pilot Projects; Placebo Control; Placebos; Population; Pregnancy; Premature Infant; Prevention; Principal Investigator; Protocols documentation; Pulmonary Circulation; Pulmonary Hypertension; Randomized; Randomized Controlled Trials; Reporting; Research Personnel; Respiratory Failure; Risk; Role; Safety; Sample Size; Sampling; Series; Severities; Severity of illness; Side; Signal Transduction; Site; Steroids; Structure; Testing; United States National Institutes of Health; Universities; Vascular Diseases; Ventilator-induced lung injury; Work; base; bench to bedside; clinical practice; design; effective therapy; endotracheal; expectation; experience; follow-up; indexing; inhaled nitric oxide; interest; meetings; mortality; neonate; novel; oxygen toxicity; patient population; persistent pulmonary hypertension; pilot trial; premature; premature lungs; prenatal; pressure; programs; respiratory; safety study; surfactant; trend

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.

吸入一氧化氮(INO)疗法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在体内的潜在作用。 预防支气管肺发育不良(BPD)，但其对肺循环的影响 早产儿受到的关注较少。早产儿特别容易患上 氧中毒和肺部炎症的不良反应，导致肺实质、呼吸道和 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，其特点是 慢性结构和功能肺血管异常。异丙酚在气管插管中的临床应用 到目前为止，患有低氧性呼吸衰竭的早产儿的结果相互矛盾。我们的 INO在早产儿(N=793)中的多中心试验接近完成，将有助于阐明iNO的作用 然而，在这群需要机械呼吸治疗低氧性呼吸衰竭的婴儿中， 新生儿科医生越来越多地避免常规的插管和机械通气，即使在大多数情况下 早产儿，选择使用早期、无创持续正压(早期 CPAP，eCPAP)，期望这种呼吸支持模式将减少急性肺损伤 每桶。不幸的是，初步观察并没有证明这种方法显著减少了 BPD的发展。尽管eCPAP降低了VILI的风险，但它可能不会改变 未成熟肺的氧毒性和肺部炎症。我们假设低剂量的iNO提供了 ECPAP期间无创操作将减少早产儿BPD的发生率，这些早产儿无需 在生命的头24小时内进行机械通气，会减少肺部早期和晚期的发现 以BPD为特征的高血压。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、掩蔽试点试验。这项研究的具体目的是：1)确定 INO降低早产儿BPD/死亡率的综合终点(500-1250克出生体重) 在生命的最初24小时内不需要插管；以及2)确定非侵入性iNO治疗 减少这一人群的早期和晚期肺血管异常。