Optimal Oxygenation in Neonatal Lung Injury

项目总结：新生儿肺损伤的最佳氧合治疗 全身低温是目前对中到重度缺氧缺血的标准护理 脑病(HIE)。缺氧缺血性脑病通常与胎粪吸入综合征(MAS)和 新生儿持续性肺动脉高压(PPHN)。治疗性体温过低会导致 肺血管收缩和加重PPHN，目前是PPHN的主要适应症 加州的体外膜氧合。最优靶位SpO2和肺活量 血管扩张剂方案可改善PPHN的肺和神经预后 他的情况并不为人所知。 我们假设目标是95%-98%的SpO2(与91%-95%的当前护理标准相比)和 静脉注射西地那非将使脑损伤最小化，并增强肺血管扩张。第一 两种SpO2靶点对气体交换和脑血流动力学的影响 全身降温72小时的范围。第二个具体目标是关注氧化应激。 以及iNO和西地那非对出生窒息后的神经保护作用 在两个不同的SpO2目标处进行通风。最终的具体目标是评估低温对 西地那非的肺血流动力学和药代动力学。 全身低温时，继发于MAS和PPHN的低氧性呼吸衰竭是常见的。 这项研究的结果将通过定义最优SpO2来指导未来临床试验的设计， 在管理患有PPHN和HIE的新生儿时，体温和肺血管扩张剂。治疗性 一种常见且价格较低的药物，如西地那非，在改善这两个方面的潜力 本提案将探讨新生儿窒息后的肺和神经后果。

Project summary: Optimal oxygenation in neonatal lung injury Whole-body hypothermia is currently the standard of care for moderate to severe hypoxic-ischemic encephalopathy (HIE). HIE is commonly associated with meconium aspiration syndrome (MAS) and persistent pulmonary hypertension of the newborn (PPHN). Therapeutic hypothermia can cause pulmonary vasoconstriction and exacerbate PPHN and is currently the leading indication for extracorporeal membrane oxygenation in California. The optimal target SpO2, and pulmonary vasodilator regimen that results in improvement in both pulmonary and neurological outcomes in PPHN and HIE is not known. We hypothesize that targeting 95-98% SpO2 (compared to 91-95% - current standard of care) and intravenous (IV) sildenafil will minimize brain injury and enhance pulmonary vasodilation. The first specific aim focuses on changes in gas exchange and cerebral hemodynamics with two SpO2 target ranges during 72-hours of whole-body hypothermia. The second specific aim focuses on oxidative stress and neuroprotection offered by iNO and sildenafil following birth asphyxia during hypothermia and ventilation at two different SpO2 targets. The final specific aim evaluates the impact of hypothermia on pulmonary hemodynamics and pharmacokinetics of sildenafil. Hypoxemic respiratory failure secondary to MAS and PPHN is common during whole-body hypothermia. Results from this study will inform the design of future clinical trials by defining the optimal SpO2, temperature, and pulmonary vasodilators while managing neonates with PPHN and HIE. The therapeutic potential of a commonly available and less expensive agent such as sildenafil in improving both pulmonary and neurological outcomes following birth asphyxia will be explored in this proposal.