Optimal Oxygenation in Neonatal Lung Injury

摘要 标题：新生儿肺损伤的最佳氧疗 目前的新生儿复苏指南建议在新生儿复苏期间使用21%的氧气 足月新生儿的初始复苏和混合补充氧的使用 保持目标饱和度，以提供足够的氧气，同时限制反应造成的损害 氧自由基。美国儿科学会建议将PaO2维持在 50毫米汞柱和80毫米汞柱用于管理患病新生儿。这些建议是基于 婴儿氧饱和度的研究和新生儿的转化性研究 无肺部疾病的动物模型。最佳氧浓度和目标血氧饱和度 有肺损伤/疾病的足月新生儿复苏和呼吸期间的范围 由该实验室对足月新生的羔羊进行测试。血氧饱和度不是氧合作用的唯一决定因素。 当考虑以保护出生后大脑功能为重点的治疗时 胎粪吸入/窒息，同样的治疗方法可能会损害肺功能。 转换到空气呼吸是一个复杂的生理事件，当有明显的肺时更是如此。 疾病。为了进一步减少氧气损伤的影响，我们建议用以下方法研究足月羔羊 急性呼吸窘迫综合征胎粪吸入致肺损伤 脐带闭塞和窒息(“窒息-MAS”)。限制最佳目标氧水平 对于两组，90%-94%和95%-99%(过去被发现是最好的治疗条件 研究)我们建议研究另外3个具体目标，以改善大脑和肺功能。 第一个具体目标将评估优化大脑氧气输送和 拔除，通过脐带挤奶程序改善出生时胎盘输血实现 这会增加循环中的胎儿红细胞。第二个目标是将目标PaCO2和pH随机设置为 在保持低肺血管阻力的同时提供最佳的脑血流， 通过监测潮气末二氧化碳进行持续管理。最后一个具体目标是研究这种影响。 目前临床上用于窒息后脑保护的低温治疗 功能。影响新生儿肺部疾病临床处理的因素很多。我们打算 明确管理标准，更好地控制影响血流动力学的因素 血流量、肺动脉压和气体交换的措施，以优化氧气 在限制无氧损伤的同时，对脑和肺功能进行输送和提取 激进分子。

SUMMARY Title: Optimal Oxygenation in Neonatal Lung Injury The current guidelines for neonatal resuscitation recommend the use of 21% oxygen during initial resuscitation of term newborn infants and use of blended supplemental oxygen to maintain target saturations to provide adequate oxygen while limiting damage from reactive oxygen radicals. The American Academy of Pediatrics recommends maintaining PaO2 between 50 and 80 mmHg in the management of sick neonates. These recommendations are based on studies using oxygen saturations in human infants and through translational studies in neonatal animal models without lung disease. Optimal oxygen concentration and target oxygen saturation range during resuscitation and ventilation of term neonates with lung injury/disease has been tested by this lab in term newborn lambs. SPO2 is not the sole determinant of oxygenation. When considering treatment that focuses on protecting brain function following birth with meconium aspiration/asphyxia, the same treatment may compromise pulmonary function. Transition to air breathing is a complex physiologic event, more so when there is significant lung disease. To further minimize the impact of oxygen damage we propose to study term lambs with lung injury induced by aspiration of meconium during gasping respirations as a consequence of umbilical cord occlusion and asphyxia (“asphyxia-MAS”). Limiting optimal target oxygen levels to two groups, 90-94% and 95-99% (that were found to be best treatment conditions during past studies) we propose to study 3 additional specific aims to improve both brain and lung function. The first specific aim will evaluate the hemoglobin level that optimizes cerebral O2 delivery and extraction, achieved by improving placental transfusion at birth using cord milking procedures that increase circulating fetal RBC’s. The second aim will randomize the target PaCO2 and pH to provide the best cerebral blood flow while maintaining low pulmonary vascular resistance, continually managed by monitoring end-tidal CO2. The last specific aim will study the influence of hypothermia treatment currently used clinically following asphyxial birth to preserve brain function. Many factors can influence newborn clinical management of lung disease. We intend to clarify management criteria to better control the factors that influence hemodynamic measures of blood flow, pulmonary artery pressure and gas exchange to optimize oxygen delivery and extraction for both brain and lung function while limiting damage from oxygen free radicals.