Optimal Oxygenation in Neonatal Lung Injury

新生儿肺损伤的最佳氧合

• 批准号: 9750728
• 负责人: Satyanarayana Lakshminrusimha
• 金额: $ 29.5万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-06 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9750728
• 关键词: 3-nitrotyrosine; Academy; Air; American; Anaerobic Bacteria; Animal Model; Antioxidants; Asphyxia; Asphyxia Neonatorum; Attenuated; Birth; Blood; Blood flow; Brain; Breathing; Carbon Dioxide; Cerebrovascular Circulation; Cerebrum; Characteristics; Clinical; Clinical Management; Clinical Protocols; Clinical Trials; Closure by clamp; Collaborations; Complex; Consumption; Disease; Dissociation; Enrollment; Environmental air flow; Equilibrium; Event; Free Radicals; Gases; Growth; Guidelines; Health; Hemoglobin; Hemoglobin concentration result; Human; Hypercapnia; Infant; Infant Care; Intestines; Lung; Lung diseases; Manuscripts; Measures; Meconium Aspiration; Metabolism; Milk; Monitor; Newborn Animals; Newborn Infant; Outcome; Oxidative Stress; Oxygen; Oxygen Therapy Care; Patients; Pediatrics; Persistent Fetal Circulation Syndrome; Physiological; Pregnancy; Premature Infant; Procedures; Progress Reports; Pulmonary Pathology; Pulmonary Vascular Resistance; Pulmonary artery structure; Pulse Oximetry; Randomized; Reactive Oxygen Species; Recommendation; Respiration; Respiratory physiology; Resuscitation; Secondary to; Solubility; Supplementation; System; Temperature; Term Birth; Testing; Therapeutic; Tissues; Transfusion; Umbilical cord structure; Variant; Work; base; brain metabolism; clinically relevant; critical period; fetal; free radical oxygen; hemodynamics; improved; induced hypothermia; lung injury; mortality; natural hypothermia; neonatal hypoxic-ischemic brain injury; neonatal lung injury; neonatal resuscitation; neonate; preservation; pressure; pulmonary function; randomized trial; standard of care; translational study; uptake; vasoconstriction

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.

总结 标题：新生儿肺损伤的最佳氧合 目前的新生儿复苏指南建议在复苏期间使用21%的氧气。 足月新生儿的初始复苏和使用混合辅助供氧， 保持目标饱和度，以提供足够的氧气，同时限制反应性损伤 氧自由基美国儿科学会建议将PaO 2维持在 50和80 mmHg用于治疗新生儿疾病。这些建议是基于 在人类婴儿中使用氧饱和度的研究和通过在新生儿中的转化研究 无肺部疾病的动物模型。最佳氧浓度和目标氧饱和度 在患有肺损伤/疾病的足月新生儿的复苏和通气期间， 在足月新生羔羊身上进行测试SPO 2不是氧合的唯一决定因素。 当考虑治疗，重点是保护脑功能出生后， 胎粪吸入/窒息，同样的治疗可能会损害肺功能。 过渡到空气呼吸是一个复杂的生理事件，尤其是当有明显的肺 疾病为了进一步减少氧损伤的影响，我们建议研究足月羔羊， 在喘息时吸入胎粪引起的肺损伤， 脐带阻塞和窒息（“窒息-MAS”）。限制最佳目标氧气水平 90-94%和95-99%两组（这是过去研究中发现的最佳处理条件 研究），我们建议研究3个额外的具体目标，以改善大脑和肺功能。 第一个具体目标将评估优化脑氧输送的血红蛋白水平， 通过使用脐带挤奶程序改善出生时胎盘输血来实现提取 增加胎儿循环中的红细胞第二个目标将随机化目标PaCO 2和pH， 提供最佳的脑血流量，同时保持低肺血管阻力， 通过监测潮气末二氧化碳来持续管理。最后一个具体的目标是研究 目前临床上用于窒息出生后的低温治疗， 功能许多因素可以影响新生儿肺部疾病的临床管理。我们打算 明确管理标准，以更好地控制影响血流动力学的因素 测量血流量、肺动脉压和气体交换以优化氧气 输送和提取，同时限制无氧损伤， 根的