Optimal Oxygenation in Neonatal Lung Injury

新生儿肺损伤的最佳氧合

基本信息

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
项目类别：
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

项目摘要

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.

概括标题：新生儿肺损伤的最佳氧合目前的新生儿复苏指南建议在新生儿复苏过程中使用 21% 的氧气。足月新生儿的初步复苏和使用混合补充氧气维持目标饱和度以提供足够的氧气，同时限制反应性损害美国儿科学会建议将 PaO2 维持在这些建议基于 50 和 80 mmHg 的患病新生儿管理。使用人类婴儿的氧饱和度进行的研究以及通过新生儿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。患有肺损伤/疾病的足月新生儿复苏和通气期间的范围该实验室对足月新生羔羊进行了测试，SPO2 并不是氧合的唯一决定因素。在考虑以保护出生后大脑功能为重点的治疗时胎便误吸/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，当肺部有明显的呼吸困难时更是如此。为了进一步减少氧气损伤的影响，我们建议对足月羔羊进行研究。喘息时因吸入胎便而引起的肺损伤脐带闭塞和窒息（“窒息-MAS”）。两组，90-94% 和 95-99%（在过去的研究中发现这是最佳治疗条件）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脑 O2 输送的血红蛋白水平，以及提取，通过使用脐带挤奶程序改善出生时胎盘输血来实现增加循环胎儿红细胞的第二个目标是将目标 PaCO2 和 pH 值随机化。提供最佳的脑血流量，同时保持较低的肺血管阻力，通过监测潮气末二氧化碳来持续管理。最后一个具体目标是研究其影响。目前临床上用于窒息产后低温治疗以保护大脑的方法许多因素会影响新生儿肺部疾病的临床治疗。根据管理标准更好地控制影响血流动力学的澄清因素测量血流量、肺动脉压力和气体交换以优化氧气输送和提取大脑和肺功能，同时限制无氧造成的损害部首。