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：新生儿肺损伤中的最佳氧合当前的新生儿复苏指南建议在期间使用21％的氧气最初对新生婴儿的初步复苏，并使用混合补充氧保持目标满足以提供足够的氧气，同时限制反应性的损害氧自由基。美国儿科学会建议维护PAO2 病态新生儿的管理50和80 mmHg。这些建议是基于在人类婴儿中使用氧饱和度和通过新生儿的翻译研究的研究没有肺部疾病的动物模型。最佳氧浓度和靶氧饱和度复苏和通风期间的肺部损伤/疾病新生儿的范围已经该实验室在术语新生羔羊中测试。 SPO2不是氧合的唯一确定剂。考虑治疗的重点是保护出生后的大脑功能胎梗抽吸/窒息，相同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，当肺有明显的肺部时，疾病。为了进一步最大程度地减少氧损害的影响由于导致胎粪造成的肺部损伤，因此脐带阻塞和窒息（“窒息”）。限制最佳靶氧水平对于两组，90-94％和95-99％（在过去发现是最好的治疗条件研究）我们建议研究3种其他特定目的，以改善大脑和肺功能。第一个具体目的将评估优化脑O2递送和的血红蛋白水平提取，通过使用绳索挤奶程序在出生时改善胎盘输血来实现这会增加循环胎儿RBC的循环。第二个目标将使目标PACO2和pH随机提供最佳的脑血流，同时保持低肺血管耐药性继续通过监视潮汐二氧化碳来管理。最后的特定目标将研究影响低温治疗目前使用临床后的进入进入刑语的临床治疗来保存大脑功能。许多因素会影响肺部疾病的新生儿临床管理。我们打算阐明管理标准以更好地控制影响血液动力学的因素血流，肺动脉压力和气体交换以优化氧气大脑和肺功能的递送和提取，同时限制无氧损害激进分子。