Optimal Oxygenation in Neonatal Lung Injury

新生儿肺损伤的最佳氧合

• 批准号: 8334978
• 负责人: Satyanarayana Lakshminrusimha
• 金额: $ 23.55万
• 依托单位: STATE UNIVERSITY OF NEW YORK AT BUFFALO
• 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 2017-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8334978
• 关键词: Academy; Alveolar; American; American Heart Association; Animal Model; Antioxidants; Asphyxia; Birth; Blood Vessels; Blood flow; Brain; Cerebrum; Coronary; Data; Defense Mechanisms; Disease; Ductal; Environmental air flow; Equilibrium; Evaluation; Free Radical Formation; Future; Goals; Grant; Guidelines; Heart Atrium; Human; Hypoxia; Infant; Injury; Knowledge; Left; Lung; Lung diseases; Meconium Aspiration; Metabolism; Modeling; Multicenter Trials; Neonatal Intensive Care; Newborn Animals; Newborn Infant; Organ; Oxidants; Oxidative Stress; Oxygen; Oxygen Consumption; Oxygen Therapy Care; Oxygen measurement, partial pressure, arterial; Pattern; Pediatrics; Persistent Fetal Circulation Syndrome; Phase; Physiological; Pregnancy; Premature Infant; Production; Publishing; Pulmonary Vascular Resistance; Reactive Oxygen Species; Recommendation; Reporting; Respiration; Resuscitation; Retinopathy of Prematurity; Risk; Supplementation; Syndrome; System; Testing; Tissues; Toxic effect; Umbilical cord structure; Venous; base; hemodynamics; lung injury; meetings; mortality; neonatal lung injury; neonatal resuscitation; neonate; oxygen toxicity; programs; respiratory; respiratory distress syndrome; surfactant deficiency; translational study; uptake

DESCRIPTION (provided by applicant): The American Heart Association recently released guidelines recommending the use of 21% oxygen during initial resuscitation of term newborn infants and use of blended supplemental oxygen to maintain target saturations in premature infants. 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 preterm and term neonates with lung injury/disease from a standpoint of tissue oxygen delivery and oxygen toxicity is not known. The overall goal of oxygen therapy is to provide adequate oxygen to meet tissue demand without risking oxygen toxicity. The overarching aim of this proposal is to determine the optimal concentration of inspired oxygen during resuscitation and ventilation of a newborn lamb with parenchymal lung disease/ lung injury. Two patterns of neonatal lung injury will be studied in this proposal. In ter lambs injury will be induced by aspiration of meconium during gasping respirations induced as a consequence of umbilical cord occlusion and asphyxia ("asphyxia-MAS" group). Preterm lambs delivered at 126d gestation (term ~ 145d) have parenchymal lung injury as a consequence of surfactant deficiency and respiratory distress syndrome ("preterm-RDS" group). Lambs will be resuscitated and ventilated with 21% oxygen, 100% oxygen or adjusted inspired oxygen concentration to maintain oxygen saturations between 85 to 89%, 90 to 94% or 95 to 99%. The first specific aim of this proposal is to determine the effect inspired oxygen concentration and saturations on oxygenation, lung oxygen uptake and oxygen delivery to the tissues. The second specific aim is to evaluate the effect of oxygen concentration and saturations on pulmonary, cerebral, coronary and ductal hemodynamics and assess delivery of oxygen to various vital organs. We intend to evaluate the risk of oxidant injury in the lung and brain associated with various levels of oxygen through our last specific aim. PUBLIC HEALTH RELEVANCE: Oxygen supplementation during resuscitation and subsequent ventilation of newborn infants with lung disease is a delicate balance between providing adequate tissue oxygen delivery and formation of free radicals that overwhelm their deficient antioxidant defense system. The recently published SUPPORT trial report has heightened concern about lack of specific physiological knowledge regarding oxygen supplementation, delivery and toxicity in newborn infants. Data obtained from this grant will provide physiological data and aid in establishment of future guidelines for optimal oxygen delivery in preterm and term neonates with lung disease.

描述（由申请人提供）：美国心脏协会最近发布了指南，建议在初次复苏新生婴儿的初始复苏期间使用21％的氧气，并使用混合补充氧气以维持早产儿的目标饱和度。美国儿科学会建议在病人的新生儿管理中维持50至80 mmHg的PAO2。这些建议是基于使用氧饱和的研究，以及在没有肺部疾病的新生动物模型中的转化研究。从组织氧递送和氧毒性的角度来看，早产和肺部疾病/疾病的早产和新生儿的通气期间，最佳氧气浓度和靶氧饱和度范围尚不清楚。氧疗法的总体目标是提供足够的氧气以满足组织需求，而不会冒氧毒性。该提案的总体目的是确定在复苏和通风的新生羔羊和实质性肺部疾病/肺损伤期间受到启发的氧气的最佳浓度。该提案将研究两种新生儿肺损伤的模式。在TER羔羊中，由于脐带闭塞和窒息（“窒息组”组），在引起的喘息呼吸期间的抽吸将引起lambs损伤。由于表面活性剂缺乏症和呼吸遇险综合征（“ Preterm-RDS”组），以126D妊娠（〜145d术语）交付的早产羔羊具有实质性肺损伤。羔羊将用21％氧，100％氧或调整后的氧气浓度复苏并通风，以将氧饱和度保持在85至89％，90％至94％或95％至99％之间。该提案的第一个具体目的是确定启发的氧气浓度和饱和对氧气，肺氧摄取和氧气递送到组织的影响。第二个具体目的是评估氧浓度和饱和对肺，脑，冠状动脉和导管血流动力学的影响，并评估氧气向各种重要器官的递送。我们打算通过我们的最后一个特定目标评估肺和大脑中与各种氧气相关的氧化剂损伤的风险。 公共卫生相关性：在复苏期间补充氧气和随后对肺部疾病的新生婴儿的通气是一个微妙的平衡，这是在提供足够的组织氧递送和形成自由基的自由基，这使其不足以使其不足的抗氧化剂防御系统淹没。最近发表的支持试验报告加剧了人们对新生婴儿补充，递送和毒性缺乏特定的生理知识的关注。从该赠款中获得的数据将提供生理数据，并有助于建立未来的指南，以在早产和肺部疾病的新生儿中递送最佳氧气。