Optimal Inspired Oxygen during Chest Compressions in Neonatal Resuscitation

摘要 出生窒息是一个全球性问题，约占250万新生儿死亡的23 每年.这些窒息的新生儿需要广泛的复苏，包括胸部 在分娩室中的心脏按压（CC），并且遭受高死亡率和神经系统发病率。的 窒息新生儿CC期间的最佳氧（O2）浓度尚不清楚。的 新生儿复苏计划（NRP）建议在CC期间提供100%吸入O2， 根据间接证据和专家意见，已显示会导致氧化损伤。另 另一方面，21%O2通气可能导致氧合不足，导致延迟肺动脉高压。 过渡和肺血管阻力（PVR）升高，这可能会进一步延长 缺氧缺血性损伤中等O2浓度（吸入O2为50%）可以平衡这两者 竞争过程和维持稳态后严重缺氧缺血性损伤心脏骤停。 在本提案中，我们计划使用以下方法确定CC期间的最佳吸入O2（21%、50%或100%）： 一项随机、设盲研究，优化了大脑和心脏的氧气输送， 围产期窒息羔羊自发循环及氧化应激 心脏骤停 为了完成这一任务，将通过脐带闭塞使21只足月胎羊窒息，导致心脏 逮捕了将羔羊随机分为3组：CC和休息期间吸入21%、50%和100%的氧气 复苏步骤将遵循NRP指南。血气和血液动力学参数将 要持续监测。羔羊将复苏20分钟或直至达到ROSC， 两者以较早者为准。在20分钟结束时，将对羔羊实施安乐死，并收集组织用于 氧化应激标志物。通过这种方式，我们可以比较生理变化和由此产生的氧化 压力标记物，以更好地了解窒息复苏过程中可能发生的情况 人类新生儿 与当前新生儿复苏实践的相关性： 尽管缺乏科学证据，但补充氧气已用于新生儿复苏， 两百多年了有越来越多的要求，以解决争议的氧气治疗期间， 足月窒息婴儿心脏骤停复苏本申请中提出的研究是 可能提供生理和生物化学数据以帮助确定最佳吸入氧气， CC并最终完善新生儿复苏指南，并可能减轻分娩负担 并发症

ABSTRACT Birth asphyxia is a global issue accounting for about 23% of approximately 2.5 million neonatal deaths each year. These asphyxiated newly born infants require extensive resuscitation including chest compressions (CC) in the delivery room, and suffer from high mortality and neurologic morbidity. The optimal oxygen (O2) concentration during CC in an asphyxiated newborn is not known. The recommendation by the Neonatal Resuscitation Program (NRP) to provide 100% inspired O2 during CC is based on indirect evidence and expert opinion which has shown to cause oxidative injury. On the other hand, ventilation with 21% O2 could lead to inadequate oxygenation resulting in delayed pulmonary transition and elevated pulmonary vascular resistance (PVR) which may further extend the window of hypoxic-ischemic injury. An intermediate O2 concentration (inspired O2 of 50%) could balance these two competing processes and maintaining homeostasis after severe hypoxic-ischemic injury in cardiac arrest. In this proposal we plan to determine the optimal inspired O2 (21%, 50% or 100%) during CC using a randomized, masked study that optimizes oxygen delivery to the brain and heart leading to early return of spontaneous circulation with minimal oxidative stress in perinatal lambs with perinatal asphyxia-induced cardiac arrest. To accomplish this 21 term fetal lambs will be asphyxiated by umbilical cord occlusion resulting in cardiac arrest. Lambs will be randomized to 3 groups: Inspired oxygen of 21%, 50% and 100% during CC and rest of the resuscitation steps will follow the NRP guidelines. Blood gases and hemodynamic parameters will be continuously monitored. Lambs will be resuscitated for 20 minutes or till the ROSC is achieved, whichever is earlier. At the end of 20 minutes, lambs will be euthanized and tissues will be collected for oxidative stress markers. In this way, we can compare physiologic changes and the resultant oxidative stress markers to better understand what may be happening during the resuscitation of an asphyxiated human newborn. Relevance to current practice in neonatal resuscitation: Despite a lack of scientific evidence, supplemental oxygen has been used in neonatal resuscitation for more than 200 years. There is a growing demand to resolve the controversy on oxygen therapy during resuscitation of term asphyxiated infants in cardiac arrest. The studies proposed in this application are likely to provide physiologic and biochemical data to aid in determining the optimal inspired oxygen during CC and eventually refine neonatal resuscitation guidelines and may reduce the burden of birth complications.