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 产房内有压迫(CC)，死亡率高，神经学发病率高。这个 窒息新生儿在体外循环过程中的最佳氧气浓度尚不清楚。这个 新生儿复苏计划(NRP)的建议，在CC IS期间提供100%激发的氧气 基于间接证据和专家意见，这表明它会导致氧化损伤。另一方面 另一方面，21%氧气的通风可能会导致氧合不足，导致肺延迟 转移性和肺血管阻力(PVR)升高，可能进一步延长 缺氧缺血性损伤。中等的氧气浓度(氧气浓度为50%)可以平衡这两者。 心脏骤停严重缺氧缺血损伤后的竞争过程和维持内环境平衡。 在本提案中，我们计划确定CC过程中的最佳激励O2(21%、50%或100%) 随机、掩蔽研究，优化向大脑和心脏的氧气输送，导致早期恢复 围产期窒息羔羊低氧化应激条件下的自主循环 心脏骤停。 为了实现这一目标，21只足月胎羊将被脐带闭塞导致心脏窒息。 逮捕。将羔羊随机分为3组：CC期间和休息时吸入21%、50%和100%的氧气 复苏步骤的一部分将遵循NRP指南。血气和血流动力学参数将 被持续监测。羔羊将被复苏20分钟或直到达到ROSC， 两者以较早者为准。20分钟后，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 应激标志物以更好地了解窒息患者复苏期间可能发生的情况 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 200多年前。越来越多的人要求解决关于氧疗的争议 心跳骤停足月窒息婴儿的复苏。本申请中建议的研究包括 可能提供生理和生化数据，以帮助确定最佳吸氧量 CC并最终完善新生儿复苏指南，可能会减轻分娩负担 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.