SURFACTANT POSITIVE AIRWAY PRESSURE AND PULSE OXIMETRY TRIAL IN EXTREMELY LBWI

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心机构，不一定为研究者机构。假设：1.相对于使用预防性/早期表面活性剂和常规通气管理的婴儿，在新生儿重症监护室（NICU）中使用早期持续正压通气（CPAP）和允许性通气策略的妊娠小于28周的婴儿持续CPAP将导致36周时无支气管肺发育不良（BPD）的存活率增加。2.相对于使用较高脉搏血氧饱和度（SpO 2）范围管理的婴儿，使用较低的SpO 2范围（85-89%）将导致存活率增加，而不会发生阈值早产儿视网膜病变（ROP）和/或需要手术干预。3.从出生时开始在产房使用CPAP和允许的呼吸机策略和/或较低的SpO 2范围将导致以下方面的减少：1）18-22个月矫正年龄时的死亡率/神经发育障碍; 2）表面活性剂治疗的发生率; 3）介入治疗的持续时间;和4）随后的发育障碍。目的：呼气末正压（PEEP）已被证明有利于维持功能性残气量。尽管到目前为止还没有关于在产房环境中维持PEEP的正式建议，但CPAP在心肺复苏期间似乎是有益的。Gregory等人在1971年首次证明，对于出生时体重<1500 g的婴儿，CPAP的使用开始于约5.9小时（+12.4小时），改善了患有呼吸窘迫的新生儿的氧合;这些观察结果随后进行了前瞻性研究，证明早期CPAP治疗的早产儿的存活率提高。未达到功能性残气量的早产儿更容易发展为需要机械通气的肺透明膜病。CPAP可以防止表面活性物质产生有限的新生儿过度消耗表面活性物质。一项前瞻性研究评价了在前表面活性剂、产前类固醇时代的早期（非产房）CPAP，该研究表明，早期CPAP可改善大于1500 g婴儿的存活率。 类似地，关于极低出生体重（ELBW）婴儿应维持的氧合水平，没有明确的建议或标准教导。由于ELBW婴儿经常出现去饱和发作，因此临床上可耐受较宽的饱和度范围，因此必须大量使用氧气补充剂。然而，氧中毒可导致慢性肺病（CLD）、ROP和其他疾病的风险增加。另外，氧限制可能会损害神经发育。脉搏血氧仪（PO）是一种较新的技术，可用于改善氧合水平的控制。通过对当前使用水平的高和低侧的氧饱和度水平进行随机对照试验，确定可预防ROP和CLD的氧合水平具有巨大的潜在益处，但不会导致神经发育障碍。然而，很少有前瞻性研究评估婴儿（尤其是ELBW婴儿）中较高与较低氧合水平的获益，这些研究均未在急性疾病期间进行。虽然回顾性队列研究表明，使用较低的SpO 2范围并遵守严格的托儿所政策可能会降低重度ROP的发生率，但目前尚未就从出生起管理ELBW婴儿的可接受SpO 2范围达成一致。 本研究旨在确定是否可以通过使用CPAP和允许通气策略而不是从产房开始的自动气管插管、表面活性剂给药和常规机械通气来降低早产儿BPD的发生率。我们还希望确定这些婴儿维持较低的氧饱和度是否会降低显著ROP的发生率。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Hypotheses: 1. Relative to infants managed with prophylactic/early surfactant and conventional ventilation, the use of early continuous positive air pressure (CPAP) and a permissive ventilatory strategy in infants of less than 28-weeks gestation with continuing CPAP in the Neonatal Intensive Care Unit (NICU) will result in an increased survival without bronchopulmonary dysplasia (BPD) at 36 weeks. 2. Relative to infants managed with a higher pulse oximetry (SpO2) range, the use of a lower SpO2 range (85-89%) will result in an increase in survival without the occurrence of threshold retinopathy of prematurity (ROP) and/or the need for surgical intervention. 3. The use of CPAP with a permissive ventilator strategy and/or a lower SpO2 range starting at birth in the delivery room will result in a decrease in: 1) mortality/neurodevelopment impairment at 18-22-months corrected age; 2) incidence of surfactant treatment; 3) duration of interventional therapies; and 4) subsequent developmental impairments. Goals: Positive end expiratory pressure (PEEP) has been shown to be of benefit in maintaining functional residual capacity. Although no formal recommendation has been made to date about maintaining PEEP in the delivery room setting, CPAP appears beneficial during cardiopulmonary resuscitation. Gregory et al in 1971 first demonstrated that the use of CPAP started at approximately 5.9 hrs (+12.4 hours) for their infants <1500 g at birth, improved oxygenation in newborn infants with respiratory distress; these observations were followed by prospective studies that demonstrated improved survival in premature infants treated with early CPAP. Premature infants who do not achieve a functional residual capacity are more likely to develop hyaline membrane disease requiring mechanical ventilation. CPAP may prevent the excessive consumption of surfactant in newborn infants with limited surfactant production. A review of prospective studies evaluating early (not delivery room) CPAP in the pre-surfactant, pre-antenatal steroid era suggested that early CPAP may improve survival in infants greater than 1500 g. Similarly, there is no definite recommendation or standard teaching regarding the level of oxygenation that should be maintained in extremely low birth weight (ELBW) infants. Oxygen supplementation has to be used liberally as ELBW infants frequently have desaturation episodes and thus wide saturation ranges are tolerated clinically. However, oxygen toxicity can result in increased risk for chronic lung disease (CLD), ROP and other disorders. Alternatively, oxygen restriction may impair neurodevelopment. The pulse oximeter (PO) is a newer technology that can be used to improve the control of oxygenation levels. There is great potential benefit to determining the oxygenation levels that prevents ROP and CLD, but does not result in neurodevelopmental impairment with a randomized controlled trial of levels of oxygen saturations on the high and low side of the currently utilized levels. However, there have been a very few prospective studies evaluating the benefit of higher versus lower levels of oxygenation in infants, especially for ELBW infants, none of which were performed during the acute illness. While retrospective cohort studies have suggested that the use of lower SpO2 ranges and adherence to strict nursery policies may result in a lower incidence of severe ROP, there is no current agreement on the accepted SpO2 ranges for managing the ELBW infant from birth. This study has been designed to determine if the incidence of BPD can be reduced in premature infants by using CPAP and a permissive ventilation strategy rather than automatic endotracheal intubation, surfactant administration, and conventional mechanical ventilation beginning in the delivery room. We also hope to determine if maintaining lower oxygen saturation in these infants will reduce the incidence of significant ROP.