Continuous Monitoring for Cerebral Pressure-Passivity in Premature Infants

描述(申请人提供)：早产儿的脑损伤是一个巨大的问题，主要是由未成熟大脑的血管调节障碍引起的脑血管机制引起的。压力被动是脑血管调节紊乱的主要表现，在早产儿缺氧缺血性脑损伤和出血性脑损伤中起关键作用。当全身血压(BP)不稳定，脑压自我调节受损时，就会出现脑压被动。我们已经证明，低血压以及血压波动和大脑压力被动在患病的早产儿中很常见。缺乏一种综合的床边技术来持续监测这些信号之间的动态关系，以识别大脑的压力被动，这阻碍了旨在预防早产儿脑损伤的合理的BP管理策略的制定。我们已经开发了这样一种系统，它可以测量连续的大脑近红外光谱(NIRS)和血压变化，以确定患病婴儿床边的大脑压力被动时期。我们测量全身血压变化和大脑近红外线血红蛋白差值(HBD)信号之间的一致性(使用传递函数分析)；然后我们推导出压力被动指数(PPI)，以量化随时间变化的压力被动。在这里提出的研究中，我们的目标是开始验证通过我们的技术测量的大脑压力被动识别即将发生的生发基质-脑室内出血(GM-IVH)的能力，该研究由每4小时一次的美国“侦察”研究检测到。此外，我们将寻求定义易受压力被动影响的全身血压和二氧化碳水平的特征。如果得到验证，这种方法将对生物医学和临床研究的进步产生巨大的好处，最重要的是最终将导致合理的以脑为导向的血流动力学管理的发展，以防止早产儿毁灭性的脑损伤。因此，这里提出的工作完全是为了最大限度地扩大机会，使这一极其脆弱的人口能够发挥其潜力，过上健康和富有成效的生活，不受疾病或残疾的阻碍。早产儿的脑血管损伤会导致破坏性的长期神经发育障碍，是一个巨大的公共卫生问题。由于对所涉及的血流动力学损伤的不完全理解，以及在损伤变得不可逆转之前无法识别这些损伤，阻碍了这种损伤的预防。我们已经开发出一种旨在填补这两个空白的技术，现在正在为其在患病早产儿中的有效性寻求支持。

DESCRIPTION (provided by applicant): Brain injury in the preterm infant is a problem of enormous magnitude and is mediated largely by cerebrovascular mechanisms emanating from disturbed vasoregulation in the immature brain. Pressure passivity is a major manifestation of disturbed cerebral vasoregulation and is pivotal in both hypoxic-ischemic (HI) and hemorrhagic brain injury in premature infants. Cerebral pressure passivity develops when systemic blood pressure (BP) is unstable and cerebral pressure autoregulation is impaired. We have demonstrated that hypotension, as well as fluctuations in blood pressure and cerebral pressure passivity are common in sick premature infants. The lack of an integrated bedside technique that continuously monitors the dynamic relationship between these signals to identify cerebral pressure-passivity has impeded the formulation of rational strategies for BP management aimed at preventing brain injury in the preterm infant. We have developed such a system that measures continuous cerebral near infrared spectroscopy (NIRS) and BP changes to identify periods of cerebral pressure passivity at the bedside of sick infants. We measure the coherence (using transfer function analysis) between changes in systemic BP and the cerebral NIRS hemoglobin difference (HbD) signal; we then derive a pressure-passive index (PPI) in order to quantify pressure passivity over time. In the research proposed here, we aim to begin validating the ability of cerebral pressure passivity measured by our technique to identify imminent germinal matrix-intraventricular hemorrhage (GM-IVH) detected by 4-hourly 'scout' US studies. In addition, we will seek to define characteristics of systemic BP and CO2 levels that predispose to pressure passivity. If validated, this approach will have enormous benefit for the advance of biomedical and clinical research and most importantly will lead to the eventual development of rational brain-oriented hemodynamic management that prevents the devastating brain injuries of prematurity. As such the work proposed here is squarely directed at maximizing opportunities for this extremely vulnerable population to fulfill their potential for a healthy and productive life unhampered by disease or disability. Cerebrovascular injury in premature infants causes devastating longterm neurdevelopmental morbidity and is a public health issue of enormous magnitude. Prevention of this injury has been impeded by an incomplete understanding of the hemodynamic insults involved and the inability to identify these insults before injury becomes irreversible. We have developed a technique that aims to fill both these voids and now seek support for its validation in sick premature infants.