Continuous Monitoring for Cerebral Pressure-Passivity in Premature Infants

描述（申请人提供）：早产儿脑损伤是一个巨大的问题，主要是由未成熟大脑血管调节紊乱引起的脑血管机制介导的。压力被动是脑血管调节紊乱的主要表现，是早产儿缺氧缺血性（HI）和出血性脑损伤的关键。当全身血压（BP）不稳定和脑压自动调节功能受损时，就会出现脑压被动。我们已经证明，低血压，以及血压波动和脑压被动在生病的早产儿中很常见。缺乏一种集成的床边技术来持续监测这些信号之间的动态关系，以识别脑压力被动，这阻碍了制定合理的BP管理策略，旨在预防早产儿脑损伤。我们已经开发了这样一个系统，可以测量连续的大脑近红外光谱（NIRS）和血压变化，以确定生病婴儿床边的脑压被动期。我们测量了全身血压变化与大脑近红外血红蛋白差异（HbD）信号之间的一致性（使用传递函数分析）；然后，我们得出一个压力被动指数（PPI），以量化压力被动随时间的变化。在这里提出的研究中，我们的目标是开始验证我们的技术测量的脑压力被动性的能力，以识别迫在眉睫的生发基质-脑室内出血（GM-IVH），通过4小时的“侦察”美国研究检测。此外，我们将试图确定系统血压和二氧化碳水平的特征，这些特征容易导致压力被动。如果得到验证，这种方法将为生物医学和临床研究的进步带来巨大的好处，最重要的是，将导致最终发展合理的以大脑为导向的血流动力学管理，防止早产儿的破坏性脑损伤。因此，这里提出的工作直接针对最大限度地为这一极其脆弱的人口提供机会，使他们能够发挥潜力，过上不受疾病或残疾影响的健康和富有成效的生活。早产儿的脑血管损伤会导致毁灭性的长期神经发育疾病，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了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。我们已经开发了一种技术，旨在填补这两个空白，现在正在寻求支持，以验证其在患病早产儿中的有效性。

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.