Real-time myoglobin saturation measurement to assess benefit of RBC transfusion

 描述(由申请人提供)：危重病人通常会因贫血来到重症监护室。虽然输血是旨在增加或维持对组织的氧气输送的护理标准，但人们对输血的益处提出了质疑，特别是在中度贫血的非出血患者中。需要一种无创性的细胞内PO2测量来评估输血对组织和器官氧充足的影响和效果。市场上新的脉搏血氧仪和近红外光谱(NIRS)设备的爆炸性增长证明，光学光谱在许多医院的非侵入性组织监测中具有吸引力。但我们还没有做到这一点--现有的临床设备还没有克服准确量化细胞生物标记物的关键障碍 对氧气很敏感。我们建议开发一种新型的、非侵入性的细胞血氧仪，它将根据光学反射光谱提供肌红蛋白饱和度的实时测量。细胞内的氧分压将根据肌红蛋白饱和度使用已知的肌红蛋白氧解离曲线来计算。持续的细胞内PO2测量将使对氧气输送和消耗的前所未有的评估成为可能。这项建议的具体目的是：1)建立一个三距离光学探头；2)开发和验证体外肌红蛋白饱和度的测量；3)在动物模型中评估RBC输注的益处。将建造一种新的探测器来测量兔子后肢表面浅、中、深组织区域的光谱。在目标2中，将开发平行因子分析(PARAFAC)模型，并使用模拟兔后肢的模型进行测试。模体将具有已知的肌红蛋白和血红蛋白饱和度和浓度，以便可以客观地评估肌红蛋白饱和度测量的准确性。最后，在目标3中，将从失血性休克的兔子身上获取光谱。这些光谱将用于校准体内的PARAFAC模型。这些模型将能够实时监测从将接受红细胞输注的中度贫血兔身上收集的新光谱中的肌红蛋白饱和度。这项研究将回答两个关键问题：在中度贫血期间，组织是否缺氧？如果是，输注红细胞能纠正缺氧吗？使用我们的新设备监测细胞内PO2将在临床实践和临床研究中具有广泛的意义。我们预计，细胞内PO2监测将成为护理缺氧患者的关键组成部分，包括败血症、休克和心力衰竭患者。我们的长期目标是开发用于救护车、急诊科、重症监护病房和手术室的临床使用的细胞血氧仪。

 DESCRIPTION (provided by applicant): Critically ill patients commonly arrive at an intensive care unit with anemia. While blood transfusions are the standard of care with the intention to increase or maintain oxygen delivery to tissues, questions have been raised about the benefit of blood transfusions, particularly in non-bleeding patients with moderate anemia. A noninvasive measure of intracellular PO2 is needed to evaluate the effect and efficacy of blood transfusions on tissue and organ oxygen sufficiency. Evidenced by the explosion of new pulse oximetry and near infrared spectroscopy (NIRS) devices on the market, optical spectroscopy is attractive for noninvasive tissue monitoring in many hospital settings. But we are not there yet - no existing clinical device has overcome the critical hurdle of accurately quantifying cellular biomarkers that are sensitive to oxygenation. We propose to develop a novel, noninvasive cell oximeter that will provide real-time measurement of myoglobin saturation from optical reflectance spectra. Intracellular PO2 will be calculated from myoglobin saturation using known myoglobin oxygen dissociation curves. Continuous intracellular PO2 measurement will allow unprecedented assessment of oxygen delivery and consumption. The specific aims of this proposal are to: 1) build a three-distance optical probe; 2) develop and validate measurement of myoglobin saturation in vitro; and 3) assess the benefit of RBC transfusion in an animal model. A new probe will be built to measure spectra from superficial, intermediate, and deep tissue regions from the surface of the rabbit hind limb. In Aim 2, Parallel Factor analysis (PARAFAC) models will be developed and tested with phantoms that model the rabbit hind limb. The phantoms will have known myoglobin and hemoglobin saturations and concentrations so that the accuracy of myoglobin saturation measurement can be objectively evaluated. Finally, in Aim 3, spectra will be acquired from rabbits subjected to hemorrhagic shock. These spectra will be used to calibrate in vivo PARAFAC models. The models will enable myoglobin saturation monitoring in real time from new spectra collected from rabbits with moderate anemia that will receive RBC transfusions. The study will answer two key questions: is tissue hypoxic during moderate anemia and if so, does RBC transfusion remedy the hypoxia? Intracellular PO2 monitoring with our new device will have broad implications in clinical practice and clinical research. We envision that intracellular PO2 monitoring will become a critical component in the care of patients with oxygen insufficiency, including those with sepsis, shock, and cardiac failure. Our long-term goal is to develop the cell oximeter for clinical use in ambulances, emergency departments, intensive care units, and operating rooms.