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

实时肌红蛋白饱和度测量以评估红细胞输血的益处

• 批准号: 8880786
• 负责人: LORILEE S. L. ARAKAKI
• 金额: $ 15万
• 依托单位: OPTICYTE, INC.
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-04-01 至 2016-08-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8880786
• 关键词: Accident and Emergency department; Algorithms; Ambulances; Anemia; Animal Model; Biological Markers; Blood; Blood Transfusion; Blood capillaries; Caring; Cells; Chemical Industry; Clinical; Clinical Research; Color; Consumption; Critical Illness; Cytochromes; Decision Making; Devices; Dissociation; Erythrocyte Transfusion; Evaluation; Explosion; Factor Analysis; Food Industry; Goals; Government; Heart failure; Hemoglobin; Hemorrhagic Shock; Hospitals; Hypoxia; In Vitro; Intensive Care Units; Intention; Left; Light; Limb structure; Marketing; Measurement; Measures; Medical; Methods; Modeling; Monitor; Morbidity - disease rate; Muscle; Muscle Cells; Myoglobin; Near-Infrared Spectroscopy; Operating Rooms; Optics; Organ; Oryctolagus cuniculus; Outcome; Oxygen; Oxygen saturation measurement; Patient Care; Patients; Peripheral Vascular Diseases; Persons; Physiologic pulse; Pulse Oximetry; Qualifying; Research; Sepsis; Shock; Skeletal Muscle; Skin; Spectrum Analysis; Standardization; Surface; Technology; Testing; Therapeutic; Time; Tissues; Training; Universities; Venous; Washington; Weight; Work; abstracting; base; capillary; clinical care; clinical practice; experience; in vivo; innovation; medical specialties; monitoring device; mortality; novel; oxidation; patient oriented; phantom model; prevent; public health relevance; standard of care; temporal measurement

 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.

 描述（由申请人提供）：重症患者通常因贫血而到达重症监护室。虽然输血是旨在增加或维持组织供氧的标准治疗方法，但人们对输血的益处提出了疑问，特别是对于患有中度贫血的非出血患者。需要对细胞内 PO2 进行无创测量来评估输血对组织和器官氧充足的影响和功效。 市场上新型脉搏血氧仪和近红外光谱 (NIRS) 设备的爆炸式增长证明，光学光谱对于许多医院环境中的无创组织监测具有吸引力。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志物的关键障碍。 对氧合敏感。 我们建议开发一种新型非侵入性细胞血氧计，它将通过光学反射光谱实时测量肌红蛋白饱和度。细胞内 PO2 将使用已知的肌红蛋白氧解离曲线根据肌红蛋白饱和度计算。连续的细胞内 PO2 测量将能够对氧气输送和消耗进行前所未有的评估。 该提案的具体目标是：1）构建三距离光学探针； 2) 开发并验证体外肌红蛋白饱和度的测量方法； 3) 在动物模型中评估红细胞输注的益处。 将建造一个新的探针来测量兔子后肢表面浅层、中间和深层组织区域的光谱。在目标 2 中，将开发平行因子分析 (PARAFAC) 模型，并使用模拟兔子后肢的体模进行测试。模型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，将从遭受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 PARAFAC 模型。该模型将能够通过从将接受红细胞输血的中度贫血兔子收集的新光谱来实时监测肌红蛋白饱和度。该研究将回答两个关键问题：中度贫血期间组织是否缺氧？如果是，红细胞输注是否可以缓解缺氧？ 使用我们的新设备进行细胞内 PO2 监测将在临床实践和临床研究中产生广泛的影响。我们预计细胞内 PO2 监测将成为缺氧患者（包括脓毒症、休克和心力衰竭患者）护理的关键组成部分。我们的长期目标是开发用于救护车、急诊室、重症监护室和手术室临床使用的细胞血氧计。