Monitoring of Cardiovascular Function in Infants By Transcutaneous Dye Dilution

通过经皮染料稀释监测婴儿心血管功能

• 批准号: 8116633
• 负责人: DANIEL PHILIPP HOLSCHNEIDER
• 金额: $ 37.63万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8116633
• 关键词: Accounting; Acute; Address; Adult; Advisory Committees; Affect; Back; Biomedical Technology; Blood; Blood Pressure; Blood Volume; Blood flow; Blood specimen; Body Size; Calibration; Cardiac; Cardiac Output; Cardiovascular Diseases; Cardiovascular Physiology; Cardiovascular system; Catheters; Childhood; Clinical; Clinical Research; Clinical Trials; Clinical assessments; Clip; Computer software; Critical Care; Critical Illness; Cutaneous; Detection; Development; Dialysis procedure; Dyes; Echocardiography; Ensure; Equation; Etiology; Evans blue stain; FDA approved; Fluorescence; Fluorescent Dyes; Fostering; Goals; Health; Hemodialysis; Human; Hypersensitivity skin testing; Hypovolemia; Indocyanine Green; Infant; Injection of therapeutic agent; Intensive Care; Interdisciplinary Study; Intravenous Bolus; Kidney; Lasers; Lead; Los Angeles; Maintenance; Measurement; Measures; Medical; Medicine; Methods; Modeling; Monitor; Myocardial dysfunction; National Center for Research Resources; Neonatal; Newborn Infant; Optics; Oryctolagus cuniculus; Outpatients; Patients; Pediatric Hospitals; Perfusion; Peripheral Resistance; Pharmaceutical Preparations; Physiologic arteriovenous anastomosis; Play; Process; Pulmonary artery structure; Radiolabeled; Recruitment Activity; Reporting; Research; Research Priority; Risk; Role; Rural; Shock; Side; Signal Transduction; Site; Skin; Source; Spectrophotometry; Strategic Planning; Stroke Volume; System; Techniques; Technology; Testing; Thermodilution; Tissues; Tracer; Translating; Translations; Ultrafiltration; Validation; Variant; Venous; base; blood perfusion; cost effective; design; falls; fetal; heart imaging; hemodynamics; human subject; improved; in vivo; innovation; instrument; instrumentation; interest; light intensity; minimally invasive; monitoring device; neonate; patient population; public health relevance; radiotracer

DESCRIPTION (provided by applicant): Cardiac output (CO) and measures of cardiac preload (central blood volume, CBV) and systemic vascular resistance (SVR) are critical clinical parameters of circulatory function. The thermodilution technique is the accepted standard for measurement of CO. However, placement and maintenance of a pulmonary artery catheter required for such a measurement is technically challenging in neonates and infants and is associated with catheter-associated complications. Blood volume measurements can be performed quantitatively, however, these typically involve injection of radiolabelled tracers and/or extensive serial blood sampling and are infrequently performed. In fact, clinical decisions about the treatment of low perfusion states (shock) in these patients are currently being made based primarily on blood pressure and other indirect, fairly unreliable signs of tissue perfusion. These limitations have motivated studies of newer, less invasive techniques. We recently described a new indicator dilution method and instrumentation for assessing CO, circulating blood volume (BV), CBV, and SVR that is based on an intravenous bolus injection of the FDA-approved drug indocyanine green (ICG) and optical measurement of circulating blood ICG fluorescence. We now propose to develop and validate a skin probe, which can be used to measure cardiovascular parameters transcutaneously. The challenge is that skin perfusion is dynamic, which can affect the intensity of the fluorescence signal. We propose to account for this variability by designing a probe that combines the optical fluorescence measurements of circulating ICG with the measurement of local blood perfusion at the skin site using the well-established laser Doppler technique. This would allow us to adjust our fluorescence dye dilution signals to accurately derive CO, CBV, and SVR, irrespective of changes in local skin perfusion. Aim 1 is to develop and validate such a skin probe in a rabbit model. Aim 2 is to validate a clinical grade skin probe in adult subjects undergoing outpatient hemodialysis at the USC/DaVita Kidney Center. Aim 3 is to test the probe in neonates and infants in the Newborn and Infant Critical Care Unit at Children's Hospital Los Angeles and compare CO values with those obtained by functional echocardiography. Currently, a strong clinical need exists for a minimally invasive technique, which can provide rapid, serial measurements of cardiac function in neonates and infants. The proposed technique will lead to the development of a practical device for monitoring CO in minimally instrumented neonates in intensive care, operative and postsurgical settings, and in patients whose condition does not justify the use of central monitoring. This application is responsive to the NHLBI's research priority for improved technologies to image the heart (Task Force Report on Research in Pediatric Cardiovascular Disease, 2002), as well as the strategic priority (2009-2013) of the NCRR to incorporate innovations in biomedical technology into clinical research, and the NIBIB's Strategic Plan (2006) to foster interdisciplinary research for the accelerated translation of promising technologies to improve human health. PUBLIC HEALTH RELEVANCE: Currently, a strong clinical need exists for a minimally invasive technique, which can provide rapid, serial measurements of cardiac function and circulating blood volume in critically ill neonates and infants whose small body size renders more invasive methods (pulmonary artery thermodilution catheter) technically challenging and associated with significant risk. In fact, clinical decisions about the treatment of low perfusion states (shock) are currently being made based primarily on blood pressure and other indirect, fairly unreliable signs of tissue perfusion. Our proposal addresses this need with the development and validation of an optical probe, which can be used to measure cardiac function through the skin for applications in neonatal critical care and in patients whose condition does not justify the use of more invasive monitoring.

描述（由申请人提供）：心输出量（CO）和心脏预紧（中央血容量，CBV）和全身血管抗性（SVR）的测量是循环功能的关键临床参数。热稀释技术是测量CO的公认标准。但是，在新生儿和婴儿中，对这种测量所需的肺动脉导管的放置和维护在技术上具有挑战性，并且与导管相关的并发症有关。可以通过定量进行血液体积测量，但是，这些测量通常涉及注射放射性标记的示踪剂和/或广泛的系列血液采样，并且很少进行。实际上，目前主要是基于血压和其他间接，相当不可靠的组织灌注迹象做出有关这些患者低灌注状态（休克）的临床决策。这些限制激发了对新的，侵入性较小的技术的研究。我们最近描述了一种用于评估CO，循环血容量（BV），CBV和SVR的新指标稀释方法和仪器，该方法基于静脉注射FDA批准的药物吲哚氰氨基绿（ICG）和循环血液ICG荧光的光学测量。现在，我们建议开发和验证皮肤探针，该探针可用于经常测量心血管参数。挑战是皮肤灌注是动态的，这会影响荧光信号的强度。我们建议使用良好的激光多普勒技术设计将循环ICG的光学荧光测量和局部血液灌注的测量结合的探针来解决这种变异。这将使我们能够调整荧光染料稀释信号，以准确地得出CO，CBV和SVR，而与局部皮肤灌注的变化无关。目标1是在兔模型中开发和验证这种皮肤探针。 AIM 2是在USC/Davita肾脏中心验证接受门诊血液透析的成年受试者的临床级皮肤探针。 AIM 3是测试洛杉矶儿童医院新生儿和婴儿重症监护病房中的新生儿和婴儿的探针，并将CO值与功能超声心动图获得的探针进行比较。当前，对微创技术的强大临床需求存在，该技术可以提供新生儿和婴儿心脏功能的快速序列测量。该提出的技术将导致在重症监护，手术和外科手术环境中的最小仪器新生儿中监测CO的实用设备，以及病情无法证明使用中央监测合理的患者。该应用对NHLBI的研究优先级有反应，以改进心脏（工作队关于小儿心血管疾病研究的研究报告报告，2002年），以及NCRR的战略优先级（2009-2013），以将生物医学技术的创新纳入临床研究和NIBIB的策略培养基（2006年）中的生物医学技术的创新（2006年）。有希望改善人类健康的技术。 公共卫生相关性：目前，对微创技术的强大临床需求存在，该技术可以提供对心脏功能的快速，连续测量的临床测量，并在重病的新生儿和婴儿中循环血容量，其体积小的身体大小会导致更具侵入性的方法（肺动脉热镇）技术挑战性和巨大风险相关。实际上，目前主要是基于血压和其他间接，相当不可靠的组织灌注迹象做出有关低灌注状态治疗（休克）的临床决策。我们的建议通过对光学探针的开发和验证来满足这一需求，光探针可用于通过皮肤测量心脏功能，以在新生儿重症监护中应用以及病情无法证明使用更多侵入性监测的患者。