Continuous hemodynamic monitoring device for improving pediatric sepsis outcomes

描述(申请人提供)：儿童败血症是导致儿童死亡的主要原因之一，全世界有50多万人死亡。治疗感染性休克儿童的一个关键目标是使心脏功能正常化，同时保持最佳的液体平衡和组织氧合水平。静脉输液复苏和管理通常是生存的关键，但也可能导致液体超载和潜在的致命下游后果。目前，缺乏足够的工具来监测患者对输液的反应，特别是那些可以安全和准确地测量心输出量或检测液体超载开始的工具。针对这一需求，我们开发了儿科感知导管？其创新的设计在标准8F儿科尿路引流导管的结构中结合了快速压力传感功能。我们的压力测量的灵敏度和频率使我们能够监测心输出量(根据传递到膀胱的心血管压力波的相对幅度)和腹内压的变化，这两者在脓毒症治疗过程中都是指导治疗决策的关键，后者可以在儿童儿茶酚胺抵抗型败血症休克的“败血症幸存者指南”中找到。与其他更具侵入性的方法相比，使用PediaSense导管测量心输出量和检测液体超载具有明显的优势。目前可用的测量心输出量的工具(即Swan-Ganz导管或基于动脉导管测量的长时间间隔分析)已被证明会给患者带来不可接受的感染风险，并显著增加护理人员的管理和维护负担。此外，检测体液超载的方法往往依赖于体检期间的观察，这些观察是间歇性的、主观的和非定量的。PediaSense设备有可能直接跟踪心输出量的变化，并连续、自动和定量地检测液体响应性和液体过载，而不会增加任何侵入性或增加护理人员的负担。我们的初步数据支持使用PediaSense测量相对心输出量的可行性，我们之前已经证明了该设备提供腹内压变化的临床相关读数的能力。在这里，我们建议使用一个幼猪模型来测试儿科感知器的能力，以提供准确的心输出量变化读数，以响应心功能的药物操作。此外，我们将根据相对心输出量和腹内压的测量，诱导液体超载，并测试儿科传感器实现这种情况的早期检测的能力。这项工作是为未来的临床研究奠定基础的关键的第一步，最终目标是改善患有感染性休克和其他形式的血流动力学损害的危重儿童的预后。

DESCRIPTION (provided by applicant): Pediatric sepsis is one of the leading causes of childhood mortality, responsible for over half a million deaths world-wide. A key goal in treating children suffering from septic shock is to normalize cardiac function while maintaining optimal fluid balance and tissue oxygenation levels. Intravenous fluid resuscitation and management is often critical to survival, but can also lead to fluid overload and potentially fatal downstream consequences. Currently there is a lack of adequate tools with which to monitor patient responses to fluid infusion, particularly those that can safely and accurately measure cardiac output or detect the onset of fluid overload. In response to this need we have developed the PediaSense catheter? Its innovative design combines fast pressure sensing functionality within the structure of a standard 8F pediatric urinary drainage catheter. The sensitivity and frequency of our pressure measurement enables the monitoring of changes in cardiac output (from the relative amplitude of cardiovascular pressure waves transmitted to the bladder) and intra-abdominal pressure, both of which can be critical in guiding treatment decisions during sepsis management and the latter of which can be found in the "Surviving Sepsis" guidelines for catecholamine resistant septic shock in children. Use of the PediaSense catheter has clear advantages over other more invasive methods to measure cardiac output and detect fluid overload. Currently available tools to measure cardiac output (i.e. the Swan-Ganz catheter or Long Time Interval analysis based on arterial catheter measurements) have been shown to incur unacceptable infection risk for the patient and significantly increase the burden on nursing staff to administer and maintain. Moreover, methods to detect fluid overload often rely on observations during physical exam which are intermittent, subjective, and non-quantitative. The PediaSense device has the potential to directly track changes in cardiac output and to detect fluid responsiveness and fluid overload continuously, automatically, and quantitatively without any additional invasiveness or further burden on nursing staff. Our preliminary data support the feasibility of measuring relative cardiac output using the PediaSense and we have previously demonstrated the capacity of the device to provide clinically relevant readings of changes in intra-abdominal pressure. Here we propose to use a juvenile porcine model to test the capacity of the PediaSense to deliver accurate readings of changes in cardiac output in response to pharmacological manipulations of cardiac function. Additionally, we will induce fluid overload and test the ability of the PediaSense to achieve early detection of this condition based on measurements of relative cardiac output and intra-abdominal pressure. This work is a crucial first step to lay the groundwork for future clinical studies with the ultimate goal of improving outcomes for critically ill children suffering from septic shock and other forms of hemodynamic insult.