Precision Guidance of Resuscitation and Deresuscitation in Sepsis

脓毒症复苏和复苏的精确指导

基本信息

批准号：
10602712
负责人：
Jonathan Feldschuh
金额：
$ 30.5万
依托单位：
DAXOR CORPORATION
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-09-01 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10602712
关键词：
Adult Affect American Antibiotics Biological Markers Blood Plasma Volume Blood Volume Blood capillaries Caring Cell Volumes Cessation of life Chest Clinical Clinical Decision Support Systems Control Groups Critical Illness Data Development Diagnosis Diagnostic Dilution Techniques Erythrocyte Transfusion Erythrocytes Evaluation Familiarity Guidelines Health Personnel Hematocrit procedure Hemoglobin Hospitalization Hospitals Hypotension Hypovolemia Hypovolemics Iatrogenesis Knowledge Liquid substance Marketing Measurement Measures Methodology Methods Operative Surgical Procedures Outcome Patients Phase Positioning Attribute Publications Randomized Randomized, Controlled Trials Recommendation Respiratory Failure Resuscitation Role Sensitivity and Specificity Sepsis Septic Shock Signs and Symptoms Small Business Innovation Research Grant Surrogate Markers System Techniques Technology Testing Time Tracer Translating United States Validation Vasoconstrictor Agents Weight Work cardiovascular collapse clinical practice commercial application commercialization comorbidity cost design electric impedance evidence base experience first-in-human hemodynamics hypoperfusion improved improved outcome maltreatment prospective prototype randomized trial septic patients standard care success support tools technological innovation tool treatment as usual treatment guidelines usability user centered design user-friendly

项目摘要

ABSTRACT Sepsis impacts 1.7 million Americans annually, leading to 270,000 deaths and $62 billion in costs. Most of the sepsis treatment follows the Surviving Sepsis Campaign (SSC) guidelines, consisting of early antibiotics, liberal fluid resuscitation, and vasopressor use in persistent hypotension. However, the fundamental assumption that sepsis universally results in high capillary leak leading to hypovolemia that benefits from aggressive fluid resuscitation, has been refuted by multiple publications suggesting improved outcomes with the administration of less or even no fluid. In fact, other studies have shown that even very restrictive fluid resuscitation might benefit septic shock. Despite these findings, U.S.-based treatment guidelines and CMS requirements are a weight-based fluid administration for all patients, irrespective of actual intravascular fluid status. Thus, there is a significant unmet need for clinically validated sepsis fluid management strategies based on precise, objective assessment of circulating BV. Daxor’s BVA-100, provides 98% accurate quantitative measurement of total blood volume, plasma volume, and red blood cell volume, which it then compares to validated patient-specific norms to provide an accurate measure of intravascular blood volume composition and derangement. A prospective randomized controlled trial (RCT) evaluated the impact of BVA in critically ill surgical patients (n=100) with septic shock, severe sepsis, severe respiratory failure, and/or cardiovascular collapse. In this study access to BVA resulted in a change in treatment in 44% of the time to patients randomized to the BV group and would have resulted in a treatment change in 61% of the patients in the control group. Additionally, the control group received red blood cell transfusions 1.5 ± 2 days later that the BVA group, at which time the abnormality became clinically evident. The preliminary work presented supports Daxor’s hypotheses that (1) sepsis patients are highly heterogeneous with respect to BV and RBCV status implying that (2) standard care decongestion strategies for treating such patients would benefit from BVA as a uniquely precise, objective diagnostic measure of intravascular BV and RBCV derangement. Here, Daxor hypothesizes that fluid management guided by direct quantification of BV status represents a potential paradigm shift in clinical practice, which to date has been based on surrogate markers that lack GS sensitivity and specificity. Transitioning this initial success to clinical acceptance requires the development of a validated, protolyzed methodology for the implementation of BVA, as well as a clinical decision-support system (CDSS) translating BVA results into actionable treatment decisions. The proposed Phase I supports the development of the Sepsis FLO (Sepsis FLuid Optimizer), a CDSS designed to precisely guide BV diagnosis and treatment in sepsis patients. This will be achieved through 1) the development of an alpha prototype through user-centered design; 2) the validation of three functional prototypes through formative usability testing; and 3) the development of a functional beta prototype. In Phase II, the Sepsis- FLO will be further validated in a RCT powered to assess improvements of clinical outcomes versus usual care.

抽象的败血症每年影响 170 万美国人，导致 27 万人死亡，造成 620 亿美元的损失。脓毒症治疗遵循脓毒症生存运动 (SSC) 指南，包括早期抗生素、自由药物然而，基本假设是，液体复苏和升压药在持续性低血压中的应用。脓毒症普遍导致高毛细血管渗漏，导致血容量减少，而侵蚀性液体则有益于血容量减少复苏，已被多个出版物反驳，表明管理改善了结果事实上，其他研究表明，即使是非常严格的液体复苏也可能会导致液体复苏。尽管有这些发现，美国的治疗指南和 CMS 要求仍然是有益的。对所有患者进行基于体重的液体管理，无论实际血管内液体状态如何。基于精确、客观的经过临床验证的脓毒症液体管理策略的重大未满足需求 Daxor 的 BVA-100 评估循环 BV，提供 98% 准确的全血定量测量。体积、血浆体积和红细胞体积，然后与经过验证的患者特定标准进行比较提供血管内血容量成分和紊乱的准确测量。随机对照试验 (RCT) 评估了 BVA 对患有脓毒症的危重手术患者 (n=100) 的影响休克、严重脓毒症、严重呼吸衰竭和/或心血管衰竭在本研究中获得 BVA。导致随机分配至 BV 组的患者在 44% 的时间内发生治疗变化，并且导致对照组 61% 的患者改变治疗。 BVA 组 1.5 ± 2 天后进行红细胞输注，此时异常已出现临床症状显然，所提出的初步工作支持 Daxor 的假设：(1) 脓毒症患者的发病率很高。 BV 和 RBCV 状态的异质性意味着 (2) 标准护理缓解充血策略 BVA 是一种独特、精确、客观的诊断措施，治疗此类患者将受益匪浅。在这里，Daxor 强调直接指导液体管理。 BV 状态的量化代表了临床实践中潜在的范式转变，迄今为止，这一转变已基于缺乏 GS 敏感性和特异性的替代标记将这一初步成功转化为临床。接受需要开发一种经过验证的、原型化的方法来实施 BVA，因为以及将 BVA 结果转化为可行的治疗决策的临床决策支持系统 (CDSS)。拟议的第一阶段支持脓毒症 FLO（脓毒症流体优化器）的开发，这是一种设计的 CDSS 精确指导败血症患者的 BV 诊断和治疗这将通过以下方式实现：1) 通过以用户为中心的设计开发阿尔法原型；2）验证三个功能原型通过形成性可用性测试；3) 开发功能性测试原型在第二阶段，脓毒症-。 FLO 将在随机对照试验中得到进一步验证，旨在评估临床结果与常规护理相比的改善情况。