Profiles and impact of venous congestion on organ function and patient outcomes in sepsis

脓毒症静脉充血对器官功能和患者预后的影响

• 批准号: 10714259
• 负责人: Robert Russell Ehrman
• 金额: $ 38.5万
• 依托单位: WAYNE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-15 至 2028-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10714259
• 关键词: Accident and Emergency department; Biological Markers; Data; Disease; Echocardiography; Functional disorder; Generations; Guidelines; Heterogeneity; Hospitalization; Hypertension; IV Fluid; Individual; Infection; Intervention; Investigation; Kidney; Knowledge; Laboratories; Lung; Machine Learning; Microscopic; Morbidity - disease rate; Myocardial dysfunction; Organ; Organ failure; Outcome; Patient-Focused Outcomes; Patients; Persons; Phenotype; Process; Prognosis; Recommendation; Renal function; Risk; Sepsis; Specific qualifier value; Stress; System; Time; Ultrasonography; Vascular Endothelium; Venous; adverse outcome; biomarker development; biomarker panel; care costs; data streams; heart function; improved; liver function; longitudinal database; mortality; novel; patient oriented; personalized care; profiles in patients; pulmonary function; response; septic; septic patients; serial imaging; targeted treatment

Abstract Sepsis is a common condition with significant morbidity, mortality, and annual costs-of-care in the billions of dollars. Despite innumerable studies on the causes of, and therapies for, sepsis, the mortality rate has not changed substantially in the last 20 years. Treatments remain generic, with current guidelines recommending the same approach for all patients, regardless of the obvious litany of differences that exist at baseline. Moreover, the blanket administration of 30cc/kg of intravenous fluid (IVF) to all patients is recognized as being directly harmful to some. Patient-level heterogeneity in prior sepsis trials is recognized as a substantial contributor to all of these problems, yet no prior investigation has attempted to identify septic phenotypes, a necessary first step towards precision care. This project will address these critical knowledge gaps by systematically characterizing profiles of patients with sepsis using a combination of sonographic and biomarker variables. This will begin at the time of presentation to the Emergency Department and continue at specified time points during hospitalization, thereby creating a rich longitudinal database from which identification of unique phenotypes will be possible. Our central hypothesis is that central venous hypertension: (i) is deleterious to the function of the lungs, liver kidneys, and vascular endothelium; (ii) is worsened by cardiac dysfunction and IVF administration; and (iii), contributes to adverse organ-specific and overall outcomes. Cardiac function will be assessed with echocardiography while congestion in the lungs, and kidneys will be assessed using previously validated sonographic markers of congestion. Biomarkers for each organ will be collected concurrently thereby increasing the fidelity of our phenotypic profiles by pairing indicators of macro- and microscopic stress and dysfunction. Classical and machine learning approaches will be used to analyze our large data-stream and develop a rule-based system to identify distinct sub-populations of sepsis patients who have greater risk/likelihood of both organ-specific and overall adverse outcomes. Completion of the project will result in generation of the first comprehensive description of septic phenotypes at the level of individual organs and the organismal level, including the effects of resuscitative interventions. The combination of longitudinal imaging and laboratory data is novel and offers potential short-term (outcome-based guidance of IVF administration and prognosis via sonographic data) and long-term (development of biomarker panels and targeted therapeutics) patient-oriented benefits.

摘要 脓毒症是一种常见的疾病，具有显著的发病率、死亡率和数十亿美元的年度护理成本。 美元.尽管对败血症的病因和治疗方法进行了无数的研究，但死亡率并不高。 在过去的20年里发生了巨大的变化。治疗仍然是通用的，目前的指南建议 对所有患者采用相同的方法，无论基线时存在的明显差异如何。 此外，向所有患者毯式施用30 cc/kg的静脉内流体（IVF）被认为是有效的。 对某些人有害。既往脓毒症试验中患者水平的异质性被认为是 所有这些问题的贡献者，但没有先前的调查试图确定脓毒症表型， 迈向精准医疗的第一步本项目将通过以下方式解决这些关键的知识差距： 使用超声和生物标志物的组合系统地表征脓毒症患者的特征 变量这将从向急诊室报告时开始开始，并在规定的时间内继续进行。 时间点，从而创建一个丰富的纵向数据库， 独特的表型将是可能的。我们的中心假设是中心静脉高压：（i）是 对肺、肝、肾和血管内皮的功能有害;（ii）因心脏病而恶化 功能障碍和IVF管理;和（iii），有助于不良器官特异性和整体结果。 心脏功能将通过超声心动图进行评估，而肺和肾脏的充血将通过超声心动图进行评估。 使用先前验证的充血超声标记进行评估。每个器官的生物标志物将 同时收集，从而增加我们的表型配置文件的保真度，通过配对指标的宏观， 微观压力和功能障碍。经典和机器学习方法将用于分析 我们的大数据流，并开发一个基于规则的系统，以确定不同的亚群败血症患者 器官特异性和总体不良结局的风险/可能性更大的患者。完成 该项目将导致产生脓毒症表型的第一个全面描述的水平， 个体器官和生物体水平，包括复苏干预的影响。相结合 纵向成像和实验室数据是新颖的，并提供了潜在的短期（基于结果的指导， IVF管理和通过超声数据的预后）和长期（生物标志物组的开发和 靶向治疗）以患者为导向的益处。