Protein-enhanced enteral nutrition and metabolomics in critically ill trauma and surgical patients

危重创伤和手术患者的蛋白质强化肠内营养和代谢组学

• 批准号: 10017298
• 负责人: GRANT E O'KEEFE
• 金额: $ 38.04万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-18 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10017298
• 关键词: APACHE III; Address; Admission activity; Affect; Age; Amino Acids; Biochemical; Biochemical Markers; Biological Markers; Caring; Characteristics; Citrulline; Clinical; Clinical Trials; Critical Illness; Data; Dietary Intervention; Dose; Enrollment; Enteral; Enteral Nutrition; Excretory function; Goals; Guidelines; Height; Hour; Infection; Injury; Intensive Care Units; Measurable; Measurement; Measures; Mechanical ventilation; Metabolic; Metabolic Pathway; Metabolism; Modeling; Nitrogen; Nutrient; Nutritional; Nutritional Support; Operative Surgical Procedures; Organ; Organ failure; Outcome; Pathway interactions; Patients; Plasma; Positioning Attribute; Prealbumin; Protein Biosynthesis; Proteins; Randomized; Randomized Clinical Trials; Recommendation; Recovery; Renal dialysis; Sampling; Serum; Severities; Severity of illness; Structure; Supplementation; Testing; Trauma; Trauma patient; Urine; Visceral; Weight; analytical method; base; care costs; circulating biomarkers; combat; cost; evidence base; improved; improved outcome; individualized medicine; innovation; metabolome; metabolomics; nitrogen metabolism; nucleic acid metabolism; nutrition; prevent; protein biomarkers; protein intake; protein metabolism; recruit; response; response to injury; restoration; sex; symposium; urinary; wound healing

PROJECT SUMMARY Our previous observations indicate that trauma victims who require artificial nutrition: 1) are likely to be undernourished during the first week after injury, 2) will often require intensive and costly support for organ failure, and 3) the amount of protein received may be an important determinant of clinical outcomes. A recent summit, convening experts concluded that we must study more thoroughly whether more protein is beneficial to critically ill patients. Determining whether and how to supplement protein intake is a critical unmet need. We have observed changes in response to injury and nutritional support that reflect suppression of protein metabolism in response to injury and a restoration of protein synthesis in response to enteral nutrition. In our studies, citrulline, an intermediate in nitrogen metabolism, stood out in our analyses as responsive to trauma and to enteral nutritional support. Citrulline is potentially relevant to a number of metabolic pathways related to protein synthesis which are important in critical illness and recovery and for these reasons, is the focus of two of our hypotheses; however, we have the opportunity to study a broad range of metabolites. We propose to recruit subjects who are enrolled in a randomized clinical trial of high dose enteral protein supplementation compared to subjects treated with standard enteral nutrition as part of an established, evidence-based approach to care. We will apply metabolomics and analytic methods to help us better understand the metabolic response to injury, and to understand how protein and other nutrients are metabolized in critically ill surgical patients and trauma victims. Our studies are innovative through the application of targeted metabolomic measurements of 200 circulating metabolic substrates and end-products, representing ~25 metabolic pathways in critically ill trauma and surgical patients over their stay in the intensive care unit. Our proposed aims are: (1) To determine the effects of early enteral protein supplementation on circulating markers of protein metabolism, (2) To determine whether we can predict urine nitrogen excretion using a combination of demographic, clinical and metabolite biomarkers; enabling us to more precisely prescribe enteral protein. Standard approaches to artificial nutritional support may not capture all the important differences that could be addressed through precision nutritional support. Our objective is to move us closer to this goal.

项目总结 我们之前的观察表明，需要人工营养的创伤受害者：1)很可能是 受伤后的第一周营养不良，2)通常需要高强度且昂贵的器官支持。 失败，以及3)接受的蛋白质的数量可能是临床结果的重要决定因素。最近 峰会，召集专家总结说，我们必须更彻底地研究更多的蛋白质是否有益 给危重病人。确定是否以及如何补充蛋白质摄入量是一个关键的未满足的问题 需要。 我们观察到了对损伤和营养支持的反应的变化，反映了对 损伤反应的蛋白质代谢和肠内营养反应的蛋白质合成的恢复。 在我们的研究中，氮代谢的中间体瓜氨酸在我们的分析中表现出对 创伤和肠内营养支持。瓜氨酸可能与许多代谢途径有关 与蛋白质合成有关，蛋白质合成在危重疾病和康复中很重要，因此， 我们的两个假设的焦点；然而，我们有机会研究广泛的代谢物。 我们建议招募参加大剂量肠内注射的随机临床试验的受试者。 蛋白质补充剂与标准肠内营养治疗的受试者进行比较， 循证护理方法。我们将应用代谢组学和分析方法来帮助我们更好地 了解对损伤的代谢反应，并了解蛋白质和其他营养物质是如何 在外科危重病人和创伤受害者体内代谢。我们的研究是创新的 应用200种循环代谢底物和最终产品的靶向代谢组学测量， 代表了危重创伤和外科患者在重症监护室期间的~25条代谢途径 护理室。我们建议的目标是：(1)确定早期肠内补充蛋白质对 蛋白质代谢的循环标志物，(2)确定我们是否可以预测尿氮排泄 使用人口统计学、临床和代谢物生物标志物的组合；使我们能够更准确地 开出肠道蛋白质的处方。 人工营养支持的标准方法可能无法捕捉到以下所有重要差异 可以通过精确的营养支持来解决。我们的目标是让我们更接近这一目标。