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: 10205096
• 负责人: GRANT E O'KEEFE
• 金额: $ 38.4万
• 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 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10205096
• 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.

项目摘要 我们以前的观察表明，需要人造营养的创伤受害者：1）可能是 受伤后的第一周，营养不良，2）通常需要大量且昂贵的器官支持 失败和3）收到的蛋白质量可能是临床结果的重要决定因素。最近 首脑会议，召集专家得出结论，我们必须更彻底地研究更多的蛋白质是否有益 重病患者。确定是否以及如何补充蛋白质摄入是关键的未修饰 需要。 我们已经观察到响应损伤和营养支持的变化，反映了抑制 蛋白质代谢响应损伤和响应肠内营养的蛋白质合成的恢复。 在我们的研究中，氮的中级代谢中的瓜氨酸在我们的分析中脱颖而出，以响应于 创伤和肠内营养支持。瓜氨酸可能与许多代谢途径有关 与蛋白质合成有关的蛋白质合成在危害疾病和康复中很重要，因此， 我们两个假设的重点；但是，我们有机会研究广泛的代谢产物。 我们建议招募参加高剂量肠道随机临床试验的受试者 与用标准肠内营养治疗的受试者相比，蛋白质补充剂是已建立的一部分， 基于证据的护理方法。我们将应用代谢组学和分析方法来帮助我们更好 了解对损伤的代谢反应，并了解蛋白质和其他营养素 在重症患者和创伤受害者中代谢。我们的研究通过 应用200个循环代谢底物和最终产品的目标代谢组学测量， 在重密集型中，代表重症患者和手术患者的代谢途径约25个代谢途径 护理部门。我们提出的目的是：（1）确定早期肠内蛋白质补充对 蛋白质代谢的循环标记，（2）确定我们是否可以预测尿液排泄 结合人口，临床和代谢物生物标志物；使我们更精确 开处方肠蛋白。 人工营养支持的标准方法可能无法捕获所有重要差异 可以通过精确的营养支持来解决。我们的目标是使我们更接近这个目标。

项目成果

Increasing Enteral Protein Intake in Critically Ill Trauma and Surgical Patients.

增加危重创伤和手术患者的肠内蛋白质摄入量。

• DOI: 10.1002/ncp.10256
• 发表时间: 2019
• 期刊: Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition
• 作者: O'Keefe,GrantE;Shelton,Marilyn;Qiu,Qian;Araujo-Lino,JoseCruz
• 通讯作者: Araujo-Lino,JoseCruz