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

项目摘要 我们以前的观察表明，需要人工营养的创伤受害者：1）很可能是 在受伤后的第一周内营养不良，2）通常需要密集和昂贵的器官支持 失败，和3）接受的蛋白质的量可能是临床结果的重要决定因素。最近的一 在峰会上，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 给重症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 需要的 我们已经观察到对损伤和营养支持的反应的变化，这些变化反映了对 蛋白质代谢对损伤的反应和蛋白质合成对肠内营养的反应的恢复。 在我们的研究中，瓜氨酸是氮代谢的中间体，在我们的分析中突出表现为对 创伤和肠内营养支持。瓜氨酸可能与许多代谢途径有关 与蛋白质合成有关的蛋白质合成在危重病和康复中很重要，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。 我们建议招募参加高剂量肠内给药的随机临床试验的受试者 蛋白质补充与接受标准肠内营养治疗的受试者相比， 循证护理。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素是如何 在外科重症患者和创伤患者体内代谢。我们的研究是创新的， 应用200种循环代谢底物和终产物的靶向代谢组学测量， 代表重症创伤和手术患者在重症监护室住院期间的约25种代谢途径 监护室。我们的目的是：（1）确定早期肠内蛋白补充对 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，使我们能够更精确地 开肠内蛋白 人工营养支持的标准方法可能无法捕捉所有重要的差异， 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一目标。

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.