Parent Brodie A, Seaton Max, Djukovic Danijel, Gu Haiwei, Wheelock Brittany, Navarro Sandi L, Raftery Daniel, O'Keefe Grant E
From the Department of Surgery (B.A.P., M.S., D.D., B.W., G.E.O.) University of Washington Medical Center Harborview, Seattle Washington; Department of Surgery (M.S.), University of Maryland, Baltimore, Maryland; Mitochondria and Metabolism Center (H.G., D.R.), University of Washington, Seattle, Washington; Department of Epidemiology and Nutrition (S.L.N.), University of Washington, Seattle, Washington.
J Trauma Acute Care Surg. 2017 Apr;82(4):704-713. doi: 10.1097/TA.0000000000001381.
Artificial nutrition support is central to the care of critically ill patients and is primarily provided enterally (EN). There are circumstances when parenteral nutrition (PN) is considered necessary. We are uncertain how each of these approaches confer clinical benefits beyond simply providing calories. We sought to better understand how each of these techniques influence metabolism in critically ill patients using a broad-based metabolomics approach. Metabolic responses to EN and PN may differ in ways that could help us understand how to optimize use of these therapies.
We prospectively enrolled subjects over 7 months in 2015 at an urban, Level I trauma center. Subjects were included before starting either EN or PN during their inpatient admission. Plasma samples were obtained between 1 and 12 hours before initiation of artificial nutrition, and 3 and 7 days later. All samples were analyzed with liquid chromatography/mass spectrometry-based metabolomics. Differences in metabolite concentrations were assessed via principal component analyses and multiple linear regression.
We enrolled 30 subjects. Among the critically ill subjects, 10 received EN and 10 received PN. In subjects receiving EN, amino acid and urea cycle metabolites (citrulline, p = 0.04; ornithine, p = 0.05) increased, as did ribonucleic acid metabolites (uridine, p = 0.04; cysteine, 0 = 0.05; oxypurinol, p = 0.04). Oxidative stress decreased over time (increased betaine, p = 0.05; decreased 4-pyridoxic acid, p = 0.04). In subjects receiving PN, amino acid concentrations increased over time (taurine, p = 0.04; phenylalanine, p = 0.05); omega 6 and omega 3 fatty acid concentrations decreased over time (p = 0.05 and 0.03, respectively).
EN was associated with amino acid repletion, urea cycle upregulation, restoration of antioxidants, and increasing ribonucleic acid synthesis. Parenteral nutrition was associated with increased amino acid concentrations, but did not influence protein metabolism or antioxidant repletion. This suggests that parenteral amino acids are used less effectively than those given enterally. The biomarkers reported in this study may be useful in guiding nutrition therapy for critically ill patients.
Therapeutic study, level III; prognostic study, level II.
人工营养支持是危重症患者护理的核心内容,主要通过肠内营养(EN)提供。在某些情况下,肠外营养(PN)被认为是必要的。我们不确定这两种方法除了单纯提供热量外,如何带来临床益处。我们试图通过广泛的代谢组学方法更好地了解这些技术中的每一种如何影响危重症患者的代谢。对EN和PN的代谢反应可能以有助于我们理解如何优化这些治疗方法使用的方式有所不同。
2015年,我们在一家城市一级创伤中心前瞻性地招募受试者,为期7个月。受试者在住院期间开始EN或PN之前被纳入研究。在开始人工营养前1至12小时以及3和7天后采集血浆样本。所有样本均采用基于液相色谱/质谱的代谢组学进行分析。通过主成分分析和多元线性回归评估代谢物浓度的差异。
我们招募了30名受试者。在危重症受试者中,10人接受EN,10人接受PN。在接受EN的受试者中,氨基酸和尿素循环代谢物(瓜氨酸,p = 0.04;鸟氨酸,p = 0.05)增加,核糖核酸代谢物(尿苷,p = 0.04;半胱氨酸,p = 0.05;氧嘌呤醇,p = 0.04)也增加。氧化应激随时间降低(甜菜碱增加,p = 0.05;4-吡哆酸降低,p = 0.04)。在接受PN的受试者中,氨基酸浓度随时间增加(牛磺酸,p = 0.04;苯丙氨酸,p = 0.05);ω-6和ω-3脂肪酸浓度随时间降低(分别为p = 0.05和0.03)。
EN与氨基酸补充、尿素循环上调、抗氧化剂恢复以及核糖核酸合成增加有关。肠外营养与氨基酸浓度增加有关,但不影响蛋白质代谢或抗氧化剂补充。这表明肠外氨基酸的利用效率低于肠内给予的氨基酸。本研究中报告的生物标志物可能有助于指导危重症患者的营养治疗。
治疗性研究,III级;预后性研究,II级。