From the Department of Surgery (D.L.H.), and Department of Anesthesiology and Pain Medicine (L.F.B., V.P., F.C.N., D.R.), University of Washington; Fred Hutchinson Cancer Research Center (S.L.N., D.R.); and Division of Trauma and Critical Care, Department of Surgery (J.C., G.E.O.), Harborview Medical Center, Seattle, Washington.
J Trauma Acute Care Surg. 2021 Jan 1;90(1):35-45. doi: 10.1097/TA.0000000000002952.
Following trauma, persistent inflammation, immunosuppression, and catabolism may characterize delayed recovery or failure to recover. Understanding the metabolic response associated with these adverse outcomes may facilitate earlier identification and intervention. We characterized the metabolic profiles of trauma victims who died or developed chronic critical illness (CCI) and hypothesized that differences would be evident within 1-week postinjury.
Venous blood samples from trauma victims with shock who survived at least 7 days were analyzed using mass spectrometry. Subjects who died or developed CCI (intensive care unit length of stay of ≥14 days with persistent organ dysfunction) were compared with subjects who recovered rapidly (intensive care unit length of stay, ≤7 days) and uninjured controls. We used partial least squares discriminant analysis, t tests, linear mixed effects regression, and pathway enrichment analyses to make broad comparisons and identify differences in metabolite concentrations and pathways.
We identified 27 patients who died or developed CCI and 33 who recovered rapidly. Subjects were predominantly male (65%) with a median age of 53 years and Injury Severity Score of 36. Healthy controls (n = 48) had similar age and sex distributions. Overall, from the 163 metabolites detected in the samples, 56 metabolites and 21 pathways differed between injury outcome groups, and partial least squares discriminant analysis models distinguished injury outcome groups as early as 1-day postinjury. Differences were observed in tryptophan, phenylalanine, and tyrosine metabolism; metabolites associated with oxidative stress via methionine metabolism; inflammatory mediators including kynurenine, arachidonate, and glucuronic acid; and products of the gut microbiome including indole-3-propionate.
The metabolic profiles in subjects who ultimately die or develop CCI differ from those who have recovered. In particular, we have identified differences in markers of inflammation, oxidative stress, amino acid metabolism, and alterations in the gut microbiome. Targeted metabolomics has the potential to identify important metabolic changes postinjury to improve early diagnosis and targeted intervention.
Prognostic/epidemiologic, level III.
创伤后，持续的炎症、免疫抑制和分解代谢可能导致恢复延迟或无法恢复。了解与这些不良结局相关的代谢反应可能有助于更早地识别和干预。我们对创伤后死亡或发生慢性危重病（CCI）的患者的代谢特征进行了描述，并假设在创伤后 1 周内就会出现差异。
对至少存活 7 天的休克创伤患者的静脉血样进行质谱分析。将死亡或发生 CCI（入住重症监护病房的时间≥14 天，存在持续的器官功能障碍）的患者与快速恢复（入住重症监护病房的时间≤7 天）的患者和未受伤的对照组进行比较。我们使用偏最小二乘判别分析、t 检验、线性混合效应回归和途径富集分析进行广泛比较，并确定代谢物浓度和途径的差异。
我们确定了 27 名死亡或发生 CCI 的患者和 33 名快速恢复的患者。患者主要为男性（65%），中位年龄为 53 岁，损伤严重程度评分 36 分。健康对照组（n=48）的年龄和性别分布相似。总体而言，在样本中检测到的 163 种代谢物中，有 56 种代谢物和 21 条代谢途径在损伤结局组之间存在差异，偏最小二乘判别分析模型在损伤后 1 天即可区分损伤结局组。在色氨酸、苯丙氨酸和酪氨酸代谢；通过蛋氨酸代谢与氧化应激相关的代谢物；包括犬尿酸、花生四烯酸和葡萄糖醛酸在内的炎症介质；以及包括吲哚-3-丙酸在内的肠道微生物组产物中观察到差异。
最终死亡或发生 CCI 的患者的代谢特征与已恢复的患者不同。特别是，我们已经确定了炎症、氧化应激、氨基酸代谢和肠道微生物组改变的标志物差异。靶向代谢组学有可能确定创伤后重要的代谢变化，以改善早期诊断和靶向干预。
预后/流行病学，III 级。
