紊乱的宿主代谢越来越被认为是败血症发病机理的支柱，但代谢动态变化及其与宿主响应其他成分的关系仍未完全理解。我们试图确定败血性休克患者的早期宿主代谢反应，并探索生物物理表型和代谢亚组之间的临床结局差异。我们测量了反映宿主免疫和内皮反应的血清代谢物和蛋白质在败血性休克患者中的水平。我们考虑了在16个美国医疗中心进行的一项已完成的II期随机对照试验的安慰剂组的患者。血清收集于基线（在确认败血性休克的24小时内），24小时和48小时入组后。建立线性混合模型以评估蛋白质分析物和代谢物的早期轨迹，分层按28天死亡状态。无监督的聚类基线代谢组学数据以识别患者亚组。在一个临床试验的安慰剂组中入组的具有血管活性药物依赖性败血性休克和中度器官功能障碍的患者。五十一个代谢物和十个蛋白质分析物在72名败血性休克患者中纵向测量。在30名（41.7％）在28天内死亡的患者中，酰基肉碱和白细胞介素8的体内浓度在基线时升高，并在早期复苏的T24和T48中持续升高。在死亡患者中乳酸酸，白细胞介素6、肿瘤坏死因子-α和血管生成素2的浓度下降速度较慢。从基线代谢物的聚类中出现了两组。第一组的酰基肉碱水平较高，在基线和术后（p < 0.05）的机能障碍和一年内更高的死亡率（p < 0.001）中有所体现。在败血性休克患者中，非幸存者表现出比幸存者更深刻和持久的蛋白质分析物失调，这是中性粒细胞激活和线粒体相关代谢紊乱所致。版权所有 ©2023 The Authors. 由 Wolters Kluwer Health，Inc. 代表危重病医学会发表。

Perturbed host metabolism is increasingly recognized as a pillar of sepsis pathogenesis, yet the dynamic alterations in metabolism and its relationship to other components of the host response remain incompletely understood. We sought to identify the early host-metabolic response in patients with septic shock and to explore biophysiological phenotyping and differences in clinical outcomes among metabolic subgroups.We measured serum metabolites and proteins reflective of the host-immune and endothelial response in patients with septic shock.We considered patients from the placebo arm of a completed phase II, randomized controlled trial conducted at 16 U.S. medical centers. Serum was collected at baseline (within 24 hr of the identification of septic shock), 24-hour, and 48-hour postenrollment. Linear mixed models were built to assess the early trajectory of protein analytes and metabolites stratified by 28-day mortality status. Unsupervised clustering of baseline metabolomics data was conducted to identify subgroups of patients.Patients with vasopressor-dependent septic shock and moderate organ dysfunction that were enrolled in the placebo arm of a clinical trial.None.Fifty-one metabolites and 10 protein analytes were measured longitudinally in 72 patients with septic shock. In the 30 patients (41.7%) who died prior to 28 days, systemic concentrations of acylcarnitines and interleukin (IL)-8 were elevated at baseline and persisted at T24 and T48 throughout early resuscitation. Concentrations of pyruvate, IL-6, tumor necrosis factor-α, and angiopoietin-2 decreased at a slower rate in patients who died. Two groups emerged from clustering of baseline metabolites. Group 1 was characterized by higher levels of acylcarnitines, greater organ dysfunction at baseline and postresuscitation (p < 0.05), and greater mortality over 1 year (p < 0.001).Among patients with septic shock, nonsurvivors exhibited a more profound and persistent dysregulation in protein analytes attributable to neutrophil activation and disruption of mitochondrial-related metabolism than survivors.Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.