Serum Levels of Branched Chain Amino Acids Predict Duration of Cardiovascular Organ Failure in Septic Shock.
Serum Levels of Branched Chain Amino Acids Predict Duration of Cardiovascular Organ Failure in Septic Shock.
复制标题
分支链氨基酸的血清水平预测败血性休克中心血管衰竭的持续时间。
DOI：
10.1097/shk.0000000000001687
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发表时间：
2021-07-01
期刊：
影响因子：
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通讯作者：
RACE Trial Investigators
中科院分区：
文献类型：
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作者：
Puskarich MA;McHugh C;Flott TL;Karnovsky A;Jones AE;Stringer KA;RACE Trial Investigators
脓毒症改变了心脏代谢燃料的偏好，这种破坏可能对心血管功能有影响。更好地理解代谢在脓毒症心血管衰竭的发展和持续中的作用，有助于确定新的药物治疗方法。二次分析的前瞻性定量1H-NMR代谢组学数据，从病人登记在第二阶段随机对照试验左旋肉碱在感染性休克。SOFA评分>=5，乳酸>=2，需要血管加压药支持至少4小时的参与者有资格入组。评估了代谢物预测a）休克在48小时内消退的生存率和b）无血管加压药天数的独立预后价值。B）。预测代谢物的浓度进行了比较，参与者之间的休克分辨率和没有在48小时。分析了228例患者的血清1H-NMR代谢组学数据。81例（36%）患者符合主要结局; 33例（14%）患者在48小时前死亡。支链氨基酸（BCAA）、缬氨酸、亮氨酸和异亮氨酸是调整多假设检验后主要结局的单变量预测因子，而缬氨酸在控制SOFA评分后仍具有显著性。当基于无血管加压药天数进行分析时，观察到类似的结果，并且在控制混杂变量并排除非存活者后持续存在。在48小时的支链氨基酸浓度显着区分休克分辨率与持续休克。在感染性休克患者中，支链氨基酸浓度独立预测休克消退时间。本研究提供了假设生成数据，以了解支链氨基酸对脓毒症心血管衰竭病理生理学的潜在贡献，为未来的研究开辟了领域。
Sepsis shifts cardiac metabolic fuel preference and this disruption may have implications for cardiovascular function. A greater understanding of the role of metabolism in the development and persistence of cardiovascular failure in sepsis could serve to identify novel pharmacotherapeutic approaches. Secondary analysis of prospective quantitative 1H-NMR metabolomic data from patients enrolled in a phase II randomized control trial of L-carnitine in septic shock. Participants with a SOFA score of >=5, lactate >=2, and requiring vasopressor support for at least 4 hours were eligible for enrollment. The independent prognostic value of metabolites to predict a) survival with shock resolution within 48 hours and b) vasopressor free days were assessed. Concentrations of predictive metabolites were compared between participants with and without shock resolution at 48 hours. Serum 1H-NMR metabolomics data from 228 patients were analyzed. 81 (36%) patients met the primary outcome; 33 (14%) died prior to 48 hours. The branched chain amino acids (BCAA), valine, leucine, and isoleucine were univariate predictors of the primary outcome after adjusting for multiple hypothesis testing, while valine remained significant after controlling for SOFA score. Similar results were observed when analyzed based on vasopressor free days, and persisted after controlling for confounding variables and excluding non-survivors. BCAA concentrations at 48 hours significantly discriminated between those with shock resolution versus persistent shock. Among patients with septic shock, BCAA concentrations independently predict time to shock resolution. This study provides hypothesis generating data into the potential contribution of BCAAs to the pathophysiology of cardiovascular failure in sepsis, opening areas for future investigations.