超选择性β1受体拮抗作用对接受去甲肾上腺素治疗的脓毒性休克患者代谢和细胞因子谱的影响：来自STRESS-L随机研究的一项子研究。

The effects of ultra-selective beta1-antagonism on the metabolic and cytokine profile in septic shock patients receiving noradrenaline: a sub-investigation from the STRESS-L Randomised Study.

作者信息

Thomas Jarrod L, McGee Kirsty C, Hossain Anower, Perkins Gavin D, Gordon Anthony C, Young Duncan, McAuley Danny, Singer Mervyn, Lall Ranjit, Kramaric Tina, Lord Janet M, Whitehouse Tony, Mur Luis A J

机构信息

Institute of Inflammation and Ageing, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.

Department of Biochemical Engineering, School of Chemical Engineering, College of Engineering and Physical Sciences, University of Birmingham, Birmingham, UK.

出版信息

Intensive Care Med Exp. 2025 Jan 22;13(1):9. doi: 10.1186/s40635-024-00708-6.

DOI:10.1186/s40635-024-00708-6

PMID:39841388

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11754546/

Abstract

PURPOSE

The landiolol and organ failure in patients with septic shock (STRESS-L study) included a pre-planned sub-study to assess the effect of landiolol treatment on inflammatory and metabolomic markers.

METHODS

Samples collected from 91 patients randomised to STRESS-L were profiled for immune and metabolomic markers. A panel of pro- and anti-inflammatory cytokines were measured through commercially acquired multiplex Luminex assays and statistically analysed by individual and cluster-level analysis (patient). Metabolite fingerprinting was carried out by flow infusion electrospray ionisation high-resolution mass spectrometry and metabolomic data were analysed using the R-based platform MetaboAnalyst. The metabolites were identified using DIMEdb (dimedb.ibers.aber.ac.uk) from their mass/charge ratios. These metabolomic data were also re-analysed using individual and cluster-level analysis. The individual-level models were adjusted for confounders, such as age, sex, noradrenaline dosage and patient (random effect).

RESULTS

Analysis was undertaken at cluster- and individual-level. There were no significant differences in cytokine concentration level between trial arms nor survivors and non-survivors over the duration of the observations from day 1 to day 4. Metabolomic analysis showed some separation in the levels of ceramides and cardiolipins between those who survived and those who died. Following adjusted analysis for confounders, plasma metabolite concentrations remained statistically different between landiolol and standard care arms for succinic acid, L-tryptophan, L-alanine, 2,2,2-trichloroethanol, lactic acid and D-glucose.

CONCLUSIONS

In a study of ICU patients with established septic shock and a tachycardia, landiolol treatment used to reduce the heart rate from above 95 to a range between 80 and 94 beats per minute did not induce significant cytokine changes. D-Glucose, lactic acid, succinic acid, L-alanine, L-tryptophan and trichloroethanol were pathways that may merit further investigation.

TRIAL REGISTRATION

EU Clinical Trials Register Eudra CT: 2017-001785-14 ( https://www.clinicaltrialsregister.eu/ctr-search/trial/2017-001785-14/GB ); ISRCTN registry Identifier: ISRCTN12600919 ( https://www.isrctn.com/ISRCTN12600919 ).

摘要

目的

“兰地洛尔与感染性休克患者的器官衰竭（STRESS-L研究）”纳入了一项预先计划的子研究，以评估兰地洛尔治疗对炎症和代谢组学标志物的影响。

方法

对91例随机分组至STRESS-L研究的患者采集样本，分析免疫和代谢组学标志物。通过商业购买的多重Luminex检测法检测一组促炎和抗炎细胞因子，并通过个体水平和聚类水平分析（患者层面）进行统计分析。采用流动注射电喷雾电离高分辨率质谱法进行代谢物指纹图谱分析，并使用基于R的平台MetaboAnalyst分析代谢组学数据。利用DIMEdb（dimedb.ibers.aber.ac.uk）根据质荷比鉴定代谢物。这些代谢组学数据也采用个体水平和聚类水平分析进行重新分析。个体水平模型针对年龄、性别、去甲肾上腺素剂量和患者（随机效应）等混杂因素进行了调整。

结果

在聚类水平和个体水平进行了分析。从第1天到第4天的观察期间，试验组之间以及幸存者和非幸存者之间的细胞因子浓度水平没有显著差异。代谢组学分析显示，幸存者和死亡者之间神经酰胺和心磷脂水平存在一些差异。在对混杂因素进行调整分析后，兰地洛尔组和标准治疗组之间，琥珀酸、L-色氨酸、L-丙氨酸、2,2,2-三氯乙醇、乳酸和D-葡萄糖的血浆代谢物浓度在统计学上仍存在差异。