Metabolomics Pilot Study Identifies Desynchronization of 24-H Rhythms and Distinct Intra-patient Variability Patterns in Critical Illness: A Preliminary Report.

Metabolomics Pilot Study Identifies Desynchronization of 24-H Rhythms and Distinct Intra-patient Variability Patterns in Critical Illness: A Preliminary Report.
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代谢组学试点研究确定了危重疾病中 24 小时节律的不同步和独特的患者内部变异模式:初步报告。

DOI:
10.3389/fneur.2020.533915
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发表时间:
2020
影响因子:
3.4
通讯作者:
Cornelissen-Guillaume G
Cornelissen-Guillaume G
中科院分区:
医学3区
文献类型:
--
作者:
Lusczek ER;Parsons LS;Elder J;Harvey SB;Skube M;Muratore S;Beilman G;Cornelissen-Guillaume G

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背景:同步昼夜节律在协调生理健康中起着关键作用。不同步的昼夜节律可能使个体易患疾病或指示潜在疾病。重症监护病房(ICU)患者可能由于ICU的破坏性环境条件和潜在的病理生理而经历昼夜节律不同步。本观察性初步研究旨在通过分析生命体征和血浆代谢物的24小时节律,确定ICU患者相对于健康对照者的24小时节律是否发生改变。方法:对5名健康对照者和5名ICU患者进行24 h的昼夜节律监测,每30 min测一次心率和血压,每1 h测一次体温,每4 h采血进行基于质谱的血浆代谢组学检测。每分钟测一次床旁声级。使用余弦法评估24小时节律的生命体征和推定血浆代谢物。结果:ICU病房噪音明显高于健康对照组,平均噪音水平高于EPA建议。健康对照组的个体和群体24小时节律普遍显著。虽然少数ICU患者在孤立变量中有明显的24小时节律,但除了皮质醇外,ICU患者作为一个群体没有发现明显的节律。这表明ICU患者的相位和振幅缺乏一致性。最后,代谢谱的主成分分析显示了血浆样本聚类的惊人模式。每个ICU患者的样本在单独的集群中清晰可辨,与健康对照的单个集群分开。结论:在这项初步研究中,与健康对照相比,ICU患者的24小时节律明显不同步。血浆代谢谱的聚类表明,代谢组学可以用于纵向跟踪个体患者的临床病程。我们的研究结果表明,ICU患者的新陈代谢和昼夜节律系统的整体紊乱应该进一步表征,以确定对患者护理的影响。
Background: Synchronized circadian rhythms play a key role in coordinating physiologic health. Desynchronized circadian rhythms may predispose individuals to disease or be indicative of underlying disease. Intensive care unit (ICU) patients likely experience desynchronized circadian rhythms due to disruptive environmental conditions in the ICU and underlying pathophysiology. This observational pilot study was undertaken to determine if 24-h rhythms are altered in ICU patients relative to healthy controls by profiling 24-h rhythms in vital signs and plasma metabolites. Methods: We monitored daily rhythms in 5 healthy controls and 5 ICU patients for 24 h. Heart rate and blood pressure were measured every 30 min, temperature was measured every hour, and blood was sampled for mass spectrometry-based plasma metabolomics every 4 h. Bedside sound levels were measured every minute. Twenty-four hours rhythms were evaluated in vitals and putatively identified plasma metabolites individually and in each group using the cosinor method. Results: ICU patient rooms were significantly louder than healthy controls' rooms and average noise levels were above EPA recommendations. Healthy controls generally had significant 24-h rhythms individually and as a group. While a few ICU patients had significant 24-h rhythms in isolated variables, no significant rhythms were identified in ICU patients as a group, except in cortisol. This indicates a lack of coherence in phases and amplitudes among ICU patients. Finally, principal component analysis of metabolic profiles showed surprising patterns in plasma sample clustering. Each ICU patient's samples were clearly discernable in individual clusters, separate from a single cluster of healthy controls. Conclusions: In this pilot study, ICU patients' 24-h rhythms show significant desynchronization compared to healthy controls. Clustering of plasma metabolic profiles suggests that metabolomics could be used to track individual patients' clinical courses longitudinally. Our results show global disordering of metabolism and the circadian system in ICU patients which should be characterized further in order to determine implications for patient care.
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