Lusczek Elizabeth R, Parsons Lee S, Elder Jesse, Harvey Stephen B, Skube Mariya, Muratore Sydne, Beilman Greg, Cornelissen-Guillaume Germaine
Department of Surgery, University of Minnesota, Minneapolis, MN, United States.
Minnesota Supercomputing Institute, University of Minnesota, Minneapolis, MN, United States.
Front Neurol. 2020 Oct 2;11:533915. doi: 10.3389/fneur.2020.533915. eCollection 2020.
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. 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. 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. 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.
同步的昼夜节律在协调生理健康方面起着关键作用。不同步的昼夜节律可能使个体易患疾病或表明存在潜在疾病。重症监护病房（ICU）的患者可能由于ICU环境干扰和潜在病理生理学而经历不同步的昼夜节律。这项观察性试点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24小时节律是否发生改变。我们对5名健康对照者和5名ICU患者的日常节律进行了24小时监测。每30分钟测量一次心率和血压，每小时测量一次体温，每4小时采集一次血液用于基于质谱的血浆代谢组学分析。每分钟测量一次床边声音水平。使用余弦分析法分别对每组个体的生命体征和推测鉴定出的血浆代谢物进行24小时节律评估。ICU患者病房的声音明显比健康对照者的病房大，平均噪音水平高于美国环境保护局的建议。健康对照者个体和作为一个群体通常具有显著的24小时节律。虽然一些ICU患者在个别变量上有显著的24小时节律，但作为一个群体，ICU患者除皮质醇外未发现显著节律。这表明ICU患者之间在相位和振幅上缺乏一致性。最后，代谢谱的主成分分析在血浆样本聚类中显示出令人惊讶的模式。每个ICU患者的样本在单独的聚类中清晰可辨，与健康对照者的单个聚类分开。在这项试点研究中，与健康对照者相比，ICU患者的24小时节律显示出明显的不同步。血浆代谢谱聚类表明，代谢组学可用于纵向跟踪个体患者的临床病程。我们的结果表明ICU患者的代谢和昼夜节律系统存在整体紊乱，应进一步加以表征，以确定对患者护理的影响。
