Neural correlates of β-lactam exposure in intensive care unit patients: an observational, prospective cohort study.

IF 4.8 2区医学 Q1 CLINICAL NEUROLOGY

Journal of Neurology Pub Date : 2025-04-07 DOI:10.1007/s00415-025-13067-3

Arnaud Zalta, Agnès Trébuchon, Géraldine Daquin, Lionel Velly, Marc Leone, Olivier Blin, Stanislas Lagarde, Romain Guilhaumou

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引用次数: 0

Abstract

Background: β-lactam-induced neurotoxicity in critical care patients can compromise clinical outcomes. Despite the growing use of therapeutic drug monitoring (TDM) for β-lactams, clear toxicity thresholds remain undefined, leaving clinicians uncertain about dosing adjustments when adverse effects occur. Identifying a relevant and easily detectable neurophysiological biomarker for β-lactam exposure would improve monitoring and prevent serious complications.

Methods: In a prospective multicenter, non-interventional study, we analyzed electroencephalographic (EEG) signals of 56 patients hospitalized in intensive care units (ICUs) receiving continuous infusions of five β-lactams (meropenem, piperacillin/tazobactam, cefepime, cefotaxime, or ceftazidime). We applied a time frequency decomposition on these EEG data to investigate quantitatively the power of neural dynamics across frequencies ranging from 1 to 45 Hz. We used a multivariate pattern decoding method to correlate the β-lactam exposure and Sepsis-related Organ Failure Assessment (SOFA) scores with the neural activity.

Results: β-lactam exposure correlated with increased β-low γ neural dynamics (20-40 Hz) (p < 0.001, FDR corrected), independent of other clinical factors or medications. β-neural activity was most pronounced in central electrodes (C3: r = 0.20, p < 0.01; C4: r = 0.26, p < 0.01) and the right frontal electrode (Fp2: r = 0.12, p = 0.02). Lower θ-α activity (3.5-5 Hz and 12-18 Hz) was associated with higher SOFA scores (p < 0.001, FDR corrected). No significant correlations were observed between other drugs (opioids, anti-seizure medications, and psychotropics) and β or θ-α dynamics.

Conclusions: These results suggest that β neural dynamics represent a potential biomarker for β-lactam exposure in ICU patients. They highlight the potential of quantitative EEG and advanced multivariate decoding methods to identify subtle neurophysiological features that are otherwise difficult to detect.

Trial registration: ClinicalTrials.gov ID NCT03339869. Registered 14 September 2017.

查看原文本刊更多论文

重症监护病房患者β-内酰胺暴露的神经相关性：一项观察性前瞻性队列研究。

背景：β-内酰胺引起的重症患者神经毒性可影响临床预后。尽管治疗药物监测（TDM）越来越多地用于β-内酰胺，但明确的毒性阈值仍未定义，这使得临床医生在发生不良反应时不确定剂量调整。确定β-内酰胺暴露相关且易于检测的神经生理生物标志物将改善监测并预防严重并发症。方法：在一项前瞻性多中心、非介入性研究中，我们分析了56例连续输注5种β-内酰胺类药物（美罗培南、哌拉西林/他唑巴坦、头孢吡肟、头孢噻肟或头孢他啶）的重症监护病房（icu）住院患者的脑电图（EEG）信号。我们对这些脑电图数据进行了时间频率分解，以定量地研究从1到45赫兹的频率范围内神经动力学的力量。我们使用多变量模式解码方法将β-内酰胺暴露和败血症相关器官衰竭评估（SOFA）评分与神经活动联系起来。结果：β-内酰胺暴露与β-低γ神经动力学（20-40 Hz）增加相关（p < 0.001， FDR校正），独立于其他临床因素或药物。β-神经活动在中央电极最为明显(C3: r = 0.20, p < 0.01；C4: r = 0.26, p < 0.01)和右侧额叶电极（Fp2: r = 0.12, p = 0.02）。较低的θ-α活动（3.5-5 Hz和12-18 Hz）与较高的SOFA评分相关（p < 0.001， FDR校正）。其他药物（阿片类药物、抗癫痫药物和精神药物）与β或θ-α动力学之间无显著相关性。结论：这些结果表明β神经动力学是ICU患者β-内酰胺暴露的潜在生物标志物。他们强调了定量脑电图和先进的多元解码方法的潜力，以识别难以检测的微妙神经生理特征。试验注册：ClinicalTrials.gov ID NCT03339869。2017年9月14日注册。

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来源期刊

Journal of Neurology 医学-临床神经学

CiteScore

10.00

自引率

5.00%

发文量

558

审稿时长

1 months

期刊介绍： The Journal of Neurology is an international peer-reviewed journal which provides a source for publishing original communications and reviews on clinical neurology covering the whole field. In addition, Letters to the Editors serve as a forum for clinical cases and the exchange of ideas which highlight important new findings. A section on Neurological progress serves to summarise the major findings in certain fields of neurology. Commentaries on new developments in clinical neuroscience, which may be commissioned or submitted, are published as editorials. Every neurologist interested in the current diagnosis and treatment of neurological disorders needs access to the information contained in this valuable journal.