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Published on: August 30, 2018
Neural correlates of β-lactam exposure in intensive care unit patients: an observational, prospective cohort study
Arnaud Zalta1,2, Agnès Trébuchon3,4, Géraldine Daquin4
1Inserm, INS, Institut de Neurosciences des Systèmes, Aix Marseille Univ, Marseille, France. arnaud.zalta@gmail.com.
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.
