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

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 analysed 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, antiseizure medications, 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.