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Minerva Anestesiologica 2015 May;81(5):497-506


language: English

Elevated β-lactam concentrations associated with neurological deterioration in ICU septic patients

Beumier M. 1, Casu G. S. 1, Hites M. 2, Wolff F. 3, Cotton F. 3, Vincent J. L. 1, Jacobs F. 2, Taccone F. S. 1

1 Department of Intensive Care, Erasme Hospital, Université Libre de Bruxelles (ULB), Brussels, Belgium; 2 Department of Infectious Diseases, Erasme Hospital, Université Libre de Bruxelles (ULB), Brussels, Belgium; 3 Department of Clinical Biochemistry, Erasme Hospital, Université Libre de Bruxelles (ULB), Brussels, Belgium


BACKGROUND: Although β-lactams are considered to have a safe therapeutic profile, neurotoxicity has been reported. The aim of this study was to assess the association between β-lactam concentrations and neurological alterations in septic ICU patients.
METHODS: Retrospective study on all ICU patients who were treated with meropenem (MEM), piperacillin-tazobactam (TZP) or ceftazidime/cefepime (CEF) and in whom at least one β-lactam trough concentration (Cmin) was determined. Drug levels were measured using high-performance liquid chromatography; Cmin was normalized to the clinical breakpoint of Pseudomonas aeruginosa (as determined by EUCAST) for each drug (Cmin/MIC). Changes in neurological status were evaluated using changes in the neurological sequential organ failure assessment score (ΔnSOFA) using the formula: ΔnSOFA = nSOFA(day of TDM) - nSOFA(ICU admission). Worsening neurological status (NWS) was defined as a ΔnSOFA ≥1 for an nSOFA on admission of 0-2.
RESULTS: We collected 262 Cmin in 199 patients (130 MEM, 85 TZP, 47 CEF). Median APACHE II score and GCS on admission were 17 and 15, respectively. Overall ICU mortality was 27 %. There were no differences in the occurrence of NWS between antibiotics (39% for MEM, 32% for TZP and 35% for CEF). The occurrence of NWS increased with increasing Cmin/MIC ranges (P=0.008); this correlation was found for TZP (P=0.05) and MEM (P=0.01), but not for CEF. Cmin/MIC was an independent predictive factor for NWS (OR 1.12 [1.04-1.20]).
CONCLUSION: We found a correlation between high β-lactam trough concentrations and increased occurrence of neurological deterioration in septic ICU patients. Although our data cannot determine causality, monitoring of β-lactam levels should be considered when deterioration of neurological status occurs during critical illness.

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