Interactions between carbapenems and valproic acid among the patients in the intensive care units

Abstract

Purpose: To evaluate risk factors for epileptic seizures or status epilepticus (SE) in patients concomitantly receiving valproic acid (VPA) and carbapenems.

Materials and methods: Adult patients in the intensive care units (ICUs) who concomitantly received VPA and carbapenems from 2007 to 2017 were included. The impacts of different carbapenems on serum concentration of VPA were compared.

Results: Among 162 patients included, 104 (64.2%) and 45 (27.8%) developed epileptic seizures and SE, respectively. The risk factors for epileptic seizures were age (per year increase, adjusted odds ratio [aOR], 1.03), initial antiepileptic regimen (monotherapy and polytherapy, aOR, 0.43 and 0.18, respectively), and VPA serum concentration after concomitant carbapenem administration (per 1 μg/mL increase, aOR, 0.96). VPA serum concentration after concomitant carbapenem administration was an independent risk factor for SE (per μg/mL increase, aOR, 0.98). Concomitant imipenem/cilastatin administration did not significantly decrease VPA serum concentration compared to that by meropenem or ertapenem. The length of stay and number of days on ventilation after concomitant carbapenem administration in the ICUs were significantly more in those with epileptic seizures or SE.

Conclusions: Carbapenems decreased VPA serum concentration and increased the risk of epileptic seizures and SE, which led to increased length of ICU stay.

Keywords: Carbapenem; Drug-drug interaction; Epileptic seizure; Status epilepticus; Valproic acid.