Delirium in critically ill patients treated with levetiracetam or brivaracetam: a comparative study

Delirium is a common complication in the Intensive Care Unit (ICU) with relevant clinical impact. Levetiracetam (LEV) and brivaracetam (BRV) are widely used antiseizure medications. LEV has been linked to behavioral adverse events, whereas evidence for BRV remains limited. The aim of this study was to compare the clinical outcomes of ICU patients with delirium exposed to LEV and BRV.

We conducted a retrospective cohort study at a tertiary hospital (2019-2024), including ICU patients aged ≥16 years treated with LEV or BRV. Patients who died before sedation weaning were excluded. The primary endpoint was the diagnosis of delirium during ICU admission. Multivariable logistic regression was performed with delirium as the dependent variable and antiseizure regimen as the main predictor, adjusted by demographic and clinical covariates.

Fifty-nine patients were included (mean age 52.8 years; 33.9% women). Thirty-six received LEV and 23 BRV. Delirium occurred in 49.2% overall, more frequently with LEV than BRV (63.9%vs. 26.1%, p = 0.005). In multivariable analysis, LEV remained independently associated with delirium (OR 16.4; 95% CI 2.9-94.3; p = 0.002). Delirium was associated with longer ICU (7 [IQR 3-19] vs. 3 [IQR 2-6] days, p = 0.035) and hospital stay (25 [IQR 10-70] vs 10 [IQR 7-22] days, p = 0.026). Among patients who developed delirium while receiving LEV, 47.8% were switched to BRV during ICU admission, and delirium resolution in ICU was more frequent in those switched compared with those not switched (90.9%vs 33.3%, p = 0.009).

In this cohort, LEV was independently associated with a higher risk of delirium compared to BRV, and inpatient LEV-to-BRV switch was associated with delirium resolution. Delirium was associated with prolonged ICU and hospital admissions. Prospective multicenter studies with standardized monitoring are needed.