Optimal Dosing of Levetiracetam for Seizure Prophylaxis in Critically Ill Patients: A Prospective Observational Study

Abstract

Objectives: Critically ill patients eliminate levetiracetam (LEV) more rapidly than healthy controls, yet low doses are commonly used for seizure prophylaxis in the ICU setting. We compared the rates of achievement of target serum levels and new onset seizure (clinical and/or electrographic) among patients who received low (500 mg bid) versus high (750–1,000 ;mg bid) dose LEV. Design: Prospective, observational study. Setting: Tertiary care, academic center. Patients: We included patients who received prophylactic LEV following traumatic brain injury, intracerebral hemorrhage, spontaneous subarachnoid hemorrhage, or supratentorial neurosurgery between 2019 and 2021. Patients with a history of seizure, antiseizure medication use, or renal failure requiring dialysis were excluded. Interventions: None. Measurements: LEV levels were obtained at steady state. The impact of low-dose versus high-dose LEV on the primary outcome of target LEV levels (12–46 μg/mL), and the secondary outcome of clinical and/or electrographic seizure, were assessed using multivariable logistic regression analyses adjusting for age, LEV loading dose, BMI, primary diagnosis and creatinine clearance (CrCl). Main Results: Of the 205 subjects included in analyses, n = 106 (52%) received LEV 500 mg bid (median 13 mg/kg/d), and n = 99 (48%) received LEV 750–1,000 mg bid (median 25 mg/kg/d). Overall, 111 of 205 patients (54%) achieved target levels: 48 (45%) from the low-dose group versus 63 (64%) from the high-dose group (odds ratio [OR] 2.1; 95% CI, 1.1–3.7; p = 0.009). In multivariable analyses, high-dose LEV predicted target levels (adjusted OR [aOR] 2.23; 95% CI, 1.16–4.27; p = 0.016), and was associated with lower seizure odds (aOR 0.32; 95% CI, 0.13–0.82; p = 0.018) after adjusting for age, loading dose, BMI, diagnosis, and CrCl. Conclusions: Underdosing of LEV was common, with only 54% of patients achieving target serum levels. Higher doses (750–1,000 mg bid) were more than twice as likely to lead to optimal drug levels and reduced the odds of seizure by 68% compared with low-dose regimens (500 mg bid).