Abstract

Introduction: Loading doses of 20 mg/kg of levetiracetam are commonly employed for refractory status epilepticus however, recent studies utilizing higher loading doses of 40-60 mg/kg have prompted a change in practice. This study aims to establish whether higher loading doses of levetiracetam lead to more rapid cessation of status epilepticus and reduced need for additional antiepileptic drugs. Methods: This was an IRB-approved, single-center, retrospective cohort study of patients admitted to a tertiary care academic medical center between April and September 2021. Patients were included if they were > 18 years of age and received levetiracetam as a loading-dose for cessation of status epilepticus. Patients were excluded if levetiracetam was administered for seizure prophylaxis. The primary outcome was unsuccessful seizure termination, defined as a requirement of an additional loading dose or an increase in maintenance doses of levetiracetam. Secondary outcomes included ICU and hospital length of stay, mortality, and need for third line treatment. Results: Of 390 patients screened for inclusion, 206 met inclusion criteria and were included in the primary analysis. Amongst patients who received a loading < 20 mg/kg, 50% had a diagnosis of epilepsy prior to admission, compared to 37.3% in the 20-40 mg/kg group and 42% in the ≥ 40 mg/kg group. Rates of ICU admission were 20%, 37.3% and 36.3%, respectively (p = 0.163). There was a statistically significant difference in ICU (3.5, 8.9, 13.5; p = 0.03) and hospital length of stay (13.1, 22.5, 30.7, p = 0) among groups. The primary outcome, unsuccessful seizure termination, was 13.8% in the < 20 mg/kg group, 12% in the 20-40 mg/kg group, and 34% in the > 40 mg/kg group. The rates of third-line therapy administration in each group was 5% vs. 13.3% vs. 22%, respectively. Conclusions: Among patients treated with loading-doses of levetiracetam > 40 mg/kg, there was a statistically significant increase in maintenance dose of levetiracetam and a trend towards more frequent administration of third-line agents. There was a longer ICU length of stay among patients administered >40 mg/kg loading dose which could have led to increased monitoring and increases in maintenance dosing of levetiracetam among that population.

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