Rapid administration of undiluted intravenous levetiracetam

Abstract

Objective Operational delays have the potential to lead to suboptimal time to seizure control during status epilepticus. Levetiracetam (LEV) is an urgent control antiepileptic medication that offers relative lack of adverse effects and ease of monitoring. There are limited data published demonstrating safety and tolerability of undiluted rapid intravenous (IV) push of LEV in doses of 1000 mg or less. The purpose of this study was to evaluate the safety of IV push administration of LEV doses up to 4500 mg. Methods This is a retrospective, observational, cohort analysis of adult patients who received at least one dose of undiluted IV push LEV from October 15, 2019 to August 31, 2020 at a large academic medical center in Phoenix, Arizona. Outcomes of interest include safety and tolerability of rapid administration of undiluted LEV. Results There were 953 unique patients included during the study period. LEV was a new medication for witnessed or suspected seizure in 51.9% of patients, and 40.7% of patients had a documented history of epilepsy or seizure disorder. There were 8561 undiluted IV push LEV doses administered, 3674 (42.9%) of which were greater than 1000 mg. LEV was administered most often through a peripheral IV (79.1%). There were 12 patients with documented adverse drug events during the study period, with four potentially directly related to IV push LEV administration. These events were limited to local injection site reactions and included redness, burning, and loss of a peripheral IV line. Significance Rapid IV administration of undiluted LEV is both safe and tolerable in doses of up to 4500 mg, allowing for rapid drug administration, which is paramount during neurologic emergencies.

Evaluation of the Safety of Rapid Administration of Undiluted High-Dose Intravenous Levetiracetam

“…3 However, now that LEV is manufactured to be buffered with a more neutral pH, the burning side effects are minimized. [3][4][5][6] Our study differs from these prior reports as the patients included in our study are 78.5% African American, which is in parallel with the population the hospital serves. Additionally, we included patients with kidney disease or on dialysis while other studies did not.…”

“…In these individuals after replacement of the IV there were no further issues. 6 In the 2019 ESETT trial, there was a non-statically significant 5% risk of hypotension with IV LEV specifically in older patients and there were no reported arrythmias in any age group. 1 Thus far, our study is the only one to assess for hemodynamic adverse events in addition to IV site problems with rapidly administered high dose IV LEV.…”

“…3 However, now that LEV is manufactured to be buffered with a more neutral pH, the burning side effects are minimized. 3-6…”

“…3 With the acidic formulation, the necessary dilution and slow infusion rate leads to potential delays in patient care which is not ideal when treating acute seizure and status epilepticus. A previous study has shown safety when rapidly infusing undiluted LEV at doses < 1000 mg. 4 In addition, very recent studies showed that high doses of LEV could be rapidly infused safely with minimal dilution in doses ranging from 1000 mg to 4500 mg. 5,6 Given the paucity of literature on this topic outside of these studies, this retrospective study aims to further the standard of care regarding the safety and efficacy of rapid administration of LEV in the setting of status epilepticus and to evaluate potential side effects beyond local site reaction.…”

Das ist neu in der Neurointensiv- und Notfallmedizin: die wichtigsten Studien des Jahres im Rück- und Überblick

“…Allerdings war in der gepoolte Analyse Levetiracetam signifikant sicherer insbesondere gegenüber Fosphenytoin (im Gegensatz zu Phenytoin), was invasive Beatmung, Atemdepression und akute Hypotension betrifft [ 11 ]. Die Verabreichung von Levetiracetam als Bolusinjektion (in Dosierungen bis 4,5 g) mutete sich auch in einer retrospektiven Kohortenstudie mit Einschluss von 953 Patienten, die 8561 Verabreichungen von Levetiracetam bekommen hatten, als sicher an [ 12 ]. Zusammenfassend scheinen (Fos)phenytoin und Levetiracetam ähnlich wirksam zu sein, wobei sich Levetiracetam als sicherer erweist, insbesondere im Hinblick auf Hypotonie.…”