Rapid administration of undiluted loading doses of levetiracetam.

OBJECTIVE: Rapid administration of antiseizure medications is a critical concept in the treatment of status epilepticus. Although undiluted levetiracetam (LEV) doses of up to 2500 mg have been evaluated, minimal data exist to support the safety of loading doses up to 4500 mg. This study will evaluate intravenous (IV) push administration of undiluted LEV from 2500 to 4500 mg for safety outcomes as well as tolerability. METHODS: This is a retrospective, observational, cohort analysis of adult patients who received at least one loading dose of undiluted IV push LEV from October 15, 2019, to April 30, 2022, at a large academic medical center in Phoenix, Arizona. Relevant outcomes include the safety and tolerability of rapid administration of undiluted LEV at higher loading doses. RESULTS: We evaluated 518 loading doses in 518 unique patients included during the study period. LEV was a new medication for witnessed or suspected seizures in 80.3% of patients, with 31.2% having a documented history of epilepsy or seizure disorder. At the time of LEV administration, 52.9% of patients were on a general medicine floor, 34.3% were in the intensive care unit, and 12.7% were in the emergency department. The median loading dose of LEV was 3600 mg (3000-4000 mg), with 4000 mg being the most common loading dose given. Peripheral IV lines were documented as the only available line in 78.6% of patients for loading dose administration. No adverse events associated with LEV administration were documented. SIGNIFICANCE: Rapid IV administration of undiluted doses of LEV is both safe and tolerable in loading doses of 2500-4500 mg, allowing for rapid drug administration in the setting of status epilepticus.

Early Experiences with Intrathecal Administration of Amphotericin B Liposomal Formulation at a Neurosurgical Center.

BACKGROUND: Intrathecal administration of amphotericin B represents an important adjunctive therapy for management of severe fungal meningitis. Intrathecal preparations have traditionally used amphotericin B deoxycholate. Liposomal amphotericin B is an alternative formulation with good clinical outcomes as systemic therapy, but scant data exist investigating intrathecal use. OBJECTIVE: The aim of this exploratory study was to evaluate outcomes following intrathecal administration of liposomal amphotericin B for treatment of severe fungal meningitis. METHODS: A national shortage of amphotericin B deoxycholate necessitated revision of institutional protocols at a southwestern neurosurgical center in Spring 2023. A starting intrathecal daily dose of 0.125-0.5 mg liposomal amphotericin B was recommended (dependent on insertion device), with 0.125-0.25 mg slow titration every 48 h and up to a 2 mg maximum daily dose. RESULTS: Four cases of fungal meningitis treated with adjunctive intrathecal amphotericin B liposomal formulation were reviewed. This included three cases of coccidioidal meningitis and one case of presumed Fusarium solani meningitis following an outbreak. All patients had initial disease improvement following initiation of intrathecal amphotericin B and were able to tolerate long-term therapy. One coccidioidal meningitis patient expired of neurologic complications shortly after being moved from the intensive care unit (ICU) to a floor unit. All other patients were successfully discharged from the hospital. New headache was the only reported adverse effect, which was managed with dose reduction and did not require therapy discontinuation. CONCLUSIONS: Liposomal amphotericin B may be feasibly administered intrathecally for the adjunctive treatment of severe fungal meningitis.