Objective:

Determine the dose of prophylactic levetiracetam (fixed and mg/kg dose) that most consistently generates therapeutic trough levels (12–46 μg/ml).

Background:

The use of prophylactic anticonvulsants among neurocritically ill patients has been controversial.  Variable results in studies of prophylactic levetiracetam may be due, in part, to underdosing and failure to obtain therapeutic levels.

Design/Methods:

A prospective cohort study was conducted. Consecutive adult neurocritical care patients that received levetiracetam for seizure prophylaxis between 7/2019-7/2022 were included. Patients with history of seizure, anti-epileptic drug use or renal failure requiring dialysis were excluded. Serum samples were collected prior to administration of the 4th dose. Levetiracetam doses were determined by the treating physician.

Results:

A total of 206 patients were evaluated (median age 64 years [range 15-89]; 46% female). Indications for seizure prophylaxis included traumatic brain injury (N=97, 47%), spontaneous subarachnoid hemorrhage (N=48, 23%), supratentorial neurosurgery (N=43, 21%), and ICH (N=18, 9%). The most common loading dose was 1000 mg (79% of patients, range 500-3000 mg) and the most common maintenance dose was 500 mg BID (52% of patients, range 500-2000 BID).  Non-therapeutic levels occurred in 94 (46%) patients. Of the patients that received 500mg (N=106), 750mg (N=46), and ≥1000mg (N=52) maintenance doses, subtherapeutic levels occurred in 55%, 30%, 38%, respectively.  Patients who received 1000 mg BID (median 11 mg/kg/dose) had the highest percentage of therapeutic levels (64%). A maintenance dose of 500 mg BID (median 7 mg/kg/dose) was associated with a likelihood ratio of 6.7 for subtherapeutic levels (P=0.035).

Conclusions:

Over 50% of patients who received 500 mg BID (7 mg/kg/dose) maintenance levetiracetam dosing had subtherapeutic levels, while 1000 mg BID (11 mg/kg/dose) was more likely to generate therapeutic levels.