Presentation

Background and Purpose: Levetiracetam is a broad spectrum antiseizure medication frequently utilized in neurocritical care to treat or prevent seizures. Levetiracetam is predominantly excreted through the renal route (~66%), exposing it to the impact of augmented renal clearance (ARC) that is frequently observed in critically ill individuals. ARC is defined as a state of renal hyperfiltration with creatinine clearance (CrCl)>130 mL/min/1.73m2. Consequently, ARC could lead to subtherapeutic levels of levetiracetam (reference range: 12-46 mg/L) and subsequent therapy failures. However, in most instances, levetiracetam is utilized for seizure prophylaxis, often resulting in subtherapeutic levels going unnoticed. However, it is still unclear how to accurately dose levetiracetam in patients experiencing ARC. Therefore, our main goal is to detect the effect of ARC on the disposition of levetiracetam in order to suggest optimized levetiracetam dosage regimens.

Methods: A prospective multicenter observational study was conducted in patients admitted to the participating neuroscience ICUs for acute neurological illnesses with levetiracetam administration. Enrolled patients had blood samples drawn to determine their plasma levetiracetam concentrations. Levetiracetam plasma concentrations were analyzed using a validated analytical method. Sampling day CrCl was measured using the 8-h urine collection method.

Results: Forty patients have been enrolled and analyzed [16(40%) traumatic brain injury, 8(20%) subarachnoid hemorrhage, 7(17.5%) intracerebral hemorrhage, 6(15%) status epilepticus, and 3(7.5%) other diagnoses]. The entire cohort ARC prevalence was 62.5%. Levetiracetam failed to control seizures in 20% of participants (50% had ARC). ARC patients had lower dose normalized area under the concentration time curve [median (IQR), 0.16(0.15) vs. 0.27(0.2) h/L p-value=0.04) and higher plasma clearance [6.28(5.44) vs. 3.7(2.68) L/h p-value=0.04]. More ARC patients exhibited a trough concentration of <12 mg/L [18(72%) vs. 8(53.3%)].

Conclusion: ARC is highly impacting levetiracetam plasma levels, potentially resulting in subtherapeutic concentrations. The current results will form the basis to conduct simulations to recommend levetiracetam optimized dosage regimens in neurocritical care.