levetiracetam and Hematoma--Subdural

To characterize the steady-state pharmacokinetics of intravenous levetiracetam in neurocritical care patients requiring seizure prophylaxis after a neurologic injury and to determine which dosing regimens achieve serum concentrations within the recommended therapeutic range of 6-20 μg/ml. DESIGN. Prospective, open-label, steady-state pharmacokinetic study.. Neurocritical care unit in a tertiary care medical center. PATIENTS. Twelve adults (five men, seven women) admitted to the neurocritical care unit who required prophylactic anticonvulsant therapy after subarachnoid hemorrhage, subdural hematoma, or traumatic brain injury.. Patients received an intravenous infusion of levetiracetam 500 mg over 15 minutes every 12 hours.. Serial blood samples were collected from all patients after a minimum of four doses of therapy. Serum levetiracetam concentrations were determined by ultraperformance liquid chromatography with tandem mass spectrometry detection, and pharmacokinetic data were analyzed by compartmental and noncompartmental methods. Monte Carlo simulations were performed for multiple levetiracetam dosing regimens to determine the probability of achieving a target trough concentration of 6 μg/ml or greater, 20 μg/ml or greater, and 6-20 μg/ml. The mean ± SD levetiracetam maximum serum concentration was 28.0 ± 8.0 μg/ml, minimum serum concentration 3.1 ± 1.8 μg/ml, half-life 5.2 ± 1.2 hours, systemic clearance 5.6 ± 1.8 L/hour, and volume of distribution at steady state 36.8 ± 6.3 L. Increasing the doses of levetiracetam increased the probability of achieving a target trough concentration of 6 μg/ml or greater but also increased the probability of achieving trough concentrations greater than 20 μg/ml. Levetiracetam doses of 1000 mg every 8 hours and 1500-2000 mg every 12 hours provided the highest probability of achieving a target trough concentration between 6 and 20 μg/ml.. Compared with previously published results in healthy volunteers and adults in status epilepticus, levetiracetam systemic clearance was faster and the terminal elimination half-life was shorter in neurocritical care patients. Higher doses or more frequent dosing may be needed to achieve target trough concentrations of 6-20 μg/ml.

Topics: Anticonvulsants; Brain Injuries; Critical Care; Female; Hematoma, Subdural; Humans; Infusions, Intravenous; Levetiracetam; Male; Middle Aged; Monte Carlo Method; Piracetam; Prospective Studies; Seizures; Subarachnoid Hemorrhage; Treatment Outcome

Although both levetiracetam and phenytoin are used for seizure prophylaxis in subdural hematomas (SDHs), there is little data on their comparative efficacies. We compared the efficacy and risk of using levetiracetam versus phenytoin for seizure prophylaxis following acute or subacute SDH diagnosis.. In this retrospective cohort study, the clinical data registry at a tertiary care hospital was searched for all cases of acute or subacute SDHs that were admitted to hospital in 2002, 2003, or 2011. Risk of clinical and/or electrographic seizures, and risk of adverse drug events were compared between the two exposure arms.. 124 subjects in the phenytoin arm and 164 subjects in the levetiracetam arm were included. There was no significant difference in clinical and/or electrographic seizure risk, though there was a decreased risk of adverse events in the levetiracetam arm (p < 0.001). In subjects with midline shift >0 mm, levetiracetam was associated with an increased risk of electrographic seizures during hospitalization (p = 0.028) and a decreased risk of adverse drug effects (p = 0.001), compared with phenytoin use.. Levetiracetam generally appears to have a similar efficacy to phenytoin in preventing clinical and/or electrographic seizures following acute/subacute SDH diagnosis, though patients with midline shift >0 mm may have associated with a higher risk of electrographic seizures on levetiracetam compared with patients on phenytoin. Levetiracetam is associated with a lower risk of adverse drug effects. A prospective, randomized study would more definitively determine any difference in efficacy and risk between phenytoin and levetiracetam.

Topics: Aged; Anticonvulsants; Female; Hematoma, Subdural; Humans; Levetiracetam; Male; Middle Aged; Phenytoin; Piracetam; Seizures