Neurocritical Care

or if a maintenance therapy needs to be initiated to prevent future seizures.

drugs, at the listed dose, can be used as a potential first choice for a second-line therapy in status

epilepticus

Valproate 40 mg/kg (maximum dose 3000 mg) intravenously

ii.

(Fos)phenytoin 20 mg/kg intravenously. (The ESETT Trial used a maximum dose of 1500 mg

for blinding purposes but this is not recommended based on the PK/PD of [Fos]phenytoin.)

iii.

Levetiracetam 60 mg/kg (maximum dose 4500 mg) intraveously

Third-line therapy (refractory)

If seizures persist after first- and second-line therapy, RSE should be treated aggressively and in a

timely manner with continuous infusion anesthetic agents. The patient should be intubated before

starting therapy.

RSE agents should be titrated to burst suppression (the almost total elimination of electrical activity

on EEG, except for short “bursts” of cortical activity [typically therapy is titrated to 2–5 bursts/

minute]) or termination of electrographic seizure activity, depending on provider preference.

Maintain established goal (burst suppression or termination of electrographic seizure activity)

for 24–48 hours before trying to taper continuous agents. In addition, optimize maintenance

anticonvulsant therapy before wean.

Continuous infusion anesthetics for RSE titrated to target burst suppression

Midazolam high-dose infusion 0.05–2 mg/kg/hour

ii.

Pentobarbital infusion (loading dose about 25 mg/kg total, continuous infusion 0.5–5 mg/kg/

hour)

iii.

Propofol infusion 20–200 mcg/kg/minute

Other options for RSE in intubated and/or nonintubated patients

Can use any of the second-line agents listed above if they have not already been administered

ii.

Lacosamide 400 mg intravenously

iii.

Topiramate 200–400 mg orally/nasogastrically

iv.

Phenobarbital 20 mg/kg intravenously

Perampanel 12 mg orally/nasogastrically

Super-refractory status epilepticus

Treatment is typically reinitiation of continuous anesthetic agents used for RSE.

Ketamine, an N-methyl-d-aspartate (NMDA) receptor antagonist, may also be considered.

Ketamine may cause emergence psychosis and hallucinations, for which midazolam may help.

Patients should have a workup for causes of super-refractory status epilepticus (e.g., autoimmune

encephalitis including paraneoplastic syndromes and, infectious encephalitis).

Nonpharmacologic therapies if medical therapy fails

Ketogenic diet: Limiting medications and nutrition to low-carbohydrate content; more likely to

be successful in pediatric patients than in adult patients because of difficulty achieving ketosis in

adults. Exact mechanism of action is unknown, but may increase sequestration of glutamate and

decrease reactive oxygen species. Benefits typically occur within 1–3 months. Must modify diet

targeting fat to carbohydrate plus protein in a 4:1 or 3:1 ratio

Vagus nerve stimulation