›Fosphenytoin IV 20 mg PE/kg at maximum 150 mg PE/min
›Infuse with cardiac monitoring — risk of hypotension and arrhythmia
›Response rate approximately 47% per ESETT trial
›Avoid in phenytoin-toxic patients
›Valproate IV 40 mg/kg over 10 minutes (max 3000 mg)
›Response rate approximately 47% per ESETT trial
›Contraindicated in pregnancy, mitochondrial disease, liver failure
›Avoid in women of childbearing potential
›Phenobarbital IV 20 mg/kg at 60 mg/min — alternative second-line agent
›Risk of respiratory depression — have airway equipment ready
›Phase 4: Third-line (40–60 minutes — refractory status epilepticus)
›Propofol IV
›Loading: 1–2 mg/kg bolus
›Infusion: 20–200 mcg/kg/min
›Titrate to burst-suppression on EEG
›Propofol infusion syndrome risk — monitor triglycerides, acidosis
›Midazolam IV infusion
›Loading: 0.2 mg/kg
›Infusion: 0.05–2 mg/kg/hr
›Titrate to seizure cessation or burst-suppression pattern
›Pentobarbital IV
›Loading: 5–15 mg/kg at 25–50 mg/min
›Infusion: 0.5–3 mg/kg/hr
›Highest efficacy for super-refractory SE, highest complication rate
›All phase 4 agents require intubation and continuous EEG monitoring
›Identify and correct provoking factors
›Electrolyte correction — hyponatremia, hypocalcemia, hypomagnesemia
›Infection treatment — antibiotics for meningitis, antivirals for HSV encephalitis
›Toxin elimination
›Medication compliance restoration in known epilepsy
›Antiseizure medication initiation decision
›Not routinely recommended after a single unprovoked seizure
›AAN/AES Level B recommendation
›Starting ASM reduces 2-year recurrence risk but does not alter long-term epilepsy development
›Initiate ASM if high recurrence risk present
›Epileptiform EEG abnormalities
›Structural brain lesion
›Nocturnal seizure
›Prior brain insult
›Initiate ASM if patient accepts after risk-benefit discussion
Antiseizure medication selection
›Levetiracetam — preferred first-line for most patients
›Starting dose 250–500 mg twice daily
›Target dose 1000–2000 mg/day in divided doses
›Broad-spectrum — effective for GTC, absence, and myoclonic seizures
›Minimal drug interactions, no organ toxicity monitoring
›Watch for irritability, mood disturbance, behavioral changes
›Preferred in women of childbearing potential
›Valproate — most efficacious for idiopathic generalized epilepsy
›Starting dose 500 mg/day
›Target dose 1000–2000 mg/day in divided doses
›Monitor valproate level (target 50–100 mg/L)
›Effective for GTC, myoclonic, and absence seizures
›Contraindicated in women of childbearing potential
›Teratogenicity: up to 10% major malformations
›Neurodevelopmental delay in up to 40% of exposed children
›Contraindicated in POLG1 mitochondrial disease
›Monitor LFTs, ammonia, CBC
›Lamotrigine — alternative for GTC
›Requires slow titration over 4–6 weeks
›Initial 25 mg/day (slower if on valproate — 12.5 mg/day)
›Target 100–400 mg/day in divided doses
›May worsen myoclonic seizures or absence — avoid in juvenile myoclonic epilepsy
›Stevens-Johnson syndrome risk — titrate slowly
›Medications that aggravate idiopathic generalized epilepsy — avoid
›Carbamazepine, oxcarbazepine, phenytoin
›Gabapentin, pregabalin
›These agents may worsen myoclonic jerks and absence seizures