What is the best course of action for managing break through seizures in patients with epilepsy?

Management of Breakthrough Seizures in Patients with Epilepsy

For breakthrough seizures in patients already on antiepileptic therapy, immediately administer IV lorazepam 4 mg at 2 mg/min, followed by a second-line agent (levetiracetam 30 mg/kg IV, valproate 20-30 mg/kg IV, or fosphenytoin 20 mg PE/kg IV) if seizures persist, while simultaneously optimizing the existing maintenance regimen and searching for precipitating factors. 1, 2

Acute Management in the Emergency Department

First-Line Treatment

• Administer IV lorazepam 4 mg at 2 mg/min immediately for any actively seizing patient, with demonstrated 65% efficacy in terminating status epilepticus 1
• Have airway equipment immediately available before administration, as respiratory depression can occur 1
• Check fingerstick glucose immediately and correct hypoglycemia while administering treatment 1

Second-Line Treatment (if seizures continue after benzodiazepines)

The three second-line agents have equivalent efficacy based on the ESETT trial (Class I evidence), with seizure cessation rates of 47% for levetiracetam, 45% for fosphenytoin, and 46% for valproate 2

Choose based on safety profile and patient characteristics:

• Levetiracetam 30 mg/kg IV over 5 minutes (approximately 2000-3000 mg for average adults) 1, 2

  • Lowest hypotension risk (0.7%) and intubation rate (20%) 2
  • No cardiac monitoring required 1
  • Preferred for elderly patients and those with cardiovascular instability 1
  • Minimal drug interactions 2

• Valproate 20-30 mg/kg IV over 5-20 minutes 1, 2

  • 88% efficacy with 0% hypotension risk in some studies 1
  • Life-threatening hypotension rate 1.6%, intubation rate 16.8% 2
  • Contraindicated in women of childbearing potential due to teratogenicity 1
  • Contraindicated in liver disease 2

• Fosphenytoin 20 mg PE/kg IV at maximum rate of 150 PE/min 1, 2

  • 84% efficacy but 12% hypotension risk 1
  • Life-threatening hypotension rate 3.2%, intubation rate 26.4% 2
  • Requires continuous ECG and blood pressure monitoring 1

Refractory Status Epilepticus (seizures continuing despite benzodiazepines and one second-line agent)

• Initiate continuous EEG monitoring at this stage 1
• Midazolam infusion: 0.15-0.20 mg/kg IV load, then 1 mg/kg/min continuous infusion, titrate up by 1 mg/kg/min every 15 minutes to max 5 mg/kg/min 1
  • 80% overall success rate with 30% hypotension risk 1
  • Lower hypotension risk than pentobarbital (30% vs 77%) 1
• Propofol: 2 mg/kg bolus, then 3-7 mg/kg/hour infusion 1
  • 73% seizure control, requires mechanical ventilation 1
  • Shorter ventilation time (4 days vs 14 days with pentobarbital) 1
• Pentobarbital: 13 mg/kg bolus, then 2-3 mg/kg/hour infusion 1
  • Highest efficacy at 92% but 77% hypotension risk 1

Optimization of Maintenance Therapy

Diagnostic Evaluation

• Obtain serum levels of current antiepileptic drugs to assess compliance and adequate dosing 1
• Question the patient about medication adherence, as non-compliance is a common cause of breakthrough seizures 1
• Search for precipitating factors: sleep deprivation, alcohol use, medication non-compliance, intercurrent illness 1
• Consider EEG to distinguish true epileptic seizures from psychogenic seizures or detect subclinical seizure activity 1

Treatment Escalation Strategy

If on levetiracetam monotherapy with breakthrough seizures:

1. First, optimize levetiracetam dosing before adding another agent 1

   • Increase to 30 mg/kg (approximately 2000-3000 mg for average adults) if not already at this dose 1
   • Higher doses achieve 68-73% efficacy in refractory seizures 1

2. If seizures persist despite optimized monotherapy, add valproate 1

   • Both agents have similar efficacy (46-47% seizure control) as second-line monotherapy 1
   • No significant pharmacokinetic interactions between levetiracetam and valproate 1
   • Monitor liver function tests due to valproate's hepatotoxicity risk 1
   • Avoid valproate in women of childbearing potential 1

3. Alternative adjuncts include lamotrigine or lacosamide 1

Maintenance Dosing After Status Epilepticus Resolution

• For convulsive status epilepticus: levetiracetam 30 mg/kg IV every 12 hours OR increase prophylaxis dose by 10 mg/kg (to 20 mg/kg) IV every 12 hours (maximum 1,500 mg) 1
• For non-convulsive status epilepticus: levetiracetam 15 mg/kg (maximum 1,500 mg) IV every 12 hours 1

Simultaneous Evaluation for Underlying Causes

While administering antiseizure medications, simultaneously search for and treat:

• Hypoglycemia (check fingerstick glucose immediately) 1, 2
• Hyponatremia 1, 2
• Hypoxia (ensure adequate oxygenation) 2
• Drug toxicity or withdrawal syndromes (consider toxicology screen) 1, 2
• CNS infection or systemic infection 1, 2
• Ischemic stroke, intracerebral hemorrhage, or mass lesion (consider neuroimaging after stabilization) 1, 2

Critical Pitfalls to Avoid

• Never use neuromuscular blockers alone (such as rocuronium), as they only mask motor manifestations while allowing continued electrical seizure activity and brain injury 1
• Do not skip to third-line agents (pentobarbital) until benzodiazepines and a second-line agent have been tried 1
• Do not delay anticonvulsant administration for neuroimaging in active status epilepticus—CT scanning can be performed after seizure control is achieved 1
• Recognize non-convulsive status epilepticus, which may require EEG monitoring, as 8% of patients have persistent electrographic seizures detectable only by continuous EEG 3, 2
• Avoid overlooking the underlying cause of the seizure, as failure to address it may lead to recurrence 2

Monitoring Requirements

• Continuous vital sign monitoring is essential, particularly respiratory status and blood pressure 1
• Be prepared to provide respiratory support regardless of administration route 1
• EEG should guide titration to achieve seizure suppression in refractory cases 1
• Monitor for breakthrough seizures, which occur in more than half of patients with refractory status epilepticus despite initial control 3