Is it concerning to still have seizures despite taking two doses of Keppra (levetiracetam) when waking up?

Yes, Ongoing Seizures Despite Two Doses of Keppra (Levetiracetam) is Highly Concerning and Requires Immediate Escalation of Care

This represents benzodiazepine-refractory status epilepticus requiring immediate administration of additional antiepileptic therapy, as seizures lasting >5 minutes or recurrent seizures without return to baseline constitute a neurologic emergency with potential for worsening brain injury. 1

Immediate Clinical Context

• Status epilepticus is defined as seizure activity lasting longer than 5 minutes or multiple seizures without return to neurologic baseline 1
• The scenario described suggests the patient has already received benzodiazepines (first-line treatment) and two doses of levetiracetam without seizure termination 1
• This constitutes treatment failure requiring immediate escalation 1

Why This is Concerning

• Ongoing seizures have the potential to worsen brain injury and increase morbidity 1
• Benzodiazepine-refractory status epilepticus carries significant mortality risk if not promptly controlled 1
• The longer seizures continue, the more difficult they become to terminate and the worse the neurological outcomes 1

Immediate Management Algorithm

Step 1: Verify Adequate First-Line Treatment

• Confirm the patient received optimal dosing of benzodiazepines as first-line therapy 1
• If benzodiazepines were inadequately dosed, this should be corrected immediately 1

Step 2: Assess Levetiracetam Dosing

• Standard loading dose for status epilepticus is 30-50 mg/kg IV at 100 mg/min 1, 2
• Maximum dose up to 4500 mg 3
• If the patient received suboptimal dosing (e.g., maintenance doses rather than loading doses), this represents inadequate treatment 2

Step 3: Add Second-Line Agent Immediately

The 2024 ACEP guidelines recommend the following second-line agents with equivalent efficacy (approximately 45-47% success rate): 1, 2

• Fosphenytoin: 18-20 PE/kg IV 1, 2

  • Higher risk of hypotension (3.2%) and cardiac dysrhythmias 1, 2

• Valproate: 20-30 mg/kg at rate of 40 mg/min 1, 2

  • Lower incidence of hypotension (0-1.6%) compared to fosphenytoin 1, 2
  • 88% efficacy in controlling seizures within 20 minutes in some studies 1, 4
  • Avoid in women of childbearing potential due to teratogenic risk 4

• Additional levetiracetam loading (if initial dose was inadequate) 1, 2

  • Lowest rate of life-threatening hypotension (0.7%) 2
  • 73% response rate in refractory status epilepticus when adequately dosed 1, 4

Step 4: Consider Third-Line Agents if Seizures Persist

If seizures continue despite second-line therapy, consider: 1

• Propofol (requires intubation): 2 mg/kg bolus; infusion of 3-4 mg/kg per hour 1
• Phenobarbital: 10-20 mg/kg; may repeat 5-10 mg/kg at 10 minutes 1
  • Higher risk of respiratory depression and hypotension 1
• Pentobarbital (requires intubation): 13 mg/kg bolus; infusion of 2-3 mg/kg per hour 1

Critical Pitfalls to Avoid

• Do not assume the patient is simply "postictal" without EEG confirmation, as nonconvulsive status epilepticus may be present 1
• Do not use maintenance doses of levetiracetam when loading doses are indicated - this is a common error that leads to treatment failure 2, 3
• Do not delay second-line therapy while waiting for drug levels - time to seizure control is critical 1
• Higher doses of levetiracetam (>40 mg/kg) are associated with increased intubation rates (45.8% vs 26.8-28.2%) without improved seizure termination 3

Additional Considerations

• Evaluate for underlying precipitants: hypoglycemia, hyponatremia, hypoxia, drug toxicity, CNS infection, stroke, or hemorrhage 2
• Consider substance-related causes: prescribed medications (tramadol) or illicit drugs (cocaine) can lower seizure threshold 1
• Assess medication compliance: noncompliance with antiseizure drugs increases likelihood of breakthrough seizures 1
• EEG monitoring is ideal but should not delay treatment - clinical seizure activity warrants immediate intervention 1

Prognosis and Monitoring

• Most common adverse effects of levetiracetam include somnolence, asthenia, dizziness, and headache - typically mild to moderate 5
• Serious adverse effects are rare but include behavioral changes, rash, and rarely hepatic failure or blood dyscrasias 5
• Continuous monitoring for respiratory depression and hypotension is essential, particularly with combination therapy 1