What is the initial treatment for breakthrough seizure in the Emergency Department (ED)?

Initial Treatment for Breakthrough Seizure in the Emergency Department

The initial treatment for breakthrough seizure in the Emergency Department should be intravenous benzodiazepines, followed by a second-line agent such as fosphenytoin, levetiracetam, or valproate if seizures persist. 1

First-Line Treatment: Benzodiazepines

• Benzodiazepines are the established first-line treatment for active seizures in the ED 2, 3
• If IV access is available, use either:
  • IV lorazepam (0.1 mg/kg) 4
  • IV diazepam (0.15 mg/kg) 4
• If no IV access is available, alternative routes include:
  • Intramuscular midazolam (shown to be non-inferior to IV lorazepam) 2, 3
  • Buccal midazolam 3
  • Intranasal midazolam 3

Critical Point: Rapid administration of benzodiazepines is essential as delayed treatment can lead to benzodiazepine pharmacoresistance and progression to self-sustaining status epilepticus 5

Second-Line Treatment (If Seizures Continue After Benzodiazepines)

According to the 2024 ACEP guidelines (Level A recommendation), emergency physicians should treat seizures refractory to appropriately dosed benzodiazepines with a second-line agent. The following agents have similar efficacy 1:

• Fosphenytoin: 18-20 PE/kg IV at maximum rate of 150 PE/min 1

  • Advantages: Can be administered IM if needed 1
  • Disadvantages: Risk of hypotension, cardiac dysrhythmias 1

• Levetiracetam: 30-50 mg/kg IV at 100 mg/min 1

  • Advantages: Favorable side effect profile, fewer drug interactions 1
  • Disadvantages: May cause nausea, rash 1

• Valproate: 20-30 mg/kg IV at maximum rate of 10 mg/kg/min 1

  • Advantages: Rapid administration possible, minimal cardiorespiratory side effects 1
  • Disadvantages: Contraindicated in liver disease, risk of thrombocytopenia 1

Evidence on Comparative Efficacy

• The ESETT trial (2019), a Class I study, found no significant difference in efficacy between levetiracetam, fosphenytoin, and valproate for terminating status epilepticus 1

  • Seizure cessation rates at 60 minutes:
    • Levetiracetam: 47%
    • Fosphenytoin: 45%
    • Valproate: 46%

• Safety considerations from ESETT 1:

  • Life-threatening hypotension: 0.7% with levetiracetam, 3.2% with fosphenytoin, 1.6% with valproate
  • Intubation rates: 20% with levetiracetam, 26.4% with fosphenytoin, 16.8% with valproate

Simultaneous Management Steps

While administering antiseizure medications, simultaneously search for and address potential causes of breakthrough seizures 1:

• Check blood glucose and treat hypoglycemia if present 1
• Evaluate for hyponatremia 1
• Assess for hypoxia and ensure adequate oxygenation 1
• Consider toxicology screen for drug toxicity 1
• Evaluate for CNS infection or systemic infection 1
• Consider neuroimaging if there's concern for stroke, hemorrhage, or mass lesion 1

Common Pitfalls to Avoid

• Delay in treatment: Early treatment is crucial to prevent pharmacoresistance. Don't wait for laboratory results before initiating treatment 5
• Inadequate dosing: Underdosing benzodiazepines is common and reduces efficacy 3
• Failure to monitor respiratory status: Benzodiazepines can cause respiratory depression, especially when given rapidly or in combination with other sedating medications 4
• Not recognizing non-convulsive status: Some patients may have subtle manifestations of ongoing seizure activity requiring EEG monitoring 1
• Overlooking the underlying cause: Treating the seizure without addressing the underlying cause may lead to recurrence 1