Initial Treatment for Breakthrough Seizure in the Emergency Department

First-Line and Second-Line Treatment

The American College of Emergency Physicians recommends intravenous benzodiazepines as the first-line treatment for breakthrough seizure in the Emergency Department, followed by a second-line agent such as fosphenytoin, levetiracetam, or valproate if seizures persist 1, 2, 3
Fosphenytoin is a second-line agent that can be administered at 18-20 PE/kg IV at a maximum rate of 150 PE/min, with advantages including the ability to be administered IM if needed, but disadvantages include the risk of hypotension and cardiac dysrhythmias 1, 4, 5, 6
Levetiracetam is a second-line agent that can be administered at 30-50 mg/kg IV at 100 mg/min, with advantages including a favorable side effect profile and fewer drug interactions, but disadvantages include the potential to cause nausea and rash 3, 6
Valproate is a second-line agent that can be administered at 20-30 mg/kg IV at a maximum rate of 10 mg/kg/min, with advantages including rapid administration and minimal cardiorespiratory side effects, but disadvantages include being contraindicated in liver disease and the risk of thrombocytopenia 1, 4, 5, 6, 7

The ESETT trial, a Class I study, found no significant difference in efficacy between levetiracetam, fosphenytoin, and valproate for terminating status epilepticus, with seizure cessation rates at 60 minutes of 47% for levetiracetam, 45% for fosphenytoin, and 46% for valproate 3, 4, 5, 6
Safety considerations from the ESETT trial include life-threatening hypotension rates of 0.7% with levetiracetam, 3.2% with fosphenytoin, and 1.6% with valproate, and intubation rates of 20% with levetiracetam, 26.4% with fosphenytoin, and 16.8% with valproate 3

While administering antiseizure medications, it is recommended to simultaneously search for and address potential causes of breakthrough seizures, including checking blood glucose and treating hypoglycemia, evaluating for hyponatremia, assessing for hypoxia and ensuring adequate oxygenation, considering toxicology screen for drug toxicity, evaluating for CNS infection or systemic infection, and considering neuroimaging if there's concern for stroke, hemorrhage, or mass lesion 1, 7

Not recognizing non-convulsive status epilepticus, which may require EEG monitoring, is a common pitfall to avoid 3
Overlooking the underlying cause of the seizure and failing to address it may lead to recurrence 1, 7