What are the medications used to treat status epilepticus?

From the Guidelines

Status epilepticus should be treated with benzodiazepines as first-line therapy, followed by valproate (40 mg/kg IV) as a second-line agent due to its efficacy and lower risk of adverse effects compared to phenytoin and fosphenytoin 1.

First-Line Therapy

Initial treatment should begin with intravenous lorazepam (0.1 mg/kg, typically 4 mg in adults) or diazepam (0.15-0.2 mg/kg, typically 10 mg in adults) as they are effective in terminating seizures quickly. If IV access is unavailable, midazolam can be given intramuscularly (10 mg) or buccally (10 mg) as an alternative.

Second-Line Therapy

If seizures persist after 5-10 minutes, second-line therapy should be initiated with valproate (40 mg/kg IV) due to its effectiveness in controlling seizures and lower risk of adverse effects such as hypotension compared to phenytoin and fosphenytoin 1. Other options for second-line therapy include fosphenytoin (20 mg PE/kg IV) and levetiracetam (60 mg/kg IV, up to 4500 mg).

Refractory Status Epilepticus

For refractory status epilepticus, continuous infusions of midazolam (loading dose 0.2 mg/kg, then 0.1-2 mg/kg/hr), propofol (1-2 mg/kg loading, then 2-10 mg/kg/hr), or pentobarbital (5-15 mg/kg loading, then 0.5-10 mg/kg/hr) should be considered with EEG monitoring 1. These medications work through different mechanisms: benzodiazepines enhance GABA inhibition, antiepileptics like phenytoin block sodium channels, and anesthetics suppress overall brain activity.

Comprehensive Management

Vital sign monitoring, airway management, and addressing the underlying cause of status epilepticus are essential components of comprehensive management. The most recent clinical policy from the American College of Emergency Physicians (ACEP) addresses key issues in the evaluation and management of adult emergency department patients presenting with seizure, providing evidence-based recommendations for treatment 1.

Key points to consider in the management of status epilepticus include:

• Prompt treatment with benzodiazepines as first-line therapy
• Use of valproate as a second-line agent due to its efficacy and lower risk of adverse effects
• Consideration of continuous infusions of midazolam, propofol, or pentobarbital for refractory status epilepticus
• Importance of vital sign monitoring, airway management, and addressing the underlying cause of status epilepticus.

From the FDA Drug Label

The effectiveness of lorazepam injection in status epilepticus was established in two multi-center controlled trials in 177 patients. For the treatment of status epilepticus, the usual recommended dose of lorazepam injection is 4 mg given slowly (2 mg/min) for patients 18 years and older. Lorazepam injection is indicated for the treatment of status epilepticus.

Status Epilepticus Medications:

• Lorazepam (IV) is a medication used to treat status epilepticus.
• The recommended dose is 4 mg given slowly (2 mg/min) for patients 18 years and older.
• If seizures cease, no additional lorazepam injection is required. If seizures continue or recur after a 10- to 15-minute observation period, an additional 4 mg intravenous dose may be slowly administered 2, 2.
• Lorazepam injection is indicated for the treatment of status epilepticus 2.

From the Research

Status Epilepticus Medications

• The first-line treatment for status epilepticus (SE) is benzodiazepines, with lorazepam being the most commonly used 3, 4, 5, 6, 7.
• If SE is not controlled within 5 to 7 minutes, second-line agents such as phenytoin or fosphenytoin are recommended 3, 4, 5, 6, 7.
• Other second-line options include valproate and levetiracetam, which may be as effective and safe as fosphenytoin and phenobarbital 4, 5, 6, 7.
• For refractory SE, continuous intravenous infusions of anesthetic medications such as midazolam, propofol, pentobarbital, and ketamine are used 4, 5, 7.
• The choice of medication should be individualized based on patient characteristics and the specific stage of SE treatment 5, 6, 7.

Treatment Stages

• The emergent treatment phase of SE involves the use of benzodiazepines as first-line therapy 7.
• The urgent treatment phase involves the use of antiseizure medicines such as phenytoin, valproic acid, and levetiracetam 7.
• The refractory SE period involves the use of continuous intravenous infusions of anesthetic medications 4, 5, 7.

Administration Routes

• Intravenous administration is the most common route for SE medications 3, 4, 5, 6, 7.
• Rectal diazepam or nasal or buccal midazolam can be used if intravenous access is not immediately available 4, 6.
• Intramuscular midazolam is also an option for easier administration in the field 6.