What is the guideline-directed plan to diagnose, workup, and treat status epilepticus in the Emergency Department (ED)?

From the Guidelines

Status epilepticus requires immediate intervention following a stepwise approach, prioritizing stabilization, benzodiazepine administration, and subsequent treatment with second-line and third-line therapies as needed, as outlined in the most recent clinical policy from the American College of Emergency Physicians (1). The initial step involves stabilizing the patient by securing the airway, ensuring breathing, and maintaining circulation. Administer oxygen, establish IV access, check glucose levels, and obtain baseline labs including electrolytes, CBC, toxicology screen, and anticonvulsant levels.

• Begin treatment with a benzodiazepine: IV lorazepam (0.1 mg/kg, max 4 mg) or IV diazepam (0.15-0.2 mg/kg, max 10 mg), as these are considered first-line treatments (1).
• If IV access is unavailable, use IM midazolam (10 mg for adults) or rectal diazepam.
• If seizures persist after 5-10 minutes, proceed to second-line therapy with IV fosphenytoin (20 mg PE/kg at 150 mg/min), valproic acid (40 mg/kg over 10 minutes), or levetiracetam (60 mg/kg, max 4500 mg over 10 minutes), with valproic acid being a recommended option due to its efficacy and safety profile (1).
• For refractory status epilepticus (seizures continuing after two medications), initiate third-line therapy with continuous infusions of midazolam (loading dose 0.2 mg/kg, then 0.1-2 mg/kg/hr), propofol (1-2 mg/kg load, then 2-10 mg/kg/hr), or ketamine (1.5-4.5 mg/kg load, then 1.2-7.5 mg/kg/hr) while preparing for ICU transfer (1). Throughout treatment, continuously monitor vital signs, EKG, and consider EEG monitoring. Simultaneously investigate and treat underlying causes such as metabolic disturbances, infection, trauma, stroke, or medication withdrawal, as these can significantly impact patient outcomes (1). This aggressive approach is necessary because prolonged seizures can cause neuronal damage through excitotoxicity and may become increasingly resistant to treatment over time.

From the FDA Drug Label

Status Epilepticus General Advice Status epilepticus is a potentially life-threatening condition associated with a high risk of permanent neurological impairment, if inadequately treated The treatment of status, however, requires far more than the administration of an anticonvulsant agent. It involves observation and management of all parameters critical to maintaining vital function and the capacity to provide support of those functions as required. Ventilatory support must be readily available The use of benzodiazepines, like lorazepam injection, is ordinarily only an initial step of a complex and sustained intervention which may require additional interventions (e.g., concomitant intravenous administration of phenytoin). Because status epilepticus may result from a correctable acute cause such as hypoglycemia, hyponatremia, or other metabolic or toxic derangement, such an abnormality must be immediately sought and corrected. Furthermore, patients who are susceptible to further seizure episodes should receive adequate maintenance antiepileptic therapy Any health care professional who intends to treat a patient with status epilepticus should be familiar with this package insert and the pertinent medical literature concerning current concepts for the treatment of status epilepticus.

The guideline-directed plan to diagnose, workup, and treat status epilepticus in the Emergency Department (ED) involves:

• Initial assessment: Identify and correct any underlying cause of status epilepticus, such as hypoglycemia or hyponatremia.
• Airway management: Ensure a patent airway and have ventilatory support readily available.
• Initial treatment: Administer a benzodiazepine, such as lorazepam, as an initial step in a complex and sustained intervention.
• Additional interventions: Consider concomitant administration of other anticonvulsants, such as phenytoin.
• Ongoing management: Provide adequate maintenance antiepileptic therapy to patients susceptible to further seizure episodes.
• Consultation: Consider consulting with a neurologist if the patient fails to respond to treatment. 2

From the Research

Diagnosis and Initial Treatment

• Status epilepticus (SE) is a neurological emergency that requires prompt diagnosis and treatment, as delay is associated with a higher likelihood of poor response to treatment and worse outcome 3.
• The initial treatment includes intravenous lorazepam (2-8 mg/70kg) or diazepam (5-20 mg/70kg) and phenytoin (1500 - 2000 mg/70 kg) which will control seizures in up to 70% of patients 4.
• If intravenous access is not immediately available, rectal diazepam or nasal or buccal midazolam should be given; this can also be used as out-of-hospital treatment to prevent or treat SE 3, 5.

Refractory Status Epilepticus

• If status epilepticus becomes resistant to the initial treatment, the patient should be managed in a monitored environment, as further therapy usually includes agents that may anaesthetise the patient 4.
• Continuous intravenous midazolam and propofol, separately or in combination, are rapidly effective for refractory SE, with pentobarbital remaining the gold standard for prolonged cases 3.
• Midazolam, propofol, pentobarbital, and ketamine are continuous intravenous infusions of anesthetic medications utilized in the refractory SE (RSE) period 6.

Monitoring and Follow-up

• EEG is essential for diagnostics and the monitoring of treatment effect 5.
• If a patient does not awaken after treatment, urgent electroencephalogram (EEG) should be obtained to rule out nonconvulsive seizure activity 3.
• In refractory SE, continuous EEG monitoring is required to recognize recurrence of seizure activity, as most seizures will be nonconvulsive 3.

Treatment Approach

• The treatment approach varies based on the time and the treatment stage of SE, with benzodiazepines considered the first-line therapy during the emergent treatment phase of SE 6.
• Antiseizure medicines such as phenytoin, valproic acid, and levetiracetam are recommended during the urgent treatment phase 6.
• Suppressive general anaesthesia, monitored by continuous EEG, is used as third-line treatment 5.