What is the management of status epilepticus?

From the Guidelines

Status epilepticus requires immediate intervention with a stepwise approach to medication management, prioritizing benzodiazepines as first-line treatment, followed by second-line therapy with levetiracetam, fosphenytoin, or valproate, as these options result in cessation of seizures in approximately half of all patients, according to the most recent evidence 1.

First-Line Treatment

The initial approach involves administering benzodiazepines, with intravenous lorazepam (0.1 mg/kg, max 4 mg) being preferred due to its longer duration of action, or midazolam (0.2 mg/kg IM, max 10 mg) if IV access is unavailable. This is based on the principle of rapidly achieving seizure control to minimize neuronal damage and improve outcomes.

Second-Line Therapy

If seizures persist after 5-10 minutes, second-line therapy should be initiated. The most recent and highest quality study 1 suggests that levetiracetam, fosphenytoin, or valproate are effective options for benzodiazepine-resistant status epilepticus, with each resulting in seizure cessation in about half of the patients. The choice among these may depend on specific patient factors, potential side effects, and the clinical context.

Refractory Status Epilepticus

For cases that are refractory to the above treatments, continuous infusions of midazolam, propofol, or pentobarbital should be considered. These options are typically reserved for severe cases due to their potential for significant side effects, including the need for close monitoring and support in an intensive care setting.

Key Considerations

Throughout the management of status epilepticus, it is crucial to:

• Ensure airway management and vital sign monitoring.
• Address underlying causes of the seizures.
• Implement continuous EEG monitoring for refractory cases to guide therapy. The aggressive treatment approach is necessary because prolonged seizures can cause neuronal damage through excitotoxicity, with increasing resistance to medications as the seizure duration extends, as highlighted by studies such as 1 and 1. However, the most recent guideline 1 emphasizes the importance of early treatment and cessation of status epilepticus to reduce morbidity and mortality, with the benefits outweighing the potential harms of adverse drug reactions.

From the FDA Drug Label

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 one 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 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. 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

The management of status epilepticus involves:

• Observation and management of vital functions
• Ventilatory support
• Administration of lorazepam injection (4 mg given slowly for patients 18 years and older)
• Additional interventions (e.g., concomitant intravenous administration of phenytoin)
• Correction of underlying causes (e.g., hypoglycemia, hyponatremia)
• Maintenance antiepileptic therapy for patients susceptible to further seizure episodes 2

From the Research

Management of Status Epilepticus

The management of status epilepticus involves a patient-specific approach, consisting of four axes: semiology, etiology, EEG correlate, and age 3. The key to effective management is recognition and prompt initiation of treatment.

First-Line Treatment

• Benzodiazepines are the first-line treatment for status epilepticus, as demonstrated by three randomized controlled trials in the hospital and prehospital settings 3.
• Lorazepam has been well established as a first-line therapy 4.
• Benzodiazepines can be administered through IV, intramuscular, rectal, or intranasal routes 3.

Second-Line Treatment

• If seizures persist, second-line treatments such as phenytoin and fosphenytoin, valproate, or levetiracetam are warranted 3.
• Levetiracetam may be recommended as a second-line treatment for status epilepticus along with phenytoin/fosphenytoin, as it has similar efficacy to fosphenytoin but higher safety 5.
• The Established Status Epilepticus Treatment Trial found that all three of these drugs (phenytoin, valproate, and levetiracetam) are similarly effective in achieving seizure cessation in approximately half of patients 3.

Refractory Status Epilepticus

• For cases of refractory and super-refractory status epilepticus, IV anesthetics, including ketamine and γ-aminobutyric acid-mediated (GABA-ergic) medications, are necessary 3.
• Barbiturate anaesthetics, such as pentobarbital, are highly effective for refractory status epilepticus and remain the only way to stop seizure activity with certainty in severely refractory cases 6.
• Continuous EEG monitoring is required to recognize recurrence of seizure activity, as most seizures will be nonconvulsive 4.

Supportive Care

• Prompt recognition and targeted therapy can reduce the risk of complications and death associated with status epilepticus 7.
• Rapid initiation of supportive measures, assessment of the cause of the seizure, and admission to an intensive care unit are essential for effective clinical management 7.
• Invasive haemodynamic monitoring is often necessary, and EEG monitoring is essential for patients with refractory status epilepticus 6.