What is the management of acute seizure?

From the Guidelines

Acute seizure management should prioritize immediate intervention with benzodiazepines, followed by second-line agents such as fosphenytoin, levetiracetam, or valproate for seizures refractory to initial treatment, as recommended by the American College of Emergency Physicians (ACEP) in 2024 1.

Initial Management

For active seizures, first ensure patient safety by placing them on their side, protecting the head, and removing dangerous objects. First-line medication is intravenous lorazepam at 0.1 mg/kg (maximum 4 mg) or diazepam at 0.2 mg/kg (maximum 10 mg), which can be repeated once after 5-10 minutes if seizures continue. If IV access is unavailable, midazolam 0.2 mg/kg can be given intramuscularly or intranasally.

Second-Line Therapy

For seizures persisting beyond 5-10 minutes after benzodiazepines, second-line therapy includes fosphenytoin (20 mg PE/kg IV), valproate (40 mg/kg IV), or levetiracetam (60 mg/kg IV, maximum 4500 mg), as these agents have similar efficacy according to the ACEP clinical policy 1.

Refractory Status Epilepticus

For refractory status epilepticus, continuous infusions of propofol, midazolam, or pentobarbital may be necessary with EEG monitoring in an ICU setting. Throughout management, maintain airway patency, provide oxygen, monitor vital signs, and check glucose levels. Benzodiazepines work by enhancing GABA inhibitory effects in the brain, while second-line agents primarily stabilize neuronal membranes through various mechanisms including sodium channel blockade. Prompt treatment is crucial as prolonged seizures can cause neuronal damage, metabolic derangements, and increased mortality. Key considerations in management include:

• Ensuring patient safety and preventing injury
• Prompt administration of first-line and second-line therapies as needed
• Close monitoring of vital signs and neurological status
• Consideration of underlying causes of seizures and management of potential complications.

From the FDA Drug Label

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). 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.

Acute Seizure Management:

• The initial dose of lorazepam for acute seizure management is 4 mg given slowly (2 mg/min) for patients 18 years and older.
• If seizures cease, no additional dose 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.
• Lorazepam injection is only an initial step in the management of status epilepticus and may require additional interventions.

From the Research

Acute Seizure Management

• Benzodiazepines are commonly used as the first-line treatment for status epilepticus, with lorazepam and diazepam being the most commonly administered benzodiazepines 3, 4.
• The time to treatment is crucial, and clinical response to benzodiazepines is lost with prolonged status epilepticus 3.
• Non-intravenous routes of midazolam, such as intranasal administration, should be considered as an equally efficacious alternative to intravenous lorazepam 3, 4.
• Outpatient therapy with benzodiazepines for the acute treatment of seizures is currently limited to rectal diazepam, but alternative routes of administration are under development 3.

Benzodiazepine Formulations

• Different benzodiazepine formulations have different efficacy profiles and pharmacokinetic and pharmacodynamic properties 4.
• Lorazepam is as efficacious and safe as diazepam-phenytoin combination in the treatment of convulsive status epilepticus in children 5.
• Midazolam nasal spray and diazepam nasal spray are FDA-approved for the treatment of seizure clusters, with differences in their formulations, effectiveness, and safety profiles 6.
• Other benzodiazepine formulations, such as buccal and intranasal midazolam, are used for treating prolonged, acute convulsive seizures in the European Union 6.

Seizure Rescue Therapies

• Seizure rescue therapies, including benzodiazepine formulations, are important for interrupting acute repetitive and prolonged seizures and preventing hospitalization 7.
• The choice of seizure rescue therapy depends on the individual patient's needs, with considerations including administration route, indication for children and adults, pharmacologic profile, and efficacy 7.
• A comparison of approved and commonly used benzodiazepine formulations can help clarify appropriate treatment for individual patients 7.