What is the management of status epilepticus?

From the Guidelines

Status epilepticus requires immediate treatment with benzodiazepines as first-line therapy, followed by second-line therapy with levetiracetam, fosphenytoin, or valproate if seizures persist, as these treatments have been shown to result in cessation of seizures in approximately half of all patients, reducing morbidity and mortality 1. The initial management includes administering intravenous lorazepam (0.1 mg/kg, maximum 4 mg) or diazepam (0.15-0.2 mg/kg, maximum 10 mg), or intramuscular midazolam (10 mg for adults >40 kg) as first-line therapy. If IV access is unavailable, rectal diazepam or buccal/intranasal midazolam can be used. Some key points to consider in the management of status epilepticus include:

• If seizures persist after 5-10 minutes, second-line therapy should be initiated with fosphenytoin (20 mg PE/kg IV at 150 mg/min), valproate (40 mg/kg IV over 10 minutes), or levetiracetam (60 mg/kg IV over 10 minutes) 1.
• For refractory status epilepticus, continuous infusions of midazolam (0.2 mg/kg bolus, then 0.1-2 mg/kg/hr), propofol (1-2 mg/kg bolus, then 2-10 mg/kg/hr), or pentobarbital (5-15 mg/kg bolus, then 0.5-10 mg/kg/hr) should be considered. Throughout treatment, it is essential to:
• Maintain airway protection
• Provide oxygen
• Establish IV access
• Check glucose levels
• Monitor vital signs Continuous EEG monitoring is also crucial for refractory cases, as the rapid treatment of status epilepticus is vital in reducing the risk of neuronal damage and mortality, which increases significantly after 30 minutes of continuous seizure activity 1.

From the FDA Drug Label

The loading dose of fosphenytoin is 15 to 20 mg PE/kg administered at 100 to 150 mg PE/min. Because of the risk of hypotension, fosphenytoin should be administered no faster than 150 mg PE/min Continuous monitoring of the electrocardiogram, blood pressure, and respiratory function is essential and the patient should be observed throughout the period where maximal serum phenytoin concentrations occur, approximately 10 to 20 minutes after the end of fosphenytoin infusions Because the full antiepileptic effect of phenytoin, whether given as fosphenytoin or parenteral phenytoin, is not immediate, other measures, including concomitant administration of an intravenous benzodiazepine, will usually be necessary for the control of status epilepticus.

Management of Status Epilepticus:

• The recommended loading dose of fosphenytoin is 15 to 20 mg PE/kg administered at a rate of 100 to 150 mg PE/min.
• Administration of fosphenytoin should not exceed 150 mg PE/min due to the risk of hypotension.
• Continuous monitoring of the electrocardiogram, blood pressure, and respiratory function is essential.
• Other measures, including concomitant administration of an intravenous benzodiazepine, may be necessary for the control of status epilepticus.
• If administration of fosphenytoin does not terminate seizures, the use of other anticonvulsants and other appropriate measures should be considered 2.

Note: The management of status epilepticus may involve the use of other medications, such as intravenous benzodiazepines, and other appropriate measures, as mentioned in the drug label 2 and 3.

From the Research

Management of Status Epilepticus

The management of status epilepticus (SE) involves a multi-step approach, with the primary goal of rapidly identifying the cause and initiating urgent pharmacological treatment 4. The following are key aspects of SE management:

• Initial Treatment: Intravenous lorazepam and intramuscular midazolam are considered the most effective treatments for early SE 4. In children, buccal midazolam has emerged as a first-line non-intravenous drug with similar efficacy and safety to other intravenous or rectal benzodiazepines 4.
• Established SE: Intravenous antiepileptic drugs, such as valproate and levetiracetam, are used in established SE 4. A meta-analysis found higher rates of seizure cessation with valproate and phenobarbital compared to levetiracetam and phenytoin 4.
• Refractory SE: Treatment options for refractory SE include intravenous anaesthetics, such as midazolam and propofol 5. Other options, such as ketamine and magnesium, have also been used with variable outcomes 4.
• Super-Refractory SE: At this stage, therapeutic decisions are based on doctor's preferences, patient factors, and the cause of SE, if identified 4. Treatment options may include non-sedating or sedating compounds, including ketamine and barbiturates 6.

Treatment Approaches

Different studies have compared the efficacy and safety of various treatment approaches for SE:

• Levetiracetam vs. Lorazepam: A randomized, open-labeled pilot study found that levetiracetam and lorazepam were equally effective in controlling SE, with levetiracetam having a more favorable tolerability profile 7.
• Benzodiazepines: Benzodiazepines are considered the first-line treatment for SE, with administration routes including IV, intramuscular, rectal, or intranasal 8.
• Second-Line Treatments: Second-line treatments, such as phenytoin and fosphenytoin, valproate, or levetiracetam, are warranted if seizures persist after initial treatment 8.

ICU Management

The management of SE in the intensive care unit (ICU) involves:

• Rapid Diagnosis: Diagnosis of convulsive SE can be made without electroencephalography (EEG), but EEG is required to reliably diagnose nonconvulsive SE 6.
• Continuous Video EEG: Continuous video EEG is necessary for the management of refractory and super-refractory SE, as these are almost always nonconvulsive 6.
• Underlying Cause: Rapidly narrowing down the underlying cause of SE is crucial, as this may guide additional management steps 6.