From the Guidelines
For refractory status epilepticus not responding to midazolam and propofol infusions, I recommend escalating to valproate as a third-line agent, given its efficacy and safety profile as demonstrated in recent studies 1.
Key Considerations
- Valproate has been shown to be at least as effective as phenytoin for refractory status epilepticus, with potentially fewer adverse effects 1.
- The recommended dose of valproate is 20 to 30 mg/kg at a rate of 40 mg/min, with potential adverse effects including dizziness, thrombocytopenia, liver toxicity, and hyperammonemia 1.
- Continuous EEG monitoring is essential to guide therapy, aiming for burst suppression.
- Addressing underlying causes such as metabolic abnormalities, infection, or structural lesions is crucial in managing refractory status epilepticus.
- Maintaining appropriate supportive care, including airway protection, hemodynamic support, and prevention of complications, is vital.
Alternative Options
- Levetiracetam (loading dose 30–50 mg/kg IV load at 100 mg/min) may be considered as an alternative to valproate, with potential adverse effects including nausea and rash 1.
- Phenobarbital (10-20 mg/kg; may repeat 5-10 mg/kg at 10 min) is another option, but it may cause respiratory depression and hypotension 1.
- Ketamine and pentobarbital may also be considered, but their use should be guided by the patient's specific clinical scenario and the potential risks and benefits.
Ongoing Management
- Super-refractory status epilepticus (continuing beyond 24 hours) may require additional therapies such as immunotherapy, hypothermia, or even surgical options in select cases.
- Regular reassessment of the patient's condition and adjustment of the treatment plan as needed is crucial in achieving optimal outcomes.
From the FDA Drug Label
Propofol injectable emulsion was found to be effective in status epilepticus which was refractory to the standard anticonvulsant therapies.
Status Epilepticus Treatment: Propofol injectable emulsion has been found to be effective in treating status epilepticus that is refractory to standard anticonvulsant therapies, including midazolam and propofol gtts 2.
- The drug label does not provide specific dosing recommendations for this indication.
- However, it is essential to note that propofol injectable emulsion should be used with caution and under close monitoring due to its potential to cause decreased blood pressure and compromised cerebral perfusion pressure.
From the Research
Status Epilepticus Refractory to Midazolam and Propofol
- Status epilepticus (SE) is a neurological emergency that requires timely pharmacological therapy to cease seizure activity 3.
- 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 3.
- For refractory status epilepticus (RSE), continuous intravenous infusions of anesthetic medications such as midazolam, propofol, pentobarbital, and ketamine are utilized 3.
- Midazolam has been shown to be effective in treating refractory generalized status epilepticus, with clinical examination and scalp electroencephalographic monitoring documenting the cessation of seizure activity within minutes of the loading dose 4.
- Propofol is also considered for treatment of refractory status epilepticus, although the most efficacious pharmacotherapeutic treatments for RSE and superrefractory status epilepticus are not clearly defined 3, 5.
Treatment Options for Refractory Status Epilepticus
- Midazolam infusion is useful in refractory status epilepticus, with its pharmacodynamic effects seen within 1 to 5 minutes of administration and anticonvulsive effects apparent as early as 5 to 15 minutes after administration 6.
- Thiopentone, propofol, or high-dose phenobarbitone are considered for treatment of refractory status epilepticus 7.
- General anesthesia with IV midazolam, propofol, pentobarbital, or thiopental could be applied for refractory SE 5.
- Ketamine, megadose phenobarbital therapy, and multiple combinations of various AEDs including high doses of oral AEDs can also be considered for refractory SE 5.
Diagnosis and Treatment of Status Epilepticus
- The definition of status epilepticus was revised recently to include continuous seizure activity lasting more than 5 minutes 5.
- The diagnosis and treatment of nonconvulsive SE (NCSE) involves the use of EEG, with a wide range of EEG abnormalities in NCSE 5.
- The treatment of convulsive SE (CSE) typically involves first-line treatment with benzodiazepine, followed by second-line treatment with intravenous doses of fosphenytoin, valproate, phenobarbital, levetiracetam, or midazolam 5.