From the Guidelines
Treatment of refractory non-convulsive status epilepticus (NCSE) should prioritize valproate as a first-line therapy due to its efficacy and safety profile, as demonstrated in studies such as 1.
Key Considerations
- Initial management involves benzodiazepines like intravenous lorazepam or midazolam, followed by anti-seizure medications such as levetiracetam, valproate, or phenytoin.
- For refractory cases, continuous infusions of midazolam, propofol, or pentobarbital should be considered with continuous EEG monitoring targeting burst suppression, as recommended by 1.
- Valproate has been shown to be at least as effective as phenytoin for refractory status epilepticus, with potentially fewer adverse effects, as seen in 1.
- The Neurocritical Care Society’s Status Epilepticus Guideline Writing Committee recommended urgent control of seizures with valproate, levetiracetam, or phenobarbital, in addition to phenytoin/fosphenytoin, highlighting the importance of valproate in treatment protocols 1.
Treatment Protocol
- Initial therapy: benzodiazepines (e.g., lorazepam 0.1 mg/kg or midazolam 0.2 mg/kg)
- Second-line therapy: valproate (40 mg/kg, max 3000 mg) or levetiracetam (60 mg/kg, max 4500 mg)
- Refractory cases: consider continuous infusions of midazolam (starting at 0.1 mg/kg/hr), propofol (starting at 1 mg/kg/hr), or pentobarbital (loading dose 5 mg/kg, maintenance 1-5 mg/kg/hr) with continuous EEG monitoring
- Super-refractory cases: consider adding ketamine (starting at 1-2 mg/kg/hr) due to its NMDA receptor antagonism, as part of a comprehensive treatment approach including ICU care and management of underlying causes, as suggested by 1.
From the FDA Drug Label
Propofol injectable emulsion was found to be effective in status epilepticus which was refractory to the standard anticonvulsant therapies.
Treatment Option for Refractory NCSE: Propofol may be considered as a treatment option for refractory non-convulsive status epilepticus (NCSE) that is unresponsive to standard anticonvulsant therapies.
- The dosage for this indication is not explicitly stated in the label, but it is mentioned that sedation maintenance dosages were generally higher than those for other critically ill patient populations.
- It is essential to note that the use of propofol in this setting should be done with caution and under close monitoring, as it can cause significant hemodynamic effects, including hypotension. 2
From the Research
Treatment Options for Refractory Non-Convulsive Status Epilepticus (NCSE)
- The treatment of refractory NCSE is not well established, and there is limited evidence to support specific treatment options 3, 4.
- Refractory status epilepticus (RSE) usually requires anesthetic doses of anti-seizure medications, and the aggressiveness of treatment should be tailored to the clinical situation 5.
- For refractory SE, continuous intravenous midazolam and propofol (alone or in combination) are rapidly effective 6.
- Ketamine is probably effective in treating refractory CSE, and may warrant earlier use; this requires further study 3.
- If an auto-immune or paraneoplastic etiology is suspected or no etiology can be identified, early treatment with immuno-modulatory agents is now recommended by many experts 3.
Medications Used in Refractory NCSE
- Phenytoin/fosphenytoin, valproic acid, levetiracetam, phenobarbital, and lacosamide are the most frequently prescribed antiseizure medications for treatment of established status epilepticus 4.
- Midazolam, propofol, or barbiturates are the most commonly used drugs for inducing pharmacological coma in generalized convulsive forms of RSE 5.
- Other treatments, such as additional anaesthetics, other antiepileptic or immunomodulatory compounds, or non-pharmacological approaches (eg, electroconvulsive treatment or hypothermia), have been used in protracted RSE 5.
Future Directions
- Substantial further research is urgently needed to identify patients with non-convulsive status epilepticus, elucidate the most efficacious antiseizure treatment, and determine whether this differs for convulsive vs. non-convulsive ESE 4.
- Well-designed prospective studies of RSE are urgently needed to support the choice of specific treatments 5.