What are the treatment options for refractory non-convulsive status epilepticus (NCSE)?

From the Guidelines

Treatment of refractory nonconvulsive status epilepticus (NCSE) should prioritize the use of levetiracetam, fosphenytoin, or valproate as second-line agents, as they result in cessation of seizures in approximately half of all patients, according to the most recent evidence 1. The management of refractory NCSE requires a step-wise approach, starting with first-line therapies such as benzodiazepines, followed by second-line agents like levetiracetam, fosphenytoin, or valproate, as recommended by the Annals of Emergency Medicine 1. Key considerations in the treatment of refractory NCSE include:

• The use of second-line agents like levetiracetam, fosphenytoin, or valproate, which have similar efficacy in stopping seizures 1
• The importance of addressing the underlying cause of status epilepticus for successful treatment
• The potential need for anesthetic agents like midazolam, propofol, or pentobarbital in cases where second-line therapies fail
• The consideration of additional options like ketamine for NMDA receptor antagonism, immunotherapy, ketogenic diet, or surgical options for super-refractory cases The most recent evidence suggests that the use of levetiracetam, fosphenytoin, or valproate as second-line agents can result in cessation of seizures in approximately half of all patients, with limited harms and a reduction in morbidity and mortality 1. In terms of specific treatment protocols, the evidence suggests that:
• Levetiracetam, fosphenytoin, or valproate can be used as second-line agents with similar efficacy 1
• Anesthetic agents like midazolam, propofol, or pentobarbital may be necessary in cases where second-line therapies fail, with dosing and titration guided by continuous EEG monitoring 1
• Additional options like ketamine, immunotherapy, ketogenic diet, or surgical options may be considered for super-refractory cases, depending on the underlying cause and clinical context.

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 options for refractory non-convulsive status epilepticus include the use of propofol, as it has been found to be effective in such cases, according to the drug label of propofol 2.

• The dosage of propofol 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 propofol should be used with caution, especially in patients with compromised ventricular function, as it can cause a decrease in blood pressure.
• The use of propofol in refractory non-convulsive status epilepticus should be considered under the guidance of a qualified healthcare professional, taking into account the individual patient's condition and medical history.

From the Research

Treatment Options for Refractory Non-Convulsive Status Epilepticus

• The treatment of refractory non-convulsive status epilepticus (NCSE) involves the use of various medications, including benzodiazepines, antiepileptic drugs, and general anesthetics 3, 4, 5, 6, 7.
• For refractory SE, continuous intravenous midazolam and propofol (alone or in combination) are rapidly effective 3.
• Other options for refractory GCSE include barbiturate anaesthetics, such as pentobarbital and thiopental sodium, which are highly effective in stopping seizure activity 4.
• Midazolam and propofol are also used in the treatment of refractory GCSE, with midazolam being effective for adults and children, and propofol being effective for adults only 4.
• The use of EEG monitoring is essential in the diagnosis and treatment of NCSE, and can help guide the treatment of refractory SE 5, 7.
• New AEDs such as IV levetiracetam and lacosamide can also be used to treat NCSE with fewer side effects and drug-drug interactions 7.
• For refractory SE, general anesthesia with IV midazolam, propofol, pentobarbital, or thiopental could be applied, and the use of ketamine, megadose phenobarbital therapy, and multiple combinations of various AEDs including high doses of oral AEDs can also be considered 7.

Medications Used in Refractory Non-Convulsive Status Epilepticus

• Benzodiazepines: lorazepam, diazepam, midazolam 3, 4, 5, 6, 7
• Antiepileptic drugs: phenytoin, fosphenytoin, valproate, levetiracetam, phenobarbital, lacosamide 4, 6, 7
• General anesthetics: propofol, pentobarbital, thiopental 4, 5, 7
• Other medications: ketamine, megadose phenobarbital therapy 7

Important Considerations in Treatment

• The treatment of refractory SE should be tailored to the clinical situation, with consideration of the patient's age, cause of SE, and clinical presentation 5.
• The use of EEG monitoring is critical in the diagnosis and treatment of NCSE, and can help guide the treatment of refractory SE 5, 7.
• The treatment of refractory SE requires a multidisciplinary approach, with involvement of neurologists, intensivists, and other healthcare professionals 4, 5, 7.