Category: Critical Care
Posted: 2/11/2025 by Jordan Parker, MD
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Background
Diagnosed by continuous seizure activity that lasts for 5 minutes or more and/or multiple seizures that occur without returning to baseline in-between each. Further classified as being convulsive or non-convulsive. Refractory status epilepticus can be defined as status epilepticus that does not respond to an adequately dosed benzodiazepine and another anti-seizure medication. The primary objective in management is to stop both clinical and electrographic seizures which can become an important point for those patients who require intubation and receive neuromuscular blockade. Essential to evaluate early for reversible causes (electrolytes, liver function, glucose, ammonia, medications) and for other precipitating causes with toxicology screening and CT head imaging with consideration for angiography and venography.
Management:
First-Line/Initial Therapy:
Lorazepam IV 0.1 mg/kg up to 4 mg per dose is the preferred agent, can be repeated after 5 minutes if seizures persist
Diazepam 0.15 mg/kg IV/0.2 mg/kg PR up to 10 mg, or midazolam IM 0.2 mg/kg up to 10 mg are also alternatives
Second-line/Urgent control: (Provided to all patients with SE after initial therapy)
- Levetiracetam 60 mg/kg, Valproate 40 mg/kg, and fosphenytoin 20 mgPE/kg were studied by Kapur et al., and they found similar rates of resolution of status epilepticus with similar rates of adverse events.
- Phenobarbital 15-20 mg/kg is another agent that has good efficacy and is remerging as an effective agent. Can cause respiratory depression at high doses.
- Keppra may have the best side-effect profile to consider.
- Valproate can cause hepatotoxicity, elevated ammonia and thrombocytopenia.
- Fosphenytoin can cause hypotension and arrhythmias.
Third-line:
Midazolam 0.2 mg/kg load followed by 0.05 – 2 mg/kg/hr infusion
Propofol 1-2 mg/kg load followed by 20-200 mcg/kg/min infusion
Ketamine 0.5 – 3 mg/kg load followed by 1.5-10 mg/kg/hr infusion
Pentobarbital 5 mg/kg load followed by 0.5-5 mg/kg/hr infusion
- Propofol carries the risk of propofol infusion syndrome with high doses or prolonged infusions, some favor midazolam because of this.
No conclusive data to support one over another.
Important Considerations
- A common mistake is to under-dose benzodiazepines for initial therapy, give the full weight-based dose as described above.
- Following initial management it is important to monitor patients with continuous EEG if they have not returned to their neurologic baseline
- Propofol, midazolam or ketamine are good options for induction for intubation.
- Consider against using etomidate for induction of intubation since it can cause myoclonus which can complicate the picture if you are already worried about seizures, can be hard to differentiate.
- If intubation is required and EEG is not readily available consider reversal of neuromuscular blockade after intubation to better monitor for continued seizures.
- If in refractory status epilepticus despite using a second-line agent and a third line agent then consider adding a second agent from the second-line/urgent control that was not previously started (fosphenytoin, valproate, levetiracetam, or phenobarbital).
Brophy GM, Bell R, Claassen J, Alldredge B, Bleck TP, Glauser T, Laroche SM, Riviello JJ Jr, Shutter L, Sperling MR, Treiman DM, Vespa PM; Neurocritical Care Society Status Epilepticus Guideline Writing Committee. Guidelines for the evaluation and management of status epilepticus. Neurocrit Care. 2012 Aug;17(1):3-23. doi: 10.1007/s12028-012-9695-z. PMID: 22528274.
Jennifer V Gettings, Fatemeh Mohammad Alizadeh Chafjiri, Archana A Patel, Simon Shorvon, Howard P Goodkin, Tobias Loddenkemper. Diagnosis and management of status epilepticus: improving the status quo. The Lancet Neurology. 2025;24(1):65-76.
Kapur J, Elm J, Chamberlain JM, Barsan W, Cloyd J, Lowenstein D, Shinnar S, Conwit R, Meinzer C, Cock H, Fountain N, Connor JT, Silbergleit R; NETT and PECARN Investigators. Randomized Trial of Three Anticonvulsant Medications for Status Epilepticus. NEJM. 2019 Nov 28;381(22):2103-2113. doi: 10.1056/NEJMoa1905795.
