Minimizing excitotoxicity early in the progression is critical to preventing long-term neuronal damage in patients with super-refractory status epilepticus1

The goal of super-refractory status epilepticus (SRSE) therapy is to minimize excitotoxic cerebral damage by terminating seizures while minimizing long-term exposure to intravenous (IV) general anesthetics and other third-line agents.1


  • Terminate electrographic seizures


  • Identify and treat underlying SRSE cause
  • Prevent and manage systemic complications
  • Wean from anesthetics
  • Improve functional outcomes and recovery after SRSE

SRSE is commonly managed in the intensive care unit (ICU) by inducing sustained electroencephalogram (EEG) burst or seizure suppression using continuous IV general anesthetics.1,2

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Clinical Recommendations for the Complex SRSE Puzzle

Get insights into current SRSE management approaches from Gretchen M. Brophy, PharmD, BCPS, FCCP, FCCM, FNCS

SRSE is typically treated with continuous IV anesthetics1,2

While the American Epilepsy Society has treatment guidelines for convulsive SE, SRSE is a distinct condition for which there are limited evidence-based treatment guidelines.1,2

Currently utilized anesthetics for SRSE may provide some control of seizures,1,2 but they carry risks, and patient exposure should be carefully managed.1-3 Currently, there are no treatments that have been FDA approved to treat SRSE.

Long-term anesthesia use exposes patients with SRSE to complications1,2

Medical complications associated with long-term anesthesia include1,2:

  • Hypotension – Anesthetics such as pentobarbital are also associated with hypotension and sometimes cardiorespiratory complications.1
  • Ventilator-associated pneumonia – Lung infection can occur in patients who are on breathing machines. A bacteria infection (commonly thought to be caused by endotracheal or tracheostomy tube) allows free passage of bacteria into the lower segments of the lung.2
  • Tracheostomy and percutaneous gastrostomy tube placement can be associated with wound infection or bleeding. Major complications associated with gastrostomy tube placement are necrotizing fasciitis and colocutaneous fistula.2
  • Drug rashes2
  • ICU-acquired weakness2

SRSE treatment modalities1,3

IV antiepileptics (AEDs) and general anesthetics are used to treat SRSE.1-4 However, no consensus exists as to the appropriate selection or sequence of therapy.1


Pharmacological treatments1-3

Continuous IV


Non-pharmacological treatments1-3

Ketogenic Diet


Electrical and Magnetic
Stimulation Therapies

Additional treatments include:1,3

  • Plasmapheresis
  • Immunotherapy
  • Anti-inflammatory/IV
  • Intravenous
    immunoglobulin (IVIG)
  • Pyridoxine
  • Magnesium infusion

Risks and benefits of SRSE
treatment approaches

The Pros and Cons of Current SRSE Treatment Options1,3,4-12

Treatment Type : Anesthetics



Strong anticonvulsant effect

Hypotension, cardiorespiratory
depression, tolerance, infection risk

Treatment Type : Anticonvulsants



May provide some control for SE

Difficulty assessing effectiveness, polypharmacy

Treatment Type : Ketogenic diet



Possible anti-inflammatory benefits

Limited case data; benefits primarily observed in children

Treatment Type : Hypothermia



Neuroprotective and reducess brain edema

Limited case data; electrolyte disturbances, coagulation, infection, cardiac arrhythmias

Treatment Type : Electrical and magnetic stimulation



Hypothesized to synchronize epileptic discharges, increase refactory period or neuronal discharge

Repeated sessions; need to wean off other drugs before treatment; long recovery time

Lack of evidence-based guidelines

Clinicians are also limited by the lack of evidence-based treatment guidelines following third-line treatment failure.1 Assessing
therapeutic outcomes is difficult due to lack of controlled data, multiple therapies, delay in responses, and varying underlying causes.1,2

Response to treatment can be measured by cEEG2,13

Discover the importance of utilizing continuous EEG monitoring in patients with SRSE
to evaulate for nonconvulsive electrographic seizures and response to treatment.


  1. Shorvon S, Ferlisi M. The treatment of super-refractory status epilepticus: a critical review of available therapies and a clinical treatment protocol. Brain. 2011;134(10):2802-2818.
  2. Hocker S, Tatum WO, LaRoche S, Freeman WD. Refractory and super-refractory status epilepticus–an update. Curr Neurol Neurosci Rep. 2014;14:452.
  3. Bayrlee A, Ganeshalingam N, Kurczewski L, Brophy GM. Treatment of super-refractory status epilepticus. Curr Neurol Neurosci Rep. 2015;15(10):66.
  4. Ferlisi M, Shorvon S. The outcome of therapies in refractory and super-refractory convulsive status epilepticus and recommendations for therapy. Brain. 2012;135(Pt 8):2314-2328.
  5. Corry JJ, Dhar R, Murphy T, Diringer MN. Hypothermia for refractory status epilepticus. Neurocrit Care. 2008;9(2):189-197.
  6. Liu Z, Gatt A, Mikati M, Holmes GL. Effect of temperature on kainic acid-induced seizures. Brain Res. 1993;631:51-58.
  7. Lundgren J, Smith ML, Blennow G, Siesjo BK. Hyperthermia aggravates and hypothermia ameliorates epileptic brain damage. Exp Brain Res. 1994;99:43-55.
  8. Schmitt FC, Buchheim K, Meierkord H, Holtkamp M. Anticonvulsant properties of hypothermia in experimental status epilepticus. Neurobiol Dis. 2006;23:689-96.
  9. Takei Y, Nishikawa Y, Tachibana M, Takami T, Miyajima T, Hoshika A, et al. Hypothermia during kainic acid-induced seizures reduces hippocampal lesions and cerebral nitric oxide production in immature rabbits. Brain Dev. 2004;26:176-183.
  10. Hrncic D, Vucevic D, Rasic A, Radosavljevic T, Mladenovic D, Susic V, et al. Moderate body hypothermia alleviates behavioral and EEG manifestations of audiogenic seizures in metaphit-treated rats. Can J Physiol Pharmacol. 2007;85:1032-1037.
  11. Wang Y, Liu PP, Li LY, Zhang HM, Li T. Hypothermia reduces brain edema, spontaneous recurrent seizure attack, and learning memory deficits in the kainic acid treated rats. CNS Neurosci Ther. 2011;17(5):271-280.
  12. Corry JJ, Dhar R, Murphy T, Diringer MN. Hypothermia for refractory status epilepticus. Neurocrit Care. 2008;9:189-197.
  13. Brophy GM, Bell R, Claassen J, et al; Neurocritical Care Society Status Epilepticus Guideline Writing Committee. Guidelines for the evaluation and management of status epilepticus. Neurocrit Care. 2012;17(1):3-23.