Refractory Status Epilepticus
If after receiving two AEDs, a patient continues to demonstrate seizure activity on physical examination or EEG, she or he is considered to have refractory status epilepticus, which is a medical emergency. Patients in refractory status epilepticus will likely require a continuous infusion of an AED as well as definitive airway management as a result of either seizure or continuous treatment. In rare cases, some patients will continue to seize despite continuous treatment. Such patients are considered to have super refractory status epilepticus, which is defined as continuing seizure activity despite treatment with general anesthetics for more than 24 hours. This condition is beyond the scope of traditional EP practice, who in this scenario would consult emergently with neurology or critical care services.
Treatment for patients with refractory status epilepticus includes propofol, high-dose midazolam, and ketamine. As previously noted, patients with refractory seizure likely will require airway management; therefore, consultation with neurology or critical care services is indicated.
Propofol
Propofol, a sedative-hypnotic agent that activates both γ-aminobutyric acid and N-methyl-D-aspartate receptors, is commonly given to patients with refractory status epilepticus. While head-to-head reviews have not shown propofol to be superior to phenobarbital or midazolam in treating refractory seizure, it is a drug that is familiar to most EPs.23 Midazolam or propofol are typically given to patients in the ED who require intubation with sedation.
With respect to side effects, propofol can cause dose-limiting hypotension. In addition, propofol infusion syndrome leading to lactic acidosis and cardiac dysfunction in patients receiving long-term propofol infusion.24 One possible infusion dose is 0.5-1 mg/kg loading dose with a continuous infusion of 2 mg/kg/h IV.
High-Dose Midazolam
High-dose midazolam may be given as an alternative to propofol as some studies have shown its efficacy in treating refractory status epilepticus.25 Continuous low-dose infusions of midazolam (0.2 mg/kg/h) have been given to patients in the neurological intensive care unit (ICU); however, there are some data to support treating with a higher dose (≥0.4 mg/kg/h).25 In one single-center retrospective trial, post discharge all-cause mortality was lower in the cohort group that received the higher dose infusion (40% vs 62%).25 Although higher rates of hypotension were noted in the high-dose group, it did not appear to affect mortality.
Ketamine
Ketamine has become a valued anesthetic in emergency medicine, and EPs have become comfortable with its dosing and safety profile. While animal studies on ketamine are promising to treat status epilepticus, human data are limited and often extrapolated from retrospective ICU data. Many patients are placed on a ketamine infusion multiple days into status epilepticus, and for this reason, ketamine is not recommended as a second-line abortive drug in the ED.26
Alternative Treatments and Super Refractory GCSE
In cases of patients with seizure activity ongoing beyond conventional therapy, other methods have been attempted to cease seizure activity and achieve burst suppression on EEG. None of these treatments is in the purview of the EP and should only be undertaken by a neurologist.