Status epilepticus (SE) can be categorized into convulsive and nonconvulsive status epilepticus (NCSE). Generalized convulsive status epilepticus is the most commonly encountered form of status epilepticus and is defined as: (1) clinical seizure activity lasting 5 minutes or longer; or (2) two or more seizures without full recovery of consciousness between them. NCSE is a persistent change in the level of consciousness or behavior associated with ongoing seizures on electroencephalogram (EEG), without convulsive activity. NCSE should be considered in patients who present after a prolonged generalized tonic-clonic seizure but do not return to baseline, and in patients who present with persistent confusion, abnormal behavior, or unexplained coma. It is often overlooked given the lack of motor manifestations. SE is a neurologic emergency associated with high morbidity and mortality, and urgent treatment is necessary. The prognosis depends both on the etiology and the duration of seizure activity. In some cases, treatment of the underlying cause of SE (e.g., autoimmune or infectious encephalitis, metabolic derangement) may be necessary to achieve successful seizure control.
The first phase of treatment comprises ensuring the airway is protected, ventilation is adequate, and the patient is hemodynamically stable. Immediate intubation is not always necessary, and use of paralytic drugs to assist intubation will confound the assessment of ongoing convulsive activity. The time of seizure onset should be determined in order to gauge the duration of SE, which impacts the decision of when to escalate therapy. Electrolytes and glucose should be assessed, and antiepileptic drug levels checked if the patient was taking these previously.
A benzodiazepine should be given as soon as possible; standard choices include either intravenous (IV) lorazepam if IV access is available or intramuscular (IM) midazolam otherwise. Adequate dosing (e.g., 4 mg of lorazepam or 10 mg of midazolam) is critical. This should be repeated after 5 minutes if seizures continue. In the prehospital setting where an IV line is not in place, midazolam IM has been demonstrated to be more efficacious than IV lorazepam because of speed and ease of administration. The patient’s need for airway protection should be continually reassessed during treatment.
If the patient fails to respond to initial therapy, second-line therapy with an IV antiepileptic medication such as levetiracetam should be started. Valproic acid and phenytoin (or fosphenytoin) may be considered as alternatives; however, levetiracetam has a better side effect profile and fewer drug interactions. Levetiracetam is renally excreted, and dosing should be adjusted in patients with renal disease. IV phenytoin should be used with caution given the risk of infusion site reactions (purple glove syndrome) and cardiac arrhythmias, particularly with rapid infusion. These risks are reduced with fosphenytoin. If seizures abate, the antiepileptic drug given should be continued as maintenance therapy pending further evaluation. Noncontrast head computed tomography should be completed as soon as safe, particularly in patients without a well-established epilepsy diagnosis.
If convulsive seizures continue despite second-line therapy for a total duration of > 30 minutes, midazolam should be started, typically given as a bolus followed by continuous infusion titrated to achieve cessation of seizure activity. Alternatives to midazolam include propofol and pentobarbital. The effectiveness of midazolam is reduced with prolonged use (> 24 hours) and may require an increase in dosing. If not already performed, intubation is mandatory at this stage. Continuous EEG monitoring for subtle or subclinical continued seizures should be initiated if possible.
In the setting of NCSE, the benefit of midazolam or other anesthetic agents to control seizures must be weighed against the nontrivial risks of these therapies. The type and manifestations of NCSE should be considered. Patients with NCSE persisting after resolution of convulsive SE or those in coma should be treated more aggressively.
If refractory seizures continue, an infusion of propofol or pentobarbital can be considered. Continuous EEG monitoring should be considered mandatory at this stage and, if not available, transfer to facility capable of providing this should be considered. Propofol has a short half-life, but may lower blood pressure and, if used for more than 48 hours, can be associated with propofol infusion syndrome (rhabdomyolysis, congestive heart failure, lactic acidosis, and hypertriglyceridemia). Pentobarbital is typically used when a patient is weaned off another third-line agent, such as midazolam or propofol, after 24 to 48 hours. Pentobarbital has a long half-life and takes several hours to reach a therapeutic level. It is very effective at achieving a burst-suppression pattern on EEG, but it is associated with high morbidity because of the prolonged duration of pentobarbital-associated comas.