While the epidemiology of SRSE is not well described, it is likely to be very similar to that of RSE. Between 38 and 60 % of episodes of refractory status epilepticus occur in patients with epilepsy [4, 5], among whom precipitating factors include low antiseizure drug levels, changes in drug regimen, drug intoxication or withdrawal, systemic infection, metabolic derangement, or progression of the underlying disease responsible for their epilepsy. RSE which develops in the absence of underlying epilepsy is most commonly due to acute encephalitis, stroke, brain tumor, traumatic brain injury, or drug or alcohol withdrawal. Myoclonic status resulting from hypoxic ischemic injury will be discussed in Chap. 18. A more comprehensive list of etiologies is shown in Table 2. Identification of the etiology is important for both treatment and prediction of outcome.

After achieving seizure control, evaluation begins with a focused history and examination. Important historical features include circumstances at seizure onset (prodromal illness, motor vehicle accident, or party suggesting substance abuse), medical history (epilepsy, neoplasms, autoimmune conditions), and active medications (cephalosporins, fluoroquinolones). The patient should be examined for signs of trauma, meningismus, and focal neurological deficits. In nearly all episodes of status epilepticus, a comprehensive laboratory evaluation including antiseizure drug levels, serum electrolytes, glucose level, urine and serum toxicology screens, troponin, lactate and creatine kinase levels, and a head computed tomography (CT) scan is warranted. Because cardiopulmonary complications are commonly associated with status epilepticus, a screening chest X-ray and electrocardiogram would aid in evaluation for aspiration, ischemic changes or development of a prolonged QTc, or other stress-related changes. When laboratory evaluation and neuroimaging do not yield an etiology for SRSE, workup continues with CSF analysis for infection and autoimmune and paraneoplastic conditions. This basic workup will identify the most common causes of SE. In addition to this evaluation, mitochondrial studies are occasionally conducted in younger patients. A stepwise approach to the evaluation of RSE etiology is presented in Table 3.

The ability to perform continuous EEG (cEEG) monitoring is a cornerstone of SRSE treatment as anesthetic agents are titrated against the EEG. Occasionally, the EEG can provide clues to the etiology of the seizures. Periodic lateralized epileptiform discharges (PLEDs) will point the practitioner to a focal intracranial lesion, while the so-called extreme delta brush suggests possible autoimmune encephalopathy, specifically anti-NMDA receptor encephalitis. PLEDs or generalized periodic epileptiform discharges (GPEDs) are a frequent finding after prolonged and untreated seizures.

Excessive glutamatergic activity from seizures is thought to trigger a cascade of electrolyte imbalances, oxidative stress, and mitochondrial dysfunction. These processes result in neuronal cell damage within a few hours of the seizure, which is the principle that drives urgent treatment. Rapid identification and treatment of the underlying etiology is critical to resolution of SRSE; however, as previously discussed, a substantial portion of patients may undergo an exhaustive diagnostic search with no identified etiology.

Widely accepted treatment recommendations for SRSE are based on small, retrospective case series and general consensus. However, anesthetic drugs used for long-term suppression of seizures in this setting can also have detrimental effects, leading some experts to reexamine their protocols. The first-line treatment for status epilepticus is benzodiazepine administration. Proven second-line therapies include fosphenytoin, valproic acid, or phenobarbital. Less established options include levetiracetam and lacosamide. Anesthetics should be considered once second-line medications fail [5]. Clinicians should progress through this protocol rapidly in convulsive status epilepticus where it is not advisable to await completion of the second-line agent to begin intubation, initiation of mechanical ventilation, and induction of an anesthetic drug. In nonconvulsive seizure types, it is often reasonable to await true failure of the second-line agent or even trial a third- or fourth-line non-anesthetic antiseizure drug prior to committing the patient to anesthesia. Any patient requiring an anesthetic drug for seizure control requires continuous EEG monitoring and admission to an intensive care unit. Table 4 provides the overall treatment algorithm, mechanism of action, recommended dosing, and adverse effects of commonly used anesthetic agents for SRSE.