How Should Status Epilepticus Be Managed?

Status epilepticus (SE) may be defined as continuous clinical and/or electrographic seizures lasting at least 5 minutes or recurrent discrete seizures without interictal recovery of consciousness. It is a medical emergency and requires prompt recognition and treatment to limit morbidity and mortality. Few randomized controlled trials exist to inform treatment, and practice algorithms vary. In response to the heterogeneity of practice, in 2012, the Neurocritical Care Society published authoritative evidence-based expert consensus guidelines for the evaluation and management of status epilepticus. This chapter provides background on the epidemiology, classification, pathophysiology, and causes of SE and focuses on evidence-based clinical management.

Epidemiology

Studies pertaining to the epidemiology of SE are limited by the changing definitions of SE over time and under-reporting. For more than 50% of cases, SE is the result of a patient’s first seizure. The incidence is thought to be grossly underestimated but has been cited as 65,000 to 150,000 in the United States per year. In a prospective population analysis of SE in Richmond, Virginia, patients were followed for 30 days after seizures were controlled or to the time of death. The incidence was found to be 41 per 100,000 per year, and there was a bimodal age distribution with clustering in the first year of life and in people older than 60 years. Those older than age 60 had the highest incidence and the highest rate of recurrence. Overall mortality was 22% despite a pediatric mortality of approximately 3%.

Classification

A common way to categorize SE is based on whether seizures are focal or generalized and whether consciousness is impaired. In simple partial SE (also termed epilepsia partialis continua when there is motor involvement), seizures emanate from a focal brain region and produce focal symptoms (e.g., unilateral twitching of a limb, aphasia) without impairment of consciousness. In complex partial SE, seizures emanate from a focal brain region, produce focal symptoms, and are associated with impaired consciousness. In generalized SE, seizures involve the entire brain, and consciousness is always impaired. Generalized and complex partial SE is considered more threatening than simple partial SE. The latter typically does not require treatment in an intensive care unit (ICU) and will not be addressed in this chapter. In the ICU, SE often occurs in patients who have preexisting altered mental status from other causes (e.g., cardiac arrest, traumatic brain injury). Therefore, for practical purposes in the ICU, seizures may be classified as (1) convulsive or nonconvulsive and (2) responsive to therapy or refractory. Convulsive SE consists of tonic-clonic movements (rhythmic jerking) and altered mental status (either as coma, lethargy, or confusion). On electroencephalogram (EEG), there are bilateral, symmetric discharges. More than half of patients with generalized convulsive SE respond to a single antiepileptic drug (AED). Development of generalized convulsive SE during hospitalization, older age, and longer duration and severity of impaired consciousness are associated with a poor outcome. Nonconvulsive SE (NCSE) is defined as seizure activity without convulsions (shaking) and is only reliably diagnosed with an EEG. In the ICU, NCSE might be included on the differential diagnosis of any patient with altered mental status. Patients with NCSE may have alterations in behavior, including agitation; aggression; alterations in thought, including confusion and psychosis; and alterations in level of arousal, ranging from lethargy to coma. There may be subtle motor signs, such as muscle twitching, nystagmus, or eye deviation, or none at all. Factors associated with a poor outcome include more serious illness as the cause of seizures, severely altered mental status, and longer seizure duration. Refractory SE may be defined as SE that does not abate after standard initial treatments, typically a benzodiazepine and a bolus of an AED. Refractory SE may be convulsive (“clinical”) or nonconvulsive (“subclinical” or “electrographic”). This diagnosis can be subjective because it is sometimes difficult to ascertain whether “adequate” therapy was administered (e.g., in the prehospital or emergency department setting). Patients with a more severe cause, advanced age, longer seizure duration, and high APACHE-2 (Acute Physiology and Chronic Health Evaluation II) scores have worse outcomes.

Pathophysiology

Seizures have an immediate and often dramatic direct effect on systemic and cerebral physiology at the organ, cellular, and molecular level. SE may result in secondary systemic complications that contribute to morbidity and mortality.

Widespread neuronal depolarization during SE results in a significant increase in the cerebral metabolic rate for oxygen. Because of metabolic autoregulation, this leads to increased systemic blood pressure and cardiac output and results in an increase in cerebral blood flow. In turn, this causes an increase in cerebral blood volume, which causes increased intracranial pressure. This can be especially problematic in patients with low intracranial compliance and can result in catastrophic intracranial hypertension and death. Systemic complications of SE include hypoxia, hypotension, metabolic acidosis, hyperthermia, rhabdomyolysis, and hypoglycemia. Hyperthermia is a result of the increased motor activity seen in seizures. For this reason, patients can also manifest secondary rhabdomyolysis and metabolic acidosis. Initial acute hypertension may give way to normotension or even hypotension. Low blood pressure potentiates brain damage because of inadequate cerebral perfusion. Hypoglycemia can be seen in late SE. Prolonged seizures cause a massive release of glutamate that initiates a cascade of processes, including mitochondrial dysfunction, oxidative stress, inflammatory reactions, and immunosuppression. This eventually leads to neuronal excitotoxicity and injury as well as cellular ischemia and, inevitably, cell death. Animal studies suggest deleterious effects on neurons when there is more than 30 minutes of seizure activity.

Etiologies

Virtually any insult to the brain may cause seizures and SE. SE may be due to acute insults, such as metabolic abnormalities (e.g., hypoglycemia, hyponatremia); hypoxia; global brain ischemia (e.g., cardiac arrest); medications; toxic ingestions; withdrawal from alcohol, benzodiazepines, and other toxins; infectious or autoimmune encephalitis; sepsis; cerebral vascular insults (bleeding more often than ischemia); acute traumatic brain injury; hypertensive encephalopathy; eclampsia; and neurosurgery. SE may also result from remote structural injury to the brain, including prior head injury, meningitis, stroke, or hypoxic-ischemic encephalopathy. It is frequently observed in patients with epilepsy because of their underlying seizure disorder, because of subtherapeutic AED levels, or because of a superimposed insult (e.g., infection). However, up to 50% of patients who have SE have no prior history of seizures.

Management

SE is a medical emergency. Time is of the essence to prevent permanent brain injury and to limit systemic complications. The longer SE lasts, the less likely it will respond to therapy. Treatment of seizures and diagnostic efforts typically proceed in parallel. Initial measures involve stabilization of the airway, breathing, and circulation coupled with emergent efforts to terminate seizures. Seizure termination occurs in successive stages, which are described in detail in the following sections. Definitive seizure control should be obtained within 60 minutes of onset if possible. There is a scarcity of randomized controlled studies to inform the optimal bundle of therapies (preferred drugs, dosages, sequence of administration) for SE, and the treatment approach outlined is largely the product of observational data and expert opinion ( Figs. 65-1 and 65-2 ).