upon completion of the chapter, the reader will be able to:
Describe the pathophysiology of status epilepticus.
Explain the urgency of diagnosis and treatment of status epilepticus.
Recognize the signs and symptoms of status epilepticus.
Identify the treatment goals for a patient in status epilepticus.
Formulate an initial treatment strategy for a patient in generalized convulsive status epilepticus.
Compare the pharmacotherapeutic options for refractory status epilepticus.
Describe adverse drug events associated with the pharmacotherapy of status epilepticus.
Recommend monitoring parameters for a patient in status epilepticus.
KEY CONCEPT Status epilepticus (SE) is a neurologic emergency that can lead to permanent brain damage or death. KEY CONCEPT SE is defined as continuous seizure activity lasting more than 5 minutes or two or more seizures without complete recovery of consciousness.1 Refractory status epilepticus (RSE) is unresponsive to emergent (first-line) or urgent (second-line) therapy.
SE can present as nonconvulsive status epilepticus (NCSE) or generalized convulsive status epilepticus (GCSE). NCSE is characterized by persistent impaired consciousness without clinical seizure activity and is diagnosed with electroencephalography (EEG). GCSE is characterized by full-body motor seizures and involves the entire brain.
EPIDEMIOLOGY AND ETIOLOGY
The incidence of SE in the United States is 12.5/100,000/year, with an in-hospital mortality rate of 9.2%,2 and an estimated annual direct cost for inpatient admissions of $4 billion.3 It occurs most frequently in males, African Americans, children, and the elderly.
KEY CONCEPT It is important to evaluate etiologies of SE for timely and optimal seizure control. Causes of SE include metabolic disturbances (eg, hyponatremia, hypernatremia, hyperkalemia, hypocalcemia, hypomagnesemia, hypoglycemia); central nervous system (CNS) disorders, infections, injuries; hypoxia; drug toxicity (eg, theophylline, isoniazid, cyclosporine, cocaine). Chronic causes of SE include preexisting epilepsy, chronic alcoholism (withdrawal seizures), CNS tumors, and strokes.4 In epileptics, the common causes of SE are anticonvulsant withdrawal or subtherapeutic levels.
Status epilepticus occurs when the brain fails to stop isolated seizures, due to a mismatch of neurotransmitters. Glutamate, the primary excitatory neurotransmitter, stimulates postsynaptic N-methyl-d-aspartate (NMDA) receptors, causing neuronal depolarization. Sustained depolarization causes neuronal injury and death.5 The primary inhibitory neurotransmitter, γ-aminobutyric acid (GABA), opposes excitation by stimulating GABAA receptors, producing hyperpolarization and inhibition of the postsynaptic cell membrane. GABA-mediated inhibition diminishes with continuous seizure activity, causing a decreased response to GABA-receptor agonists.6 Seizures lasting more than 30 minutes cause significant injury and neuronal loss because of excessive electrical activity and cerebral metabolic demand. Decreased GABAA-receptor response and increasing neuronal injury with prolongation of seizure activity necessitates rapid control of SE.
Systemic changes appear in two phases during SE. Phase I occurs during the first 30 minutes, and phase II occurs after 30 to 60 minutes.7