Chapter 74: Status Epilepticus

KEY CONCEPTS

• Status epilepticus (SE) is a neurologic emergency that may be associated with significant morbidity and mortality.

• Generalized convulsive status epilepticus (GCSE) is defined as any recurrent or continuous seizure activity lasting longer than 30 minutes in which the patient does not regain baseline mental status. Any seizure that does not stop within 5 minutes should be aggressively treated as impending SE.

• There are two types of SE, GCSE and nonconvulsive status epilepticus (NCSE). GCSE is the most common type and can be divided into four stages: (1) impending, (2) established, (3) refractory, and (4) super-refractory.

• Although the pathophysiology of GCSE is unknown, experimental models have shown that there is a dramatic decrease in γ-aminobutyric acid (GABA)–mediated inhibitory synaptic transmission and that glutamatergic excitatory synaptic transmission sustains the seizures.

• During prolonged GCSE, GABA_A receptors move from the synaptic membrane into the cytoplasm where they become functionally inactive. A loss of these receptors on the synaptic surface may result in time-dependent pharmacoresistance to benzodiazepines. The number and activities of glutamatergic N-methyl-D-aspartate (NMDA) receptors also increase, suggesting a role for ketamine.

• The main purpose of treatment is to prevent or decrease morbidity and mortality of prolonged seizures. Pharmacologic treatment needs to be rapid and aimed at terminating both electrical and clinical seizures. The probability of poorer outcomes increases with an increased length of electroclinical seizure activity.

• Although IM midazolam, IV lorazepam, IV diazepam, and IV phenobarbital effectively terminate seizures lasting at least 5 minutes, IV lorazepam is the preferred benzodiazepine for initial treatment of GCSE because of its efficacy and long duration of action in the central nervous system (CNS). In patients without an established IV site, midazolam is the preferred benzodiazepine for intramuscular and intranasal administration.

• Although practice is slowly moving to other anticonvulsants, the hydantoins (ie, phenytoin, fosphenytoin) continue to be the long-acting anticonvulsants used most frequently. Insufficient data exist regarding the comparative efficacy of these two anticonvulsants; however, fosphenytoin is better tolerated and hence preferred. Either should be given concurrently with benzodiazepines.

• The second anticonvulsant administered is less effective than the first “standard” anticonvulsant in both adults and pediatric patients. The third anticonvulsant may be significantly less effective.

• If GCSE is not controlled by two anticonvulsants (a benzodiazepine and a standard antiepileptic drug), it is considered to be refractory. In these cases, anesthetic doses of midazolam, pentobarbital, or propofol may be used and assessed with continuous EEG monitoring.

Preclass Engaged Learning Activity

In preparation of the class session, provide missing information (if available) for the following table.

Case Question: An order is written for a 15-mg PE/kg fosphenytoin loading dose for a 60-kg patient. The dose is added to 50 mL ...