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KEY CONCEPTS

KEY CONCEPTS

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

  • image 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 treated aggressively as impending SE.

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

  • image The pathophysiology of GCSE is unknown; however, experimental models show a dramatic decrease in γ-aminobutyric acid (GABA)–mediated inhibitory synaptic transmission and that glutamatergic excitatory synaptic transmission sustains the seizures.

  • image During prolonged GCSE, GABAA receptors move from the synaptic membrane into the cytoplasm, becoming functionally inactive. Receptor loss on the synaptic surface may result in time-dependent benzodiazepine pharmacoresistance. Glutamatergic N-methyl-D-aspartate (NMDA) receptors also increase in number and activity, suggesting a role for ketamine.

  • image Treatment is done 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.

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

  • image The hydantoins (ie, phenytoin, fosphenytoin) continue to be the long-acting antiseizure medications used most frequently, although this is changing. The comparative efficacy of these two antiseizure medications is still unknown; however, fosphenytoin is better tolerated and hence preferred. Either should be given concurrently with benzodiazepines.

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

  • image If GCSE is not controlled by two antiseizure medications (a benzodiazepine and a standard antiseizure medication), it is considered refractory. In these cases, anesthetic doses of midazolam, pentobarbital, or propofol may be used and monitored with a continuous electroencephalogram (EEG).

BEYOND THE BOOK

BEYOND THE BOOK

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 of an appropriate fluid and is given at the maximum administration rate. There are questions about the rate settings for the infusion device (mL/min) and how long it will take to infuse the dose. Complete the following table.

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