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Harrison’s Manual of Medicine




Defined as continuous seizures (>15–30 min) or repetitive, discrete seizures with impaired consciousness in the interictal period. Condition may occur with all kinds of seizures: grand mal (tonic-clonic) status, myoclonic status, petit mal status, and temporal lobe (complex partial) status. Generalized, tonic-clonic seizures are most common and are usually clinically obvious early in the course. After 30–45 min, the signs may become increasingly subtle and include mild clonic movements of the fingers or fine, rapid movements of the eyes. In some situations, EEG may be the only method of diagnosis. Generalized status may be life-threatening when accompanied by hyperpyrexia, acidosis (from prolonged muscle activity), or respiratory or cardiovascular compromise. Irreversible neuronal injury may occur when tonic-clonic seizures persist for more than 2 h.
Principal causes of tonic-clonic status are antiepileptic drug withdrawal or noncompliance, alcohol-related, refractory epilepsy, CNS infection, drug toxicity, metabolic disturbances, CNS tumors, cerebrovascular disease, and head trauma.

TREATMENT   (Fig. 38-1)

FIGURE 38-1. Pharmacologic treatment of generalized tonic-clonic status epilepticus in adults. IV, intravenous; PE, phenytoin equivalents. The horizontal bars indicate the approximate duration of drug infusions.

Generalized tonic-clonic status epilepticus is a medical emergency. Pts must be evaluated promptly and appropriate therapy instituted without delay. In parallel, it is essential to determine the cause of the seizures to prevent recurrence and treat any underlying abnormalities.
1.   Assess carefully for evidence of respiratory or cardiovascular insufficiency. With careful monitoring and standard airway protection, pts usually do not require intubation (if intubation is necessary, use short-acting paralytics). Treat hyperthermia. Establish IV and administer 50 mL 50% dextrose in water, 100 mg thiamine, and 0.4 mg naloxone (Narcan).
2.   Perform a brief medical and neurologic examination; send samples for laboratory studies aimed at identifying metabolic abnormalities (CBC with differential, serum electrolytes including calcium, liver and renal function tests, toxicology if indicated).
3.   Administer lorazepam, 0.1 mg/kg (4–8 mg) at 2 mg/min.
4.   Immediately after lorazepam, administer phenytoin, 20 mg/kg (1000–1500 mg) IV slowly over 20 min (50 mg/min) or fosphenytoin, 20 mg/kg (150 mg/min). Monitor bp, ECG, and, if possible, EEG during infusion. Phenytoin can cause precipitous fall in bp if given too quickly, especially in elderly pts. (Do not administer phenytoin with 5% dextrose in water—phenytoin precipitates at low pH. This is not a problem with fosphenytoin.) If seizures are not controlled, a repeat bolus of phenytoin (5–10 mg/kg) or fosphenytoin (5–10 mg/kg) may be given.
5.   If seizures persist, administer phenobarbital 20 mg/kg (1000–1500 mg) slowly over 30 min. Endotracheal intubation will often be required by this stage. If seizures continue, give additional dose of phenobarbital (5–10 mg/kg).
6.   If seizures remain refractory after 60–90 min, consider placing pt in midazolam, propofol, or pentobarbital coma. Consultation with a neurologist and anesthesiologist is advised.

The mortality rate is 20% in tonic-clonic status, and the incidence of permanent neurologic sequelae is 10–30%.

For a more detailed discussion, see Lowenstein DH: Seizures and Epilepsy, Chap. 360, p. 2354, in HPIM-15.


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