Phenytoin and now fosphenytoin are probably the most frequently used anticonvulsants for SE. The older formulation (phenytoin in a basic solution including ethylene glycol) is still used because its cost is substantially lower. However, intravenous phenytoin has three major disadvantages:
The newer formulation (fosphenytoin, a phenytoin prodrug) can be administered more quickly, an important advantage when seizures must be controlled quickly. Because a basic solution is not required for dissolving fosphenytoin, intramuscular administration is safe and extravasation carries little risk.
Cardiac rhythm abnormalities and hypotension can occur with both formulations.
Both phenytoin and fosphenytoin cause minimal sedation. This advantage over other anticonvulsants is probably overstated but it may be pertinent for patients with head trauma, hemorrhage, or raised intracranial pressure, for whom it is important to monitor alertness. Patients with GCSE are unconscious, and the most immediate concern is stopping the seizures.
In the absence of acute structural lesions, both phenytoin and fosphenytoin may be successful alone in up to 80% of patients with GCSE. If either is used, oral phenytoin can then become a long-term maintenance medication. This obviates the necessity of changing or adding drugs.
Patients may need adjunctive benzodiazepines to interrupt convulsions if they occur during phenytoin infusion. The VA Cooperative Study, for instance, found that phenytoin with diazepam stopped GCSE more quickly than phenytoin alone. Many authorities recommend phenytoin as the primary treatment of GCSE, sometimes after initial interruption of convulsions with a benzodiazepine.
A usual loading dose for phenytoin is 15 mg/kg, but 20 mg/kg is reasonable before concluding that phenytoin is insufficient. It should be given by intravenous bolus or in saline solution at a maximum rate of 50 mg/min. (It may precipitate in glucose solutions.) Intramuscular phenytoin is poorly absorbed and should not be used.
The usual loading dose for fosphenytoin is 15-20 mg phenytoin equivalent (PE)/kg. It can be administered as quickly as 150 mg PE/min and there are theoretical advantages to doing so. Rapid rates are associated with greater risk of cardiac toxicity with both formulations, however. Intramuscular fosphenytoin is safe and readily absorbed; a "loading dose" typically leads to therapeutic levels within half an hour.
Conduction defects are the primary cardiac toxicity, but hypotension is not rare. Cardiac monitoring is appropriate during phenytoin infusion. Elderly patients or those with cardiac disease may not tolerate phenytoin as well as phenobarbital. Acute toxicity is more closely related to the infusion rate than to total dose. Patients with possible complications may tolerate greater doses in slower infusions.
Reviewed and revised February 2004 by Thaddeus Walczak, MD, MINCEP® Epilepsy Care, Minneapolis, MN
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