If convulsions do not stop after the second dose of phenobarbital, phosphenytoin is used. Phosphenytoin is a prodrug of phenytoin. Plasma phosphatase enzymes cleave phenytoin from phosphenytoin. Phosphenytoin acts on sodium current. The loading dose is 10 mg/kg. It should be infused intravenously at a rate no faster than 1 mg/kg per minute (same as phenobarbital). If the seizure persists after 10 minutes, a second dose of phosphenytoin of 10 mg/kg should be administered. If the seizure stops, no further antiepileptic medication is given and a phenytoin level is taken after 6 hours. The maintenance dose of intravenous phosphenytoin is 3 to 5 mg/kg per day divided in two doses. Phosphenytoin is as cardiotoxic as phenytoin. The advantage of phosphenytoin is that it is water soluble and has less toxicity at the site of infusion.
If phenobarbital and phosphenytoin do not stop the seizures, the patient should be placed on continuous EEG recording or near infrared spectroscopy and 0.1 mg/kg intravenous lorazepan should be administered. The same dose of lorazepan may be repeated in 10 minutes if the seizure persists. Another option in patients unresponsive to phenobarbital and phosphenytoin is to use intravenous valproic acid. Intravenous valproic acid may be useful to achieve a therapeutic level quickly. The intravenous dose of valproic acid can be calculated by considering that each 1 mg/kg of valproic acid given intravenously raises the serum concentration by about 3 micrograms per milliliter.Elevation of serum ammonia may occur with intravenous valproic acid.
Oral antiepileptic drugs are used as soon as possible if seizures stop or are relatively controlled. Phenobarbital, phenytoin, valproic acid, carbamezapine, and lamotragine can be used. The dose of carbamezapine is 5 mg/kg every 12 hours. No loading dose is necessary. Carbamezapine acts on sodium current. The loading dose of oral valproic acid is 20 to 26 mg/kg. The maintenance dose of oral valproic acid is 5 to 10 mg/kg. Valproic acid acts on sodium current and GABA receptors. Carbamezapine and valproic acid levels should be monitored and kept within the usual therapeutic range. Lamotrigine at a dose of 4.4 mg/kg per day can be used as a single dose for 3 days and then divided in two doses. Brain surgery should be considered in cases of focal pathology.