Phenobarbital is often used if phenytoin is insufficient, but it is frequently avoided out of fear it will cause sedation or respiratory compromise (especially after several doses of benzodiazepines). One of its advantages is a relative lack of cardiac toxicity until very high doses are reached.
Phenobarbital has been compared favorably with a combination of diazepam and phenytoin; in the VA Cooperative Trial, clinical response was actually faster with phenobarbital. Respiratory depression and hypotension are likely if phenobarbital, a barbiturate, is used together with benzodiazepines.
Loading with up to 20 mg/kg is reasonable. It may be administered as quickly as 100 mg per minute in normal-size adults if respirations are carefully monitored. Loading is faster than with phenytoin, but its lipid solubility is lower and brain penetration is slower. Nevertheless, phenobarbital may act quickly, even before therapeutic levels are established.
Some SE may be refractory to phenytoin, but high enough doses of phenobarbital will control almost all seizures. Very high doses require artificial ventilation and may cause hypotension, but they may be tolerated better than expected. Sedation must be expected with high doses, but levels below 40 mcg/mL should not produce prolonged coma.
Reviewed and revised February 2004 by Thaddeus Walczak, MD, MINCEP® Epilepsy Care, Minneapolis, MN
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