Status epilepticus fosphenytoin

Status epilepticus (Fosphenytoin) IV Loading dose 15-20 mg PE/kg infused at rate of 100-150 mg PE/min. 

Seizures. Simple isolated seizures may require only observation and supportive care. Repetitive seizures or status epilepticus require therapy. Give IV diazepam or lorazepam followed by fosphenytoin and/or phenobarbital. Pancuronium may also be considered. 

The therapeutic plasma level of phenytoin for most patients is between 10 and 20 g/mL. A loading dose can be given either orally or intravenously the latter, using fosphenytoin, is the method of choice for convulsive status epilepticus (discussed later). When oral therapy is started, it is common... 

Fosphenytoin, a prodrug of phenytoin, is soluble in water, easier and safer to administer its conver-tion in the blood to phenytoin is rapid and it may be used as an alternative to phenytoin for status epilepticus (Table 20.1). 

DeToledo JC, Ramsay RE. Fosphenytoin and phenytoin in patients with status epilepticus improved tolerability versus increased costs. Drug Saf 2000 22(6) 459-66. 

Status epilepticus Lorazepam, diazepam, phenytoin, or fosphenytoin Phenobarbital (long term)... 

Fosphenytoin sodium (Fig. 20.5) is a soluble pro-drug disodium phosphate ester of phenytoin (142 mg/mL) that was developed as a replacement for parenteral phenytoin sodium to circumvent the pH and solubility problems associated with parenteral phenytoin sodium formulations (36,37). Unlike phenytoin, fosphenytoin is freely soluble in aqueous solutions and is rapidly absorbed by the IM route. It is rapidly metabolized (conversion half-life, 8-15 minutes) to phenytoin by in vivo phosphatases. Therapeutic free (unbound) and total plasma phenytoin concentrations are consistently attained following IM or IV administration of fosphenytoin (26). It is administered IV following benzodiazepines for control of status epilepticus or whenever there is a need to rapidly achieve therapeutic plasma concentrations. Severe bradycardiac adverse events to fosphenytoin, including some fatalities, have been reported (38). A dose reduction in patients who are elderly or have renal or hepatic impairment has been suggested. 

A 4-year-old previously healthy girl presented with new-onset seizures associated with fevers, headache, and malaise. She developed status epilepticus resistant to intravenous tenzodiaz-epines, fosphenytoin, levetiracetam, valproate, pentobarbital, and ketamine. An initial MRI brain scan was unremarkable. Isoflurane was begun, and an MRI scan 14 days later showed hyperintense T2 signals in the cerebellar vermis and cerebellar hemispheres. The isoflurane concentration was reduced to 0.5% and a further scan after 31 days of isoflurane therapy showed improvement in the signal abnormalities. Her isoflurane exposure was 1382% concentration-hours/1257 MAC-hours. She remained minimally conscious. 

Status epilepticus is traditionally defined as a situation where there is continuous seizure activity for a period of 30 minutes or where there are a continuous series of seizures during which the sufferer does not regain consciousness. More recently, it has been suggested that any continuous seizure period of longer than 5 minutes should be classified as status epilepticus. In these situations the treatment employed may well consist of one of the previously indicated antiepileptic dmgs such as clonazepam (Fig. 13.15), phenobarbital and phenytoin (Fig. 13.15) or alternatively diazepam, fosphenytoin (a prodrug of phenytoin), loraze-pam, midazolam and paraldehyde (Fig. 13.16) may be employed. For the drugs used in the treatment of status epilepticus, the formulation and dose differ from conventional doses due to the situation and thus many of these will be administered by intravenous injection, intravenous infusion, buccal or rectal administration. 

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