The stage of established status epilepticus can be operationally defined as status epilepticus which has continued for 30 minutes in spite of early stage treatment. The time is chosen because physiological decompensation will usually have begun. Intensive care facilities are desirable, as status epilepticus at this stage carries an appreciable morbidity. There are three alternative treatment options. These are phenobarbitone (10 mg/kg), phenytoin (15-20 mg/kg), or fosphenytoin (a phenytoin pro-drug); all are given by intravenous loading followed by repeated oral or intravenous supplementation. Diazepam is often given with phenytoin or fosphenytoin (either at this or the early stage of status epilepticus), combining the fast acting but short lasting effect of diazepam with the slow onset but long lasting effect of phenytoin.
Numerous alternative treatment options exist. Although once popular, continuous benzodiazepine and chlormethiazole infusions on the ward are hazardous and are now not recommended. Infusions of most benzodiazepines result in accumulation and so persistent action. This often results in sudden hypotension and respiratory and circulatory collapse. Unfortunately this problem is compounded by the difficulties, in most centres, of monitoring benzodiazepine plasma concentrations. Furthermore tolerance to the antiepileptic action of benzodiazepines occurs with prolonged administration, requiring higher doses that are potentially dangerous. There may also be recurrence of seizures on drug withdrawal. Chlormethiazole, which is not licensed in the United States, is an easily administered agent. Infusions, however, can be complicated by hypotension, cardiac depression, and respiratory arrest and, like benzodiazepines, this drug shows a propensity for dangerous accumulation with prolonged administration.36,37 Of other alternatives, paraldehyde is difficult to use as an intravenous preparation, decomposes in light, and in overdose there are potentially serious toxic side effects. It may be useful in premonitory stages per rectum, but in established status epilepticus where an intravenous infusion is indicated, its use is limited.36 There have been uncontrolled studies of the use of intravenous sodium valproate at this stage at high doses of at least 15 mg/kg followed by an infusion of 1 mg/kg/h;38 experience of sodium valproate in status epilepticus, however, remains limited. Lorazepam and lidocaine (lignocaine) are essentially short term therapies, and so should not be employed at this stage.
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