Page 337 - ILAE_Lectures_2015

seizures do not tend to recur. Indeed, there is evidence to suggest that given with barbiturate
anaesthesia, it can reduce the relapse rate with anaesthetic withdrawal.

The main disadvantages of phenobarbitone are its potential to cause sedation, respiratory
depression, and hypotension; although in practice these effects seem slight except at high
levels or with rapidly rising levels, its safety at even high doses is well established. The well-
known chronic side effects of phenobarbitone in long-term therapy are of little relevance in
the emergency situation of status epilepticus. The drug is eliminated slowly and, although
this is of no importance on initial phenobarbitone loading, on prolonged therapy there is a
danger of accumulation and blood level monitoring is essential. In the newborn period dosing
is more difficult than in adults, as the pharmacokinetics change rapidly during the first weeks
and months of life. The drug has a strong tendency to autoinduction. Phenobarbitone is a
stable preparation, which does not easily decompose, and the drug is not absorbed by plastic.
It should not be used in a solution containing other drugs (for example, phenytoin), as this
may result in precipitation.

The usual recommended adult intravenous loading dose of phenobarbitone is 10 mg/kg (doses
of up to 20 mg/kg have been used and recommended), given at a rate of 100 mg/minute (i.e.
a total of about 700 mg in seven minutes). This should be followed by daily maintenance
doses of 14 mg/kg. In neonates, initial phenobarbitone loading doses of between 12 and 20
mg/kg have been recommended to produce therapeutic levels, with subsequent
supplementation of 34 mg/kg per day, to a maximum dose of 40 mg/kg. In older children,
loading doses of between 5 and 20 mg/kg are recommended and maintenance doses of 14
mg/kg, although much higher doses have been safely given. After loading, maintenance doses
can be given by the oral, intravenous, or intramuscular route. Phenobarbitone is usually
presented in 1 ml ampoules containing 200 mg of phenobarbitone sodium.

Valproate
There is a long history of the anecdotal use of intravenous valproate in status epilepticus.
Only recently have randomised trials demonstrated potential as a treatment in status
epilepticus, and it can be used as an alternative to phenytoin. The possible advantages of
valproate are a low incidence of respiratory and cardiac depression, but other potential side
effects such as prolonged bleeding time, hepatic dysfunction, pancreatitis and
hyperammonaemia have not been adequately assessed in large studies, and valproate should
be avoided in patients with hepatic or mitochondrial disease. Valproate is available as an
intravenous solution (100 mg/ml) and can be given by infusion at a dose of 2030 mg/kg
over about 15 minutes.

Thiopentone
Thiopentone is the compound traditionally used for barbiturate anaesthesia in status
epilepticus, at least in Europe. It is an effective AED, and may have additional cerebral-
protective effects. In the doses used in status epilepticus it has an anaesthetic action, and all
patients require intubation and most artificial ventilation. The most troublesome side effect
is persistent hypotension and many patients require pressor therapy. Thiopentone has
saturable pharmacokinetics and a strong tendency to accumulate. Thus if large doses are
given, blood levels may remain very high for protracted periods, and days may pass before
consciousness is recovered after drug administration is discontinued. Blood level monitoring,
both of the thiopentone and its active metabolise pentobarbitone, is therefore essential on
prolonged therapy. Other toxic effects on prolonged therapy include pancreatitis and hepatic
disturbance, and thiopentone may cause acute hypersensitivity. It should be administered
cautiously in the elderly, and in those with cardiac, hepatic, or renal disease.

Although it has been in use since the 1960s in status epilepticus, formal clinical trials of its
safety and effectiveness in either adults or children are few. A full range of intensive care