Page 334 - ILAE_Lectures_2015

thiopentone, the intravenous non-barbiturate propofol or continuous midazolam infusion. A
non-randomised comparison of propofol and thiopentone was unable to detect any clinically
significant differences between the drugs. Other drugs in current use include the intravenous
anaesthetic pentobarbitone (not available in the UK).

At this stage, the use of immunosuppression with steroids and even intravenous
immunoglobulin/plasma exchange should be considered, as there is growing evidence for the
role of autoantibodies (especially against NMDA receptors) in the aetiology of refractory
status epilepticus.

Patients require the full range of intensive care facilities, including EEG monitoring, and care
should be shared between anaesthetist and neurologist. Experience with long-term
administration (hours or days) of the newer anaesthetic drugs is very limited. The modern
anaesthetics have, however, important pharmacokinetic advantages over the more traditional
barbiturates.

Once the patient has been free of seizures for 1224 hours and provided that there are
adequate plasma levels of concomitant antiepileptic medication, then the anaesthetic should
be slowly tapered.

Antiepileptic drugs

Diazepam
Diazepam is highly effective in a range of seizure types. Its pharmacology and clinical effects
have been extensively studied in adults, children, and the newborn, and it has been shown to
be highly effective in a wide range of status epilepticus types. Diazepam can be given by
intravenous bolus injections or by the rectal route in the premonitory stage, and has a rapid
onset of action. Sufficient cerebral levels are reached within one minute of a standard
intravenous injection, and rectal administration produces peak levels at about 20 minutes.
Diazepam is rapidly redistributed after acute administration, and thus has a relatively short
duration of action. After repeated dosing, diazepam accumulates, resulting in higher peak
levels, which persist. This can result in sudden and unexpected CNS depression and
cardiorespiratory collapse. Diazepam is metabolised by hepatic microsomal enzymes.
Respiratory depression, hypotension, and sedation are the principal side effects. Sudden
apnoea can occur, especially after repeated injections or if the injection is administered at too
fast a rate.

Bolus intravenous doses of diazepam should be given in an undiluted form at a rate not
exceeding 25 mg/minute, using the Diazemuls formulation. Diazepam may be given
rectally, either in its intravenous preparation infused from a syringe via a plastic catheter, or
as the ready-made, proprietary, rectal tube preparation Stesolid, which is a convenient and
easy method. Diazepam suppositories should not be used, as absorption is too slow. The adult
bolus intravenous or rectal dose in status epilepticus is 1020 mg, and additional 10 mg doses
can be given at 15 minute intervals, to a maximum of 40 mg. In children, the equivalent bolus
dose is 0.20.3 mg/kg. A continuous infusion of benzodiazepine has also been used, but there
is now little place for this mode of administration. The solution should be freshly prepared,
and no drugs should be admixed.

The usual intravenous formulation is as an emulsion (Diazemuls) in a 1 ml ampoule
containing 5 mg/ml or as a solution in 2 ml ampoules containing 5 mg/ml. Stesolid is the
usual rectal formulation consisting of a 2.5 ml rectal tube containing 5 mg or 10 mg diazepam.
The intravenous solution can also be instilled rectally.