Propofol

In recent times, there has been a vogue for the use of non-barbiturate anaesthesia in status epilepticus; of the currently available compounds, propofol39,59-66 is probably the drug of choice. Published experience of its use in status epilepticus is limited. Propofol is a highly effective and non-toxic anaesthetic. In experimental models, it has anticonvulsant activity at subanaesthetic doses, probably via its action in potentiating GABA receptors.67 Propofol also has neuroexcitatory effects possibly through subcortical disinhibition resulting in muscle rigidity, opisthotonos, and abnormal movements including myoclonus; these can be and have been mistaken for seizures. Seizures have, however, been reported with propofol withdrawal, and experimental evidence suggests that this is a rebound phenomenon similar to the GABA withdrawal syndrome. Propofol has also been reported at low doses to activate the electrocorticogram, but this is a property that it shares with other anaesthetics including the barbiturates.

Propofol is extremely soluble in lipid and has a high volume of distribution. It thus acts very rapidly in status epilepticus. Its effects are maintained while the infusion is continued, and recovery following discontinuation of the drug is also very quick - in marked contrast to thiopentone. Theoretically, there is a danger of accumulation on very long term therapy, but this has not been reported in practice. Propofol administration causes profound respiratory and cerebral depression (requiring the use of assisted respiration, the full panoply of intensive care, and monitoring), but only mild hypotension, and has few cardiovascular side effects. Long term administration causes marked lipaemia and may result in acidosis and rhabdomyolysis. It also has to be noted that there is a significant mortality reported in patients treated with status, although this is usually attributed to the status itself. However, some authorities consider that prolonged therapy may carry significant risks which are currently under-recognised. This is especially so in young children in whom it should not generally be recommended. The use of propofol in refractory status epilepticus is based upon several case reports and one comparative study. This study was non-randomised and compared propofol against pentobarbital anaesthesia in 16 patients. There was no significant difference detected between the two therapies in efficacy, time on ICU, or outcome. Neither therapy was universally effective, although a greater proportion had their seizures controlled with high dose barbiturate therapy. The dose of propofol necessary to control status epilepticus is greater than that when it is used as a sedative, but less than the dose required when it is used alone for total anaesthesia.

In status epilepticus, the following regimen can be used: an initial 1-2 mg/kg bolus dose is given, which can be repeated if seizures continue, succeeded by an infusion of 1-15 mg/kg/h guided by EEG. The dose should be gradually reduced, and the infusion tapered 12 hours after seizure activity is halted. Due to the risk of rebound seizures, the dose should be tapered at a rate of 5% of the maintenance infusion per hour (that is, over approximately 24 hours). In the elderly, doses should be lower. It is available as 20 ml ampoules containing 10 mg/ml as an emulsion.

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