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Re: The treatment of convulsive status epilepticus in children

We were concerned about the Status Epilepticus Working party's recent recommendations on the dose of phenobarbitone (20mg/kg intravenously in 20 minutes) in the management of convulsive status epilepticus (CSE).[1]

A large randomised double blind controlled study showed that phenobarbital given at a dose of 20mg/kg as a prophylactic agent in children with cerebral malaria was associated with doubling of mortality.[2] The risk was significantly increased in children who had received diazepam, particularly more than 3 doses. The most likely explanation for the increased mortality was phenobarbital-induced respiratory depression.

Phenobarbital 20mg/kg infused over 4 hours and 20mg/kg intramuscularly achieved serum concentrations within accepted therapeutic range (10-30mg/l). However phenobarbital concentrations were slightly lower in children who died compared to survivors.[2] Thus 20mg/kg phenobarbital may be associated with an increased in mortality and this dose needs to be studied in the context of CSE in other children before it can be recommended as safe, particularly in smaller Accident and Emergency (A&E) departments and resource poor countries which lack facilities for ventilation.

In another study, phenobarbitone 10mg/kg intramuscularly achieved peak plasma concentrations exceeding 10mg/l in over 90% of children.[3] The pharmacokinetic data suggests that 15mg/kg may be more appropriate dose, although this would have to be studied in the context of CSE.

The working party correctly states that the guideline cannot cover all possible circumstances and clinical situations. Although lorazepam is cheaper than diazepam in the UK, it is much more expensive than diazepam in Africa and not widely available. We are concerned that drugs that may be useful, as anticonvulsants in resource poor countries, like paraldehyde are becoming more difficult to obtain and the manufacturing companies are thinking of withdrawing them. Measures should therefore be taken to ensure that cheap and effective drugs remain widely available and guidelines for management of CSE take this into consideration.

Dr BM Wamola MBChB
Dr BR Ogutu MMed
Dr CRJC Newton FRCPCH
Bwamola@kilifi.mimcom.net

Kenya Medical Research Institute
Center for Geographic Medicine Research-Coast
P.O. Box 428
Kilifi, Kenya

References
(1) Status Epilepticus Working Party. The treatment of convulsive status epilepticus in children. Arch Dis Child 2000;83:415-19.

(2) Crawley J, Waruiru C, Mithwani S, Mwangi I, Watkins W, Ouma D, Winstanley P, Peto T, Marsh K. Effect of phenobarbital on seizure frequency and mortality in childhood cerebral malaria: a randomised, controlled intervention study. Lancet 2000;355:701-6.

(3) Winstanley PA, Newton CRJC, Pasvol G, Kirkham FJ, Mberu E, Peshu N, Ward SA, Were JB, Warrel DA, Marsh K. Prophylactic phenobarbitone in young children with severe falciparum malaria: pharmacokinetics and clinical effects. Br J Clin Pharmac 1992;33:149-54.