Benzodiazepines for prolonged seizures
- Correspondence to Dr Mark Anderson, Great North Children's Hospital, Newcastle Upon Tyne Hospitals NHS Trust, Queen Victoria Road, Newcastle Upon Tyne NE1 4LP, UK;
- Accepted 20 August 2010
Convulsive status epilepticus is a common emergency condition in paediatric practice. Classically, it is defined as continuous or recurrent seizure activity lasting for longer than 30 min in which the patient does not regain baseline mental status.1 Commonly, intervention is recommended after only 5 min of seizure activity2 as neuronal damage may begin to occur after this period, and the longer a seizure continues, the less likely it is to stop spontaneously.3 It seems likely, however, that mortality and morbidity after prolonged seizures should often be dependent upon underlying aetiology rather than duration of seizure activity.4 Repetitive serial seizures (ie, seizure clusters with return to baseline between events, but occurring frequently enough to be highly disruptive) and non-convulsive status epilepticus are also relatively common in children with epilepsy and are associated with significant morbidity.5
Diazepam, lorazepam and midazolam, the drugs most widely used to stop prolonged seizures, are members of the benzodiazepine family, a class of psychoactive drugs with varying hypnotic, sedative, anxiolytic, anticonvulsant, muscle relaxant and amnesic properties.6 Differences in their affinity for receptor subtypes account for different pharmacological effects, in combination with widely varying pharmacokinetic profiles. These pharmacokinetic differences often impose specific routes of administration and specific formulations for individual members of the benzodiazepine family. The aim of this review is to detail their clinical pharmacology as it relates to their use in the management of prolonged seizures in children.
How do they work?
Benzodiazepines produce their range of effects by modulation of the γ-aminobutyric acid receptor subtype A (GABAA). The GABAA receptor comprises five subunits; each receptor is assembled from a combination of polypeptides, most commonly two αs, two βs and one γ, although several other subunits exist (eg, δ, ε, π, θ and ρ).7 The combination of different subunits governs the …