Failure of antiepileptic treatment

The antiepileptic drugs used in status epilepticus are highly effective. If seizures continue despite emergency therapy, it is important to reassess the clinical circumstances, as there are often complicating remediable factors influencing the response to treatment.72 The most common of these are listed in Box 6.5.

Management of tonic-clonic status epilepticus

• The annual incidence of tonic-clonic status is about 18-28 cases per 100 000 persons. It occurs most frequently in children, the mentally handicapped, and in those with structural cerebral disorders. It can develop de novo usually due to an acute cerebral insult, or in patients with established epilepsy where drug withdrawal is often the immediate cause. The mortality rate is about 20% with most patients dying of the underlying condition rather than the status itself.

• Experimental work suggests that compensatory physiological mechanisms protect homoeostasis for the first 30-60 minutes of continuing seizures. If seizures persist for longer periods, however, a series of physiological changes occur, resulting in the breakdown of cerebral autoregulation and a fall in cerebral blood flow. The failure to meet the high metabolic demands of cerebral tissue can result in permanent cerebral damage.

• Other complications include hyperpyrexia, massive autonomic activation, pulmonary hypertension and oedema, intracranial hypertension, cardiac arrhythmia and failure, hypoglycaemia, acidosis, rhabdomyolysis, disseminated intravascular coagulation, and cardiac, respiratory, renal, or hepatic failure.

• General treatment measures should proceed in stages: (1) cardiorespiratory function should be secured; (2) regular monitoring and emergency drug therapy should be commenced, and investigations initiated; (3) aetiology should be established, and hypotension and medical complications treated. If seizures are continuing, the patient should be transferred to intensive care, and seizure, EEG, and sometimes intracranial pressure monitoring applied.

• A suggested regimen for emergency antiepileptic drug therapy is as follows: (1) Premonitory stage (pre hospital): diazepam 0-2-0-3 mg/kg (usual adult dose 10-20 mg) can be given by rectal or intravenous administration, or midazolam by buccal (10 mg) or intranasal (0-2 mg/kg) administration. (2) Early status: lorazepam 0-07 mg/kg (usual adult dose 4 mg), which can be repeated after 10 minutes. (3) Established status: phenobarbitone 10 mg/kg given intravenously at an infusion rate of 100 mg/min (usual adult dose is 700 mg given over seven minutes), or phenytoin at a dose of 15-18 mg/kg at a rate of 50 mg/min (usual adult dose is 1000 mg given over 20 min) or fosphenytoin at a dose of 15-20 mg phenytoin equivalents/kg at a rate of 150 mg phenytoin equivalents/min. (4) Refractory status: general anaesthesia with either thiopentone initially with a 100-250 mg bolus injection, followed by further 50 mg boluses, and then a continuous infusion (usual dose 3-5 mg/kg/h), or propofol initially with a 2 mg/kg bolus dose, repeated if necessary, and then a continuous infusion of up to 15 mg/kg/h or midazolam initially with a 0-15 mg/kg bolus followed by an infusion of 0-05-0-4 mg/kg/h. Maintenance antiepileptic drug therapy should be given concurrently.

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