MANAGEMENT OF ACUTE ANTICONVULSANT OVERDOSE

Epilepsy is the most common serious neurological condition. Overdoses with anticonvulsants are common and produce major morbidity, in many c ases requiring intensive care medicine and prolonged hospital stays. H owever, fatalities are uncommon. Management in most cases centres on s upportive measures. In general, with perhaps the exception of valproic acid (sodium valproate) and carbamazepine, the effects seen in overdo se tend to be exacerbations of the adverse effects observed with lower doses of these drugs. The drugs used to treat epilepsy are diverse an d come from several classes. With acute phenytoin ingestion, the predo minant effects include ataxia, lethargy and nystagmus. Cardiovascular toxicity is rare after oral ingestion and patients do not require rout ine cardiac monitoring. Clinical signs and symptoms in overdoses of va lproic acid are believed to be a combination of the effects of the par ent drug and the metabolite 2-en-valproic acid. Prominent effects may include lethargy, coma, cerebral oedema, thrombocytopenia and metaboli c acidosis. Cerebral oedema typically becomes clinically apparent 2 to 3 days after overdose, while the nadir of the haematological injury t ends to be 3 to 5 days after overdose. Most patients who have taken an overdose of valproic acid will do well with gastrointestinal decontam ination and aggressive supportive care only. Haemodialysis use must be weighed against its risks, but may prevent cerebral oedema, thrombocy topenia and prolonged coma. In overdose with carbamazepine, many of th e effects seen may be related to mechanisms secondary to the tricyclic structure that the drug shares with the cyclic antidepressants. The m ain risks are coma, seizures, depression of respiratory drive (requiri ng mechanical ventilation) and ventricular arrhythmias. The management of patients with carbamazepine overdose is primarily supportive. Larg e overdoses may require intubation and mechanical ventilation. The ris ks involved in haemoperfusion suggest that this procedure is warranted only in patients with ventricular dysrhythmia or unstable cardiac sta tus that has not responded to conventional therapies. Overdose with th e succinimides is rare. The effects seen include lethargy, coma and re spiratory depression. The treatment of an overdose of the succinimide derivatives is primarily supportive. Symptoms of phenobarbital (phenob arbitone) overdose are generally exacerbations of the CNS depressant e ffects seen with therapeutic concentrations, i.e. slurred speech, somn olence, ataxia, obtundation and coma. With severe intoxication, hypote nsion and depressed cardiac output may be seen. In most cases of pheno barbital overdose, the patient will do well with gastrointestinal deco ntamination and aggressive supportive care only. Multiple-dose activat ed charcoal has been shown to reduce serum drug concentrations; howeve r, no clear improvement in clinical effects has been shown. Haemoperfu sion can restore haemodynamic stability and improve the level of consc iousness, However, due to the usual successful outcome of supportive t herapies, the risks involved in haemoperfusion appear warranted only i n patients with unstable cardiac status that has not responded to conv entional therapies. The predominant toxic effects of benzodiazepines i nclude sedation, ataxia, dizziness, slurred speech. confusion and atax ia. Significant effects, such as respiratory depression and death, are most likely to occur in the setting of co-ingestants or parenteral ad ministration. The management of benzodiazepine overdose is primarily s upportive. Routine flumazenil use in such patients should be avoided. There are limited data on the effects of the newer anticonvulsants, fe lbamate, gabapentin and lamotrigine, in overdose. Felbamate has produc ed only mild effects of agitation; ataxia and somnolence after ingesti on of 10 times the recommended daily dose. Overdoses of gabapentin hav e produced dizziness and diarrhoea, and those of lamotrigine lethargy, ataxia and nystagmus. Clinically insignificant, but mild, cardiovascu lar toxicity of sinus tachycardia and widened QRS interval has also be en reported with lamotrigine overdose. The treatment of the newer anti convulsants in overdose is essentially supportive after decontaminatio n with activated charcoal.