Benzodiazepine antagonists. An update of their role in the emergency care of overdose patients.

The benzodiazepine antagonist flumazenil is a very valuable tool in the diagnosis and treatment of intoxications in which benzodiazepines are involved. In case of a positive response, patients will regain consciousness immediately, thus verifying the diagnosis and making a brief history possible to identify other drugs that might be involved. Moreover, invasive diagnostic and therapeutic procedures like gastric lavage, lumbar puncture, mechanical ventilation, etc., may then be unnecessary. In cases of pure benzodiazepine overdose a single injection of flumazenil 0.2mg should be given, followed by individually titrated increments of 0.1 mg/min until the patient is awake and responsive. In these cases a total dose of 2mg is usually sufficient. Higher doses of flumazenil may be necessary in cases of combined drug overdose. Because of its high therapeutic index, the administration of flumazenil is usually not accompanied by serious adverse effects. Benzodiazepine withdrawal syndromes characterised by transient anxiety and depression can occur, but the incidence is low. Increases of blood pressure and heart rate due to a release of catecholamines are possible, which might endanger patients with cardiovascular diseases. In severe cases, seizures have been observed which usually respond well to small doses of benzodiazepine agonists. In all cases of successful treatment it should be remembered that the effect of flumazenil deteriorates after 1 to 2h, which usually leads at first to resedation. In these patients additional bolus injections or a continuous infusion (0.1 to 0.5 mg/h) may be necessary. The effectiveness of flumazenil in cases of alcohol (ethanol) poisoning is questionable and should be further investigated.