Benzodiazepine poisoning. Clinical and pharmacological considerations and treatment.

Benzodiazepines are among the most frequently prescribed drugs worldwide. This popularity is based not only on their efficacy but also on their remarkable safety. Pure benzodiazepine overdoses usually induce a mild to moderate central nervous system depression; deep coma requiring assisted ventilation is rare, and should prompt a search for other toxic substances. The severity of the CNS depression is influenced by the dose, the age of the patient and his or her clinical status prior to the ingestion, and the coingestion of other CNS depressants. In severe overdoses, benzodiazepines can occasionally induce cardiovascular and pulmonary toxicity, but deaths resulting from pure benzodiazepine overdoses are rare. Quantitative determinations of benzodiazepines are not useful in the clinical management of intoxicated patients since there is no correlation between serum concentrations and pharmacological and toxicological effects. Benzodiazepine overdoses occurring during pregnancy rarely induce serious morbidity in mothers or fetuses, although large doses administered near delivery can induce respiratory depression in neonates. The teratogenic potential of benzodiazepines remains controversial, but is probably small if it exists at all. There is clear evidence that the prolonged use of even therapeutic doses of benzodiazepines will lead to dependence. The risk of developing significant withdrawal symptoms is related to dosage and duration of treatment. Prevention of gastrointestinal absorption should be initiated in all intentional benzodiazepine overdoses. Forced diuresis and dialysis techniques are not indicated since they will not significantly accelerate the elimination of these agents. Intravenous administration of flumazenil, a pure benzodiazepine antagonist, effectively reverses benzodiazepine-induced CNS depression.