[Prolonged coma caused by diazepam sedation in ventilated patients. Diagnostic and therapeutic use of the benzodiazepine antagonist Ro 15-1788].

Repeated administration of diazepam in two ventilated patients had caused drug cumulation and coma over several days. In both cases central nervous depression could be demonstrated by the benzodiazepin antagonist Ro 15-1788 which induced reversal of coma. Estimation of plasma concentrations in a 70-year-old female patient 150 hours after the last administration showed a diazepam concentration of 437 ng/ml and a desmethyl-diazepam concentration of 483 ng/ml. The calculated elimination half-life of these substances were 109 and 403 hours. In the second case benzodiazepin could be demonstrated in urine for 10 days after withdrawal of medication. These observations suggest that diazepam is not a suitable drug for prolonged sedation in artificially ventilated patients. The benzodiazepin antagonist Ro 15-1788 represents a valuable diagnostic aid in ascertained or suspect cases of benzodiazepin intoxications. It can also be used therapeutically for reversal of central nervous depression.