Prolonged sedation requiring mechanical ventilation and continuous flumazenil infusion after routine doses of clorazepam for alcohol withdrawal syndrome.

We report the cases of two patients who developed prolonged sedation after routine doses of clorazepam for alcohol withdrawal syndrome. They required prolonged mechanical ventilation (10 days for both patients) followed by continuous flumazenil infusion (16 days for one patient and 3 days for the other) to avoid reintubation. In the two patients, nordazepam accumulation (main active metabolite of clorazepam) was demonstrated as the cause of the coma. This accumulation could be attributed, in one case, to impaired hepatic cytochrome P 450 3A4 activity. Caution is required when prescribing benzodiazepines to alcoholic patients and the use of benzodiazepine which do not undergo hepatic oxidation by cytochrome P 450 such as oxazepam or lorazepam is suggested.