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 co ntinuous flumazenil infusion (16 days for one patient and 3 days for the ot her) to avoid reintubation. In the two patients, nordazepam accumulation (m ain active metabolite of clorazepam) was demonstrated as the cause of the c oma, This accumulation could be attributed, in one case, to impaired hepati c cytochrome P 450 3A4 activity. Caution is required when prescribing benzo diazepines to alcoholic patients and the use of benzodiazepine which do not undergo hepatic oxidation by cytochrome P 450 such as oxazepam or lorazepa m is suggested.