USE OF FLUMAZENIL IN THE DIAGNOSIS AND TREATMENT OF PATIENTS WITH COMA OF UNKNOWN ETIOLOGY

Objectives: To evaluate the use of single-dose flumazenil in the diagn osis of coma of unknown etiology, and of continuous flumazenil infusio n in the treatment of benzodiazepine-induced coma. Design: Prospective study. Setting: Emergency room and general medicine ward of a teachin g hospital. Patients: A total of 42 comatose adults in whom metabolic, neurologic, or traumatic causes of coma were excluded. Interventions. a) Intravenous bolus injections of 0.25 mg flumazenil were given at 1 -min intervals, either until improvement by two coma grades or a total dose of 2.0 mg was reached. b) Loading doses as in (a) followed by a maintenance infusion administered as long as indicated by repeated com a grade evaluation. Measurements and Main Results: a) Of 34 patients, 28 received only the flumazenil loading dose responded promptly. Twent y-one of 25 available urine samples of the responding patients contain ed only benzodiazepine metabolites. Four urine samples contained benzo diazepines in combination with other drugs. Six patients did not respo nd to the flumazenil loading dose. The urine of three patients contain ed a combination of benzodiazepines and another coma-exerting drug; th e remaining three were negative. A total of 24 patients, who initially responded to flumazenil loading, deteriorated to their previous coma state and were admitted to the general medical ward. Six (25%) patient s developed complications related to hospitalization and their bedridd en state. b) Eight other patients, who deteriorated after an initial l oading dose, received a second iv bolus of flumazenil, followed by mai ntenance infusions over 5 to 24 hrs. Their hospital course was unevent ful. Conclusions. These findings indicate that flumazenil is safe and effective in the diagnosis of benzodiazepine-induced coma. Furthermore , the use of continuous flumazenil maintenance infusion is of consider able therapeutic value in patients who exhibit deterioration after ini tial response to the single loading dose.