Reversal of sedation by prolonged infusion of flumazenil (Anexate, Ro 15–1788)

A 22-year-old male was involved in a road traffic accident and sustained multiple injuries. He received an infusion of midazolam to sedate him during a period of artificial ventilation. His conscious level remained depressed 36 hours after the infusion was discontinued but the sedation was completely reversed with flumazenil. An infusion was started because of the short duration of action of flumazenil, and continued for 8 days. The infusion was stopped seven times during this period and on each occasion except the last, his conscious level deteriorated but returned to normal when flumazenil was administered again. Plasma concentrations of midazolam and alpha-hydroxymidazolam were measured and found to be low during this period. Possible explanations for this finding are discussed.