Accumulation of midazolam after repeated dosage in patients receiving mechanical ventilation in an intensive care unit

Abstract

Midazolam hydrochloride is a recently introduced imidazobenzodiazepine. Its potency and rapid onset and short duration of action after a single intravenous bolus make it an ideal agent for premedication or induction in anaesthesia for short surgical, endoscopic, and dental procedures. These same pharmacokinetic features would seem to make the drug an ideal sedative for patients receiving mechanical ventilation. A chance observation of an unusually high plasma midazolam concentration (750 μg/1) in a seriously ill 75 year old needing prolonged intermittent positive pressure ventilation for unexplained respiratory depression, however, led us to examine the problem in three other patients with a similar clinical course.