[Sedation induced by midazolam in intensive care: pharmacologic and pharmacokinetic aspects]

Abstract

Objective: Review on midazolam in order to optimize drug utilisation and therapeutic monitoring.

Data sources: Research of English or French articles published until August 2001, using Medline database. The key words were: midazolam, pharmacokinetics, pharmacodynamic, sedation, drug interaction.

Study selection: Original articles, clinical cases and letters to the Editor were selected. Animal studies were excluded.

Data extraction: The articles were analysed according to their interest in midazolam clinical practice.

Data synthesis: Midazolam is a benzodiazepine widely used in intensive care unit, as a sedative, anxiety-relieving, and amnesic drug. Midazolam could be used in patients with cardiac, or respiratory failure, and in neurosurgery. A great interindividual variability on pharmacokinetic and pharmacodynamic response was observed. In intensive care patients, elimination half-life is known to be widely increased. Midazolam is metabolised by hepatic microsomes. The major metabolite is the 1-hydroxymidazolam, which is pharmacologically active. A prolonged sedation due to an accumulation of conjugated metabolite was observed in renal failure patients. Enzymatic inductors or inhibitors could influence pharmacokinetics and pharmacodynamic effects of midazolam.

Conclusion: According to midazolam pharmacokinetic and pharmacodynamic variability, an individual dosage adjustment is essential for long-term sedation. Target controlled sedation could be a mean to limit the variability and to reach quickly the pharmacodynamic effect.