[Sedation induced by midazolam in intensive care: pharmacologic and pharmacokinetic aspects].
OBJECTIVE
Review on midazolam in order to optimize drug utilisation and therapeutic monitoring.


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


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


METHODS
The articles were analysed according to their interest in midazolam clinical practice.


RESULTS
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.


CONCLUSIONS
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.
Université Claude Bernard Lyon 1, institut des sciences pharmaceutiques et biologiques, département de pharmacie clinique, de pharmacocinétique et d'évaluation du médicament, 8, avenue Rockefeller, 69373 Lyon, France.
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Bolon
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Boulieu
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Flamens
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Paulus
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Bastien
D003422:Critical Care; D004347:Drug Interactions; D006801:Humans; D006993:Hypnotics and Sedatives / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D008874:Midazolam / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D014018:Tissue Distribution
D006993:Hypnotics and Sedatives; D008874:Midazolam