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Published on: October 17, 2013
[Sedation induced by midazolam in intensive care: pharmacologic and pharmacokinetic aspects]
M Bolon1, R Boulieu, C Flamens
1Université 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.
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.
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