Relation of sedation and amnesia to plasma concentrations of midazolam in surgical patients

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Abstract
The kinetics and dynamics of midazolam were investigated in 20 female patients undergoing lower abdominal surgery. The relation between the plasma concentrations of midazolam and pharmacokinetic end points was evaluated after an intravenous infusion regimen in 10 patients given an epidural anesthetic. The remaining 10 patients were anesthetized with a totally intravenous anesthetic technique with midazolam and alfentanil. The effect was assessed by means of a rating scale divided into degree of sedation and amnesia. A good correlation was found between plasma level of midazolam and pharmacodynamic response. The relation between the quantal response data and the plasma concentration was represented by an s‐shaped concentration‐effect curve. Despite similar kinetics of midazolam in the two groups, the postoperative drowsiness was more pronounced in the group receiving total intravenous anesthesia. The concomitant administration of alfentanil shifted the concentration‐effect curve regarding sedation to the left. Clinical Pharmacology and Therapeutics (1988) 43, 324–331; doi:10.1038/clpt.1988.39