Document Detail


Population pharmacokinetics of midazolam administered by target controlled infusion for sedation following coronary artery bypass grafting.
MedLine Citation:
PMID:  9856717     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Midazolam is commonly used for short-term postoperative sedation of patients undergoing cardiac surgery. The purpose of this multicenter study was to characterize the pharmacokinetics and intersubject variability of midazolam in patients undergoing coronary artery bypass grafting. METHODS: With institutional review board approval, 90 consenting patients undergoing coronary artery bypass grafting were enrolled at three study centers. All subjects received sufentanil and midazolam via target-controlled infusions. After operation, midazolam was titrated to maintain deep sedation for at least 2 h. It was then titrated downward to decrease sedation for a minimum of 4 h more and was discontinued before tracheal extubation. Arterial blood samples were taken throughout the study and were assayed for midazolam and 1-hydroxymidazolam. Midazolam population pharmacokinetic parameters were estimated using NONMEM. Cross-validation was used to estimate the performance of the model. RESULTS: The pharmacokinetics of midazolam were best described by a simple three-compartment mammillary model. Typical pharmacokinetic parameters were V1 = 32.2 l, V2 = 53 l, V3 = 245 l, Cl1 = 0.43 l/min, Cl2 = 0.56 l/min, and Cl3 = 0.39 l/min. The calculated elimination half-life was 15 h. The median absolute prediction error was 25%, with a bias of 1.4%. The performance in the cross-validation was similar. Midazolam metabolites were clinically insignificant in all patients. CONCLUSIONS: The intersubject variability and predictability of the three-compartment pharmacokinetic model are similar to those of other intravenous anesthetic drugs. This multicenter study did not confirm previous studies of exceptionally large variability of midazolam pharmacokinetics when used for sedation in intensive care settings.
Authors:
K Zomorodi; A Donner; J Somma; J Barr; R Sladen; J Ramsay; E Geller; S L Shafer
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Publication Detail:
Type:  Clinical Trial; Journal Article; Multicenter Study; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Anesthesiology     Volume:  89     ISSN:  0003-3022     ISO Abbreviation:  Anesthesiology     Publication Date:  1998 Dec 
Date Detail:
Created Date:  1998-12-31     Completed Date:  1998-12-31     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  1300217     Medline TA:  Anesthesiology     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1418-29     Citation Subset:  AIM; IM    
Affiliation:
Department of Anesthesia, Stanford University, California, USA.
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Coronary Artery Bypass*
Female
Hemodynamics / physiology
Humans
Hypnotics and Sedatives / administration & dosage,  blood,  pharmacokinetics*
Infusions, Intravenous
Male
Midazolam / administration & dosage,  blood,  pharmacokinetics*
Middle Aged
Models, Biological
Postoperative Care / methods
Reproducibility of Results
Respiration, Artificial
Chemical
Reg. No./Substance:
0/Hypnotics and Sedatives; 59467-70-8/Midazolam

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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