Document Detail

Pharmacokinetics of midazolam in resuscitated patients treated with moderate hypothermia.
MedLine Citation:
PMID:  23192725     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Patients who remain comatose after resuscitation are treated with moderate hypothermia. Little is known about the pharmacokinetics of drugs in patients who are treated with moderate hypothermia.
OBJECTIVE: We investigated the pharmacokinetics of midazolam in resuscitated patients treated with moderate hypothermia in comparison to normothermic and non-resuscitated patients.
SETTING: This study was performed on the ICU of a Dutch non-academic hospital. The study population consisted of nine patients in the hypothermic group and eight patients in the control group.
METHOD: The resuscitated patients were cooled to a target temperature of 33 °C and rewarmed 24 h after start of cooling. Midazolam was given as continuous infusion. The control group consisted of non-resuscitated ICU-patients who were treated with midazolam as sedative. Plasma concentration-time data were collected for midazolam and its metabolites.
MAIN OUTCOME MEASURE: Non-linear mixed effect modelling was used to analyze midazolam population pharmacokinetics and identify possible covariates.
RESULTS: A two-compartment pharmacokinetic model best describes the data. The pharmacokinetic models of the investigated groups are not significantly different. Pharmacokinetic parameter estimates for midazolam for the hypothermic group are a body clearance (CL) of 12.6 l/h, an apparent volume of the central compartment (V1) of 19.1 l, an apparent volume of the peripheral compartment (V2) of 108 l and an intercompartmental clearance (Q) of 18.4 l/h. Estimated parameters for the control group are CL of 14.2 l/h, a V1 of 15.7 l, a V2 of 171 l and Q of 25.6 l/h. In the covariate analysis, body temperature did not significantly improve the model.
CONCLUSION: We found no significant difference in the pharmacokinetics of midazolam between resuscitated patients treated with hypothermia during 24 h and the control group.
Diane E T Bastiaans; Eleonora L Swart; Jesse P van Akkeren; Luc J J Derijks
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Publication Detail:
Type:  Controlled Clinical Trial; Journal Article     Date:  2012-11-29
Journal Detail:
Title:  International journal of clinical pharmacy     Volume:  35     ISSN:  2210-7711     ISO Abbreviation:  Int J Clin Pharm     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-04-03     Completed Date:  2013-09-23     Revised Date:  2014-07-31    
Medline Journal Info:
Nlm Unique ID:  101554912     Medline TA:  Int J Clin Pharm     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  210-6     Citation Subset:  IM    
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MeSH Terms
Coma / therapy
Hypnotics and Sedatives / pharmacokinetics*
Hypothermia, Induced / methods*
Intensive Care Units
Midazolam / pharmacokinetics*
Middle Aged
Models, Biological
Nonlinear Dynamics
Prospective Studies
Tissue Distribution
Reg. No./Substance:
0/Hypnotics and Sedatives; R60L0SM5BC/Midazolam

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

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