Document Detail

Development of acute tolerance to the EEG effect of propofol in rats.
MedLine Citation:
PMID:  15980043     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: A previous study in rats with propofol suggested the development of acute tolerance to the EEG effect. The aim of this study was to evaluate acute tolerance by means of EEG-controlled closed-loop anaesthesia as this approach allows precise determination of drug requirement to maintain a defined drug effect. METHODS: Ten male Sprague-Dawley rats [weight 402 (40) g, mean (SD)] were included in the study. The EEG was recorded with occipito-occipital needle electrodes and a modified median frequency (mMEF) of the EEG power spectrum was used as a pharmacodynamic control parameter. The propofol infusion rate was controlled by a model-based adaptive algorithm to maintain a set point of mMEF=3 (0.5) Hz for 90 min. The performance of the closed-loop system was characterized by the prediction error PE=(mMEF-set point)/set point. Plasma propofol concentrations were determined from arterial samples by HPLC. RESULTS: The chosen set point was successfully maintained in all rats. The median (SE) and absolute median values of PE were -5.0 (0.3) and 11.3 (0.2)% respectively. Propofol concentration increased significantly from 2.9 (2.2) microg ml(-1) at the beginning to 5.8 (3.8) microg ml(-1) at 90 min [mean (SD), P<0.05]. The cumulative dose increased linearly, with a mean infusion rate of 0.60 (0.16) mg kg(-1) min(-1). The minimum value of the mean arterial pressure during closed-loop administration of propofol was 130 (24) mm Hg, compared with a baseline value of 141 (12) mm Hg. CONCLUSIONS: The increase in propofol concentration at constant EEG effect indicates development of acute tolerance to the hypnotic effect of propofol.
H Ihmsen; M Schywalsky; A Tzabazis; H Schwilden
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Publication Detail:
Type:  Journal Article     Date:  2005-06-24
Journal Detail:
Title:  British journal of anaesthesia     Volume:  95     ISSN:  0007-0912     ISO Abbreviation:  Br J Anaesth     Publication Date:  2005 Sep 
Date Detail:
Created Date:  2005-08-03     Completed Date:  2005-09-23     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0372541     Medline TA:  Br J Anaesth     Country:  England    
Other Details:
Languages:  eng     Pagination:  367-71     Citation Subset:  IM    
Klinik für Anästhesiologie, Friedrich-Alexander-Universität Erlangen-Nürnberg, Krankenhausstrasse 12, 91054 Erlangen, Germany.
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MeSH Terms
Anesthetics, Intravenous / administration & dosage,  blood,  pharmacology*
Dose-Response Relationship, Drug
Drug Delivery Systems
Drug Tolerance*
Electroencephalography / drug effects*
Propofol / administration & dosage,  blood,  pharmacology*
Rats, Sprague-Dawley
Reg. No./Substance:
0/Anesthetics, Intravenous; 2078-54-8/Propofol

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