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Modeling the effect of sevoflurane on corrected QT prolongation: a pharmacodynamic analysis

 Dong Woo Han  ;  Kyungsoo Park  ;  Seong Bok Jang  ;  Steven E. Kern 
 ANESTHESIOLOGY, Vol.113(4) : 806-811, 2010 
Journal Title
Issue Date
Adult ; Anesthetics, Inhalation/adverse effects* ; Anesthetics, Inhalation/pharmacokinetics ; Data Interpretation, Statistical ; Dose-Response Relationship, Drug ; Electrocardiography/drug effects* ; Female ; Humans ; Long QT Syndrome/chemically induced* ; Long QT Syndrome/physiopathology ; Male ; Methyl Ethers/adverse effects* ; Methyl Ethers/pharmacokinetics ; Middle Aged ; Models, Statistical ; Preanesthetic Medication ; Young Adult
BACKGROUND: Sevoflurane may prolong the corrected QT (QTc) interval in healthy humans when administered for induction and maintenance of anesthesia. Little information is available about the dose-response relationship of sevoflurane on the QTc interval. We performed a pharmacodynamic analysis of the relationship between end-tidal sevoflurane concentration (CET) and the QTc.

METHODS: Twenty-one patients aged 20-50 yr were enrolled in this study. Sevoflurane concentrations were progressively increased and then decreased over 15 min at the start of anesthesia; CET and automated QT interval were recorded continuously. Pharmacodynamic analysis using a sigmoid Emax model was performed to assess the concentration-effect relationship.

RESULTS: Maximal CET was 4.30 ± 0.33%. Measured baseline and maximally prolonged QTc interval values were 351.7 ± 15.4 ms and 397.8 ± 17.5 ms, respectively. During sevoflurane anesthesia, increased concentrations were correlated with prolonged QTc interval. Hysteresis between the CET and QTc interval were observed and accounted for in the model. Ce50 and ke0 were 2.5 ± 1.4 and 2.0 ± 1.0, respectively. The median prediction error, median absolute prediction error, and the coefficient of determination (R) were 0.02%, 0.75%, and 0.95, respectively. The effect-site concentration (Ce50) and QTc interval data fit to a sigmoid Emax model.

CONCLUSIONS: Among patients receiving sevoflurane for anesthesia, QTc interval changes correlate to anesthetic level. The Ce50 for significant QTc change is at clinically relevant levels of sevoflurane anesthesia.
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1. College of Medicine (의과대학) > Dept. of Anesthesiology and Pain Medicine (마취통증의학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
Yonsei Authors
Park, Kyungsoo(박경수) ORCID logo https://orcid.org/0000-0002-6972-1143
Jang, Seong Bok(장성복)
Han, Dong Woo(한동우) ORCID logo https://orcid.org/0000-0002-8757-663X
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