Response Surface Modeling of the Interaction between Propofol and Sevoflurane

  • Peter M. Schumacher
    Senior Researcher.
  • Jan Dossche
    Resident.
  • Eric P. Mortier
    Professor and Chair, Department of Anesthesia, Ghent University Hospital, Gent, Belgium.
  • Martin Luginbuehl
    Staff Member, Department of Anesthesiology and Pain Therapy, University Hospital Bern, Bern, Switzerland.
  • Thomas W. Bouillon
    Senior Expert Modeler, Modeling & Simulation Pharmacology, Novartis Pharma AG, Basel, Switzerland.
  • Michel M. R. F. Struys
    Professor and Chair, Department of Anesthesia, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands, and Professor, Department of Anesthesia, Ghent University, Gent, Belgium.

抄録

<jats:sec> <jats:title>Background</jats:title> <jats:p>Propofol and sevoflurane display additivity for gamma-aminobutyric acid receptor activation, loss of consciousness, and tolerance of skin incision. Information about their interaction regarding electroencephalographic suppression is unavailable. This study examined this interaction as well as the interaction on the probability of tolerance of shake and shout and three noxious stimulations by using a response surface methodology.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>Sixty patients preoperatively received different combined concentrations of propofol (0-12 microg/ml) and sevoflurane (0-3.5 vol.%) according to a crisscross design (274 concentration pairs, 3 to 6 per patient). After having reached pseudo-steady state, the authors recorded bispectral index, state and response entropy and the response to shake and shout, tetanic stimulation, laryngeal mask airway insertion, and laryngoscopy. For the analysis of the probability of tolerance by logistic regression, a Greco interaction model was used. For the separate analysis of bispectral index, state and response entropy suppression, a fractional Emax Greco model was used. All calculations were performed with NONMEM V (GloboMax LLC, Hanover, MD).</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>Additivity was found for all endpoints, the Ce(50, PROP)/Ce(50, SEVO) for bispectral index suppression was 3.68 microg. ml(-1)/ 1.53 vol.%, for tolerance of shake and shout 2.34 microg . ml(-1)/ 1.03 vol.%, tetanic stimulation 5.34 microg . ml(-1)/ 2.11 vol.%, laryngeal mask airway insertion 5.92 microg. ml(-1) / 2.55 vol.%, and laryngoscopy 6.55 microg. ml(-1)/2.83 vol.%.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusion</jats:title> <jats:p>For both electroencephalographic suppression and tolerance to stimulation, the interaction of propofol and sevoflurane was identified as additive. The response surface data can be used for more rational dose finding in case of sequential and coadministration of propofol and sevoflurane.</jats:p> </jats:sec>

収録刊行物

  • Anesthesiology

    Anesthesiology 111 (4), 790-804, 2009-10-01

    Ovid Technologies (Wolters Kluwer Health)

被引用文献 (1)*注記

もっと見る

問題の指摘

ページトップへ