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GENERAL ARTICLES

Isobolographic Analysis of Propofol-Thiopental Hypnotic Interaction in Surgical Patients

H. Ronald Vinik, MD^*, Edwin L. Bradley, Jr., PhD, and Igor Kissin, MD, PhD

Departments of *Anesthesiology and Biostatistics, University of Alabama at Birmingham, Birmingham, Alabama; and Department of Anesthesia, Harvard Medical School, Brigham and Women’s Hospital, Boston, Massachusetts

Address correspondence and reprint requests to H. Ronald Vinik, MD, Eye Foundation Hospital, Department of Anesthesia, 1720 University Blvd., Birmingham, AL 35233. Address e-mail to ronald.vinik{at}ccc.uab.edu

Drugs acting via the same mechanism interact additively, whereas a supraadditive effect can result from an interaction of drugs with different mechanisms of action. Hypnotic midazolam-propofol and midazolam-thiopental interactions are supraadditive. In contrast to midazolam, the mechanisms of actions of propofol and thiopental are quite similar. The aim of this study was to test the hypothesis that similarity in the mechanisms of action of propofol and thiopental results in the additive hypnotic interaction. We studied the hypnotic effects of thiopental, propofol, and their combinations in 150 unpremedicated patients in a randomized, double-blind fashion. The ability to open eyes on command was used as an end point. Dose-response curves for the drugs given separately and in combinations at three different dose ratios between the drugs were determined by using a probit procedure, and the 50% effective dose values were compared by using isobolographic and algebraic (fractional) analysis. The hypnotic propofol-thiopental combination was additive with all dose ratios between components of the combination. The absence of propofol-thiopental synergy, as demonstrated with midazolam-thiopental or propofol-midazolam combinations, suggests that the mechanisms underlying the hypnotic effects of propofol and thiopental, in contrast to the above combinations with midazolam, are very similar and could be identical.

Implications: The propofol-thiopental hypnotic interaction is additive.

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Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999