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ANESTHETIC PHARMACOLOGY

Inhaled Anesthetics Do Not Combine to Produce Synergistic Effects Regarding Minimum Alveolar Anesthetic Concentration in Rats

Edmond I. Eger, II, MD^*, Michael Tang^*, Mark Liao, BS^*, Michael J. Laster, DVM^*, Ken Solt, MD, Pamela Flood, MD, Andrew Jenkins, PhD^||, Douglas Raines, MD, Jan F. Hendrickx, MD^¶, Steven L. Shafer, MD^¶**, Tanifuji Yasumasa, MD, and James M. Sonner, MD^*

From the *Department of Anesthesia and Perioperative Care, University of California, San Francisco, California; Department of Anesthesia and Critical Care, Massachusetts General Hospital, and Department of Anaesthesia, Harvard Medical School, Boston, Massachusetts; Department of Anesthesiology, Columbia University, New York City, New York; ||Department of Anesthesiology, Emory University, Atlanta, Georgia; ¶Department of Anesthesia, Stanford University, Stanford, California; **Department of Biopharmaceutical Science, UCSF, San Francisco, California; and Department of Anesthesiology, Jekei University School of Medicine, Tokyo, Japan.

Address correspondence and reprint requests to Dr. Edmond I Eger II, Department of Anesthesia, S-455, University of California, San Francisco, CA 94143-0464. Address e-mail to egere{at}anesthesia.ucsf.edu.

BACKGROUND: We hypothesized that pairs of inhaled anesthetics having divergent potencies [one acting weakly at minimum alveolar anesthetic concentration (MAC); one acting strongly at MAC] on specific receptors/channels might act synergistically, and that such deviations from additivity would support the notion that anesthetics act on multiple sites to produce anesthesia.

METHODS: Accordingly, we studied the additivity of MAC for 11 anesthetic pairs divergently (one weakly, one strongly) affecting a specific receptor/channel at MAC. By "divergently," we usually meant that at MAC the more strongly acting anesthetic enhanced or blocked the in vitro receptor or channel at least twice (and usually more) as much as did the weakly acting anesthetic. The receptors/channels included: TREK-1 and TASK-3 potassium channels; and -aminobutyric acid type A, glycine, N-methyl-d-aspartic acid, and acetylcholine receptors. We also studied the additivity of cyclopropane-benzene because the N-methyl-d-aspartic acid blocker MK-801 had divergent effects on the MACs of these anesthetics. We also studied four pairs that included nitrous oxide because nitrous oxide had been reported to produce infraadditivity (antagonism) when combined with isoflurane.

RESULTS: All combinations produced a result within 10% of that which would be predicted by additivity except for the combination of isoflurane with nitrous oxide where infraadditivity was found.

CONCLUSIONS: Such results are consistent with the notion that inhaled anesthetics act on a single site to produce immobility in the face of noxious stimulation.

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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