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Anesth Analg 2009; 109:801-806
© 2009 International Anesthesia Research Society
doi: 10.1213/ane.0b013e3181aff364
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ANESTHETIC PHARMACOLOGY

Increasing the Duration of Isoflurane Anesthesia Decreases the Minimum Alveolar Anesthetic Concentration in 7-Day-Old but Not in 60-Day-Old Rats

Greg Stratmann, MD, PhD, Jeffrey W. Sall, MD, PhD, Edmond I. Eger, II, MD, Michael J. Laster, DVM, Joseph S. Bell, BA, Laura D. V. May, MA, Helge Eilers, MD, Martin Krause, MD, Frank v. d. Heusen, MD, and Heidi E. Gonzalez

From the Department of Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, California.

Address correspondence and reprint requests to Greg Stratmann, MD, PhD, Department of Anesthesia and Perioperative Care, University of California San Francisco, Box 0464, Room U286, 513 Parnassus Ave., San Francisco, CA 94143. Address e-mail to stratman{at}anesthesia.ucsf.edu.

BACKGROUND: While studying neurotoxicity in rats, we observed that the anesthetic minimum alveolar anesthetic concentration (MAC) of isoflurane decreases with increasing duration of anesthesia in 7-day-old but not in 60-day-old rats. After 15 min of anesthesia in 7-day-old rats, MAC was 3.5% compared with 1.3% at 4 h. We investigated whether kinetic or dynamic factors mediated this decrease.

METHODS: In 7-day-old rats, we measured inspired and cerebral partial pressures of isoflurane at MAC as a function of duration of anesthesia. In 60-day-old rats, we measured inspired partial pressures of isoflurane at MAC as a function of duration of anesthesia. Finally, we determined the effect of administering 1 mg/kg naloxone and of delaying the initiation of the MAC determination (pinching the tail) on MAC in 7-day-old rats.

RESULTS: In 7-day-old rats, both inspired and cerebral measures of MAC decreased from 1 to 4 h. The inspired MAC decreased 56%, whereas the cerebral MAC decreased 33%. At 4 h, the inspired MAC approximated the cerebral MAC (i.e., the partial pressures did not differ appreciably). Neither administration of 1 mg/kg naloxone nor delaying tail clamping until 3 h reversed the decrease in MAC. In 60-day-old rats, inspired MAC of isoflurane was stable from 1 to 4 h of anesthesia.

CONCLUSIONS: MAC of isoflurane decreases over 1–4 h of anesthesia in 7-day-old but not in 60-day-old rats. Both pharmacodynamic and a pharmacokinetic components contribute to the decrease in MAC in 7-day-old rats. Neither endorphins nor sensory desensitization mediate the pharmacodynamic component.






Lippincott, Williams & Wilkins Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins and Stanford University Libraries' HighWire Press®. Copyright 2009 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999 HighWire Press
Copyright © 2009 by the International Anesthesia Research Society.