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Thermoregulatory defect in rats during anesthesia.

B A Hitt, R I Mazze, T L Cook

    Anesthesia and Analgesia
    |January 1, 1977
    PubMed
    Summary

    Phenobarbital combined with sevoflurane or enflurane anesthesia, under heat stress, proved lethal to Fischer 344 rats. This highlights a potential thermoregulatory defect in rats, not observed in guinea pigs or mice.

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    Area of Science:

    • Anesthesiology
    • Toxicology
    • Comparative Physiology

    Background:

    • Phenobarbital is a common sedative and anesthetic agent.
    • Certain anesthetic agents can pose risks under specific physiological conditions.
    • Thermoregulation is critical during anesthesia.

    Purpose of the Study:

    • To investigate the toxicity of sevoflurane, enflurane, and methoxyflurane in phenobarbital-treated rats.
    • To determine the role of heat and soda lime in potentiating anesthetic toxicity.
    • To compare the toxic response across different rodent strains, guinea pigs, and mice.

    Main Methods:

    • Male rats (Fischer 344, Sprague-Dawley, Brattleboro, Wistar), mice (balb/C), and guinea pigs (Hartley) were administered phenobarbital in drinking water.
    • Animals were exposed to various volatile anesthetics (sevoflurane, enflurane, methoxyflurane, isoflurane, halothane) in a closed chamber.

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  • Experiments included conditions with soda lime (CO2 absorbent) and exogenous heat (39°C water blanket).

    • Main Results:

    • 86% of Fischer 344 rats on phenobarbital died when exposed to sevoflurane or enflurane with heat or soda lime.
    • Phenobarbital-treated rats exposed to methoxyflurane showed lesser effects.
    • Rats on tap water or without heat/soda lime, and guinea pigs/mice, were unaffected.

    Conclusions:

    • A species-specific thermoregulatory defect, triggered by heat, likely underlies the observed toxicity in phenobarbital-treated rats.
    • The combination of phenobarbital, specific anesthetics (sevoflurane, enflurane, methoxyflurane), and heat stress creates a lethal environment for Fischer 344 rats.
    • Guinea pigs and mice do not exhibit this sensitivity, suggesting interspecies differences in anesthetic metabolism or thermoregulation.