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Barbiturate Anesthesia and Alcohol Tolerance in A Rat Model

Received from the Department of Anesthesiology, Michael Reese Hospital and Medical Center, Chicago, Illinois, the Pritzker School of Medicine, University of Chicago, Chicago, Illinois, the Department of Anesthesia, Rush Presbyterian-St. Luke's Medical Center, Chicago, Illinois, and the Department of Anesthesiology, University of Nebraska Medical Center, Omaha, Nebraska.

Abstract

Anesthetic responses to a variety of barbiturates were examined in adult male rats rendered alcohol-tolerant by administration of an ethanol-containing balanced liquid diet for 3 weeks. Within 9 hours of withdrawing the diets, groups of 10–15 ethanol-fed rats and pair-fed controls were injected intraperitoneally with one of the following drug/dose combinations: thiamylal 20, 40, or 60 mg/kg; methohexital 10, 20, or 40 mg/g; secobarbital 20, 30, or 40 mg/g; pentobarbital 10, 20, or 40 mg/g; or phenobarbital 80, 120, or 160 mg/g. Each animal was monitored for time to loss of righting reflex (onset of anesthesia), absence of response to a painful stimulus (analgesia), and sleeping time (duration of anesthesia). None of these three anesthetic responses differed significantly in ethanol-fed and control ruts with any dose of thiamylal, methohexital, or secobarbital. In contrast, all three responses were significantly less in rats given the middle dose of pentobarbital (20 mg/kg) than they were in control rats. Onset and duration of anesthesia were also shorter with the middle dose of phenobarbital (120 mg/kg), but analgesia was not. The results of this study, in combination with others, suggest that 1) cross-tolerance to anesthetic effects of barbiturates in ethanol-tolerant rats is not uniform with all barbiturates: and 2) because shorter-acting barbiturates show negligible cross-tolerance with alcohol, higher doses of these agents may not be required for satisfactory anesthesia in chronically alcoholic humans.

Key Words: ALCOHOL—tolerance • HYPNOTICS, barbiturates — interactions with alcohol • INTERACTIONS (DRUG) — barbiturates and alcohol