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Six healthy subjects received ethanol 0.35, 0.70, and 1.05

Inspired isoflurane concentration for anesthetizing 50 percent of adult albino mice (ED50) was 1.33 percent (1.20 to 1.47, 95 percent confidence interval). Ethanol anesthetizing dose was 5.09 (4.74 to 5.47) gm./kg. intraperitoneally (I.P.). Twenty, 39, and 79 percent of this ethanol anesthetic dose reduced isoflurane ED50 by 0, 8, and 70 percent, respectively. Thus, acute combinations of ethanol and isoflurane are more effective than either alone but less than the expected sum. Mice receiving no other fluid than 10 percent alcohol developed cross-tolerance to isoflurane. After 10 days of continuous alcohol ingestion, isoflurane ED50 increased to 1.54 (1.36 to 1.75) and after 20 days to 1.69 (1.55 to 1.84) percent. Combined with 2 and 4 gm./kg. of alcohol I.P., isoflurane ED50 in these mice decreased to 1.34 (1.26 to 1.42) and 0.73 (0.62 to 0.85) percent. Cross-tolerance acquired by these alcohol-consuming mice persisted through 55 days after stopping alcohol (ED50 1.65 percent), but returned to control values after 80 days (1.32 percent).