No effect of age on the dose requirement of thiopental in the rat.
With increasing human age (20-80 years), the electroencephalogram (EEG) dose requirement for the intravenous anesthetic thiopental decreases approximately 10% per decade of life. The goal of this study was to compare the dose required to attain isoelectric EEG in young (4-5 month) vs. aged (24-25-month) Fischer 344 rats. One second isoelectricity was found to be an endpoint where minimal cardiorespiratory depression occurred. The effects of age, infusion rate, and repeated administration were examined in nine young and nine old rodents. Thiopental dose requirement increased with increasing infusion rates. Repeated administration at two-day intervals did not demonstrate tolerance to thiopental. No difference in thiopental dose requirement was detected in the young vs. elderly rats. In a separate group of five young and five old rats, thiopental plasma, brain, heart, and CSF concentrations were measured when five seconds of EEG isoelectricity was achieved: no consistent differences were noted. The rat may not be an appropriate model to investigate acute age-related anesthetic effects in humans, because cardiovascular changes with age are dissimilar between species.
Harashima
H
H
University of Tokushima, Faculty of Pharmaceutical Sciences, Japan.
Ebling
W F
WF
Wada
D R
DR
Stanski
D R
DR
D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism*; D000704:Analysis of Variance; D018686:Anesthetics, Intravenous / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004569:Electroencephalography / Q000187:drug effects*; D006801:Humans; D007262:Infusions, Intravenous; D007526:Isoelectric Point; D009206:Myocardium / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D013874:Thiopental / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology
D018686:Anesthetics, Intravenous; D013874:Thiopental