PMID: 3729056Jul 1, 1986Paper

Increased sensitivity to etomidate in the elderly: initial distribution versus altered brain response

J R ArdenD R Stanski


To determine the effect of aging on the pharmacokinetics and pharmacodynamics of etomidate, we administered etomidate (5 to 10 mg/min) by intravenous infusion to 21 healthy surgical patients, age 22 to 82 yr. Etomidate produced progressive slowing of the EEG to an easily recognized pattern (stage 3) that determined the dosage endpoint. Subsequent power-spectrum analysis of the EEG gave the median frequency. Median frequency values and simultaneous measurements of blood etomidate concentration were incorporated into a sigmoid Emax pharmacodynamic model that permitted an estimate of IC50, the blood etomidate concentration which produced a 50% reduction in the median frequency. The dose of etomidate required to reach the uniform EEG endpoint decreased significantly with increasing age (r2 = .68) as did the dose needed to produce maximal median frequency depression (r2 = .69). None of the parameters of the pharmacodynamic effect model, including IC50, correlated with age, suggesting that increased brain sensitivity in the elderly does not cause the age-related change in dose requirement. The initial distribution volume for etomidate decreased significantly with increasing age (r = .56), implying that a higher initial blood concentr...Continue Reading


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