The effect of increasing age on thiopental disposition and anesthetic requirement

The dose of thiopental required to induce anesthesia in adults decreases with age. The pharmacokinetic and pharmacodynamic properties of thiopental were studied in two groups of surgical patients to determine the mechanism of this decrease. In one group (29 patients 19-88 yr of age), thiopental was infused at a rate of 75-150 mg/min until the electroencephalogram (EEG) demonstrated early burst suppression (phase III). Arterial blood samples were obtained frequently during and after the infusion to measure serum thiopental concentrations, and power spectral analysis was used to calculate the spectral edge (Hz), defined as the frequency below which 95% of the EEG power is located. Pharmacodynamic modeling was used to relate the serum thiopental concentrations to the spectral edge in order to estimate the individual patient's brain sensitivity to thiopental. In a second group (28 patients 24-88 yr of age), pharmacokinetics were determined after a bolus or rapid infusion of thiopental. Arterial blood samples were obtained frequently to characterize the initial distribution phases, sampling continued for 24-48 h to characterize elimination processes. The dose of thiopental required to achieve early burst suppression on the electroencephalogram (EEG) decreased linearly and significantly with age. Pharmacodynamic modeling also demonstrated that brain sensitivity to thiopental does not change with age. The age-related decrease of the thiopental dose requirement is due to a change in the initial distribution of the drug. That is, the initial distribution volume (central compartment, or V1) of thiopental decreases exponentially with age. This smaller initial distribution volume in the elderly results in higher serum levels after a given dose of thiopental.