The mechanism of reducing thiopentone dose in elderly patients undergoing surgery
Ho, S.T.; Hu, O.Y.; Pao, L.H.; Ho, W.; Lee, S.C.
Proceedings of the National Science Council Republic of China. Part B Life Sciences 12(1): 1-8
1988
ISSN/ISBN: 0255-6596 PMID: 3406206 Document Number: 318814
The dose of thiopentone required to induce anesthesia in adults decreasing with age is not due to pharmacodynamic change. The change of pharmacokinetic properties of thiopentone with age in undergoing surgery patient's arterial blood was was investigated in seven elderly (67-82 yr) and six young (21-33 yr) patients of both sexes. Thiopentone (3 mg Kg-1) was administered intravenously and arterial blood samples were obtained immediately after the injection to measure plasma and red blood cell thiopentone concentrations by an HPLC method. Plasma protein binding was studied using ultracentrifuge method. The disappearance of thiopentone from the arterial blood was described by a two-compartment open model. The distribution rate constant (.alpha.) was significantly larger in the young patients (p < 0.001). The distribution half-life was longer in the elderly (p < 0.05). Both the input microscopic rate constant, K21, and the exit microscopic rate constant, K12, with the central compartment were significantly larger in the young patients. (p < 0.02 and p < 0.001, respectively). The difference between the exit and input microscopic rate constant, K12-K21, was much larger in the young patients (p < 0.001). The plasma protein binding was significantly reduced in the elderly (p < 0.05). The apparent overall volume of distribution, Vd was not significantly different between young and elder patients. However, the volume of distribution of the central compartment was smaller in the young patients (p < 0.05). This was probably due to the difficulty of estimation of initial thiopentone plasma concentration post-equilibrium in the central compartment after administration of thopentone. Also, the initial thiopentone plasma concentrations at 1 min, 1.5 min and 2 min were significantly higher in the elderly after the same dose, 3 mg kg-1, was given. From the slower distribution, the lower extent of plasma protein binding and the higher arterial plasma levels in the elderly after a given dose of thiopentone, it is suggested that the slower distribution and lower plasma protein binding are predominant in determining the lower dose requirement in the elderly patients.