The effect of age on systemic absorption and systemic disposition of bupivacaine after subarachnoid administration

Abstract

In order to evaluate the role of the pharmacokinetics of the age-related changes in the clinical profile of spinal anesthesia with bupivacaine, we studied the influence of age on the systemic absorption and systemic disposition of bupivacaine after subarachnoid administration in 20 male patients (22-81 yr), ASA Physical Status 1 or 2, by a stable isotope method. After subarachnoid administration of 3 ml 0.5% bupivacaine in 8% glucose, a deuterium-labeled analog (13.4 mg) was administered intravenously. Blood samples were collected for 24 h. Plasma concentrations of unlabeled and deuterium-labeled bupivacaine were determined with a combination of gas chromatography and mass fragmentography. Biexponential functions were fitted to the plasma concentration-time data of the deuterium-labeled bupivacaine. The systemic absorption was evaluated by means of deconvolution. Mono- and biexponential functions were fitted to the data of fraction absorbed versus time. The maximal height of analgesia and the duration of analgesia at T12 increased with age (r = 0.715, P < 0.001; r = 0.640, P < 0.01, respectively). In 18 patients the systemic absorption of bupivacaine was best described by a biexponential equation. The half-life of the slow systemic absorption process (r = -0.478; P < 0.05) and the mean absorption time (r = -0.551; P < 0.02) decreased with age. The total plasma clearance decreased with age (r = -0.650, P < 0.002), whereas the mean residence time and terminal half-life increased with age (r = 0.597, P < 0.01; r = 0.503, P < 0.05). The observed changes in the clinical profile with age cannot be attributed to changes in the systemic absorption profile after subarachnoid administration, but may be related to changes in the pharmacodynamics of local anesthetics.