[Pharmacokinetic studies of blood protein binding of bupivacaine following acute preoperative hemodilution].

Abstract

This randomized study was designed to determine the effects of isovolemic hemodilution and lumbar epidural anesthesia on plasma concentrations of bupivacaine in patients scheduled for endoprosthetic hip surgery. PATIENTS, MATERIALS AND METHODS. The patients were randomly assigned to two groups. In a hemodilution group (n = 15), which included patients undergoing lumbar epidural anesthesia following isovolemic hemodilution (15 ml/kg body weight), withdrawn blood was substituted by colloidal solution (hydroxyethyl starch solution 6%, 450/0.7; ratio of replacement 1:1). Controls were 15 patients who were not subjected to isovolemic hemodilution; epidural anesthesia only was performed. Both groups had identical fluid pretreatment (1000 ml Ringer's solution) before injection of the epidural bupivacaine dose (mean 14 ml, 0.75%); central venous blood samples were drawn at short intervals over 180 min. Both, the total plasma concentrations and the free bupivacaine fractions were determined by HPLC and ultrafiltration. RESULTS. Peak bupivacaine plasma levels (mean 1.30 microgram/ml) were found 10 min after application of the analgesic dose in the control patients. In contrast, in hemodiluted patients mean maximum plasma levels of bupivacaine were measured between the 20th and 30th min, with peak levels of only 0.75 microgram/ml plasma. The unbound bupivacaine levels were not significantly different in both groups over the entire measuring period despite the differing total bupivacaine concentrations. Therefore, protein binding of bupivacaine was about 6% lower in the hemodilution group, especially during the period shortly after injection. DISCUSSION. We conclude that isovolemic hemodilution leads to lower plasma bupivacaine concentrations after epidural anesthesia, probably due to an increased volume of distribution. Protein binding of bupivacaine is reduced by hemodilution; the free, non-protein-bound concentrations of local anesthetic were not associated with any systemic side effects in this study.