Clinical Pharmacokinetics of Local Anaesthetics

Abstract

The introduction of the new long acting local anaesthetics, bupivacaine and etidocaine, has stimulated an expansion of interest in regional anaesthesia, particularly for obstetrical applications and pain therapy. Systemic toxicity following injection of local anaesthetics occurs albeit infrequently, and tentative correlations have been made between the onset of CNS and cardiovascular effects and circulating drug concentrations in both adults and neonates. Amongst other factors, interpretation of these relationships depends upon blood distribution and plasma binding of the agents, sampling sites and acid-base balance. The disposition kinetics and placental transfer of the amide type agents have been well characterised. In adults their clearance is almost entirely hepatic but in neonates an increase in the renal component is, in part, a reflection of the immaturity of some of the enzymes responsible for their metabolism. Ester type agents are rapidly hydrolysed by plasma pseudocholin-esterase and this has led to a preference for chloroprocaine in some obstetric procedures. Major determinants of the systemic absorption of the agents after perineural administration include their physicochemical and vasoactive properties, perfusion and tissue binding at the site of injection and whether or not adrenaline has been added. In respect of blood drug concentrations achieved after various regional anaesthetic procedures, the margin of systemic safety appears to favour bupivacaine and etidocaine compared to shorter acting analogues such as lignocaine and mepivacaine. The time course of local anaesthetic remaining at the site of injection has been calculated following intravenous regional anaesthesia and peridural block. This has allowed prediction of the local and systemic accumulation of the drugs following continued dosage. Blood concentrations of local anaesthetics after perineural injection are not closely related to age, weight or pregnancy but may be influenced by diseases associated with haemodynamic changes and by other drugs given at or around the time of regional blockade. © 1979, ADIS Press Australasia Pty Ltd.. All rights reserved.