Factors affecting the pharmacokinetics and neural block characteristics after epidural administration of local anaesthetics

Epidural anaesthesia has been shown to have a good clinical efficacy, but is hampered by a wide variability in the pharmacokinetics and neural block characteristics, resulting in a poor controllability of the spread of anaesthesia. The extent of the epidural neural blockade depends on the processes that occur during the transfer of local anaesthetics from the site of injection to the site of action. These processes include the longitudinal spread and the local tissue distribution. The longitudinal spread may be affected by anatomical and physiologic alterations, associated with increased age and local tissue distribution is influenced by the physicochemical and chiral properties of local anaesthetics. Determination of the absorption kinetics after epidural administration of local anaesthetics is important because it determines the relationship between neural blockade and the amount of drug remaining at or near the site of injection and the risk of systemic toxicity. Factors, such as age and enantiomer-specific disposition and elimination may contribute to the differences between local anaesthetics and individual patients. Pharmacokinetic-pharmacodynamic (PK/PD)-models for neuraxial blockade have been developed for epidural and subarachnoid administration of local anaesthetics. These models are able to explain a part of the variability by introducing covariates in the model. Furthermore, these models are able to make predictions about important clinical endpoints. Although these models still have to be validated for different clinical situations, the models may help to predict anaesthetic requirements for individual patients or new drug development in future.