[Pharmacokinetics and pharmacodynamics of local anesthetics]

In clinical practice the efficacy of local anaesthesia is judged by the time of onset, duration and the quality of sensory and motor blockade. Apart from the physicochemical properties of local anaesthetics, a sufficient blockade depends on the volume and the concentration which are applied. Generally increasing the dose leads to a better quality of blockade as well as a higher risk of toxicity. This dilemma is evident in procedures, where, due to continuous or repetitive application within one day, the applied total dosage exceeds the recommended maximum limit. The values regarding maximum doses published in the German Pharmacopeia ("Rote Liste") can be defined as being more or less the product of the volume of distribution and the toxic concentration in the plasma. According to that formula the maintainance doses for continuous techniques in regional anaesthesia are derived from the product of the elimination half-life and the toxic plasma concentration. The values for toxic plasma concentrations are difficult to define since only the free protein-unbound fraction of a local anaesthetic is responsible for undesired side-effects. This fraction can be influenced by acidosis, body temperature and shortage of specific binding protein. Some well documented case reports show that another major cause of acute toxicity is nearly always due to inadvertent intravascular injections. This event can occur nearly unnoticed and leads to life-threatening complications even with lower doses than the recommended maximum doses. Only the application of high concentrations into well vascularised regions is followed by a similarly quick development of high plasma levels. Typical kinetics of local anaesthetics are presented for various methods of regional anaesthesia informing the anaesthetist on corresponding plasma concentrations if the recommended maximum doses are exceeded and thus he gets useful information for his daily work.