Toxikologie der Lokalan�sthetika

Abstract

Regardless of their specific physico-chemical properties and chemical structures, all local anaesthetic agents block neuronal voltage-gated sodium channels, and thus suppress conduction in peripheral nerves. Since these ion channels ubiquitously appear in excitable membranes, systemic accumulation of local anaesthetic agents may affect the functional integrity of these structures. Clinically, local anaesthetic-induced systemic toxicity results in central nervous and cardiovascular malfunction. With regard to CNS toxicity, symptoms which are largely drug-independent appear in a characteristic biphasic sequence. Nevertheless, the plasma levels necessary to provoke these symptoms are to a large extent agent-specific. Initially, these toxic mechanisms are due to a selective blockade of cortical inhibitory neurons, which enables the formation of seizure potentials within subcortical structures. With high cerebral drug levels, however, excitatory neurons are also increasingly blocked, resulting in coma, apnoeic episodes and circulatory failure. Direct cardiac effects of local anaesthetics can be divided into (i) stereospecific inhibition of intracardial conduction and (ii) unspecific inhibition of myocardial energy supply and ion channels. The corresponding spectrum of symptoms is not uniform and may range from extreme bradycardia, (malignant) ventricular arrhythmia to refractory cardiac arrest. Local tissue toxicity has to be strictly delimited from systemic toxicity and allergies, respectively, which are mainly caused by aminoester agents. Local anaesthetics may cause neuronal and striated muscle injury at the site of injection. With regard to (central) neurotoxicity, "transient neurologic symptoms" and "cauda equina syndrome" have been increasingly recognised. However, the clinical relevance of local anaesthetic-induced myotoxicity is still controversly discussed. In order to avoid systemic accumulation of local anaesthetic agents, several safety procedures have to be considered during the application of these drugs. The treatment of systemic toxicity is strictly dependent on the expression of symptoms. However, hypoxia and acidotic episodes must be avoided and must be treated aggressively.

Bupivacaine crystal deposits after long-term epidural infusion

“…At this point interventional pain therapy, such as epidural analgesia can be introduced with much greater efficacy [12]. Tissue toxicity to LA has been documented in animal studies particularly at higher concentrations [2,3,4,6,7,8,11,13,14,15,16,17,18,19,20,25,29,31,32,33,34,37,38] but seldom observed using the recommended clinical concentrations in humans [1,15,22,23,24,26,28,31].…”

“…[31] apart from a few case reports [1,15,22,23,24,26,28]. To explain the mechanism of tissue toxicity various pathophysiological pathways of LA or LA mixtures in different human and animal tissues, such as skin, soft tissue, muscle and neurological tissue are discussed but the pathogenesis has not been elucidated in detail [1,13,19,20,29,32,33,34,35,36,37,38]. Particularly, only limited information is available on the extended epidural administration of continuous infusion of LA or LA mixtures for weeks and months.…”

Paraesthesia in Regional Anaesthesia

“…Furthermore local anaesthetics may cause neural membrane lysis due to detergent properties (Kitagawa et al 2004). The size of these effects is strongly influenced by a prolonged duration of exposure and higher concentration of the local anaesthetics, with in vitro the lowest neurotoxicty for procaine, mepivacaine and lidocaïne compared with ropivacaine and bupivacaine (Hogan 2008;Perez-Castro et al 2009), however most clinical relevant toxicity is attributed to high concentrations of lidocaïne (Zink & Graf 2003).…”

“…Animal data suggest moreover that amino-ester agents like procaine and tetracaine are more neurotoxic than amino-amide agents like lidocaïne and bupivacaine (Zink & Graf 2003).…”

“…anti-microbial preservatives added to multi-use vials, anti-oxidants or addition of epinephrine or bicarbonate, may also cause nerve damage (Hogan 2008;Zink & Graf 2003).…”