Myotoxizität von Lokalanästhetika

Abstract

Intramuscular injections of local anaesthetic agents regularly result in reversible muscle damage, with a dose-dependent extent of the lesions. All local anaesthetic agents that have been examined are myotoxic, whereby procaine produces the least and bupivacaine the most severe muscle injury. The histological pattern and the time course of skeletal muscle injury appear relatively uniform: hypercontracted myofibrils become evident directly after injection, followed by lytic degeneration of striated muscle sarcoplasmic reticulum myocyte edema and necrosis. Intriguingly, in most cases myoblasts, basal laminae and connective tissue elements remain intact which subsequently ensures complete muscular regeneration. Subcellular pathomechanisms of local anaesthetic myotoxicity are still not understood in detail. Increased intracellular Ca(2+) levels are suggested to be the most important element in myocyte injury, since denervation, inhibition of sarcolemmal Na(+) channels and direct toxic effects on myofibrils have been excluded as sites of action. Although experimental myotoxic effects are impressively intense and reproducible, only few case reports of myotoxic complications in patients after local anaesthetic administration have been published. In particular, the occurrence of clinically relevant myopathy and myonecrosis has been described after continuous peripheral blockades, infiltration of wound margins, trigger point injections, peribulbar and retrobulbar blocks.

Rotator cuff healing after continuous subacromial bupivacaine infusion: an in vivo rabbit study

“…28–30,43 Despite these studies, the available literature suggests that myotoxicity following injection with a local anesthetic is subclinical and reversible, likely due to short exposure time. 10,22,29,30,46,48 However, with the advent of continuous infusion pain pumps, it is presently unknown whether local anesthetic may cause more significant (i.e., irreversible) muscle damage due to prolonged exposure time to the muscle tissue.…”

Modification of Bupivacaine-Induced Myotoxicity with Dantrolene and Caffeine In Vitro

“…[28][29][30] Local toxic effects are known from histopathologic examinations, but there is still little knowledge about causative pathophysiology. 1,8,10,14,15,31 Because of unknown tissue concentrations, variable resorption, and a generally high tissue regeneration, the clinical relevance of LA-induced myotoxicity remains uncertain. However, because regional anesthesia is being used in more and more clinical settings, there is increasing interest in local tissue damage.…”

“…[2][3][4][5] All recently used LAs have myotoxic effects, with bupivacaine causing the most severe structural long-term damage in clinically used concentrations. 1,[6][7][8][9][10][11][12][13] Various in vitro models have demonstrated influence of both LAs in terms of concentration and time of exposure. 14,15 Furthermore, we could previously show various sensitivities of different cell culture types.…”

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.…”