The myotoxicity of bupivacaine, a ³¹P n.m.r. investigation

Local anaesthetic-induced myotoxicity in regional anaesthesia: a systematic review and empirical analysis

“…8,9,18,47,53,58,59,64,65,69,73,75,77,80e82 The time duration of muscle tissue recovery was reported to be between 14 and 30 days; this time was needed for muscle fibres to regenerate, 16,46,57,74,76,79,83 myofibril diameter to normalise, 48,50 and tissue inflammation to resolve. 26,51,63 This is notably longer than the 14 days of normal muscle regeneration time. 85 Results of human studies…”

“…Regardless of concentration, the site of LA injection in muscle tissue became the site of a localised inflammatory response, 2,58,61,63 marked by aggregation of inflammatory cells, including neutrophils, lymphocytes, and macrophages. 2,22,26,51,52,60,61,63,72,74,81 Injections of low concentrations of any of bupivacaine, 61,63 mepivacaine, 2 lidocaine, 2,63 procaine, 2 ropivacaine, 58 and liposomal ropivacaine 58 into muscle tissue resulted in a purely inflammatory infiltrate that appeared between 24 h and 1 week 2,58,61,63 at the injection site. Similar inflammatory changes were observed with high concentrations of mepivacaine, 2 lidocaine, 2 and procaine.…”

“…concentration and duration). Classifying recovery as minimal (0e25%), partial (25e50%), major (>50%), and complete (100%), complete recovery was noted in 21 studies, 10e12, 16,26,46,48e50,52,56e58,63,67,68,72,74,76,78,84 partial in 17 studies, 12,19,20,22,28,51,52,54,55,61,63,66,68,70,71,79,83 and minimal in 4 studies. studies.…”

“…The study designs varied between case series/studies, 5e7, 86,88e99,101,105,107,109,111,113,118 experimental studies, 119 retrospective cohort analyses, 4,100,102e104,110,114,117 and prospective cohort analyses. 47,61,63,87,106,112,115,120 None of the human studies were randomised controlled trials. The surgical procedures examined included orthopaedic procedures in five studies (6121 patients) 6,7,63,86,87 and ophthalmologic procedures in 32 studies (44 478 patients), 4,5,88e117 and one study (case report, one patient) examined dental 118 procedures.…”

Local anesthetic myotoxicity

“…30,35 Clinical observations highlight this biphasic effect as local anesthetics fail to induce generalized muscle damage after intravenous blockades or systemic administration, with resulting plasma concentrations markedly smaller than 1 mmol/L. 36,37 Furthermore, the receptor interactions appear to be pH dependent. 38 Only the free bases induce Ca 2ϩ release from intracellular storage sites, whereas protonated local anesthetic molecules inhibit Ca 2ϩ conduction across SR membranes.…”