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  • Title: Local toxicity from local anesthetic polymeric microparticles.
    Author: McAlvin JB, Reznor G, Shankarappa SA, Stefanescu CF, Kohane DS.
    Journal: Anesth Analg; 2013 Apr; 116(4):794-803. PubMed ID: 23460564.
    Abstract:
    BACKGROUND: Local tissue injury from sustained-release formulations for local anesthetics can be severe. There is considerable variability in reporting of that injury. We investigated the influence of the intrinsic myotoxicity of the encapsulated local anesthetic (lidocaine, low; bupivacaine, high) on tissue reaction in rats. METHODS: Cytotoxicity from a range of lidocaine and bupivacaine concentrations was measured in C2C12 myotubes over 6 days. Rats were given sciatic nerve blocks with 4 microparticulate formulations of lidocaine and bupivacaine: 10% (w/w) lidocaine poly(lactic-co-glycolic) acid (PLGA), 10% (w/w) bupivacaine PLGA, 50% (w/w) lidocaine PLGA, and 50% (w/w) bupivacaine PLGA. Effectiveness of nerve blockade was assessed by a modified hotplate test and weightbearing measurements. Myotoxicity was scored in histologic sections of injection sites. Bupivacaine and lidocaine release kinetics from the particles were measured. RESULTS: Median sensory blockade duration for 50% (w/w) lidocaine was 255 (90-540) minutes versus 840 (277-1215) minutes for 50% (w/w) bupivacaine (P = 0.056). All microparticulate formulations resulted in myotoxicity. The choice of local anesthetic did not influence the severity of myotoxicity. Median myotoxicity scores for 50% (w/w) lidocaine compared with 50% (w/w) bupivacaine at 4 days were 3.4 (2.1-4.2) vs 3.3 (2.9-3.5) (P = 0.44) and at 14 days 1.9 (1.8-2.4) vs 1.7 (1.3-1.9) (P = 0.23), respectively. CONCLUSIONS: Lidocaine and bupivacaine PLGA microspheres resulted in similar degrees of myotoxicity, irrespective of drug loading. Intrinsic myotoxicity did not predict tissue injury from sustained release of these anesthetics. Caution is warranted in the use of such devices near muscle and nerve.
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