Local toxicity from local anesthetic polymeric microparticles.
Local toxicity from local anesthetic polymeric microparticles.
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DOI：
10.1213/ane.0b013e31828174a7
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发表时间：
2013-04
影响因子：
5.7
通讯作者：
Kohane DS
中科院分区：
文献类型：
--
作者：
McAlvin JB;Reznor G;Shankarappa SA;Stefanescu CF;Kohane DS
用于局部麻醉剂的缓释制剂的局部组织损伤可能是严重的。在报告这种伤害方面有很大的差异。我们研究了内在的肌肉毒性的包裹局部麻醉药（利多卡因，低，布比卡因，高）对组织反应的影响。在6天内在C2 C12肌管中测量了一系列利多卡因和布比卡因浓度的细胞毒性。用利多卡因和布比卡因的4种微粒制剂给予大鼠坐骨神经阻滞：10%（w/w）利多卡因聚乳酸-共-乙醇酸（PLGA）、10%（w/w）布比卡因PLGA、50%（w/w）利多卡因PLGA和50%（w/w）布比卡因PLGA。通过改良的热板试验和负重测量评估神经阻滞的有效性。在注射部位的组织学切片中对肌毒性进行评分。测量颗粒中布比卡因和利多卡因的释放动力学。50%（w/w）利多卡因的中位感觉阻滞持续时间为255（90-540）min，50%（w/w）布比卡因为840（277-1215）min（P=0.056）。所有微粒制剂均导致肌毒性。局麻药的选择不影响肌毒性的严重程度。50%（w/w）利多卡因与50%（w/w）布比卡因相比，第4天时的中位肌毒性评分分别为3.4（2.1-4.2）vs. 3.3（2.9-3.5）（P=0.44）和14天时的1.9（1.8-2.4）vs. 1.7（1.3-1.9）（P=0.23）。利多卡因和布比卡因PLGA微球导致类似程度的肌肉毒性，无论药物负荷。内源性肌毒性不能预测这些麻醉剂持续释放引起的组织损伤。在肌肉和神经附近使用此类器械时应谨慎。
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. 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 weight-bearing measurements. Myotoxicity was scored in histologic sections of injection sites. Bupivacaine and lidocaine release kinetics from the particles were measured. Median sensory blockade duration for 50% (w/w) lidocaine was 255 (90–540) min versus 840 (277–1215) min 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 to 50% (w/w) bupivacaine at 4 days was 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) versus 1.7 (1.3–1.9)(P=0.23) respictively. 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.