Tissue injury from tricyclic antidepressants used as local anesthetics
Tissue injury from tricyclic antidepressants used as local anesthetics
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DOI：
10.1213/01.ane.0000184129.50312.c1
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发表时间：
2005-12-01
影响因子：
5.7
通讯作者：
Kohane, DS
中科院分区：
文献类型：
--
作者：
Barnet, CS;Louis, DN;Kohane, DS
已报告三环类抗抑郁药（TCA）用作局部麻醉剂的神经毒性。我们研究了TCA引起组织损伤的假设，特别是肌肉毒性，与许多局麻药一样。向动物坐骨神经注射0-80 mM多塞平、阿米替林或布比卡因（1.5 mL，用于组织学研究，0.3 mL，用于神经行为研究）。注射后4天，TCA引起缺血性组织损伤。皮下组织显示扩张和硬化，伴有出血和与上覆皮肤粘连。肌肉弥漫性苍白。组织学检查显示肌肉和周围软组织凝固性坏死，受影响区域附近的血管中有血栓形成。这些发现在布比卡因中大大减少。注射TCA和注射布比卡因的动物也出现了特征性局部麻醉剂肌毒性。阿米替林被证明不如布比卡因作为局部麻醉剂有效：提供100分钟的神经阻滞所需的浓度分别为20 mM和3 mM。接受大浓度阿米替林的一些动物出现神经阻滞的自发复发或具有不可逆的神经阻滞，这两者都可能反映神经损伤。在注射布比卡因的动物中均未出现这一结果。与传统的局部麻醉剂相比，TCA似乎没有任何优势，而且确实有明显增加毒性的风险。
Neurotoxicity has been reported with tricyclic antidepressants (TCAs) used as local anesthetics. We examined the hypothesis that TCAs cause tissue injury, particularly myotoxicity, as occurs with many local anesthetics. Animals were given sciatic nerve injections with 0-80 mM doxepin, amitriptyline, or bupivacaine (1.5 mL, for histological studies, 0.3 mL, for neurobehavioral studies). Four days after injection, the TCAs caused ischemic tissue injury. Subcutaneous tissue showed expansion and hardening, with hemorrhage and adhesion to overlying skin. Muscle was diffusely pale. Histopathology showed coagulative necrosis of muscle and surrounding soft tissues, with thrombus formation in vasculature near affected areas. These findings were much reduced with bupivacaine. TCA-injected and bupivacaine-injected animals also developed characteristic local anesthetic myotoxicity. Amitriptyline proved less potent than bupivacaine as a local anesthetic: the concentrations required to provide 100 min of nerve block were 20 mM and 3 mM, respectively. Some animals receiving large concentrations of amitriptyline developed spontaneous recrudescence of nerve blockade or had irreversible nerve blockade, both of which may reflect nerve injury. Neither finding occurred in animals injected with bupivacaine. TCAs do not appear to offer any advantages over conventional local anesthetics and do appear to risk substantially increased toxicity.