Fukushima Fernanda B, Barros Guilherme A M, Marques Mariângela E A, Vidal Edison I O, Ganem Eliana M
Department of Anesthesiology, São Paulo State University-UNESP, Botucatu/SP, Brazil.
Anesth Analg. 2009 Sep;109(3):965-71. doi: 10.1213/ane.0b013e3181ad581e.
As a result of amitriptyline's vast array of actions, it could potentially be used as an intraspinal adjuvant in neuraxial anesthesia and/or in the treatment of refractory neuropathic pain. None of the previous studies examining the safety profile of intraspinal single doses of amitriptyline found signs of toxicity at concentrations below 15.4 mM/L (0.5%) and the current hypothesis regarding the pathophysiology of amitriptyline toxicity suggests it might be safe at low concentrations while still having relevant clinical effects. Hence, we conducted this study to assess the clinical and histological toxicity of intraspinal amitriptyline at the lowest dosages previously known to be effective.
Twenty-one dogs were randomized to receive a 1-mL single intraspinal dose of one of the three solutions: saline (0.9%), amitriptyline (0.15%), or amitriptyline (0.3%). The dogs were evaluated clinically 1 h after awakening from anesthesia and 21 days later. At 21 days, all animals were killed, and histological sections of the spinal cord and surrounding meninges were retrieved for analysis.
All dogs recovered motor function, anal sphincter tone and sensibility. With the exception of one dog in the 0.15% amitriptyline group, all animals in both amitriptyline groups had marked adhesive arachnoiditis, which was absent in the control group. No evidence of direct neural damage was found on histological sections stained by glial fibrillary acidic protein technique in any of the study animals.
The intraspinal administration of amitriptyline to dogs even in low concentrations is strongly associated with the development of intense meningeal adhesive arachnoiditis and is not safe even at low concentrations for which there was no previous evidence of toxicity.
由于阿米替林具有多种作用，它有可能用作神经轴麻醉的脊髓内佐剂和/或用于治疗难治性神经性疼痛。之前关于脊髓内单剂量阿米替林安全性的研究均未发现浓度低于15.4 mM/L（0.5%）时有中毒迹象，目前关于阿米替林中毒病理生理学的假设表明，其在低浓度时可能是安全的，同时仍具有相关临床效果。因此，我们开展了本研究，以评估脊髓内给予已知最低有效剂量的阿米替林后的临床和组织学毒性。
将21只犬随机分为三组，分别接受1 mL脊髓内单剂量的三种溶液之一：生理盐水（0.9%）、阿米替林（0.15%）或阿米替林（0.3%）。犬在麻醉苏醒后1小时及21天后进行临床评估。21天时，处死所有动物，取出脊髓和周围脑膜的组织切片进行分析。
所有犬均恢复了运动功能、肛门括约肌张力和感觉。除0.15%阿米替林组的一只犬外，两个阿米替林组的所有动物均有明显的粘连性蛛网膜炎，而对照组未出现。在任何研究动物中，通过胶质纤维酸性蛋白技术染色的组织切片上均未发现直接神经损伤的证据。
即使以低浓度向犬脊髓内注射阿米替林，也与强烈的脑膜粘连性蛛网蛛网膜炎的发生密切相关，即使在之前没有中毒证据的低浓度下也不安全。
