Anesthesiology Department, Sao Paulo State University, Botucatu/SP, Brazil.
Anesth Analg. 2012 Feb;114(2):450-5. doi: 10.1213/ANE.0b013e31823a5d1b. Epub 2011 Dec 13.
The N-methyl-d-aspartate receptor antagonist ketamine and its active enantiomer, S(+)-ketamine, have been injected in the epidural and subarachnoid spaces to treat acute postoperative pain and relieve neuropathic pain syndrome. In this study we evaluated the effects of a single dose of preservative-free S(+)-ketamine, in doses usually used in clinical practice, in the spinal cord and meninges of dogs.
Under anesthesia (IV etomidate (2 mg/kg) and fentanyl (0.005 mg/kg), 16 dogs (6 to 15 kg) were randomized to receive a lumbar intrathecal injection (L5/6) of saline solution of 0.9% (control group) or S(+)-ketamine 1 mg/kg(-1) (ketamine group). All doses were administered in a volume of 1 mL over a 10-second interval. Accordingly, injection solution ranged from 0.6% to 1.5%. After 21 days of clinical observation, the animals were killed; spinal cord, cauda equina root, and meninges were removed for histological examination with light microscopy. Tissues were examined for demyelination (Masson trichrome), neuronal death (hematoxylin and eosin) and astrocyte activation (glial fibrillary acidic protein).
No clinical or histological alterations of spinal tissue or meninges were found in animals from either control or ketamine groups.
A single intrathecal injection of preservative-free S(+)-ketamine, at 1 mg/kg(-1) dosage, over a concentration range of 6 to 15 mg/mL injected in the subarachnoid space in a single puncture, did not produce histological alterations in this experimental model.
N-甲基-D-天冬氨酸受体拮抗剂氯胺酮及其活性对映体 S(+)-氯胺酮已被注射到硬膜外和蛛网膜下腔,以治疗急性术后疼痛和缓解神经病理性疼痛综合征。在这项研究中,我们评估了在犬脊髓和脑膜中单剂量的无防腐剂 S(+)-氯胺酮(通常在临床实践中使用的剂量)的效果。
在麻醉(静脉注射依托咪酯(2mg/kg)和芬太尼(0.005mg/kg))下,16 只(6 至 15 公斤)狗随机接受腰椎蛛网膜下腔注射(L5/6)生理盐水(对照组)或 S(+)-氯胺酮 1mg/kg(-1)(氯胺酮组)。所有剂量均在 10 秒内以 1mL 的体积给药。因此,注射溶液的浓度范围为 0.6%至 1.5%。经过 21 天的临床观察后,处死动物;取出脊髓、马尾神经根和脑膜进行组织学检查,采用光镜观察脱髓鞘(Masson 三色)、神经元死亡(苏木精和伊红)和星形胶质细胞激活(胶质纤维酸性蛋白)。
无论是对照组还是氯胺酮组的动物,都没有发现脊髓组织或脑膜的临床或组织学改变。
单次蛛网膜下腔注射无防腐剂的 S(+)-氯胺酮,剂量为 1mg/kg(-1),浓度范围为 6 至 15mg/mL,在单次穿刺时注入蛛网膜下腔,在该实验模型中不会引起组织学改变。