Estudio de toxicidad aguda S(+)-Ketamina y RS-Ketamina administrada por vía subaracnoidea en conejos. Comparación con lidocaína.
ABSTRACT There are published numerous studies on the ketamine administered by experimentation subarachnoid animal route and in humans, nevertheless the data on the neurotoxicity that produces are controverted. The work hypothesis is based on to demonstrate that to the isomer levogiro of the ketamine (S(+)K) and the racemic mixture of the ketamine without preservative (RSK) administered by subarachnoid route in rabbits produce blockade both sensitive and motor and have little toxicity neurological. 60 white rabbits were used of race New Zealand male of between 2-3 kg of weight. The study was randomized and double blind person. The 60 rabbits distributed themselves in 6 groups of 10 rabbits, according to the drug administered by subarachnoid route: S+K: 2mg/Kg. RSK: 4mg/Kg. Lidocaine(L)2%: 1'5mg/Kg. L5%: 4mg/Kg. Like negative control physiological serum 0'9%(SF): 0'2 mililiter and positive control: Phenol 8%:6 mg/Kg, administered a volume of 0'2 mililiter. After the subarachnoid injection of the drug it was come to motor and sensitive clinical valuation: immediate, up to the 5 minutes, 30 and until the disappearance of the effects and up to 48 hours. The adjudged valuation to each one of the three ítems was: 0 = normal answer, 1 = answer diminished as opposed to normality and 2 = absent answer. To the 7 days rabbits were sacrificed and immediately it was come to the dissection and extraction of a block of lumbar vertebrae and first sacred and another block a thoracic level. They were included in formaldehyde to 10% during 7 days, later the spinal marrow was extracted, cuts were made up to 1 micron, they were used the hematoxylin-eosin´s stain to value the structures cellular and luxol phase blue for the cases of mielina. White substance components suchs as cellular components, astrocytes, oligodendroglia and myelin sheath were evaluated. Grey substance components such as cellular components, oligodendroglia, astroglia and the neurons were as well evaluated. A valuation from 0 occurred to 3, value 0 corresponded to normality, value 1 to slight injuries, value 2 to moderate injuries and value 3 to serious injuries. The statistical analysis of the data was made with computer science program SPSS version 9.0, by the Kruskall-wallis test and the Tau-b of Kendall test. The results were considered significant when p<0'05. Since the evaluation clinic significant differences between group SF with the others were observed of groups. In the group of rabbits to which it was injected SF were not observed alterations, in the rest of groups was sawn paralysis of the legs back. In the evaluation made to the 30 minutes there were differences significant between groups SF, S+K and RSK in which had disappeared as well the blockade motor as the blockade sensitive, when they were compared with groups L5% and F8% in which a more intense blockade persisted . In evaluation carried out 48 hours after the injection, showed paralysis irreversible only in the animals corresponding to group F8%. All the histologys structures studied of the samples of the rabbits pertaining to groups S+K, RSK, L2% and L5% showed significant differences when they were compared with groups negative and positive control. F8% produced injuries from moderate degree to severe degree, L5% produced injuries both intense and moderate degree. The S+K, RSK and L2% were the less damaging drugs. Given the little toxicity of the S+K and the RSK, they could be used in human beings for regional anesthesia and for the treatment of chronic pain from any resistant etiology to the therapy with morphine, such as in guidelines well combined.
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Advisor:Gallego García, Juan; Errando Oyonarte, Carlos
School:Universitat de València
Source Type:Master's Thesis
Date of Publication:04/21/2005