Clinical and neurotoxic effects of chronic epidural and intrathecal administration of racemic ketamine or S(+)-ketamine with preservative or preservative-free in rabbits

Abstract

Nowadays, ketamine is used in subanesthetic doses as adjuvant during general or regional anesthesia and as part of protocols for the treatment of post-operative or chronic pain. When administrated by epidural route, ketamine is an efficient analgesic without inducing cardio-respiratory effects, urinary retention, pruritus and motor or sensitive alterations. Analgesic effects of epidural and intrathecal S(+)-ketamine, the levogiral isomer of ketamine, were reported in man, dog, and in the horse. According to some authors the main limiting factor for epidural and intrathecal use of these drugs is its potential neurotoxicity. However, data about the neurotoxic effects of ketamine are in conflict in humans and in animals, and there are little information available about neurotoxic effects of S(+)-ketamine. Some authors did not observe neurological damage, while others found minimal or moderate toxicity associated with the use of preservatives or high concentrations of ketamine, and is possible that an important difference between the epidural and intrathecal effects of drugs exist. For these reasons, and due to the low number of similar studies, we propose to evaluate the clinical and neurotoxic effects of epidural or intrathecal injection of racemic ketamine or S(+)-ketamine, with preservative and preservative-free, in rabbits chronically instrumented with epidural or intrathecal catheters. (AU)