Repeated epidural injections of ketamine with preservative benzethonium chloride produce evidence for neurotoxicity in rabbits

WOS: 000185739800014Background and objectives: In this study, we investigated whether repeated doses of 1% ketamine with preservative benzethonium chloride, administered into the epidural space of the rabbit, caused direct neurotoxicity. Methods: Twelve rabbits were randomly assigned to two groups (ketamine and control). After the animals were anesthetized, lumbar epidural catheters were placed for repeated epidural drug delivery. The ketamine group received 1% ketamine with preservative benzethonium chloride (0.5 ml) and the control group received isotonic saline (0.5 ml) once a day for 14 consecutive days. The day after the last injection, the animals were reanaesthetized, the left and right ventricles were cannulated and perfused with 2% glutaraldehyde, 1% formaldehyde mixture, in 0.1 mol/l phosphate buffer. Then, laminectomy was performed. A five centimetre segment of the spinal cord was removed and examined by light and electron microscopy to observe possible histological changes. Microscopic examinations were performed by coding each animal by a neuro-histologist who was blinded as to the source of each specimen. Results: Ketamine-treated rabbits showed significant histological changes at light and electron microscopy findings compared with the control group (p < 0.05). Conclusions: These changes suggested a neurotoxic effect of ketamine with preservative benzethonium chloride following chronic epidural administration