Histopathology after repeated intrathecal injections of preservative-free ketamine in the rabbit: a light and electron microscopic examination.

Epidural and spinal administration of ketamine has been used in humans. Single-dose studies have shown that preservative-free ketamine lacks neurotoxic effects, but there are no studies after repeated administrations. The aim of this study was to examine the effects of daily administration of preservative-free ketamine. Fourteen New Zealand albino rabbits were assigned to two groups receiving either intrathecal preservative-free ketamine 5 mg, 0.5 mL 1% solution (eight rabbits) or saline 0.5 mL (six rabbits) once a day for 14 consecutive days. The rabbits had a total subcutaneous implanted intrathecal catheter, which was introduced during general anesthesia. On Day 15 the rabbits were anesthetized and in vivo fixated by transcardial perfusion with Tyrode's solution followed by a mixture of 2% glutaraldehyde and 1% formaldehyde in a 0.1 mol/L phosphate buffer. A segment 5 cm on each side of the catheter tip was removed and kept in a cold solution of the fixative. Light microscopic, electron microscopic, and morphometric examinations showed no differences between the spinal cords from the rabbits injected with ketamine versus saline. Intrathecal ketamine produced motor impairment for a period of 15 min. We conclude that repeated intrathecal administration of preservative-free ketamine confirms the lack of neurotoxicity from single-dose studies.