Fm. Borgbjerg et al., HISTOPATHOLOGY AFTER REPEATED INTRATHECAL INJECTIONS OF PRESERVATIVE-FREE KETAMINE IN THE RABBIT - A LIGHT AND ELECTRON-MICROSCOPIC EXAMINATION, Anesthesia and analgesia, 79(1), 1994, pp. 105-111
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 administr
ations. The aim of this study was to examine the effects of daily admi
nistration of preservative-free ketamine. Fourteen New Zealand albino
rabbits were assigned to two groups receiving either intrathecal prese
rvative-free ketamine 5 mg, 0.5 mt 1% solution (eight rabbits) or sali
ne 0.5 mt (six rabbits) once a day for 14 consecutive days. The rabbit
s had a total subcutaneous implanted intrathecal catheter, which was i
ntroduced during general anesthesia. On Day 15 the rabbits were anesth
etized and in vivo fixated by transcardial perfusion with Tyrode's sol
ution followed by a mixture of 2% glutaraldehyde and 1% formaldehyde i
n a 0.1 mol/L phosphate buffer. A segment 5 cm on each side of the cat
heter tip was removed and kept in a cold solution of the fixative. Lig
ht microscopic, electron microscopic, and morphometric examinations sh
owed no differences between the spinal cords from the rabbits injected
with ketamine versus saline. Intrathecal ketamine produced motor impa
irment for a period of 15 min. We conclude that repeated intrathecal a
dministration of preservative-free ketamine confirms the lack of neuro
toxicity from single-dose studies.