Neurotoxicity of subarachnoid preservative-free S(+)-ketamine in dogs

Subarachnoid S(+)-ketamine is a matter of much debate as the results regarding its toxicity are contradictory.

Our objective was to investigate possible histopathological alterations after subarachnoid administration of different doses of preservative-free S(+)-ketamine to dogs.

A randomized, blind, prospective experimental study.

Center for Research on Pain at the Federal University of Maranhão, Brazil.

Sixteen adult mongrel dogs of both sexes, each weighing 11 to 20 kg were divided into 3 groups: Group I (n=6), 0.7 mg/kg-1 S(+)-ketamine; Group II (n=6), 0.5 mg/kg-1 S(+)-ketamine, and a control group, Group III, (n=4), 0.9% NaCl. All substances were administered in one mL volume doses. The animals were kept in captivity for 2 weeks; after this period, they were put down and lumbar and sacral portions of the spinal cords were removed for histological examination using conventional light microscopy.

There were histological alterations in the spinal cords of the test subjects in the control group. Comparison showed significant histological abnormalities in Groups I and II when compared to the control group, including gliosis, axonal edema, central chromatolysis, lymphocyte infiltration and fibrous thickening of the dura mater.

Test subjects received only a single dose each. The observation period was not very long, less than a month.

Subarachnoid administration of S(+)-ketamine without preservative caused histological lesions on the spinal cord and meninges in the dogs studied. S(+)-ketamine should not be given to clinical patients in this way until further evaluation of the significance of this toxicity has been conducted.