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

Background: Subarachnoid S(+)-ketamine is a matter of much debate as the results regarding its toxicity are contradictory. Objectives: Our objective was to investigate possible histopathological alterations after subarachnoid administration of different doses of preservative-free S(+)-ketamine to dogs. Study design: A randomized, blind, prospective experimental study. Setting: Center for Research on Pain at the Federal University of Maranhao, Brazil. Methods: 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 Ill, (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. Results: 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. Limitations: Test subjects received only a single dose each. The observation period was not very long, less than a month. Conclusions: 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.