Subarachnoid ketamine in swine - Pathological findings after repeated doses: Acute toxicity study

Background and Objectives. The purpose of this study was to investigate whe ther 5% ketamine with and without preservative, administered intrathecally to swine, produced a clinical anesthetic effect and caused direct subacute neurotoxicity. Methods. Twenty pigs were used. Under general anesthesia, a subarachnoid catheter was placed at L5-L6 or L6-S1 spinal interspace. Five animals were used for initial clinical evaluation of the anesthetic effects of subarachnoid ketamine (12.5 and 25.0, and 500 mg). Two animals were exc luded because of bloody taps, two served as controls (catheterization witho ut drug administration), four received ketamine racemate (25.0 mg/d), four received ketamine racemate preservative free (25.0 mg/d), and three receive d benzethonium chloride, the ketamine excipient (0.05 mg/d). All drugs were administered for 7 days. The catheters were withdrawn at the end of the tr eatment period. Alter 35 days, the pigs were euthanized and the spinal cord removed and preserved for histopathologic study with hematoxilyn-eosin and luxol-fast blue myelin staining. Histopathologic effects were defined as a bsent/minimal mild. or severe by a pathologist, unaware of group allocation , by evaluating the presence and intensity of peripheral and/or central chr omatolysis, spongiosis, neuronal loss, perivascular neuroglia, neuronolysis , and myelin degeneration. Results. All doses of ketamine produced immediat e cutaneous anesthesia and motor block; benzethonium chloride did not. Hist opathologic examination showed no neurotoxic effect of ketamine without pre servative; ketamine with preservative showed a discrete neurotoxic effect, and the preservative alone produced a moderate neurotoxic effect. Conclusio ns. Clinically, in swine, subarachnoid ketamine without preservative is a s afe and effective anesthetic and did not show significant neurotoxic effect s. However, ketamine with preservative produces minimal changes, and benzet honium chloride alone produces moderate neurotoxic effects.