Subarachnoid ketamine in swine--pathological findings after repeated doses: acute toxicity study.
OBJECTIVE
The purpose of this study was to investigate whether 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 excluded because of bloody taps, two served as controls (catheterization without drug administration), four received ketamine racemate (25.0 mg/d), four received ketamine racemate preservative free (25.0 mg/d), and three received 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 The catheters were withdrawn at the end of the treatment period. After 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 absent/minimal, mild, or severe by a pathologist, unaware of group allocation, by evaluating the presence and intensity of peripheral and/or central chromatolysis, spongiosis, neuronal loss, perivascular neuroglia, neuronolysis, and myelin degeneration.


RESULTS
All doses of ketamine produced immediate cutaneous anesthesia and motor block; benzethonium chloride did not. Histopathologic examination showed no neurotoxic effect of ketamine without preservative; ketamine with preservative showed a discrete neurotoxic effect, and the preservative alone produced a moderate neurotoxic effect.


CONCLUSIONS
Clinically, in swine, subarachnoid ketamine without preservative is a safe and effective anesthetic and did not show significant neurotoxic effects. However, ketamine with preservative produces minimal changes, and benzethonium chloride alone produces moderate neurotoxic effects.
Errando
C L
CL
Servicio de Anestesiología, Reanimación y Tratamiento del Dolor, Centro de Investigación, Hospital General Universitario, Valencia, Spain. errando@ctv.es
Sifre
C
C
Moliner
S
S
Valía
J C
JC
Gimeno
O
O
Mínguez
A
A
Boils
P
P
D000698:Analgesia / Q000009:adverse effects / Q000379:methods; D000700:Analgesics / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D000891:Anti-Infective Agents, Local / Q000008:administration & dosage / Q000633:toxicity; D001558:Benzethonium / Q000008:administration & dosage / Q000633:toxicity; D002404:Catheterization / Q000379:methods; D004334:Drug Administration Schedule; D005260:Female; D007649:Ketamine / Q000008:administration & dosage / Q000633:toxicity*; D008297:Male; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology; D013346:Subarachnoid Space; D013552:Swine
D000700:Analgesics; D000891:Anti-Infective Agents, Local; D001558:Benzethonium; D007649:Ketamine