RESUMO
BACKGROUND: Ketamine and S(+)-ketamine have been advocated for neuraxial use in the management of postoperative pain and severe intractable pain syndromes unresponsive to opioid escalation. Although clinical experience has accumulated with S(+)-ketamine, safety data on toxicity in the central nervous system after neuraxial administration of S(+)-ketamine are conflicting. In this study, neurologic and toxicologic effects on the spinal cord from repeated daily intrathecal administration of commercially available, preservative-free S(+)-ketamine were evaluated against placebo in a randomized, blinded design. METHODS: Eighteen white New Zealand rabbits were assigned to two groups receiving either 0.5 ml intrathecal S(+)-ketamine, 0.5% solution (12 rabbits), or 0.5 ml saline (6 rabbits) once a day for 7 consecutive days. During general anesthesia, an intrathecal catheter was placed between the fifth and sixth spinous processes (lumbar). Neurologic (according to Tarlov criteria) and histopathologic assessments were performed after 7 days of treatment. RESULTS: Postmortem investigation of the spinal cord and nerve roots revealed histopathologic lesions suggestive of toxic damage in 11 rabbits, from the group of 12 animals receiving S(+)-ketamine. These results were significantly different compared with 5 control animals (no histologic changes observed). There was no significant difference in neurologic status between the two groups after 7 days of intrathecal treatment. CONCLUSIONS: The authors conclude that repeated intrathecal administration of preservative-free S(+)-ketamine in a clinically relevant concentration and dosage has, considering the extent and severity of the lesions, a toxic effect on the central nervous system of rabbits.
Assuntos
Anestésicos Dissociativos/toxicidade , Antagonistas de Aminoácidos Excitatórios/toxicidade , Ketamina/toxicidade , Doenças da Medula Espinal/induzido quimicamente , Raquianestesia , Anestésicos Dissociativos/administração & dosagem , Animais , Antagonistas de Aminoácidos Excitatórios/administração & dosagem , Feminino , Injeções Espinhais , Ketamina/administração & dosagem , Transtornos dos Movimentos/etiologia , Transtornos dos Movimentos/fisiopatologia , Coelhos , Medula Espinal/patologia , Doenças da Medula Espinal/patologia , EstereoisomerismoAssuntos
Clonidina/administração & dosagem , Bombas de Infusão , Meperidina/administração & dosagem , Meperidina/química , Neoplasias/complicações , Dor/tratamento farmacológico , Analgésicos/administração & dosagem , Analgésicos/química , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/química , Clonidina/química , Misturas Complexas/administração & dosagem , Misturas Complexas/química , Combinação de Medicamentos , Estabilidade de Medicamentos , Humanos , Neoplasias/tratamento farmacológico , Dor/etiologia , SíndromeRESUMO
IMPLICATIONS: Neuropathic cancer pain caused by tumor infiltration in the sacral plexus is primarily treated by nonsteroidal antiinflammatory drugs, antidepressants, anticonvulsants, and opioids. In one patient with severe pain despite pharmacotherapy, a catheter for the continuous administration of local anesthetics was inserted along the first sacral root, resulting in markedly improved analgesia.