RESUMO
To determine whether daily intraventricular injection of gentamicin sulfate is ototoxic, adult male rabbits were given 0.2 ml of saline (group 1; n = 8) or 0.25 mg/kg of gentamicin sulfate in 0.2 ml of saline (group 2; n = 7) by intraventricular infusion once a day for 21 d. All rabbits were also given intramuscular gentamicin sulfate, 2 mg/kg, twice daily. Before and after antibiotic treatment, brainstem auditory evoked responses (BAERs) were recorded. During the experimental period, neurologic examinations were performed on all rabbits. After treatment, the animals were euthanized; brain tissue and cochleas were then removed for histopathologic examination. The ratios of neurologic abnormalities observed in group 1 and 2 animals, respectively, were 0/8 and 5/7; of abnormal BAERs, 0/8 and 5/7; of abnormal brain morphology, 2/5 and 6/6; and of abnormal cochlear morphology, 0/6 and 7/7. The electrophysiologic evidence of auditory deficit and the structural evidence of ototoxic insult are significantly associated (p less than or equal to 0.006) with intraventricularly administered gentamicin sulfate. These data suggest that intraventricular gentamicin should be used with caution.
Assuntos
Tronco Encefálico/efeitos dos fármacos , Potenciais Evocados Auditivos/efeitos dos fármacos , Gentamicinas/toxicidade , Células Ciliadas Auditivas/efeitos dos fármacos , Animais , Comportamento Animal/efeitos dos fármacos , Encéfalo/patologia , Células Ciliadas Auditivas/ultraestrutura , Injeções Intraventriculares , Masculino , CoelhosRESUMO
To determine whether daily intraventricular injection of gentamicin sulfate would cause neurologic or morphologic abnormalities of the central nervous system, adult male rabbits were given gentamicin sulfate, 2 mg/kg, intramuscularly twice a day plus saline, 0.2 ml (group 1), or gentamicin, 0.05 mg/kg (group 2), 0.25 mg/kg (group 3), or 0.5 mg/kg (group 4), given as the sulfate intraventricularly once a day. The majority of the animals in group 4 developed neurologic abnormalities which progressed to death in animals that were not euthanized; neuropathologic studies revealed chemical ventriculitis and meningitis that were associated with high levels of gentamicin in the cerebrospinal fluid and tissue of the central nervous system. Similar neurologic and morphologic changes were seen in most animals of group 3 but not in rabbits of groups 1 and 2. The ototoxicity and nephrotoxicity of gentamicin are well known; these data indicate that it may be toxic to the central nervous system as well.