To determine whether an enrofloxacin–silver sulfadiazine emulsion (ESS) labeled for treatment of otitis externa in dogs has ototoxic effects in rabbits following myringotomy.
6 healthy adult New Zealand White rabbits.
Rabbits were anesthetized for brainstem auditory-evoked response (BAER) tests on day 0. Myringotomy was performed, and BAER testing was repeated. Saline (0.9% NaCl) solution and ESS were then instilled in the left and right middle ears, respectively, and BAER testing was repeated prior to recovery of rabbits from anesthesia. Application of assigned treatments was continued every 12 hours for 7 days, and rabbits were anesthetized for BAER testing on day 8. Rabbits were euthanized, and samples were collected for histologic (6 ears/treatment) and scanning electron microscopic (1 ear/treatment) examination.
Most hearing thresholds (11/12 ears) were subjectively increased after myringotomy, with BAER measurements ranging from 30 to 85 dB in both ears. All day 8 hearing thresholds exceeded baseline (premyringotomy) values; results ranged from 30 to 85 dB and 80 to > 95 dB (the upper test limit) in saline solution–treated and ESS-treated ears, respectively. All ESS-treated ears had heterophilic otitis externa, epithelial hyperplasia of the external ear canal, various degrees of mucoperiosteal edema, and periosteal new bone formation on histologic examination. Scanning electron microscopy revealed that most outer hair cells in the ESS-treated ear lacked stereocilia or were absent.
CONCLUSIONS AND CLINICAL RELEVANCE
Results supported that ESS has ototoxic effects in the middle ear of rabbits. Further research is needed to confirm these findings. Myringotomized laboratory rabbits may be useful to study ototoxicity of drugs used in human medicine.
3 dogs were examined because of a sudden onset of signs of pain (1 dog) or paraparesis (2 dogs).
Neurologic findings consisted of myelopathy affecting the lumbar intumescence (1 dog) and T3-L3 myelopathy (2 dogs). In all dogs, MRI revealed spinal cord compression caused by L3-4 disk herniation. All dogs underwent routine surgical decompression of the intervertebral disk herniation. During MRI and decompressive surgery, physiologic variables were monitored. Immediately after surgery, all dogs were paraplegic with pelvic limb neurologic dysfunction consistent with myelopathy affecting the L4 through caudal spinal cord segments.
TREATMENT AND OUTCOME
Within 24 hours after surgery, repeated MRI in all dogs revealed hyperintensity in the spinal cord gray matter of the lumbar intumescence on T2-weighted images. In the absence of neurologic improvement, dogs were euthanized at 3, 91, and 34 days after surgery. Postmortem microscopic examination of each dog's spinal cord at the lumbar intumescence revealed necrosis of the gray matter with relative white matter preservation suggestive of an ischemic injury.
Dramatic neurologic deterioration following decompressive surgery for intervertebral disk herniation in dogs may be associated with the development of poliomyelomalacia secondary to ischemia. In these 3 dogs, ischemia developed despite probable maintenance of normal spinal cord blood flow and perfusion during anesthesia. To exclude other causes, such as compression or hemorrhage, MRI was repeated and revealed hyperintensity of the spinal cord gray matter on T2-weighted images, which microscopically corresponded with ischemic neurons and neuronal loss.