Hearing Preservation After Penetrating Cochlear Injury.

OBJECTIVES: To share results and recommendations for management of penetrating cochlear injury. METHODS: A patient underwent repair of a penetrating cochlear injury after a projectile led to a traumatic cochleostomy with a narrow miss of the facial nerve and intracranial carotid artery. RESULTS: Postoperatively, the patient's audiogram demonstrated a pure tone average of 47.5 dB for air conduction and 35 dB for bone conduction, worse in the high frequencies, with a Word Recognition Score of 76%. CONCLUSIONS: Hearing loss from a penetrating cochlear injury can be mitigated with early repair, minimizing inner ear trauma, and steroid use to treat posttraumatic labyrinthitis.

Preventing labyrinthitis ossificans: the role of steroids.

OBJECTIVE: To identify a possible relationship between the administration of steroids at the time of diagnosis of bacterial meningitis and the development of labyrinthitis ossificans. DESIGN: Retrospective analysis of the charts of 38 children requiring cochlear implantation who presented with bacterial meningitis and then developed bilateral profound deafness. The patients' charts were reviewed for age at diagnosis, the type of antibiotic administered, and the administration, dosage, and duration of steroid (dexamethasone) therapy. Labyrinthitis ossificans was established by preoperative computed tomographic and/or magnetic resonance imaging and by the intraoperative findings as described in the operative report. PATIENTS AND METHODS: Patients were 38 children who received cochlear implantation by a single senior otolaryngologist for bacterial meningitis-related deafness. Ten patients' charts (26%) were available for full review; 9 of these 10 patients had documented pneumococcal meningitis and the other patient had Haemophilus influenzae-type meningitis. RESULTS: One of the 6 patients who received steroid therapy at the time of initial illness had documented evidence of labyrinthitis ossificans either radiographically or at the time of surgery. All 4 patients who failed to receive steroid therapy developed labyrinthitis ossificans. The results achieve statistical significance by chi2 analysis and a t test (P<.01). CONCLUSION: The results of this retrospective study are highly suggestive of a role for steroids in preventing the development of labyrinthitis ossificans in children with pneumococcal meningitis.

Antibiotic prophylaxis in clean and clean-contaminated ear surgery.

BACKGROUND: Ear surgery may be performed in the treatment of chronic otitis media, ossicular chain disorders, tympanic membrane perforations and otitis media with effusion. Postoperative infection in ear surgery may result in: Wound infections Infection of the middle ear or mastoid resulting in discharge from the ear canal Failure of the tympanic membrane to close Labyrinthitis due to infection in, or adjacent to, the inner ear These complications may be associated with discomfort and inconvenience for the patient, an increase in morbidity and an increase in the costs of medical care. OBJECTIVES: The objective of this review was to assess the effects of local and/or systemic antibiotics for preventing complications such as postoperative discharge, graft failure and labyrinthitis in patients undergoing clean or clean-contaminated ear surgery. SEARCH STRATEGY: We searched MEDLINE (searched January 1966 to December 2002), EMBASE (searched January 1980 to December 2002), the Science Citation Index, The Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane Library, Issue 4 2002); the Cochrane Acute Respiratory Infections Group and Cochrane Ear, Nose and Throat Group Specialised Registers and proceedings of scientific meetings. The date of the last search was December 2002. We also contacted investigators in the field (Govaerts, Antwerp). Bibliographies of identified articles were screened for further relevant trials. No language restriction was applied. SELECTION CRITERIA: Randomised or quasi-randomised trials involving: PARTICIPANTS: patients undergoing clean or clean-contaminated types of ear surgery. Skull base surgery was excluded. INTERVENTION: any regimen of local and/or systemic antibiotic prophylaxis administered at or around the time of surgery compared to placebo, no antibiotic, or an alternative intervention group. OUTCOME MEASURES: infection, discharge, graft failure, labyrinthitis, adverse effects of prophylaxis. DATA COLLECTION AND ANALYSIS: When possible, investigators were contacted for additional information on data and methodological issues. At least two reviewers independently extracted data and assessed trial quality. MAIN RESULTS: Eleven studies were included in the review. The methodological quality of the trials was fair to good. However, most studies presented insufficient detail on methodological data. Although definitions of outcome measures were heterogeneous, pooling of results was possible. There were no significant differences between antibiotic prophylaxis groups and control groups in terms of reduction of postoperative infections, graft failures, draining outer ear canals and adverse drug effects. REVIEWERS' CONCLUSIONS: There is no strong evidence that the large scale use of prophylactic of antibiotics in clean and clean-contaminated ear surgery is helpful in reducing postoperative complications such as wound infection, discharge from the outer ear canal, labyrinthitis and graft failure.

Comparative perilymph permeability of cephalosporins and its significance in the treatment and prevention of suppurative labyrinthitis.

Cephalosporins are nonototoxic antibiotics that provide excellent coverage for almost all bacteria that can cause suppurative labyrinthitis. In this study we performed comparative perilymph permeability determinations of the three cephalosporins that we deemed to have the most clinical potential in these varied situations. Perilymph pharmacokinetic profiles were established for ceftazidime, cefuroxime, and cefotaxime and its metabolite desacetylcefotaxime in 36 guinea pigs by using the technique of high-performance liquid chromatography. At 1, 2, 3, 4, and 6 hours after intravenous administration of the three cephalosporins at a dose of 100 mg/kg of body weight, ceftazidime consistently exhibited the highest perilymph concentration. Desacetylcefotaxime showed the next highest capacity for penetration into perilymph. Keeping in mind that the choice of drug for the treatment of suppurative labyrinthitis should be based foremost on culture and sensitivity studies, we consider ceftazidime to be the first-line agent for treatment and prevention of both meningogenic labyrinthitis and labyrinthitis complicating acute or chronic otitis media.

ALH-L1005 attenuates endotoxin induced inner ear damage.

OBJECTIVE: To assess whether this compound (ALH-L1005) is conceivably an effective agent in protecting against cochlear damage induced by LPS. MATERIALS AND METHODS: Tube formation using human umbilical vein endothelial cell (HUVEC) and matrix metalloproteinase (MMP)-9 inhibition assay was performed. 24 guinea pigs were randomly divided into three groups. Intratympanic instillation of LPS (n=8) as negative control, instillation of oxytetracycline 1h after LPS as positive control (n=8), and intratympanic instillation of ALH-L1005 (n=8) 1h after LPS were considered experimental group. Evaluation by auditory brainstem response (ABR) measurement, cochlear blood flow, and blood-labyrinth barrier (BLB) permeability were performed. Cochlear hair cells were observed by field emission-scanning electron microscopy (FE-SEM). MMP-9 activation was measured by gelatin zymography. RESULTS: For HUVEC, the tube formation was suppressed in a dose dependant manner. ALH-L1005 inhibited the MMP-9 activity prominently. It also attenuated the elevation of LPS-induced hearing threshold shift and recovery of CBF. By FE-SEM, cochlear hair cells could be preserved in experimental group. ALH-L1005 significantly reduced the BLB opening compared to LPS group. Active MMP-9 expression could be detected in the LPS group. In contrast to ALH-L1005 group, active MMP-9 expression was not detected. CONCLUSION: Our results conclude that ALH-L1005 showed a protective effect in the cochlear lateral wall damage induced by LPS.

Matrix metalloproteinase inhibitor attenuates cochlear lateral wall damage induced by intratympanic instillation of endotoxin.

OBJECTIVE: Oxytetracycline and ilomastat are inhibitors of matrix metalloproteinases (MMPs). Their efficacy in protecting against cochlear damage induced by the intratympanic instillation of lipopolysaccharide (LPS), as a means of inducing labyrinthitis, was investigated. MATERIALS AND METHODS: Experiments were performed in 21 young male guinea pigs. Intratympanic instillation of LPS was done in the control group (n=7). Intratympanic instillation of oxytetracycline or ilomastat was done after LPS instillation in the experimental group. Measurements of auditory brainstem response (ABR) and cochlear blood flow (CBF) were performed. The organ of Corti was evaluated by field emission scanning electron microscopy (FE-SEM). The blood-labyrinth barrier (BLB) integrity was evaluated with Evans blue uptake. Gelatin zymography was used to assess the expression of active MMP-2 and MMP-9. RESULTS: Ears treated with MMP inhibitors were significantly protected from hearing loss compared to the LPS group. In LPS group, there was a significant decrease of CBF. However, experimental group displayed a statistically significant recovery of CBF. FE-SEM revealed hair cell damage in the LPS-treated group, but hair cells presented a normal appearance in MMP inhibitors. The LPS group showed a marked increase of Evans blue extravasation in the cochlea. However, MMP inhibitors significantly reduced the BLB opening. Active MMP-9 was expressed in the LPS group. Treatment with MMP inhibitors attenuated active MMP-9 expression. CONCLUSION: The MMP inhibitors oxytetracycline and ilomastat protect from cochlear lateral wall damage caused by LPS-induced labyrinthitis.

Invasion of the inner ear by Haemophilus influenzae type b in experimental meningitis.

Bacterial interstrain variation for cochlear invasion was studied by intraperitoneal inoculation of infant rats with Haemophilus influenzae type b. Eight pairs of CSF isolates from children with or without deafness due to meningitis were injected into half of each litter in separate experiments. At 48 h, quantitative CSF culture results and CSF white blood cell counts were equivalent for the two groups. Organisms within the cochlea were detected in four of eight animals in each group. There was no difference between the deaf and nondeaf isolates in the degree or frequency of inner ear inflammation in formalin-fixed sections. In separate experiments, animals were inoculated with H. influenzae type b and 24 h later treated with ampicillin, or ampicillin plus dexamethasone. At 48 h, although CSF white blood cell counts were significantly reduced in the steroid group, no difference was noted in the degree of cochlear inflammation between the two groups. The ability of H. influenzae type b to invade the inner ear of infant rats does not correlate with the development of sensorineural deafness in children following H. influenzae type b meningitis. Steroid administration does not appear to diminish the inflammatory reaction within the cochlea more than antibiotics alone in this model, but may delay CSF sterilization by ampicillin.

Intratympanic immunosuppressives for prevention of immune-mediated sensorineural hearing loss.

HYPOTHESIS: Round window membrane application of immunosuppressives reduces cochlear inflammation and hearing loss in a guinea pig model of sterile labyrinthitis. BACKGROUND: Systemic immunosuppressives are used to treat sensorineural hearing loss due to inflammation (autoimmune, bacterial, viral), which in animal models causes hearing loss. Transtympanic application of drugs is an attractive and possibly efficacious method of treatment that avoids systemic toxicities. METHODS: Sterile labyrinthitis was created using keyhole limpet hemocyanin (KLH). Dexamethasone (0.048 mg/day and 0.288 mg/day), cyclosporine (0.5%), prednisolone acetate (1%), fluorouracil, (5%), and FK506 (0.01%) were delivered to the round window membrane with one injection (filling middle ear space) or osmotic minipumps. Efficacy was evaluated by auditory brainstem response and histology. RESULTS: No drug was effective at reducing hearing loss or inflammation. CONCLUSION: Local application of immunosuppressives did not suppress inner ear inflammatory infiltrates and hearing loss in KLH-induced labyrinthitis in a guinea pig model.

Ganciclovir prophylaxis for cochlear pathophysiology during experimental guinea pig cytomegalovirus labyrinthitis.

The effectiveness of the antiviral agent ganciclovir (9-[1,3-dihydroxy-2-propoxymethyl]guanine) against guinea pig cytomegalovirus was tested in vitro in guinea pig embryonic fibroblasts and in vivo in an experimental guinea pig cytomegalovirus labyrinthitis model. In vitro, ganciclovir completely prevented guinea pig cytomegalovirus infection of guinea pig embryonic fibroblasts at concentrations above 32.6 micrograms/ml. In vivo, antibody-negative animals had an average 17-dB elevation in their auditory nerve compound action potential thresholds (P less than 0.01, t test) and showed signs bilaterally of guinea pig cytomegalovirus labyrinthitis 8 days after intrathecal inoculation of virus. Ganciclovir administration starting 1 day before inoculation prevented the development of both cochlear histopathologic change and hearing loss. Guinea pig cytomegalovirus meningitis was observed in both the drug-treated and untreated groups. High-pressure liquid chromatography confirmed the presence of ganciclovir in the serum, perilymph, and cerebrospinal fluid of the drug recipients. Prophylactic ganciclovir thus can protect the cochlea from the histopathologic changes and hearing loss normally associated with experimental guinea pig cytomegalovirus labyrinthitis.