Intra-cochlear Flushing Reduces Tissue Response to Cochlear Implantation.

INTRODUCTION: Intraoperative trauma leading to bleeding during cochlear implantation negatively impacts residual hearing of cochlear implant recipients. There are no clinical protocols for the removal of blood during implantation, to reduce the consequential effects such as inflammation and fibrosis which adversely affect cochlear health and residual hearing. This preclinical study investigated the implementation of an intra-cochlear flushing protocol for the removal of blood. METHODS: Three groups of guinea pigs were studied for 28 days after cochlear implantation; cochlear implant-only (control group); cochlear implant with blood injected into the cochlea (blood group); and cochlear implant, blood injection, and flushing of the blood from the cochlea intraoperatively (flush group). Auditory brainstem responses (ABRs) in addition to tissue response volumes were analyzed and compared between groups. RESULTS: After implantation, the blood group exhibited the highest ABR thresholds when compared to the control and flush group, particularly in the high frequencies. On the final day, the control and blood group had similar ABR thresholds across all frequencies tested, whereas the flush group had the lowest thresholds, significantly lower at 24 kHz than the blood and control group. Analysis of the tissue response showed the flush group had significantly lower tissue responses in the basal half of the array when compared with the blood and control group. CONCLUSIONS: Flushing intra-cochlear blood during surgery resulted in better auditory function and reduced subsequent fibrosis in the basal region of the cochlea. This finding prompts the implementation of a flushing protocol in clinical cochlear implantation. LEVEL OF EVIDENCE: N/A Laryngoscope, 134:1410-1416, 2024.

Protecting against electrode insertion trauma using dexamethasone.

OBJECTIVE: To compare the benefits of a dexamethasone-eluting array for hearing preservation and cochlear histopathology in low trauma (soft-surgery) and high trauma models of cochlear implant surgery. METHODS: Adult guinea pigs were implanted with an intra-cochlear array using two different surgical procedures: either a soft-surgery approach or following generation of electrode insertion trauma (high trauma). Two methods of dexamethasone delivery were evaluated: elution from an electrode array alone, and elution from a cochlear implant electrode array in combination with a pre-operative systemic injection. All electrode arrays were implanted for a period of 4 weeks. Outcome measures at 4 weeks post-implantation included auditory brainstem response (ABR) thresholds, histological analysis of spiral ganglion neuron density, fibrotic tissue, new bone growth, and cochlear damage. RESULTS: Animals exposed to high surgical trauma showed greater hearing loss than those in the low trauma model, irrespective of the presence of dexamethasone. Whilst the area of intra-cochlear fibrotic tissue growth post-implantation was also independent of dexamethasone administration, new bone growth was significantly reduced in its presence. Our high trauma model effectively obliterated the organ of Corti and significantly reduced spiral ganglion neuron densities in the lower basal turn. This trauma-induced reduction in spiral ganglion neuron survival decreased with the inclusion of a dexamethasone-eluting array. A pre-operative systemic injection of dexamethasone did not significantly improve any outcome measures beyond those provided with a dexamethasone-eluting array alone. CONCLUSION: Dexamethasone-eluting intra-cochlear arrays may inhibit osteoneogenesis, and reduce spiral ganglion neuron loss following traumatic cochlear implantation.

Meningitis and a safe dexamethasone-eluting intracochlear electrode array.

OBJECTIVES: To evaluate the potential risk of pneumococcal meningitis associated with the use of a dexamethasone-eluting intracochlear electrode array as compared with a control array. METHODS: In two phases, adult Hooded-Wistar rats were implanted via the middle ear with an intracochlear array and were inoculated with Streptococcus pneumoniae 5 days post-surgery. Phase I created a dosing curve by implanting five groups (n = 6) with a control array, then inoculating 5 days later with different numbers of S. pneumoniae: 0 CFU, 10(3) CFU, 10(4) CFU, 10(4) CFU repeated, or 10(5) CFU (colony forming units). A target infection rate of 20% was aimed for and 10(4) CFU was the closest to this target with 33% infection rate. In phase II, we implanted two groups (n = 10), one with a dexamethasone-eluting array, the other a control array, and both groups were inoculated with 10(4) CFU of S. pneumoniae 5 days post-surgery. RESULTS: The dexamethasone-eluting array group had a 40% infection rate; the control array group had a 60% infection rate. This difference was not statistically significant with a P value of ≥0.5. CONCLUSION: The use of a dexamethasone-eluting intracochlear electrode array did not increase the risk of meningitis in rats when inoculated with S. pneumoniae via the middle ear 5 days following implantation.

Development of a safe dexamethasone-eluting electrode array for cochlear implantation.

OBJECTIVES: Cochlear implantation can result in trauma leading to increased tissue response and loss of residual hearing. A single intratympanic application of the corticosteroid dexamethasone is sometimes used clinically during surgery to combat the potential effect of trauma on residual hearing. This project looked at the safety and efficacy of dexamethasone eluted from an intracochlear array in vivo. METHODS: Three trials were conducted using normal hearing adult guinea pigs implanted with successive iterations of dexamethasone-eluting (DX1, DX2, and DX3) or non-eluting (control) intracochlear electrode arrays. The experimental period for each animal was 90 days during which hearing tests were performed at multiple time points. RESULTS: There was no significant difference between matched control array and dexamethasone array groups in terms of spiral ganglion neuron density, organ of Corti condition, or fibrosis and ossification. A cochleostomy seal was present in all implanted cochleae. There were no differences in the degree of hearing threshold shifts between DX1 and DX3 and their respective control arrays. Cochleae implanted with DX2 arrays showed less hearing loss and marginally better spiral ganglion neuron survival than their control array counterparts. Post-explant inspection of the DX2 and DX3 arrays revealed a difference in pore density following dexamethasone elution. CONCLUSION: The dexamethasone doses used were safe in the guinea pig cochlea. Dexamethasone did not inhibit formation of a cochleostomy seal. The level of hearing protection afforded by dexamethasone eluting from an intracochlear array may depend upon the degree of elution and level of trauma inflicted.

Effects of steroids and lubricants on electrical impedance and tissue response following cochlear implantation.

The present study examined the effects of steroids and lubricants on electrical impedance and tissue response following cochlear implantation in animal models. Guinea pigs were implanted following either no treatment, or intrascalar injection with dexamethasone, triamcinolone, sodium hyaluronate or saline. Cats were implanted following either no treatment, or intrascalar injection with dexamethasone, triamcinolone or a mixture of triamcinolone with sodium hyaluronate. In guinea pigs, impedance changes and intracochlear tissue response were less for the hyaluronate and saline groups. In cats, impedance in the dexamethasone group increased similar to non-treated cats. Impedance of triamcinolone treated cats remained low for about two months after implantation, before increasing to levels similar to the other groups. Significant fibrous tissue growth was observed histologically. The results of the present study indicate that a single intracochlear application of hyaluronate or triamcinolone may postpone, but will ultimately not prevent the rise in impedance following cochlear implantation.