Ototoxicity of otic drops applied to the middle ear in the chinchilla

Previous studies have shown that the application of topical otic drops to the external ear canals of animals with patent tympanostomy tubes may result in hearing impairment and cochlear hair cell loss. Otic drops are used in patients with tympanostomy tubes or tympanic membrane perforations and could have deleterious effects on the human membranous labyrinth. This report describes the inner ear damage that occurred after direct application of aminoglycoside-containing otic drops to the middle ears of experimental animals. The membranous labyrinths of 25 chinchillas were studied two days to five months after application of Cortisporin otic suspension (which contains neomycin, polymyxin B, hydrocortisone, and propylene glycol) to the middle ear cavity. Application of 0.5 ml of Cortisporin resulted in degeneration of all inner and outer hair cells throughout the cochlea, as well as severe damage to the stria vascularis. Moderate to severe degeneration of the vestibular receptor organs was also observed. The endolymphatic sacs showed dark-staining endolymph, cellular debris, and macrophages in the sac lumina, as well as increased activity of the epithelial lining.     

Inflammatory effects of otic drops on the middle ear

Combination topical otic preparations are used to treat many infections of the external and middle ears. Despite the presence of ototoxic drugs in a number of these drops and convincing evidence of sensorineural hearing loss in humans and animal studies (Meyerhoff et al., presented at Southern Section Triological Meeting, Jan. 1983) following use of these medications, otic drops remain the cornerstone of treatment for many infectious disorders of the ear. Twelve chinchillas underwent bilateral tympanostomy tube placement and daily instillation of Cortisporin Otic Suspension (polymyxin B, neomycin, hydrocortisone, propylene glycol) in the right external auditory canal for 7 consecutive days. The animals were sacrificed 3 days later, 10 days following initiation of the Cortisporin Otic Suspension treatment. Following routine preparation of the temporal bones for light microscopy, the tissue was evaluated for evidence of inflammatory changes. All 12 animals demonstrated granulation tissue, effusion and focal hemorrhage in the ears subjected to the Cortisporin Otic Suspension. All of the contralateral control ears were normal. The present data suggest that this inflammatory response is due to a topical irritant effect of the otic preparation.     

Tympanostomy tubes and liquids--an in vitro study

Placement of tympanostomy tubes is the most frequently performed otolaryngologic procedure. The common practice is to forbid swimming and to recommend limitation of liquids entering the external auditory canal based upon the premise that liquids entering the external auditory canal will pass freely into the middle ear space via the tube and thus contaminate the space. Indeed, otologic medications (drops) are presumed and are observed to enter the middle ear space by this same route. The physical characteristics of the middle ear and drumhead with a tube in place were examined and a model constructed to test by observation these characteristics. Measurements of the surface tension of water, 2N saline, Cortisporin suspension ear drops, and soapy bath water were performed to provide a clinical correlate. The study implies that limitation of swimming activities or liquid exposure of the ear with a tympanostomy tube in all children may be inappropriate.     

Inflammatory effects of topical antibiotic suspensions containing propylene glycol in chinchilla middle ears

This study examines the occurrence of inflammatory changes and cholesteatoma in the middle ears of seven chinchillas after the application of topical antibiotic suspensions containing two different concentrations of propylene glycol. The preparations used were Cortisporin otic suspension, which contains neomycin, polymyxin B, hydrocortisone, and 10.5% propylene glycol, and Cortisporin ophthalmic suspension, containing the same ingredients, but only a 2% concentration of propylene glycol. Six weeks after the administration of the Cortisporin preparations, applied to the middle ear through a transbulla approach, no cholesteatomas were found in the seven ears treated with the ophthalmic suspension. Evidence of mild inflammation was present in only two of these ears. In the seven contralateral ears treated with the otic suspension, middle ear adhesions were found in six, cholesteatoma was present in four, serous effusions were found in three, and one had a large tympanic membrane perforation. The ears that showed cholesteatomas also had histologic evidence of squamous metaplasia, granulation tissue, and erosion of the underlying bone. We submit that the pathologic responses of the middle ear mucosa treated with the otic suspension, were due to an inflammatory response to the higher concentration of propylene glycol compared to that of the ophthalmic suspension.     

Effect of Cortisporin Otic Suspension on Cochlear Function and Efferent Activity in the Guinea Pig

To predict cochlear receptor cell insult from therapeutic aminoglycoside antibiotics, we sought to determine whether the presence of subtoxic concentrations of Cortisporin otic suspension in the cochlea can be detected by measuring changes in efferent suppression of compound action potentials recorded from the round window. Olivocochlear efferent suppression in an earlier study was reversibly inhibited by injections of gentamicin in guinea pigs. Using that same technique, we found that 2.0 μL of Cortisporin otic suspension (neomycin, polymyxin B, hydrocortisone) placed on the round window of guinea pigs in varying concentrations causes a rapid, permanent alteration in thresholds. Solutions of Cortisporin otic suspension diluted to a concentration of 1:20 yield a reversible loss of efferent suppression without measurable changes in compound action potential. These data suggest that the presence of Cortisporin otic suspension can be detected functionally in the cochlea at very low concentrations prior to the development of a threshold shift.     

Effects of common topical otic preparations on the morphology of isolated cochlear outer hair cells

Otic drops are commonly used not only for otitis externa but also for otorrhea in the presence of tympanostomy tube or tympanic membrane perforation. Many studies have demonstrated the ototoxicity of common otic preparations such as Cortisporin otic drops. Recent studies have suggested the use of fluoroquinolone antibiotic drops as an alternative owing to their excellent antimicrobial coverage and no ototoxic effect. The purpose of this study was to assess the relative ototoxicity of four common otic preparations by direct exposure to isolated cochlear outer hair cells (OHCs). OHCs from adult chinchilla cochlea were exposed to standard bathing solution (control), Cortisporin, Cipro HC, Ciloxan, and Floxin. The cells were observed using an inverted microscope, and the images recorded in digital still-frame and video, and analyzed on the Image Pro-Plus 3.0 program. As measured by time to cell death and change in morphology of OHCs, Cortisporin was most toxic to OHCs. Among the fluoroquinolone drops, Floxin was more toxic than Ciloxan or Cipro HC.     

Effect of artificial airway on ear complications from hyperbaric oxygen

Hyperbaric oxygen treatment is associated with an increased risk of barotrauma to the tympanic membrane and middle ear. An artificial airway may compromise normal eustachian tube function and equilibration of middle ear pressures. This retrospective study was designed to evaluate the risk of middle ear complications in 267 patients receiving hyperbaric oxygen (HBO) therapy and to compare those with and without artificial airways. Charts of all patients were reviewed for middle ear and tympanic membrane complications and myringotomy tube placement. Eighteen of the 267 patients had artificial airways. Seventeen (94%) of these 18 patients developed middle ear or tympanic membrane complications, and 11 (61%) required tympanostomy tubes for pain, hemo-tympanum, or serous otitis. In contrast, 114 (45.8%) of the 249 patients without airways developed ear complications, and 53 (21.3%) required tympanostomy tubes. These results suggest that patients with an artificial airway who are receiving HBO therapy are at greater risk for developing tympanic membrane and middle ear complications than nonintubated patients. Similarly, patients with artificial airways receiving HBO frequently require placement of tympanostomy tubes.     

A prospective study of infection following tympanostomy and tube insertion

An incidence of postoperative infection of up to 15 percent has been reported following middle ear ventilation tube surgery. This rate of complication would be considered unacceptable following most other operative procedures. A controlled prospective study of 107 children undergoing tympanostomy and tube surgery over a 1-year period was undertaken. Subjects were randomly assigned to receive antibiotic-steroid otic drops at the time of surgery and for 1 week afterward, oral ampicillin for 24 hours preceding and 3 days following surgery, or no prophylactic treatment. The overall infection rate within four weeks of surgery was 12 percent. Purulent otorrhea occurred in 18 percent of those receiving no prophylactic treatment, in 13 percent receiving ampicillin, and in 6 percent receiving antibiotic-steroid otic drops. Postoperative infection was related to preoperative history of status otitis media and to previous placement of ventilation tubes.     

Safety of ototopical antibiotics

A prospective randomized study analyzing the safety and efficacy of a single dose of ototopical antibiotics following human middle ear tympanostomy tube insertion was performed. Fifty children undergoing bilateral tympanostomy tube insertion were studied by the placement of 0.5 mL of Cortisporin Otic Suspension (COS; Burroughs Wellcome Co., Research Triangle Park, N.C.) to one middle ear space by random assignment. Preoperative and postoperative audiograms were obtained, and the presence of otorrhea was noted. In one patient sensorineural hearing loss of 6 dB developed bilaterally, which was symmetric in both the treated and the untreated ear. This preliminary study showed no statistical difference in hearing loss or postoperative otorrhea associated with a single application of Cortisporin to the middle ear space.     

Effects of Common Topical Otic Preparations on the Morphology of Isolated Cochlear Outer Hair Cells

Otic drops are commonly used not only for otitis externa but also for otorrhea in the presence of tympanostomy tube or tympanic membrane perforation. Many studies have demonstrated the ototoxicity of common otic preparations such as Cortisporin® otic drops. Recent studies have suggested the use of fluoroquinolone antibiotic drops as an alternative owing to their excellent antimicrobial coverage and no ototoxic effect. The purpose of this study was to assess the relative ototoxicity of four common otic preparations by direct exposure to isolated cochlear outer hair cells (OHCs). OHCs from adult chinchilla cochlea were exposed to standard bathing solution (control), Cortisporin, Cipro HC®, Ciloxan®, and Floxin®. The cells were observed using an inverted microscope, and the images recorded in digital still-frame and video, and analyzed on the Image Pro-Plus® 3.0 program. As measured by time to cell death and change in morphology of OHCs, Cortisporin was most toxic to OHCs. Among the fluoroquinolone drops, Floxin was more toxic than Ciloxan or Cipro HC.     

Is there an ototoxicity risk from Cortisporin and comparable otic suspensions? Distortion-product otoacoustic emission findings

The purpose of this investigation was to use distortion-product otoacoustic emission (DPOAE) testing to address the issue of possible ototoxicity from the use of neomycin/polymyxin B/hydrocortisone otic suspension following tympanostomy tube placement. We retrospectively reviewed our clinical records and identified 36 children (52 ears) who had met our three study criteria: (1) unilateral or bilateral placement of transtympanic ventilation tubes, (2) treatment for 3 to 5 days with neomycin/polymyxin B/hydrocortisone drops, and (3) postoperative evaluation by DPOAE testing. We identified another set of 36 children (52 ears) who had not received these drops and who had not undergone tube placement but who had been evaluated by DPOAE testing to serve as a control group. We found no significant differences in DPOAE amplitudes between the treatment and control groups. These findings are consistent with decades of clinical experience indicating that neomycin/polymyxin B/hydrocortisone otic suspension is safe when used responsibly.     

Middle ear cholesteatoma: an animal model

Topical otic preparations now in clinical use contain a variety of antibiotics and solvents that may produce severe inflammation if they reach the middle ear cavity. This report describes the response of the chinchilla middle ear to direct application of one such preparation that appears to act as a nonspecific irritant. Cortisporin otic suspension (containing neomycin, polymyxin B, hydrocortisone, and propylene glycol) was introduced into the bullae of 32 chinchillas that were kept alive for four days to five months before histologic examination of their temporal bones. All the experimental animals had tissue damage and inflammation within the middle ear. The changes observed included proliferation of ciliated and secretory columnar cells, formation of granulation tissue, bone erosion, and osteoneogenesis. Some areas of the mucosa underwent metaplasia to stratified squamous epithelium; this metaplastic epithelium, however, did not produce keratin. In the majority of animals kept for two months or more, cholesteatoma was identified in the middle ear. The cholesteatomas appeared to develop as a result of penetration of external canal epidermis through intact tympanic membranes or as the result of migration of epidermis through perforations. The experimental cholesteatomas behaved like those seen clinically in humans, with extensive erosion of bony structures within the middle ear.     

Laser eustachian tuboplasty: a preliminary report

OBJECTIVES/HYPOTHESIS: Surgical correction of eustachian tube dysfunction remains an elusive challenge. Repeat ventilation tube placement is often inadequate to prevent tympanic membrane and middle ear complications. Endoscopic analyses of eustachian tube dynamics have localized the site of primary pathophysiology to within the cartilaginous tube. The study investigated the feasibility, safety, and efficacy of a new endoluminal eustachian tube operation for the treatment of eustachian tube dysfunction. STUDY DESIGN: Prospective, institutional review board-approved surgical trial in a tertiary-care medical center. METHODS: Ten patients with more than 5 consecutive years of intractable otitis media with effusion recurring after two or more tympanostomy tube placements were treated with unilateral laser eustachian tuboplasty. Surgery was performed on an outpatient basis with the use of general anesthesia and combined both transnasal and transoral approaches. A 980-nm diode or argon laser was used to vaporize an appropriate amount of mucosa and cartilage on the posterior wall of the tubal lumen. Preoperative and postoperative dynamic video eustachian tube function analyses were compared. Outcome measures were presence or absence of middle ear effusion and impedance tympanograms. RESULTS: Five patients had at least 12 months of follow-up, and three of them had absence of any effusion (60%). Two patients had recurrence of their otitis media with effusion and required tympanostomy tubes again. Five patients had at least 6 months of follow-up, and four of them had absence of any effusion. The remaining patient had recurrence of otitis media with effusion and received a tympanostomy tube again. Overall results for all 10 patients after 6 months were 7 free of effusion (70%). There were no intraoperative complications. Postoperative complications were limited to minimal peritubal adhesions and one intranasal synechia. CONCLUSIONS: Preliminary results suggest that laser eustachian tuboplasty is safe and efficacious in the treatment of intractable eustachian tube dysfunction. Further study will be necessary to determine whether laser eustachian tuboplasty is a suitable alternative to repeated tympanostomy tube placement in selected patients.     

Hyperbaric oxygen therapy: effect on middle ear and eustachian tube function.

Hyperbaric oxygen therapy (HBO) involves intermittent inhalation of 100% oxygen under a pressure greater than 1 atm. It is an important mode of adjuvant therapy for disease processes such as decompression sickness, osteomyelitis, carbon monoxide poisoning, and poorly healing wounds. Patients undergoing this therapy often complain of ear pain and/or fullness which can be transient or long standing. This prospective study objectively measured the changes in eustachian tube function before and after HBO treatment in 33 adult patients by the 9-step inflation-deflation test described by Bluestone. The results show 15 of the 33 patients (45%) had evidence of eustachian tube dysfunction after treatment was initiated. Of these, 15 (100%) developed the sensation of fullness, 13 (87%) developed serous otitis media, and 7 (47%) required tympanostomy tubes. The overall incidence of middle ear problems was 27 patients (82%) experiencing a sensation of fullness, 17 (52%) developing serous otitis media, and 8 (24%) requiring tympanostomy tubes. The middle ear complications reported in this study are much higher than those in previous reports in the literature. Twelve of 33 patients presented with a subjective history of eustachian tube dysfunction, and all 12 (100%) developed fullness in their ears and serous otitis media during the course of the treatment. The findings reveal that patients manifesting eustachian tube dysfunction after their first HBO treatment were at significantly greater risk toward developing symptoms of fullness and serous otitis media, often requiring tympanostomy tube placement. In addition, a history of eustachian tube dysfunction accurately predicted the development of fullness and serous otitis media.     

Determination of ototoxicity of common otic drops using isolated cochlear outer hair cells.

OBJECTIVES: Otic drops are commonly used not only for otitis externa, but also for otorrhea in the presence of tympanostomy tubes or tympanic membrane perforations. Many studies have demonstrated the ototoxicity of common otic preparations such as Cortisporin otic drops (Monarch Pharmaceuticals, Bristol, TN). The purpose of this study was to assess the relative ototoxicity of common otic preparations by direct exposure to isolated cochlear outer hair cells (OHCs). METHODS: OHCs from adult chinchilla cochlea were exposed to standard bathing solution (control), acetic acid, Acetasol HC (Alpharma USPD Inc., Baltimore, MD), Gentacidin (CIBA Vision Ophthalmics, Atlanta, GA), and Tobradex (Alcon, Fort Worth, TX). The cells were observed using an inverted microscope, and the images were recorded in digital still-frame and video, and analyzed on the Image Pro-Plus 3.0 program (Media Cybernetics, Silver Spring, MD). RESULTS AND CONCLUSIONS: As measured by time to cell death and change in morphology of OHCs, acetic acid with or without hydrocortisone was most toxic to OHCs. Cortisporin was more cytotoxic than gentamicin and Tobradex.     

Implications of laser assisted tympanostomy in adults.

OBJECTIVES: To assess outcome in adult individuals undergoing laser-assisted tympanostomy without ventilation tube placement. STUDY DESIGN: Case series with 2-month follow-up. SETTING: Faculty practice, research protocol, tertiary care academic medical center. PATIENTS AND METHOD: Laser-assisted tympanostomy was performed on a total of 142 ears (108 individuals). Indications included serous otitis media with effusion (66 ears/47 patients), functional eustachian tube dysfunction (48 ears/36 patients), acute otitis media (19 ears/16 patients), and endoscopic visualization of the middle ear (9 ears/9 patients). INTERVENTION: The laser-assisted tympanostomy procedure is performed with a CO2 laser under local anesthesia on an outpatient basis. MAIN OUTCOME MEASURES: Patency time of the tympanostomy, presence of fluid after the closure of the tympanostomy, tympanometry and tone audiometry findings, relief of symptoms. RESULTS: Middle ear disease was resolved after the closure of tympanostomy in 47.9% of patients with serous otitis media with effusion. In 79.1% of patients with functional eustachian tube dysfunction, symptoms were diminished. All patients with acute otitis media had a satisfactory outcome. Laser-assisted tympanostomy was found to be quite helpful in patients undergoing middle ear endoscopy. CONCLUSIONS: Laser-assisted tympanostomy without ventilation tubes provides a safe alternative surgical option in adult patients in certain cases. The selection criteria for this procedure are addressed in detail.     

Tube patency: Is there a difference following otic drop administration?

Purpose

Many surgeons instill peri-operative otic drops to maintain tube patency. A post-hoc analysis of three randomized, controlled studies involving a one-time administration of ciprofloxacin (OTO-201) given instead of otic drops perioperatively was conducted to evaluate tube patency in patients who did and did not receive otic drops as defined within the study protocol.

局麻下咽鼓管球囊扩张术加鼓膜置管术治疗顽固性分泌性中耳炎

目的：探讨局麻下咽鼓管球囊扩张术加鼓膜置管术治疗顽固性分泌性中耳炎的临床疗效。方法收集顽固性分泌性中耳炎患者20例（24耳）,于门诊局麻下,结合鼻内镜经鼻腔径路行咽鼓管咽口球囊扩张,并行鼓膜置管。所有患者均于术后3个月拔出T型管。结果术后随访6个月,18例患者耳闷塞感、听物朦胧感症状明显减轻,未再出现鼓室内积液。2例术后仍有耳内闷胀及听力下降,耳内镜检查示鼓室积液未吸收,再次置入T型通气管后症状改善。结论局麻下行咽鼓管球囊扩张术加鼓膜置管术治疗顽固性分泌性中耳炎疗效显著,对于改善咽鼓管功能方法安全可行,并发症极小,是一种微创的新方法。     

Ototoxicity of neomycin and polymyxin B following middle ear application in the chinchilla and baboon

Previous experimental studies have demonstrated structural damage of the organ of Corti and stria vascularis following application of combination antibiotic otic drops to the middle ear. In this investigation the ototoxic effects of neomycin and polymyxin B (two antibiotics often used together in ototopical preparations) were separately evaluated after administration of each agent to the middle ear cavities of chinchillas and baboons. The antibiotics were administered in saline solution at the same concentrations used in Cortisporin Otic Suspension (3.5 mg/ml neomycin base, 10,000 units/ml polymyxin B). In both the rodent and primate, polymyxin B consistently produced greater cochlear damage than did neomycin. In fact, the extent of hair cell loss and strial injury produced by polymyxin B alone was, in many cases, comparable to that previously observed after application of Cortisporin Otic Suspension itself. Hair cell loss in the baboon was markedly less severe than in the chinchilla. It is believed that differences in position and structure of the round window membrane are important factors in the differing levels of ototoxicity observed in the rodent and primate.