Symposium participants Glen R. Croxson, MB, BS, FRACS (Symposium Chairman) Dr, Croxson is a member of the De- partment of Otolaryngology-Neadand Neck Surgery at the University of Sydney. New South Wales, Australia {He specializes in otology and skull ery and hasa special interest in disorders of the facial nerve. His research interests include quantitative analysis of facial movement. Harvey Coates, MS, FRAC Dr. Coates is.a senior ENT surgeon at the Princess Margaret Hospital for Children in Perth, Western Australia, NP Bi 1 speciabizes in pediowric otology and obstructive sleep disorders and has a particular interest in treating his country’s Aborigine population ain ) Joseph E. Dohar, MD, MS, FAAP, FACS Dr. Doha is a pediatric otolaryngolo- stat Children's Hospital in Pitts: | burgh. His primary interests are ear disease and airway wound healing in children. ‘Thomas Deitmer, MD, PhD Prof. Deitmer is head of the Dej ment of Otolaryngology at Klinikum Dortmund Teaching Hospital in Dort mund, Germany. Likeall otolaryngol ogists in Germany, he is a generalist ©) Michael Hawke, MD Prof, Hawke is in the Department of _ Otolaryngology at the University of Toronto. His research interests inc ville. Heisalso an associate professorin the Department of Otolaryngology and the Department of Hearing and Speech Sciences. cear disease, sleep disorders, and sinus disease, David S. Haynes, MD Dr. Haynes is director of otology and neurotology at the Vanderbilt Univer- sity Medical Centersnd the St. Thom Hospital Neuroscience Insitute in Nash. 2 ENT-Ear, Nose & Throat Journal + Suppl 1 + August 2002, John Rutka, MD, FRESC Dr. Rutka is a staff neurotologist and associate professor in the Depart- ment of Otolaryngology atthe Univer- sity of Toronto. He is also ditector of the Ear Pathology Research Labora- tory and cadirector of the University Health Network Centre for Advanced Hearing and Bal ‘ance Testing and the Multidisciplinary Neurotolo at Toronto Hospital Peter S. Roland, MD Dr. Roland is chairman of the Depart- ment of Otolaryngology-Head and Neck Surgery at the University of ‘Texas Southwestem Medical Center in Dallas. He specializes in otology and neurotology. Andreas Schapowal, MD Dr. Schapowal is a specialist in ear, nose, and throat diseases, xllergolo, andcinical immunology inLandquart Switzerland. His primary research in- terest is allergology. He is also presi- dent of the Swiss Academy of Medi- ccine and Ethics and a Lieutenant Colonel in the Swiss Army Medical Corps. Paul Van de Heyning, MD, PhD Prof. Van de Heyning is chairman of the Department of Otorhinolaryngol ogy at the Antwerp University Hospi- {alin Belgium. He specializes in otol- ogy, neurotology.andobstructivesteep apnea syndrome, Soren Vesterhauge, MD, DMSe Dr. Vesterhauge is in the Department of Otolaryngology-Head and: Neck Surgery, Rigshospitalet, Copenhagen, Denmark. He is also a senior clinical lecturer in otolaryngology at Copen- hagen University. His pructice is fo 1y. otosurgery, neurotology, and cused on tdi medicine.Update on topical ototoxicity in chronic suppurative otitis media John Rutka, MD, FRCSC I detine chronic suppurative otitis media (CSOM) as a persistent orrecurrent bacterial infection of the middle ear that is characterized by a tympanic membrane perfor tion, hearing toss, and persistent or recurrent otorrhea. Uncomplicated CSOM canbe managed quite safely met ally because itis primarily a mucosal problem, CSOM. accompanied by cholesteatoma is more difficult and is ‘usually managed by surgery: left untreated, itcan be fatal, ‘The primary reason we treat CSOM is to prevent nplications. The most feared complication is an ot0- genic intracranial brain abscess. Nunez and Browning reported that the annual risk of such an abscess in active CSOM is only 1 in 10,000.! However, the lifetime risk in an individual aged 30 years is | in 200. Nunez and Browning also reported that this risk is three times higher in men and that 5% of these abscesses occur in the im- mediate postoperative period following mastoidectomy. Ototoxicity in CSOM {define ototoxicity as the tendency of certain substances; to cause functional impairment and cellular damage to tissues of the external, middle, and especially the inner regardless of whether the offending agent is applied systemically or topically. ‘The major recognized groups of systemic ototoxic drugs identified in clinical practice are the aminoglyco- sides, traditional time-honored medications such as the ‘quinines and salicylates, chemotherapeutic agents (cis- platinum in particular), and diuretics. One interesting facet of ototoxicity isthat we often fail to realize that when ‘adrug gets into the inner ear, it often stays there, This might be one reason that one of the risk factors for sy’ temic gentamicin toxicity is a second treatment course ‘There are three major groups of topical ototoxic drugs: the aminoglycosides (e.g., streptomycin, neomycin, and gentamicin) the antifungals (e.g. gentian violet), and the antisepties (e.g., alcohol and chlorhexidine). Whichever wgent i put into the middle ear space will most likely reach the inner ear eventually. Given time, most topical substancescan pass through the round window membrane and into the inner ear. For this reason, one should never use a chlorhexidine pre aration during ear surgery if, for imple. there is hole in the tympanic membrane. ototopieal preparations are effec- 18+ ENT-Ear, Nose & Throat Journal » Suppl 1 » August 2002 in treating CSOM, but practice patterns vary and continue to evolve. Some 15 years ago, these patterns were drastically different in the United Kingdom and the United States. In 1988, @ survey of general prac- itioners in the U.K. revealed that 66% did not prescribe «topical agent for otorshea in a patient whose eardrum was perforated.? Moreover, 85% said they would not use ‘topical agent in a patient with post-tympanostomy tube otorshea (PTTO). The primary reason for this reluctance was the risk of ototoxicity and its complications. ‘The opposite was true among otolaryngologists in the United States, as Lundy and Graham reported in 1993.) ‘They found that 84% of otolaryngologists used an ot0- topical agent in the presence of draining perforation, and 9456 did so in a patient with PTO. Most of these phy cians said that they had no compunction aboutusing drops because they were perfectly safe, even those drops that contained an aminoglycoside. We have since come to learn more about topical ototox- icity. In 1999, the National Formulary passed by the British Parliament limited the duration of therapy with a topical agent containing an aminoglycoside to 7 days because of mounting evidence that these preparations are ototoxic. Although ototoxicity from topical aminoglycosides is relatively uncommon considering the large numnber of patients who are treated with them every year, the risk is -gligible and is probably higher than we previously estimated, There are many reasons why topical ototoxie- ity does not oceur as often as one might expect. For example, drops might not get through the membrane of a very small perforation. Other reasons have to do with round window membrane permeability, the staus of eustachian tube function, mechanical barriersin the round window niche (e.g., mucosal webs), and an individual patient's inherent susceptibility to aminoglycosides. Studies of topical gentamicin ototoxicity "New information obtained from gentamicin studies has since prompted otolaryngologists in North America to rethink our practice patterns and become much more cautious about using topical aminoglycosides in patients with perforated eardrums. Over the past decade, we have been using topical gentamicin in very high doses to treatUPDATE ON TOPICAL OTOTOXIOITY IN CHRONIC SUPPURATIVE OTTIS MEDIA Ménire’s disease. The aim was to cure vertigo by indu ing a“chemical labyrinthectomy.” According to Blakley* ‘and Gustafson and Pensak.' intratympanic gentamicin, especially in high doses, reportedly controlled vertigo in 80 to 100% of patients with Méniére’s disease. Initially, our preferred technique in Toronto for gen: tamicin ablation was to place the tubing of a butterfly catheter through a myringotomy hole inthe eardrum. We ‘would then inject 1.5 ml of solution that contained ap- proximately 25 mg/ml of gentamicin three times. a day for 3 days. Within a week, patients would typically become profounclly vertiginous. They did not become vertiginous during the actual treatment; the reaction was delayed. We later realized the reason forthis, Following absorption of the drops through the round window membrane, gentami- cin has to travel from the basal turn of the cochlea and through all its tums before it reaches the neuroepithelium of the otolithic organs and the semicircular canals in the vestibule where it does its damage. This takes time. Having become sensitized to the effects of topical gentamicin in the treatment of Ménitre's dise began to recognize a pattern in some rather interesting ‘cases at our specialized multidisciplinary neurotology clinic at the University of Toronto, By taking a thorough history. performing a proper otoneurologic examination, and analyzing laboratory data, we believe we now have incontrovertible evidence that 29 patients have been re- ferred to us with topical gentamicin ototoxicity. The patients in question had all used commercially available topical gentamicin preparations for an average of 16 days, before they became toxic in the presence of a tympanic membrane perforation, and their earts) had stopped charging overthe treatment course many days previously. ‘These drops were probably safe over the short term, but ‘over a longer course, they reached the inner ear and the patient became toxic. Some of these patients developed bilateral toxicity when the drops were applied. injudi- ciously to both ears. To illustrate the seriousness of top! cal gentamicin toxicity, nine of our patients developed oscillopsia and/or ataxia, and seven of them never te- tured to work. In fact, five of them eventually were unable to walk and became confined to wheelchairs. In view of topical gentamicin’s ability to cause ototox- icity unintentionally, we wondered if perhaps we could use these drops therapeutically to purposely cause oto10x- ity in patients with Ménibre's disease. Indeed, we tested this theory on 20 patients with unilateral Méniére's dis ease by placing a ventilation tube into the posteroinferior quadrant of the tympanic membrane, close to where the round window niche would be located. We then gave these patients follow-up instructions to lie on their side and put 5 or6 drops into the affected ear three times aday. We told them to administer the drops until they became constantly vertiginous tor 2 days, and then to stop. ‘The vast majority of these patients became toxic by about day 12. We compared their pre-and post-treatment electronystagmography and audiogram results. In the patients whom we ablated for Ménigre’s disease. we found that the excitability-sifference curve shifted up. In fact, the findings were almost identical to what we saw when we used a very high concentration of gentamicin initially fora shorter period of time. Therefore, the use of aaless concentrated form of topical gentamicin foralonger period of time will yield the same results, Well over SO% of these patients ultimately had no response to ice-water calories, and another 25% demonstrated significant changes in excitability difference. The reason that the Méniete’s patients became toxic before those whom we believe sustained inadvertent toxicity for treatment of middle ear disease resides inthe Fact that, unlike the latter group, the Méniére’s patients had no inflammatory or infective response in the middle ear prior to treatment, Comments Dr. Croxson: Both Gilehrist et al” and Black et al? described vestibular recovery following gentamicin in- jury. Have you had any clinical experience with this? Dr. Rutka: No, but I'm sure it happens. One reason we do not see it often is because a patient might have already recovered by the time he or she is referred to us. Another reason is that most patients with a unilateral vestibular loss compensate for it fairly well if they're young and reasonably motivated. It's also quite likely that the treat- ing physicians not infrequently ascribe dizziness to the elfcts of the infection itself rather than to the treatment. ‘The important point is that the drops we use are pretty effective, regardless of whether they're aminoglycosides oF fluoroquinolones. But certainly the downside with topical gentamicin is that it is toxic to the vestibular structures when it is used too long. especially after the iniddle ear inflammatoryfinfective process has resolved. References 1. Nune? DA, Brossning GG, Risks of developing an orogenic incracranial abscess. Laryngol Oto! 1990: 1D4:468-72, Bickerton RC, Roberts C, Litle JT. Survey of general prac ers tratment ofthe wischarging ear. Br Med (Clin Res Ed) 296164950. 3. Lundy LB, Graham MD, Otetoxicity and ototapical medicutions A survey of otoaryngologists, Am J Oto 1993:1 4141-6 4. Blakley BW. Update on intratympanic zentamicin for Meniere’s disease. Laryngoscope 2000; 10236 40. 5. Gusatson LM, Penssk ML. Inner ear perfusion therapy: An Uupuate, Clinical Opinion in Heal and Neck Surpery 2000:8:398- sin, 6. Gilehni DP, Cuntoys 1S, Carvright AD, eal. High acceler tion impulsive rations reveal severe long-term deficits of the horizontal vestibulo-ccular reflex inthe guinea pig. Exp Brain Res 1998; 123:242-54, 7. Black FO. Gianna-Poulin C, Peszneeker SC. Re \estibularotoiorieity, Otol Neurotol 2001:22:662-71 ery from Volum 1 + Suppl 1+ 19