published by BC Decker,
Beck: Good Morning Dr. Rutka. Thanks for meeting with me today.
Rutka: Hi Dr. Beck. I appreciate the opportunity to talk about the book, Ototoxicity. Id like to mention that my colleague and co-editor is Peter Roland MD, from the University of Texas Southwestern Medical Center at Dallas.
Beck: Id like to learn a little about your professional background, if you dont mind?
Rutka: Sure thing. I grew up in Toronto and attended school there. I graduated with my medical degree in 1979 from Queens University. My ENT and neurotology training was obtained in a few locationsthe University of Witswatersrand in South Africa, the University of Toronto, and at Cambridge University in England.
Im currently an associate professor in the department of otolaryngology at the University of Toronto. My primary interest is the treatment and removal of skull base tumors, disorders of dizziness and imbalance, their physiology and treatment, and also for the last decade or so, Ive been very interested in clinical ototoxicity of the vestibular and cochlear systems.
Beck: Thanks John. Id like to start by noting that I have read the book, and its a thorough and comprehensive text. I am not aware of another book with so much information totally focused on ototoxicity. The book opens with basics such as anatomy and physiology of the hearing and balance systems, and quickly progressing to Systemic Toxicity, Topical Toxicity, Interventions, Therapeutic Uses of Ototoxic Effects, and finally and importantly Medico Legal concerns. Lets take a brief tour of some f these topics. Can you please tell me about Systemic Toxicity?
Rutka: Sure Doug. Its been known for many years that certain substances impact and effect inner ear function. For example, the quinines, the heavy metals and the salicylates -- such as the common aspirin, were among some of the first drugs discovered to cause hearing loss. In fact, rheumatologists used to advise their patients to take salicylates until their ears started to ring or buzz, and then back off so the appropriate dose, depending on the situation could be determined. However, salicylates are somewhat unusual because their effects are generally reversible, whereas just about every other ototoxic drug causes permanent damage to the cochlea or the vestibular system.
Beck: I know there is no universal hard and fast number, but in general, for an adult, how many adult aspirins would it take before you were likely to see ototoxic effects?
Rutka: Of course, as you noted, the variation is tremendous. Perhaps 10 adult aspirin per day is the threshold from which you would likely see tinnitus or hearing loss. And again, some people may have effects after just a few aspirin, and perhaps some could take a few more.
Beck: I suspect the most common aural presentation of ototoxicity would be bilateral tinnitus and bilateral high frequency sensorineural hearing loss?
Rutka: Yes, those are the most common cochlear effects.
Beck: Please tell me about loop diuretics and how they relate to ototoxicity?
Rutka: Loop diuretics are agents primarily used to lower blood pressure. They act by blocking the reabsorption of chloride and sodium ions from the kidney in the Loop of Henle. The most common loop diuretics are furosemide, bumetanide and ethacrynic acid. These drugs are also used to treat congestive heart failure, renal failure and cirrhosis. These drugs are additionally used with newborns in the neonatal intensive care unit to treat bronchopulmonary disorders. Unfortunately loop diuretics can produce transient or permanent hearing loss and likely vestibular symptoms too. Large bolus amounts are probably the most damaging, and that method of administration might also cause tinnitus even without hearing loss. Lastly, loop diuretics have not been very well studied with respect to their potential vestibular impact, but the vestibular impact does appear to be less pronounced than the cochlear effect.
Beck: My recollection is that patients taking loop diuretics are more susceptible to noise induced hearing loss than they would otherwise be?
Rutka: Yes, that does seem to be the case, adding insult to injury! If the patient is on loop diuretics, it is a good idea to avoid excessive noise.
Beck: Another very common drug associated with significant ototoxicity is cisplatin. Would you please tell us about that?
Rutka: Cisplatin is among the most common drugs used with cancer patients. It is well known to cause nausea and vomiting in most patients, and has ototoxic effects in a large portion of the patients receiving it, too. However, it is a very useful and effective anti-cancer drug -- and thats why it is used so commonly. For example, when used in tandem with other agents, it is the standard treatment for many cancers; lung, head and neck, testicular, cervical etc. So yes, it has significant side effects, and they are not to be taken lightly, but they must be considered in perspective, along with the benefits too. More recently, other platinum agents have been introduced, such as carboplatin, which appears less ototoxic. These newer drugs hold promise too, but the major concern when using chemotherapeutic agents is controlling or ridding the patient of their cancer, so we have to balance the disease process and the treatment side effects. Interestingly, regarding the probable site of cochlear damage, basic science research has identified that cisplatin appears to target outer hair cells (OHCs), whereas carboplatin appears to more toxic to the inner hair cells (IHCs). In future this finding might be further applied to the basic physiology of hearing and how both the inner and outer hair cells interact.
Beck: Before I let you go, I wonder if you can tell me a little about the ototoxic issues related to aminoglycoside antibiotics?
Rutka: Absolutely, aminoglycoside use is very common and those related drugs represent a very important class of antibiotics. Aminoglycosides can be used not only systemically but topically too. Drugs in this class have been around since the 1940s or so and include agents like gentamicin, kanamycin, neomycin, tobramycin and streptomycin. The advantage of these drugs is that for gram negative organisms, they are very effective and powerful. Further, gram negative infections typically have a higher rate of mortality than gram positive infections, so again, these are very important drugs Interestingly their ototoxic effects can be somewhat selective within the inner ear. Streptomycin for example has been found to be primarily vestibulotoxic, while having minimal impact on hearing. So, its been known for sometime that this drug can cause a bilateral vestibular loss in certain individuals. Other aminoglycosides have primarily cochlear effects. So these are things to watch for, as they have variable effects on the ear.
Beck: Isnt streptomycin making a comeback now?
Rutka: Yes, so to speak especially with the resurgence of multi-drug resistant TB. Nevertheless we often use the toxic effects of these agents topically to treat patients with incapacitating vertigo. For example, when we perform a chemical labyrinthectomy for incapacitating Menieres disease, we typically use gentamicin as it is primarily vestibulotoxic and not cochleotoxic. The drug is instilled directly into the middle ear such that we can chemically deafferentate the vestibular portion of the inner ear without further injuring the cochlea much of the time.
Beck: Dr. Rutka, this is really fascinating information. Im very grateful to you for sharing your time and knowledge with us. Youve been very generous with your time, and I am aware that our time is about up. The book is absolutely excellent and I certainly recommend it!
Rutka: Thank you Dr. Beck, its a pleasure to work with you too.
Ototoxicity, by Peter Roland MD and John Rutka MD
BC Decker, Hamilton Ontario
published by BC Decker,