Ototoxicity.

Transcription

1 Ototoxicity stein.htm Slide 2 Definition of Ototoxicity Ototoxicity is damage to the ear- cochlea, auditory nerve or sometimes the vestibular system. Over 100 classes of drugs have been associated with ototoxicity Slide 3 The damage is caused mostly by medication- a group of antibiotics harmful are the aminoglycoside group All end with the suffix Mycin e.g Gentamycin Loop diuretics are ototoxic and work on the kidneys Examples are Furosemide, ethacrynic acid, torsemide A loop diuretic is a drug used to treat: high blood pressure

2 swelling due to heart failure or renal insufficiency. The strength of the dose can have a more serious ototoxic effect. Other ototoxic drugs: Platinum based chemotherapy agents such as cisplatin Non-steroidal anti-inflammatory drugs (NSAIDS) e.g meloxicam Slide 4 Symptoms of ototoxic drugs Partial to profound hearing loss- typically bilateral Vertigo or unsteadiness Tinnitus Effects can be reversible, irreversible or both dependent upon the drug. Slide 5 Discovery of ototoxicity Ototoxicity discovered with Streptomycin in 1944 Used to successfully treat TB. Patients treated were found to develop irreversible cochlear and vestibular function. Led to the development of other aminoglycosides 2 other particularly toxic drugs from the mycin group are Gentamycin and Tobramycin. Gentamycin and Tobramycin are used to treat gram negative bacterial infections. Gram negative bacteria are resistant to multiple drugs and increasingly resistant to antibiotics. Gram negative infections pneumonia, blood stream infections, wound or surgical site infections and meningitis in the healthcare setting and E Coli. Slide 6 Damage to the vestibular system is one of the adverse effects of aminoglycoside antibiotics. A bilateral vestibular loss doesn t produce intense vertigo, vomiting and nystagmus but a headache, feeling of ear fullness, imbalance to the point of not being able to walk.

3 Slide 7 Nystagmus is involuntary rhythmic shaking or wobbling of the eyes. The affected person may suffer from positional nystagmus. Positional nystagmus- fast eye movements that the person has no control over. Influenced by the position of the body or the head and the person will feel dizzy. If severe, can lead to unsteadiness and oscillopsia. Slide 8 Oscillo- to swing and opsis vision. It is a visual disturbance where the objects in sight appear to oscillate. The effects are mild blurring to rapid periodic jumping- person will suffer dizziness and nausea. Slide 9 Acute cochlear damage might present itself as tinnitus. Early hearing loss may go unrecognised by the patient as it affects the thresholds in the high frequencies (above 4000Hz). If drug continues lower frequencies are affected and hearing loss could become profound if the drug is continued. Stop drug early in the course of the damage, further loss may be prevented and partial recovery of auditory thresholds may be possible. The loss -permanent. Slide 10 Ototoxicity process The toxic mechanism of the cochlear is poorly understood. Simplified- free radicals activate and react with other substances and this can stimulate the death of the cells. This damages the outer hair cells leading to permanent hearing loss. It may be that antibiotics bind to receptors and damage nerve cells. There are other drugs that can be given to help prevent this damage. Kanamycin, neomycin and amikacin are predominantly toxic to the cochlea. The toxins can enter the inner ear through the blood stream, inhalation or diffusion from the middle ear to the inner ear. Chemotherapy agents damage the cochlear by causing high frequency hearing loss and tinnitus. It depends on the dose- Cisplatin is absorbed by the cochlear hair cells and produces another substance that causes the damage. Carboplatin Slide 11 Other ototoxicity is caused by:

4 Quinine ( temporary hearing loss and tinnitus) & heavy metals such as mercury or lead ( permanent balance problems). At high doses aspirin can cause high pitched tinnitus and hearing loss in both ears, reversible if the drug is stopped Ototoxic chemicals like toluene, work together (interact) with mechanical stresses on the hair cells (caused by noise) to contribute to hearing loss so the effects together are far worse. Other environmental chemicals include butyl nitrate, carbon disulphide, styrene, manganese, xylene- permanent hearing losses. Slide 12 Noise alone- risk factor 4.1 Solvent mixture alone risk factor 5.0 Noise and Toluene risk factor Slide 13 Toluene- 2.6 million tons are produced annually via pollution and emissions. Used in chemicals, paints, adhesives, rubber etc produces cochlear damage (causing a 3-6 khz dip) similar to noise. Sweeteners were discovered when they were experimenting on toluene derivatives. Carbon monoxide & arsenic- produces changes to the cell in the Organ of Corti. There are some Current uses of some aminoglycoside: Gentamycin can be used to our advantage with Meniere s disease by destroying the inner ear and stopping the vertigo but causing permanent deafness. - affecting cochlea and vestibular system. Erythromycin- one of the safest of the group Slide 14 Variables in effects and importance of monitoring hearing Generally antibiotic induced ototoxicity is bilaterally symmetrical but can be asymmetrical. The time of onset is unpredictable and a marked hearing loss can even occur after a single dose. Also hearing loss can occur several weeks or months after the completion of the course. It is important that patients are monitored for up to 6 months after completion of their course.

5 Minimising ototoxicity The benefits weighed against the potential risks- use alternatives. No therapy can reverse ototoxic effects; however scientists are constantly seeking new methods to minimize the ototoxic effects. The way the drugs are taken can affect the ototoxicity- mouth less ototoxic that those injected into the veins and ear drops and creams that are applied to the skin containing antibiotics can have their ototoxic effects eliminated. Some people are more susceptible to ototoxicity. Aminoglycoside ototoxicity is more likely to occur with larger doses, higher blood levels or longer duration of therapy. High risk patients are the elderly or those who already have liver and kidney damage, pre-existing hearing problems,family history of ototoxicity, receiving loop diuretics. A genetic link has also been found Slide 15 Prevention of aminoglycoside ototoxicity Prevention of aminoglycoside ototoxicity involves monitoring drug levels, kidney function as well as a baseline hearing assessment. Daily administration of the aminoglycosides reduces incidence of ototoxicity. Identify high risk patients and choose alternatives As aminoglycosides remain in the cochlea long after therapy has ended, instruct patients to avoid noisy environment for 6 months as they remain susceptible to noise damage. Prevention of loop diuretic ototoxicity Loop diuretic ototoxicity affects 6-7 % of patients taking loop diureticsdepends on dose, infusion rates, kidney history and any other ototoxic medication that may be being taken. Giving the lowest dose that is effective Aminoglycoside with loop diuretic together - not recommended Patients with renal failure fall into the high risk group- they will end up with permanent hearing loss- avoid this Slide 16 Monitoring of chemotherapy ototoxicity

6 Cisplatin is used in to treat certain cancers. Damages the structures in the cochlea causing death of the outer hair cells Damaging effects can continue after the drug has been stopped. Incidence and severity of ototoxicity depends on the dose, infusion rate, condition of the kidneys and other ototoxic agents. Incidence & severity is higher in the paediatric population and in patients who are having radiotherapy of the head & neck. Tinnitus is a symptom. Hearing loss bilateral, SNHL, irreversible and progressive. It may appear as a severe loss after a single dose or after several days or months after the last dose. Baseline hearing checks and follow ups that last after course has ended. Avoidance of noise for 6 months Aspirin ototoxicity Salicylates- Aspirin Used widely Enters the cochlea. Can cause problems even at low doses Symptoms include tinnitus. Sometimes hearing loss mild to moderate and bilaterally symmetric. It recovers within hours of stopping the drug. Quinine ototoxicity Quinine Historically used to treat malaria but also medication for night cramps. Can produce tinnitus, hearing loss, vertigo. Hearing loss is usually SNHL and reversible. A characteristic SN notch at 4000 Hz is often present. Slide 17 General Monitoring Many chemicals and drugs affect the higher frequencies first. High frequency audiometry is helpful to detect amino-glycoside induced or cisplatin induced ototoxicity (above 8000 Hz and up to 16 or 20 khz. There are currently no tinnitus monitoring procedures. To monitor dizziness use Dizziness Handicap Inventory - not designed for this.

7 Self-assessment questionnaire- identifies the difficulties that someone is experiencing because of their dizziness. Answers are yes, no and sometimes- score attached. There are a range of questions that help to identify the level of handicap from the score. The human ear is capable of amplifying faint sounds to increase our hearing range and reducing the energy of loud sounds to protect the ears from damage. This occurs because the active mechanism of the cochlear amplifier. The outer hair cells change their shape in response to sound- elongating and shortening. Some animals, including birds can regenerate damaged hair cells but this doesn t happen naturally in mammals. Mammals grow inner hair cells before they are born. Ongoing research proving successful at transplanting stem cells (these have the potential to become specialised cells such as blood cells, muscle or inner hair cells) and from this some of the cells have migrated to the damaged cochlea and repaired sensory cells. Slide 18 Considerations of ototoxicity and hearing aid fitting Damaged hair cells with SNHL mean that there will be problems with recruitment and possibly tinnitus. With the outer hair cell damage means there is loss of the active mechanism. This affects the tuning curves- they become much broader, Effect is the frequency selectivity is significantly reduced. This will mean speech is unclear in background noise. If inner hair cells are damaged, thresholds will be elevated because the basilar membrane has to vibrate a lot more for sound to travel up the auditory nerve. The sound signal that travels up the nerve may be noisy (suffer from interference) and where the IHC s are not functioning there will be dead regions. Audiogram may give a misleading impression of the amount of high frequency hearing loss for a tone whose frequency falls in a dead region. Because of this there may be sound distortions. The output of the hearing aid will need careful consideration. Slide 19

8 Otosclerosis What is otosclerosis Otosclerosis is a disorder affecting collagen Cause is obscure- theories include metabolic disorders, vascular disease, infection, and trauma. Normally, bone is broken down and remodelled. In Otosclerosis- remodelling process becomes faulty. New bone deposited at certain sites- oval and round window. It depends where the bone is laid down whether the hearing is sensory, neural, mixed. The laying down of the abnormal bone is very gradual but the condition progressive. The abnormal bone reduces the movement of the stapes which reduces the amount of sound that is transferred to the cochlea. Slide 20 Incidence Hereditary in at least 70% cases so that 2 in 3 people with otosclerosis have other family members with the condition. The gene is dominant which means you have a 50/50 chance of getting it if one of your parents suffer from italthough not everyone with the gene develops symptoms. A virus MAY play a part- measles virus numbers of people diagnosed has decreased since the measles virus vaccination. Measles virus may activate the gene responsible for otoscerosis. Usually begins in bony labyrinth and is recognised when it affects middle ear. Begins in one ear but can then affect the other (unilateral in 10-15%). Caucasians are the most affected race. However, post mortem- present in 10 % of the population but many have never had any symptoms so the condition did not get diagnosed. Age of onset The age of onset can be around teens to late middle adult life but most people notice it around 30 years- more common in females. Hearing loss worse in pregnancy. Hearing loss- mild for a number of years before getting worse. In others hearing loss quickly gets worse. At first normal bone is absorbed and replaced by vascular, spongy osteoid tissue. Bone becomes thicker and less vascular. Unless the otosclerosis encroaches on the oval window, a conductive deafness does not occur. Can

9 have otosclerosis of the temporal bone and not be aware of it. Some causes are genetic and others are non genetic. Slide 21 Symptoms and Diagnosis Deafness - diagnosed by the clinical findings, which include progressive conductive hearing loss, normal tympanic membrane Carhart s notch at 2 khz. Tinnitus in about 4 out of 5 cases (in the head) Paracusis willisi where you tend to hear better where there is a lot of background noise. Slide 22 The cochlea promontory may have a faint pink tinge in 10% reflecting the vascularity of the lesion- it is known as Schwartze s sign. Dizziness and balance problems occur in 1 in 4 cases where the balance mechanism of the cochlea (semicircular canals) is affected. Weber test is lateralised to affected ear Tympanometry may show stiffening of the ossicular chain with absent acoustic reflex. Person sometimes exhibits a bluish cast over the whites of the eyes. may also complain of difficulty hearing when chewing. When the bone around the otic capsule is involved, a sensory hearing loss occurs which cannot be corrected with surgery- some medications can slow it down. The sensory loss can be worsened by lack of blood supply. Can spread to vestibular canals causing episodes of unsteadiness. Some similarities with other conditions that affect bone growth called Paget s disease and osteogenesis imperfecta (brittle bone disease) - no evidence to prove any link. Slide 23 Risk Factors Race- more common in white and Asian populations Sex- more common in women Age- usually presents between years Positive family history Drinking non-fluoridated water - controversial

10 Treatment Treatment relies on 2 options- hearing aids and surgery Hearing aids are effective for a conductive loss but more powerful amplification may be required as the disease progresses. Bone anchored hearing aids can be considered. The first operations were carried out in the 1870 s. Attempted without antibiotics or a microscope. The stapes was mobilised without ossicular chain reconstruction. Later the stapes was removed leaving the oval window open. Both techniques increased the transmission of sound but there were some fatal cases of meningitis caused by exposing the perilymph to bacteria. By the 1930 s a new technique was developed- fenestration. Immediate results were good but then over time the condition would return when the abnormal bone re-formed. Until recently, the standard procedure was a stapedectomy, where the stapes was removed and replaced with a small Teflon prosthesis. The poorer ear is operated on. The operation had a success rate of 80% (depending on the surgeon) chance of damage to the cochlea- causing hearing loss or tinnitus. Giddiness experienced by some because of perilymph leaking. If chorda tympani was bruised, a metallic taste would be experienced. The chorda tympani is related to taste. The chances of this damage have been reduced by a modification to the procedure- stapedotomy. A tiny hole is drilled in the stapes footplate. Fine vein graft covers the hole and a piston is placed onto this and attached to the incus. This seals the inner ear fluids off reducing the risk of leakage. Possible drug treatments with no scientific support There have been thoughts that fluoride had something to do with Otosclerosis as the number of cases went down when it was added to drinking water. Fluoride therapy was a treatment but it is no longer recommended as it is controversial. Oestrogen blockers may be helpful Bisphosphonates- medication for osteoporosis has been another suggested medication. Slide 24 Possible complications of surgery

11 Loss of hearing 1 in 100 (this is why the poorer ear is selected first- total loss in some) Dizziness common afterwards with nausea & vomiting. Usually settles down. Sometimes prolonged Taste disturbance- if chorda tympani is affected. Usually temporary but permanent in 1 in 10 cases. Reaction to ear dressings- allergy Tinnitus particularly if hearing worsens Slide 25 Considerations of otosclerosis and hearing aid fitting Need to look at the type of hearing loss We know that conductive losses require more gain than sensory-neural hearing losses. REM and conductive hearing losses needs careful interpretation because it is difficult to know what is transmitted through the middle ear due to the effects of the conductive component. A conductive loss that is stable will provide a baseline measure. NAL does not deal with conductive losses According to the British Society of Audiology guidance on real ear measurements 2007 for a person with a significant conductive hearing loss use >15dB air bone gap over an average of 500, 1000 and 2000Hz and add a percentage of the conductive element (between 25 and 75% to include the overall gain. Remember that the disease progresses so stronger amplification may be required over time. Slide 26 Otitis Media Otitis Media is inflammation of the middle ear. It is a generic term for different types of ear infections. Function of the Eustachian Tube

12 The Eustachian tube runs from the middle ear to the back of the throat and it function is to equalise pressure in the middle ear and as drainage. Open/close when we yawn or swallow. In children, heads are smaller- anatomical differences - tube is shorter, narrower and at a different angle. The muscles don t work as effectively and if the adenoids are enlarged, easily become blocked at one end. Colds and allergy can block the Eustachian tube. Eustachian Tube Dysfunction In Eustachian Tube Dysfunction- if the tube is not able to open, the air inside the middle ear cannot be renewed - absorbed by the lining in the middle ear. Negative middle ear pressure. If this continues - watery exudate drains into the ear from the middle ear lining- Eustachian tube is blocked, it cannot drain away. Slide 27 Acute (Suppurative) Otitis Media Acute rapid onset following a short but severe course Suppurative formation of pus or discharge ASOM- inflammation of the mucous membrane lining the middle ear cleft (this includes the Eustachian tube and tympanic cavity, mastoid antrum and mastoid air cells). This inflammation is produced by pus forming bacteria. The organisms and bacteria responsible: Slide 28 Adenovirus Rhinovirus Pneumococcus Haemophilus Influenzae Streptococcus Staphylococcus AOM is more common in children but can occur in adults due to URTI, sinusitis, severe allergies or flying with a cold. Slide 29

13 Signs TM will be inflamed, bulging or opaque Purulent (contains discharge or pus) ear discharge Perforation which may be hard to see Mastoid tenderness Slide 30 Symptoms The symptoms will be pain, due to the pressure build up from the fluid, fluid may contain pus- raised temperature. The pressure build up- perforate the tympanic membrane. There may be unsteadiness and a headache. The pus filled fluid escapes and the pain disappears. Antibiotics may be required to deal with the bacterial infection. Pain decreases with perforation. To treat we needs to test cause of infection to identify the most suitable antibiotic. Slide 31 Risk factors Age- common in young children who have poorer immunity Adenoids Frequent URTI Prematurity Craniofacial abnormalities Nurseries Not breast fed Poor socio-economic conditions Cold weather Pre-existing middle ear effusion Slide 32 Chronic Suppurative Otitis Media Chronic- long standing Suppurative formation of pus and discharge It involves a perforation and active bacterial infection. If active middle ear infection TM will not heal.

14 It begins with acute infection. Irritation and inflammation of the middle ear lining which creates swelling. The cycle of inflammation, infection and granulation tissue continues to destroy surrounding bony margins, leading to various complications. Slide 33 The bacteria responsible for the infections include: Pseudomonas aeroginosa Staphylococcus aureus Proteus species Klebsiella pneumonia Diptheroids Some of these bacteria attach to the diseased lining in the middle ear. Then they produce enzymes that prevent normal immune responses to fighting infection. This leads to bone erosion. The symptoms are: Hearing loss which may be mild to moderate conductive unless the bacteria penetrates the inner ear and causes damages, in which case the loss will be sensory or mixed. There will also be fever, Vertigo pain. Slide 34 There are 2 forms of the disease and The placement of the perforation determines whether the ear is safe or unsafe. A perforation around the attic region- unsafe, in the tubo-tympanic region is considered safe. Tubo-tympanic suppuration can occur in children and adults. Complications rare. The perforation is in the pars tensa and there is no local destruction. Surgery is indicated if the ear will not dry up and the repair perforationadvisable. Attico-antral-disease involves infection of the attic, antrum or mastoid process. There may be a cholesteatoma in the pars flaccida and post superior portion of the pars tensa. Can lead to destruction of bone towards the middle cranial fossa as well as damage to the contents of the middle ear. So as well as hearing loss there is danger to life. Complications- cholesteatoma. Slide 35

15 Cholesteatoma A cholesteatoma forms when the skin of a punctured eardrum grows into the hole in the middle ear or when there is a retraction pocket in the ear drum. It looks like an onion- layers of white skin in a ball. If infection, the skin will continue to grow into a cholesteatoma. Produces osteolytic enzymesdestroying bone. As the anatomical position of the cholesteatoma is close to the brain, the complications are quite serious and include: Hearing loss Vertigo Headaches Facial nerve palsy Meningitis Epidural abscess Treatment is surgery- mastoidectomy Slide 36 Otitis Media with Effusion Effusion- seeping of watery fluid from tissue There is thick or watery fluid behind TM but no ear infection. Fluid sterile. Symptoms involve hearing loss and fullness in the ear but no pain or fever. TM will be an abnormal colour- yellow, blue or amber. There may be loss of light reflex or diffused light reflex. TM may be retracted. Air bubbles or a fluid level may be visible Most cases are self-limiting and last for 6-8 weeks. However, if grommets are recommended if the OME lasts for 4 months or more, If there is structural damage to the middle ear or TM, Or if there is recurrent acute otitis media Unilateral middle ear fluid in an adult requires further investigation to exclude a tumour of the post nasal space which blocks the Eustachian tube like enlarged adenoids Slide 37 Consideration of otitis media and hearing aid fitting The first consideration is that no active infection or discharge is present.

16 The type of hearing loss is conductive and fluctuating so adjustments are required for the prescription and further fine tuning may be required as the hearing changes. The rigidity of the tympanic membrane with the presence of fluid will increase the risk of feedback occurring.