Ototoxicity Flashcards
What is the textbook definition of ototoxicity?
- Any source of non-mechanical, non-disease damage to the ear
- Includes: medications, solvents, heavy metals, possibly asphyxiants
- Most often used in content of clinical, medication-induced hearing loss or vestibular dysfunction
What is the operational definition of ototoxicity?
- Based on grading scales
- Beneficial for: consistency, objectivity, approachable numbers to non-audiologists
What are some benefits to using grading scales?
- Defined parameters, operational definition
- Rank or grade the degree of hearing loss
- Provide government agencies with data to judge drug safety
- Assess effectiveness or oto-protective interventions
- Assess genetic susceptibility to ototoxicity
Describe the ASHA Ototoxicity Grading Scale.
-Binary: yes/no ototoxicity:
20 dB+ decrease in pure-tone threshold at 1 test frequency
OR
10 dB+ decrease at 2 adjacent test frequencies
OR
Loss of response at 3 consecutive test frequencies where responses were previously attained
-Threshold change confirmed on retest
Describe the NCI ototoxicity grading scale.
-Grading of adverse events, hearing change, and/or therapeutic needs
-Graded on a scale of 0-5:
Grade 0 = no adverse event
Grade 1 = mild adverse event
Grade 2 = moderate adverse event
Grade 3 = severe adverse event
Grade 4 = life-threatening adverse event
Grade 5 = fatal adverse event
-Grading is different for adults vs. pediatrics
Describe the monitoring for FDA approval of new drugs.
- Phase 1: safety
- Phase 2: efficacy, optimum dose-response
- Phase 3: large scale study to detect side effects not identified ini first 2 phases
- Phase 4: further evaluation on subpopulations such as children, pregnant women, and the elderly
Describe Brock criteria for monitoring ototoxicity.
-Grading of hearing loss at the end of trial:
Grade 0 = thresholds <40 dB at all frequencies
Grade 1 = thresholds 40 dB+ at 8 kHz
Grade 2 = thresholds 40 dB+ 4-8 kHz
Grade 3 = thresholds 40 dB+ 2-8 kHz
Grade 4 = thresholds 40 dB+ 1-8 kHz
Describe Boston SIOP grading scale for ototoxicity.
-Grading of hearing loss
Grade 0 = hearing threshold up to 20 dB at all frequencies
Grade 1 = thresholds > 20 dB above 4 kHz
Grade 2 = thresholds > 20 dB at 4 kHz+
Grade 3 = thresholds > 20 dB at 2 or 3 kHz+
Grade 4 = thresholds > 40 dB at 2 kHz+
How can ototoxicity be defined?
- Textbook definition
- Operational (i.e. grading scales)
- Functional (i.e. WR decline)
What medications have been linked to ototoxicity?
- Aminoglycoside antibiotics
- Antineoplastic drugs
- Loop diuretics
- Chelating agents
- Anti-inflammatory drugs
- Ototopic agents
What are aminoglycoside antibiotics?
- EX: gentamicin, neomycin, streptomycin
- First discovered by Albert Schatz in Selman Waksman’s lab in 1944 (ototoxicity was first noted by Feldman & Hinshaw in 1945)
- Among the most commonly used antibiotics worldwide (i.e. TB, CF, serious infections)
- Side effects include ototoxicity and nephrotoxicity
What are audiological manifestations of aminoglycoside antibiotic ototoxicity?
1) HL
- Bilateral, HF SNHL
- Onset is often delayed days or weeks after onset of therapy
- Most often permanent
2) Tinnitus
- Immediately following first treatment
- Typically occurs before HL
What are vestibular manifestations of aminoglycoside antibiotic ototoxicity?
1) Acute
- Headaches
- Nausea, vomitting, imbalance
- Vertigo
2) Chronic
- Difficulty with sudden movements
- Imbalance when walking
3) Compensatory
- Centrally mediated
What are antineoplastic drugs?
- Platinum compounds:
1) Cisplatin - Kills cancer cells by binding DNA, resulting in kinked helix (cannot bind so cell dies)
- Ototoxicity is typically bilateral, symmetrical, sensory, permanent, HF
- Onset: gradual, progressive, cumulative, or sudden
- Evidence of progression after cisplatin is d/c
2) Carboplatinum
- Less cochleotoxic than cisplatin
- Indications are similar to cisplatin
What are loop diuretics?
- Drugs that inactivate the Na-K pump at the loop of Henle in the kidney
- Prevent reabsorption of Na, K, chloride, and water (potent diuretics)
- Indications: heart failure, edema, hypertension, ascites from liver failure
- Ototoxicity: tinnitus, flat SNHL, rare reports of vertigo
- Toxicity related to:dosing, concomitant aminoglycoside Rx, renal function/failure
What are chelating agents?
-Used to treat iron overload, sickle cell disease, etc.
What are anti-inflammatory drugs?
1) Salicylates (ASA)
- Mild to moderate SNHL
- Reduced OAEs due to decreased cochlear blood flow
- Recovery in 24-72 hours after cessation of drugs
2) Quinine
- Indications: antimalarial, nocturnal leg cramps
- Bilateral, symmetrical SNHL
- Reduced WR
- HF tinnitus
- Typically reversible
What are ototopic agents?
EX: solvents, antiseptics, antibiotics
- Indications: suppurative OM, otorrhea following myringotomy and tubes, draining mastoid cavities, OE
- Low incidence of ototoxicity
What is the audiologist’s role in ototoxicity monitoring?
- Monitor for ototoxicity
- Establishing goals of a monitoring program
- Participation in therapeutic decision making
Why do we monitor for ototoxicity?
- Ensure early identification of hearing loss
- Prevent functional hearing loss (i.e. treatment alternatives, smaller/less frequent doses, d/c treatment)
- Care and support of patient and family
- Evaluate drug safety
What are some considerations for ototoxicity monitoring?
- Patient age and medical status
- Underlying diagnosis
- Purpose of monitoring
- How will a change in hearing be defined and reported?
- What is at stake?
What are some age-related considerations in ototoxicity monitoring for neonates?
- NICU admissions receive prophylactic or empiric treatment with gentamicin
- Broad spectrum specificity toward organisms commonly encountered in neonatal sepsis
- Considered clinically essential despite known ototoxicity and nephrotoxicity
- Higher incidence of HL in NICU babies is of unknown etiology (but aminoglycoside use is a common risk factor)
What are some factors potentiating aminoglycoside ototoxicity in neonates?
- Concurrent medications (i.e. loop diuretics)
- Inflammatory status
- Genetics
- Noise levels in the NICU
What does JCIH recommend for neonates taking aminoglycosides for 5 days+?
- Diagnostic follow-up by 9 months of age
- No specific screening/monitoring protocol for ototoxicity in neonates
What are challenges to monitoring neonates for ototoxicity?
- Timing and feasibility of test (baseline often cannot be completed before drug administration)
- Focus of test (i.e. NBS looks for mild-mod HL in MFs but ototoxicity monitoring requires HFs)
- Serial ABR or OAE is labor-intensive, difficult to interpret in premies
- Noise from medically-necessary interventions
What are recommendations for ototoxicity prevention in neonates?
- Minimize use of aminoglycosides
- Monitor level of ambient noise in NICU and take steps to mitigate
- Prenatal testing for genetic risk factors
- Education of parents and NICu staff regarding the risk of progressive or late-onset HL and importance of follow-up
Describe age-related considerations in ototoxicity monitoring in pediatrics.
-Childhood cancers are most often treatment with platinum (cisplatin) chemotherapy
What are cisplatin ototoxicity risk factors in pediatrics?
- Younger age
- Dose
- Cranial radiation
- Concomitant use of other ototoxins during treatment (i.e. aminoglycosides, loop diuretics)
- Genetic predisposition
How is cranial radiation a risk factor for cisplatin ototoxicity in pediatrics?
- Increased risk of HL as radiation dose increases
- HL might not appear until 18 months+ after tx completion
- May develop transient or permanent CHL
- Combination of cisplatin and radiation therapy potentiates the ototoxic effect of cisplatin
Describe the impact of cisplatin ototoxicity in pediatrics.
- Reduces utility of cisplatin therapy by limiting dose escalation
- Precludes investigation of novel strategies to enhance cisplatin cytotoxicity
- Infants and young children at critical stage of development
- Older children and adolescents: educational achievement, social-emotional development, QOL
Describe the suggested pediatric monitoring protocol: 5;0+.
- Evaluate at baseline, during therapy, and end of therapy/school re-entry
- AC 0.5-8 kHz (BC when indicated)
- EHF
- Otoscopy
- Immittance
- DPOAE
- Suprathreshold speech recognition
- Question about tinnitus
Describe the suggested pediatric monitoring protocol: 0;8-4;11.
- Evaluate at baseline, during therapy, and end of therapy/school re-entry
- AC 0.5-8 kHz (BC when indicated)
- Otoscopy
- Immittance
- DPOAE
- Suprathreshold speech recognition (when possible)
Describe the suggested pediatric monitoring protocol: infant or unresponsive patient.
- Evaluate at baseline, during therapy, and end of therapy/school re-entry
- Tone evoked ABR/ASSR (>4 kHz if possible)
- Otoscopy
- Immittance
- DPOAE
- Behavioral audiometry as soon as patient is able
Describe SIOP Minimal Test Battery for ototoxicity monitoring in pediatrics.
- Sequence for testing: used only when complete evaluation is not possible
- Purpose: direct testing to critical components for grading hearing loss
- Improve consistency of data in multi-center studies
- Allow grading when only 2-3 frequencies can be measured
- Children tested with minimal battery will require complete evaluation as soon as child is able
What adult cancers are usually treated with platinum-based chemotherapy?
- Head and neck
- Lung
- Colorectal
- Bladder
- Germ cell
- Ovaria
- Testicular
What are the general goals for adult ototoxicity monitoring programs?
- Use of standard definition of threshold shift
- Pre-treatment counseling regarding potential ototoxicity
- Baseline evaluation before (or early in) treatment
- Monitoring evaluations at sufficient intervals to document hearing loss progress or fluctuation
- Post-treatment evaluation followed by longer term monitoring
When should adult OMPs start?
- Cisplatin: no later than 24 hours after initial treatment and retest prior to each subsequent dose
- Aminoglycoside: no later than 72 hours after initial administration and monitor at least weekly during treatment
When should post-treatment evaluation for adult OMP occur?
- Immediately post-treatment
- Follow-up at 3 and 6 months post-treatment
What are baseline, monitoring test components for adult OMP?
- Otoscopy
- Tympanometry
- AC 250-8000 Hz
- BC
- EHF
- OAE
- Speech audiometry
What are additional adult OMP components?
- OAEs (focus on HF)
- Lack of guideline for testing/interpretation
- Standard clinical protocol?
What are some advantages/limitations of EHFs?
- Advantages: monitoring above 8 kHz more sensitive to ototoxic changes, intra-subject variability is within standard test-retest criteria
- Limitations: requires “add-on” of extended high frequencies to audiometer, increases test time
What are some OMP service gaps?
- Inconsistent referrals
- Scheduling limitations
- Location and space limitations
- Staffing limitations
Describe OMP service gap: inconsistent referrals.
- Self-referral and physician referral after treatment
- Multiple staff shifts and rotating residents made in-service training difficult
- Insufficient lead time prior to treatment
- Solutions:
- Participation in oncology multidisciplinary team clinics
- Referrals from pharmacy
Describe OMP service gap: logistical barriers.
- Patient schedules and compliance with audiology visits
- Audiology not near the oncology or infectious disease locations
- Other appointments running late
- Number of schedulers, booths, and audiologists
- Solutions:
- Dedicated appointment slots/rooms/staff
- Creative scheduling
What are some advantages to ABR monitoring for ototoxicity?
- Reliable, portable, objective
- Greater dB than OAEs
- May capture pre-clinical changes
- Helpful in cases when patient is very ill and/or uncooperative
What are some limitations to ABR monitoring for ototoxicity?
- Lengthy
- Lacks frequency specificity at high stimulus levels
- High frequency stimuli may not be available
- May require sedation
- Sensitivity and specificity for detecting ototoxic changes unknown
What are some advantages to OAE monitoring for ototoxicity?
- Efficient, portable, and reliable objective tool
- May capture pre-clinical changes
- Helpful in cases when patient is very ill and/or uncooperative
What are some limitations to OAE monitoring for ototoxicity?
- Limited ability to assess the higher frequencies
- No widely accepted standard for change
- Limited dB range
- Obscured by ME disease
- Require careful measurement
- Sensitivity and specificity for detecting ototoxic changes unknown
What are requirements of otoprotective drugs?
- Effective
- Safe for human administration
- Clinically feasible
- No interference with primary drug
Where are we with regard to otoprotective agents?
- Currently, no drug is FDA approved to prevent or treat ototoxic hearing loss in humans
- In/approaching clinical trials for:
- Protection for cisplatin-induced ototoxicity, noised-induced HL, aminoglycoside-induced ototoxicity
