Intratympanic steroid injection for sudden sensorineural hearing loss ...

Hemodialysis International 2014; 18:192–214

Intratympanic steroid injection for sudden sensorineural hearing loss in a patient on hemodialysis Rui-Xin WU,1 Chun-Chi CHEN,1 Chih-Hung WANG,2 Hsin-Chien CHEN2 1 Department of Medicine, Division of Nephrology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; 2Department of Otolaryngology–Head and Neck Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan

Abstract Sudden sensorineural hearing loss (SSNHL) is being described with increasing incidence among patients with end-stage renal disease (ESRD) undergoing hemodialysis (HD). There are no widely accepted guidelines in the medical literature for the appropriate management of this medical emergency. Administration of systemic steroids remains the mainstay of the management of SSNHL in conjunction with the supportive treatment, in this vulnerable group of patients, as well. However, encouraged by the evolving evidence on the efﬁcacy of the intratympanic steroid injections (ITSI) in the treatment of SSNHL among patients without renal disease—we successfully treated SSNHL in an elderly diabetic with sepsis due to bilateral pneumonitis undergoing regular HD treatment with multiple ITSI and antibiotics resulting in complete recovery of hearing function within 3 months of onset of the ﬁrst symptoms. Key words: Sudden sensorineural hearing loss, chronic kidney disease, hemodialysis, intratympanic steroid injection

INTRODUCTION The incidence of reported sensorineural hearing loss (SNHL) among patients with chronic kidney disease (CKD) is up to 77 %, considerably higher than in the general population.1 Bergstrom et al. reported SNHL in 40% of the patients on regular hemodialysis (HD).2 Several etiological factors have been linked to sudden SNHL in renal failure including the use of ototoxic medications (antibiotics, e.g., aminoglycosides, vancomycin, Correspondence to: H-C. Chen, MD, PhD, Department of Otolaryngology-Head and Neck Surgery, Tri–Service General Hospital, 325, Cheng-Kung Road, Sec. 2, Neihu District, Taipei 114, Taiwan. E-mail: [email protected]

and macrolides, antiplatelet agents, e.g., aspirin and plavix, acetaminophen, diuretics, etc.), electrolyte disturbances, hypertension, infections, and sepsis besides the HD treatment itself.1,3,4 SSNHL is defined as a rapid decline in hearing over 3 days or less affecting 3 or more frequencies by 30 dB or greater.5 SNHL caused by aminoglycosides is often bilateral and irreversible while that because of infection, sepsis, electrolyte/osmotic disturbances during HD, may be fluctuating and reversible, hence temporary in nature.6–8 Thus, possibility of spontaneous recovery after an acute insult is resolved—cannot be ruled out.7,9 Elderly, children, diabetics, and those with sickle cell anemia, leukemia and other malignancies, and genetically predisposed—seem to be particularly vulnerable to SNHL.10–12

© 2013 International Society for Hemodialysis DOI:10.1111/hdi.12062

195

Case Reports

Intratympanic steroid injections (ITSI) are being increasingly used in the treatment of SSNHL who have failed systemic therapy.13,14 However, there is paucity of well-designed randomized controlled trials involving HD patients. Thus, the efficacy and safety of ITSI in this patient population remains debatable. We, hereby present a case of an elderly gentleman with end-stage renal disease (ESRD) undergoing regular HD who developed SSNHL 3 days after being treated for bilateral pneumonitis and recovered completely in 3 months with the ITSI.

CASE REPORT A 70-year-old gentleman with ESRD undergoing maintenance HD three times per week for the last 6 years— presented to emergency room with sudden onset of hearing impairment in the right ear following a febrile illness associated with productive cough of 2 days duration. He had long-standing type 2 diabetes mellitus, systemic hypertension, and stable coronary artery disease. There was no history of underlying hearing deficit prior to the current episode. His routine medications included insulin, amlodipine, valsartan, carvedilol, aspirin, vitamin B complex, folic acid, calcium carbonate, and epoetin beta, leading to acceptable therapeutic targets of blood pressure, blood sugar, and hemoglobin. A recent HbA1C value was 6.2%. He had no exposure to ototoxic antibiotics, such as aminoglycosides and vancomycin, over the past 6 years. Moreover, he was not on diuretics or nonsteroidal antiinflammatory drugs. He had his arteriovenous fistula (AVF) created about 3 months before commencement of hemodialysis. However, he required frequent angioplasties to preserve the patency of AVF in due course of time. He was adequately dialyzed three times per week with each session lasting for 4 hours using high-flux polysulfone membrane and a bicarbonate dialysate. On physical examination, his blood pressure was 162/ 98 mmHg, heart rate was 74 beats per minute, respiratory rate 19 per minute, and body temperature 38.2°C. Auscultation of the lungs revealed bilateral coarse crackles, while the rest of the physical examination was unremarkable. No skin eruptions, engorged jugular veins, and edema of lower limb were present. A detailed ear, nose, and throat examination showed no abnormality. Laboratory values were significant for leukocytosis with a white blood cell (WBC) count of 21760/μL, mild normocytic anemia with hemoglobin 9.2 g/dL, elevated serum level of C-reactive protein at 5.79 mg/dL, and electrolytes within the normal range. A chest radiograph showed patchy infiltrations in the lower lung fields bilaterally. An audiogram

196

showed asymmetrical hearing acuity with mild hearing impairment in his right ear on the day of admission (Figure 1B). The auditory brainstem response for neural evaluation was within normal limits. He was admitted with a provisional diagnosis of health care-associated pneumonia and received intravenous piperacillin/tazobactam (2 g/0.25 g given every 8 hours), a known less-ototoxic broad-spectrum antibiotic. Concerned for active infection, intravenous or oral steroids were not given for his mild SSNHL. On the third day after admission, he became afebrile and his WBC returned to normal (8900/μL). The results of blood and sputum cultures were negative, and specific tests for atypical pathogens including Mycoplasma, Chlamydia, and Legionella were all nonreactive. However, on the fifth day after admission, the patient complained that he could not hear. Pure tone audiometry (PTA) showed a severe hearing loss in both ears (Figure 1B). Magnetic resonance imaging was performed to rule out central, vascular, or cranial nerve lesions. Because of progressive hearing loss and concern regarding the use of systemic steroids, we decided to use ITSI for our patient with an active infection and diabetes mellitus. The frequency of ITSI was administered once every 2 days for three sequential doses starting on the third day after the sudden onset of bilateral hearing loss (Figure 1A). The patient was put in supine position on the therapeutic chair and the ITSI was done under an otoscopy at ENT department when he was admitted. He also received concomitant oral medications, such as vasodilators (Nicametate citrate) and vitamin B complex for 2 months. The patient’s hearing acuity was restored gradually without the support of hearing aids during 3 months follow-up, as shown in Figure 1. The technique for intratympanic steroid injection is described briefly as follows: Local anesthesia of the tympanic membrane was achieved using a pump spray to instill xylocaine 10% (10 mg/dose, AstraZeneca AB, Södertälje, Sweden), which was allowed to remain in the canal for approximately 15 min. The patient was placed in a supine position, and his head was turned 45 degrees to the opposite side. After removal of anesthetic agent and sterilization of the external ear with 70% ethanol, the anteroinferior tympanic membrane was punctured once with a 25-gauge spinal needle attached to a 1-mL syringe containing Rinderon (4 mg/mL, China Chemical & Pharmaceutical Co., Hsinchu County, Taiwan) under an otoscopy. Then, 0.5 mL of Rinderon was instilled into the middle ear through the syringe. The procedure was performed bilateral. Subsequently, two doses were administered (one on each of two successive days) without 10% xylocaine spray.


Case Reports

Figure 1 The time course of intratympanic steroid injection (ITSI) and the change in hearing level (HL) are shown for this patient. (A) Initially, mild sudden hearing impairment in the right ear was noted on day 1, then severe bilateral hearing loss on day 5. Starting on the third day after the sudden onset of severe hearing loss, ITSI was given once every 2 days for three doses. The average HL at 500, 1000, and 2000 Hz had been restored by the 3-month follow-up visit. (B) The HL at different frequencies is demonstrated by pure tone audiogram on days1, 5, 30, and 90.

DISCUSSION The reported incidence of idiopathic SSNHL is approximately 1% of all cases of SNHL.15 However, multiple factors could contribute to the development of SSNHL including advanced age, diabetic status, infections, ototoxic medications, and uremia among patients with ESRD, as shown in our patient. Based on earlier literature findings, the frequency of SSNHL has been acknowledged to be increased with advanced age.15,16 Fetterman et al. also reported that hypertension (17.2%) and diabetes (5.7%) are common in SSNHL patients.17 Patients undergoing HD for ESRD are at high risk for developing catheter-related bloodstream infections (CRBSI), but our patient did not have the history of CRBSI and the use of antibioticheparin lock, which has the potential to cause ototoxicity.3


A few case reports have been demonstrated SSNHL in association with Mycoplasma and Chlamydia psittaci pneumonia.18,19 No specific bacteria or viral IgM antibody (herpes simplex virus, measles, mumps, or cytomegalovirus) was detected in the patient. He was treated for pneumonitis with piperacillin/tazobactam, which has not been reported for the ototoxicity. None of our patient received ototoxic drugs such as aminoglycoside antibiotics and furosemide at least within 3 months. Although a specific etiology could not be identified in our patient, more clinical manifestations of SSNHL should be elucidated in patients undergoing HD for CKD. In CKD patients on HD, the occurrence of SSNHL and the process of SNHL has been proposed to share a common mechanism.20 Lin et al. reported that the incidence of SSNHL was 1.57 times higher in patients with CKD than in those

197

Case Reports

without CKD; SSNHL has an incidence of about 7 per 1000 (252/37,421) per year among persons with CKD.20 They also showed that in persons with CKD, age was an independent risk factor for SSNHL with increased incidence of SSNHL in the subgroups of patients of ages 50–64 years and >64 years. Other risk factors for SSNHL included male gender, long duration of disease, and comorbid conditions including diabetes. There are only few small studies and case reports related to SSNHL among ESRD patients undergoing regular HD, with wide variations in the management of hearing impairment. Makita et al. in their review described 30 ESRD patients who developed SSNHL while undergoing regular HD; hearing impairment was unilateral in most of the cases.21 However, it was bilateral in three patients; nearly 40% of them lost hearing despite being treated with oral/IV steroids. A case report describes a patient with diabetes suffered from irreversible bilateral SSNHL receiving amikacin as an antibiotic-heparin lock on HD.3 Another recent report describes two patients with renal failure and irreversible bilateral SSNHL occurred after a few sessions of HD.4 Of total six HD patients reported to have bilateral SSNHL, only one (16.6%) had subsequent improved hearing. Thus, according to these reports, the prognosis would be poor for SSNHL in patients undergoing HD for ESRD. An alternative and effective treatment is needed to restore hearing in patients with SSNHL in the presence of ESRD on HD, especially when hearing loss is bilateral. SSNHL has been considered an otologic emergency and should be evaluated urgently by detailed history, tuning fork test, neurotologic examination, and comprehensive tests.16 The treatments for SSNHL include multiple modalities, such as oral or intravenous steroids, vasodilators, plasma expanders, anticoagulants, diuretics, and antivirals.15,16 The systemic steroids has been used currently as a mainstay of treatment of SSNHL, but it may produce unexpected side effects and be limited in cases of diabetes, hypertension, concurrent infection, or peptic ulcers, which are also common in CKD patients.22,23 ITSI is becoming an option for treatment of SSNHL for patients in whom systemic steroids are contraindicated or not tolerated. Since the first use of ITSI as salvage therapy after failure to initial systemic steroid, ITSI has been also performed as an initial primary treatment without using systemic steroids or as a concurrent treatment with systemic steroids.13,14,23 A systematic review has been welldocumented to determine the evidence for efficacy of ITSI treatment for the management of SSNHL.14 Although the meta-analysis reveals uncertain outcome of ITSI in

198

patients having SSNHL, there were reported successful trials in which ITSI was performed as an initial treatment without using systemic steroids and early treatment with ITSI in severe to profound SSNHL improves speech discrimination performance.14,22–25 In animal models, ITSI results in significantly higher perilymph concentrations of steroids than intravenous or oral administration, which is the most probable mechanism explanation for the hearing improvement under ITSI treatment.26,27 There is no apparent difference in the efficacy of dexamethasone relative to methylprednisolone.14 For the studies review, not even the exact timing of final outcome assessment is standard, but suggested to benefit from longer term follow-up of at least 3 months.14 As presented in our patient, the hearing got significant 20 dB PTA improvement on the third day after ITSI treatment, 20 dB of that observed between the 15th and the 30th days, and a 10 dB PTA improvement still existed at between the 30th day and the 90th day (Figure 1). We thought the hearing got improved significantly 3 days after ITSI treatment, in which the effect was contributed to the steroid administration. Then, oral concomitant medical treatment (vasodilators and vitamins) may account for the effect of the remaining hearing gain. Most studies of ITSI have reported no serious complications and relatively easy to perform; however, some important complications have been reported, including vertigo, tinnitus, aggravation of hearing loss, otitis media, and tympanic membrane perforation.23,25 In our case, we used ITSI on the third day after sudden onset of hearing loss. Initially, the patient complained of mild vertigo, but did not report vertigo following the second and third injection. In summary, SSNHL is a medical emergency that requires early detection and the prompt management to restore the hearing function with steroids and specific treatment of the underlying illness. ITSI could be an effective alternative to the present conventional treatment of SSNHL among ESRD patients undergoing HD. However, further larger multicenter prospective studies are necessary to establish the role of ITSI in the treatment of SSNHL among HD patients. Manuscript received February 2013; revised May 2013.

REFERENCES 1 Bazzi C, Venturini CT, Pagani C, Arrigo G, D’Amico G. Hearing loss in short- and long-term haemodialysed patients. Nephrol Dial Transplant. 1995; 10:1865–1868.


Case Reports

2 Bergstrom L, Jenkins P, Sando I, English GM. Hearing loss in renal disease: Clinical and pathological studies. Ann Otol Rhinol Laryngol. 1973; 82:555–576. 3 Saxena AK, Panhotra BR, Naguib M. Sudden irreversible sensory-neural hearing loss in a patient with diabetes receiving amikacin as an antibiotic-heparin lock. Pharmacotherapy. 2002; 22:105–108. 4 Lasisi OA, Salako BL, Kadiri S, et al. Sudden sensorineural hearing loss and hemodialysis. Ear Nose Throat J. 2006; 85:819–821. 5 Wilson WR, Byl FM, Laird N. The efficacy of steroids in the treatment of idiopathic sudden hearing loss. A double-blind clinical study. Arch Otolaryngol. 1980; 106:772–776. 6 Fausti SA, Henry JA, Schaffer HI, Olson DJ, Frey RH, McDonald WJ. High-frequency audiometric monitoring for early detection of aminoglycoside ototoxicity. J Infect Dis. 1992; 165:1026–1032. 7 Gatland D, Tucker B, Chalstrey S, Keene M, Baker L. Hearing loss in chronic renal failure-hearing threshold changes following haemodialysis. J R Soc Med. 1991; 84:587–589. 8 Johnson DW, Mathog RH. Hearing function and chronic renal failure. Ann Otol Rhinol Laryngol. 1976; 85:43– 49. 9 Mattox DE, Simmons FB. Natural history of sudden sensorineural hearing loss. Ann Otol Rhinol Laryngol. 1977; 86:463–480. 10 Mace AD, Ferguson MS, Offer M, Ghufoor K, Wareing MJ. Bilateral profound sudden sensorineural hearing loss presenting a diagnostic conundrum in a child with sickle cell anaemia. J Laryngol Otol. 2009; 123:811– 816. 11 Naithani R, Chandra J, Mathur NN, Narayan S, Singh V. Hearing loss in chronic myeloid leukemia. Pediatr Blood Cancer. 2005; 45:54–56. 12 Chau JK, Cho JJ, Fritz DK. Evidence-based practice: Management of adult sensorineural hearing loss. Otolaryngol Clin North Am. 2012; 45:941–958. 13 Silverstein H, Choo D, Rosenberg SI, Kuhn J, Seidman M, Stein I. Intratympanic steroid treatment of inner ear disease and tinnitus (preliminary report). Ear Nose Throat J. 1996; 75:468–471. 474, 476 passim. 14 Spear SA, Schwartz SR. Intratympanic steroids for sudden sensorineural hearing loss: A systematic review. Otolaryngol Head Neck Surg. 2011; 145:534–543.


15 Hughes GB, Freedman MA, Haberkamp TJ, Guay ME. Sudden sensorineural hearing loss. Otolaryngol Clin North Am. 1996; 29:393–405. 16 Shikowitz MJ. Sudden sensorineural hearing loss. Med Clin North Am. 1991; 75:1239–1250. 17 Fetterman BL, Saunders JE, Luxford WM. Prognosis and treatment of sudden sensorineural hearing loss. Am J Otol. 1996; 17:529–536. 18 Shanon E, Zikk D, Redianu C, Eylan E. Sudden deafness due to infection by Mycoplasma pneumoniae. Ann Otol Rhinol Laryngol. 1982; 91:163–165. 19 Brewis C, McFerran DJ. ‘Farmer’s ear’: Sudden sensorineural hearing loss due to Chlamydia psittaci infection. J Laryngol Otol. 1997; 111:855–857. 20 Lin C, Hsu HT, Lin YS, Weng SF. Increased risk of getting sudden sensorineural hearing loss in patients with chronic kidney disease: A population-based cohort study. Laryngoscope. 2013; 123:767–773. 21 Makita Y, Osato S, Onoyama K, Fujishima M, Fujimi S. Idiopathic sudden sensorineural hearing loss in patients undergoing long-term haemodialysis. Int Urol Nephrol. 1995; 27:487–493. 22 Kakehata S, Sasaki A, Oji K, et al. Comparison of intratympanic and intravenous dexamethasone treatment on sudden sensorineural hearing loss with diabetes. Otol Neurotol. 2006; 27:604–608. 23 Han CS, Park JR, Boo SH, et al. Clinical efficacy of initial intratympanic steroid treatment on sudden sensorineural hearing loss with diabetes. Otolaryngol Head Neck Surg. 2009; 141:572–578. 24 Hong SM, Park CH, Lee JH. Hearing outcomes of daily intratympanic dexamethasone alone as a primary treatment modality for ISSHL. Otolaryngol Head Neck Surg. 2009; 141:579–583. 25 Kim YH, Park KT, Choi BY, et al. Early combination treatment with intratympanic steroid injection in severe to profound sudden sensorineural hearing loss improves speech discrimination performance. Eur Arch Otorhinolaryngol. 2012; 269:2173–2178. 26 Parnes LS, Sun AH, Freeman DJ. Corticosteroid pharmacokinetics in the inner ear fluids: An animal study followed by clinical application. Laryngoscope. 1999; 109:1–17. 27 Chandrasekhar SS. Intratympanic dexamethasone for sudden sensorineural hearing loss: Clinical and laboratory evaluation. Otol Neurotol. 2001; 22:18–23.

199