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Three Part Question

In adult patients with [sudden onset unilateral idiopathic sensorineural hearing loss] is early use of [oral steroid therapy or intratympanic steroid therapy] better at improving [time to recovery and outcome] as first line therapy.

Clinical Scenario

A fifty-six year old woman presents at your Emergency clinic with a twenty-four hour history of sudden onset of left sided sensorineural hearing loss. She has no associated co-morbidities. Following a normal examination, a diagnosis of idiopathic sudden sensorineural hearing loss (ISSNHL) is made. You think that she would benefit from a course of steroids as first line therapy but are unsure of the best method of delivery. You discuss the options with your colleagues, one advises oral steroids whilst the other advocates the use of intratympanic delivery. You wonder what would be the best course of action.

Search Strategy

Medline search from 1948 to November 2013 using the Pubmed interface (("steroids"[MeSH Terms] OR "steroids"[All Fields] OR "steroid"[All Fields]) AND sudden[All Fields] AND ("hearing loss, sensorineural"[MeSH Terms] OR ("hearing"[All Fields] AND "loss"[All Fields] AND "sensorineural"[All Fields]) OR "sensorineural hearing loss"[All Fields] OR ("sensorineural"[All Fields] AND "hearing"[All Fields] AND "loss"[All Fields]))) AND ("humans"[MeSH Terms] AND English[lang]). Related articles and references were screened for suitable articles.

Search Outcome

Three hundred articles were found using the reported search strategy. From these six articles were identified that provided the best evidence to answer the question.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Rauch et al 2011 USA	250 patients Unilateral idiopathic sudden sensorineural hearing loss (ISSNHL) presenting within 14 days of onset of 50 decibels (dB) or higher of pure tone average hearing threshold across 4 contiguous frequencies 121 patients treated with oral prednisolone 129 patients received intratympanic (IT) injection	Prospective randomised non-inferiority study.	Primary outcome: Change in hearing from first audiogram and two months after treatment (dB PTA). Non-inferiority defined as less than a 10 dB difference in hearing outcome between treatments Secondary outcome: Hearing, PTA at 6 months. Difference in PTA between affected and unaffected ear at 2 months and 6 months. Word recognition score at 2 months and 6 months. Adverse events. Treatment regime: Oral prednisolone 60mg/d for 14 days followed by 5 day taper course. Total 19 days. IT: Four 1ml doses 40mg/ml of methylprednisolone over 2 weeks. Primary analysis based on intention-to-treat.	At 2 months: Oral group change in Pure tone audiogram (PTA) by 30.7dB IT group change in PTA by 28.7dB No significant difference between the two groups Hypothesis of the inferiority of IT steroid to oral steroid was rejected	Pre-enrollment steroid use patients included. Non-blinded uncontrolled study Bias from intention to treat analysis on non-inferiority.
Dispenza et al. 2011 Italy	46 patients ISSNHL loss of at least 30 dB across 3 contiguous frequencies Group A 25 patients treated with IT therapy. Group B 21 patients treated with oral steroids	Prospective randomised study	Improvement of 10dB on PTA. Treatment regime: Oral prednisolone: 60mg/day tapered over 14 days IT: 4mg/ml dexamethasone weekly for total of 4 injections	20/25 group A (80%) and 17/20 group B (81%) showed improvement. PTA improvements between the two treatments was not statistically significant (p=0.61) No significant difference in recovery times between the treatment groups (p=0.63)	Difference in onset of hearing loss between 2 groups. Difference in time to starting treatment between 2 groups. - Both limit analysis Non-blinded, uncontrolled study Small sample size Non-powered study
Hong et al 2009 South Korea	75 patients ISSNHL loss of 30 dB or more over 3 contiguous frequencies occurring within 3 days or fewer. IT group 38 patients. Oral steroid group 37 patients. Exclusion criteria: Meniere’s disease, vertigo, diabetes, tumors, treatment onset >15 days.	Randomized control study	Pre-treatment, post-treatment and contralateral PTA hearing levels. Post-treatment hearing measurements at 3 months. Improvement in hearing thresholds by frequency. Hearing recovery expressed according to Siegel’s criteria. Statistical analysis by t-test and Chi-square test Outcome assessors blinded. Treatment regime: IT: 0.3-0.4cc 5mg/ml dexamethasone – once a day over 8 days. Oral: tapering dose – 60mg for 4 days, 40mg for 2 days, 20mg for 2 days	No significant difference in pure-tone averages or hearing recovery rate. Threshold improvement at 4000Hz and 8000Hz statistically higher in oral group. No side effects in either group.	Not double-blinded Not analysed on intention to treat basis. Confounders: Oral prednisolone group received additional peripheral vasodilator and ginkgo biloba. Non-powered study
Lim et al. 2013 South Korea	60 patients – 20 per group ISSNHL >30dB in 3 contiguous frequencies within 3 days. Group I – oral prednisolone Group II – IT dexamethasone Group III – oral prednisolone + IT dexamethasone	Prospective randomised study	Hearing change evaluated by pre/post treatment PTA. 10dB difference = significant. Recovery rate as assessed by AAO-HNS Clinical Practice Guidelines (hearing ≥ 10 dB and word recognition score ≥ 10% is defined as hearing recovery). Power sample size n=20. Treatment regime: Group I: 60mg/ day 5 days, 40mg/day 2 days, 20mg/day 2 days, 10mg/day 1 day. (10 days) Group II: IT twice/week for 2 weeks (4 total). 0.3-0.4ml 5mg/ml dexamethasone. Group III: Oral prednisolone 2 weeks + IT 2 weeks Outcome assessors blinded.	No statistical difference between the 3 groups in hearing gain. No significant difference in hearing gains at different frequencies between the treatment groups. No statistical difference in recovery rate between the groups.	Different duration of oral prednisolone treatment regime between group I and III. Small sample size. Not double blind placebo controlled study.
Battaglia et al. 2008 USA	51 patients >20dB unilateral hearing loss over 3 contiguous frequencies with <6 week history of ISSNHL with no identifiable cause Group A (17 patients) – IT dexamethasone + placebo taper Group B (18 patients) – oral prednisolone with placebo IT injection Group C (16 patients) – IT dexamethasone and oral prednisolone	Multicentre double-blind placebo controlled randomised study	Complete recovery = recovery of hearing to within 5% of contralateral speech discrimination score (SDS) or 5dB of contralateral PTA. Partial recovery = PTA improvement of 15dB 25% increase in SDS = significant. Treatment regime: Oral – 60mg 7 days, 50mg 2 days, 40mg 2 days, 30mg 1 day, 20mg 1 day, 10mg 1 day (or placebo capsules). IT injection – 0.5-0.7ml 12mg/ml once a week for 3 weeks (or saline placebo). Audiogram prior to each injection and 4 weeks after final injection. PTA measured at 500, 1000, 2000Hz. Speech discrimination measured.	Significant improvement in PTA and SDS in all 3 groups (p<0.01, Wilcoxon signed rank test) No significant difference between Groups A and B. Significant improvement in Group C compared to Group B in proportion of patients achieving at least 15dB PTA improvement (p =0.02, Kruskal-Wallis test). Significant improvement SDS among all treatment groups. Significant improvement in Group C versus Groups A and B in complete and partial hearing recovery. No long-term steroid complications.	Small sample size Power study estimated required population of 64 per group which increased to 92 patients per group. Study prematurely terminated. Variability in clinician motivation to recruit patients.
Bae et al. 2013 South Korea	735 patients Divided into 3 groups depending on treatment received. Group 1 – IT steroid (94 patients) Group 2 – Oral steroid (444 patients) Group 3 – IT + oral steroid (197 patients)	Retrospective multicentre study	Hearing evaluation (PTA) before initial treatment and 4 weeks following final treatment. Improved hearing = >10dB HL decrease in average air conduction threshold at 500, 1000, 2000 and 3000 Hz.	No significant difference in hearing gain (p=0.147) or hearing improvement (p=0.067) between the 3 groups.	Non-randomised retrospective study. Inclusion of patients with chronic medical conditions affecting the treatment they received. No power study

Comment(s)

The incidence of diagnosed ISSNHL is between 5-20 per 100,000 people per year. Systemic corticosteroids have traditionally been used in the management of these patients, however the use of intratympanic steroids in the acute setting is recently being investigated. The ideal steroid treatment regime is yet to be determined and varies between the different studies. The majority of current studies have small sample sizes and are uncontrolled, further powered randomised controlled studies are required to establish a significant difference between the two therapies.

Clinical Bottom Line

There is no significant difference in outcome between an intratympanic steroid regime versus a high dose oral steroid regime for patients with sudden onset unilateral idiopathic sensorineural hearing loss.

References

1. Rauch et al. Oral vs intratympanic corticosteroid therapy for idiopathic sudden sensorineural hearing loss: a randomized trial
2. Dispenza et al. Treatment of sudden sensorineural hearing loss with transtympanic injection of steroids as single therapy: a randomized clinical study.
3. Hong et al. Hearing outcomes of daily intratympanic dexamethasone alone as a primary treatment modality for ISSHL.
4. Lim et al Efficacy of 3 different steroid treatments for sudden sensorineural hearing loss: a prospective, randomized trial.
5. Battaglia et al. Combination therapy (intratympanic dexamethasone + high-dose prednisone taper) for the treatment of idiopathic sudden sensorineural hearing loss
6. Bae et al. Efficacy of intratympanic steroid therapy for idiopathic sudden sensorineural hearing loss: comparison with systemic steroid therapy and combined therapy