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Three Part Question

In [an adult patient presenting with sudden onset idiopathic sensorineural hearing loss] does [antiviral medication] improve outcome [time to and degree of hearing recovery and subjective improvement in symptoms]?

Clinical Scenario

A 52 year-old women presented to the emergency department with a history of sudden onset of hearing loss in her right ear, which came on over the preceding hour. She had no past medical history of note. Examination of the ear was unremarkable and Weber’s / Rinne’s tests suggested that her hearing loss was sensorineural in nature. A diagnosis of sudden onset idiopathic sensorineural hearing loss (SSHL) was made. The ENT surgeon on call was contacted and advised prescribing acyclovir. You wonder what the evidence is to support this strategy.

Search Strategy

MEDLINE: [exp HEARING LOSS, SUDDEN or exp HEARING LOSS, SENSORINEURAL or sensorineural AND hearing AND loss.ti,ab or sensorineural AND deafness.ti,ab or sudden AND deafness.ti,ab or sudden AND hearing AND loss.ti,ab] and [exp ANTIVIRAL AGENTS or antivir*.ti,ab].
EMBASE: [exp PERCEPTION DEAFNESS or exp SUDDEN DEAFNESS or sensorineural AND hearing AND loss.ti,ab or sensorineural AND deafness.ti,ab or sudden AND deafness.ti,ab or sudden and hearing and loss. ti,ab] and [exp ANTIVIRUS AGENTS or antivir*.ti,ab].

MEDLINE search (1950-Dec, 2011)
EMBASE search (1980-Dec, 2011)

Search Outcome

The Medline search identified 175 papers, 164 were irrelevant and 5 were excluded as they were not randomised controlled trials (RCTs), all of these papers were observational studies. The Embase search identified 506 papers, 494 were irrelevant and 6 were excluded as they were not RCTs (all observational studies). The same six papers were identified by both Medline & Embase searches. They include one systematic review and one meta-analysis performed by the same author and 4 RCTs. The systematic review included all 4 RCTs identified in the original search. Only 2 of the 4 RCTs were used in the meta-analysis, the other 2 were excluded as they provided inadequate raw data. All RCTs identified compared antivirals combined with steroids vs steroids alone.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Stockroos RJ, Albers FW, Tenvergert EM 1998 Netherlands	44 patients presenting with cochlear hearing loss of unknown aetiology. Randomised to receive acyclovir 10mg/kg iv tds and prednisolone 1mg/kg iv (tapering dose to 0) or prednisolone alone for seven days.	Randomised, double blind placebo controlled trial.	Primary outcome: hearing recovery of over 10 dB (pure tone audiometry).	No significant difference.	Small study. No power calculation. More patients with profound hearing loss were allocated to the placebo group than the treatment group. No intention to treat analysis. Incomplete data reporting. No allocation concealment.
			Secondary outcomes: subjective assessments (improvement in hearing, pressure sensation, dizziness / tinnitus).	No significant difference.
Tucci DL, Farmer JC, Kitch RD, Witsell DL 2002 U.S.A	84 patients presenting with cochlear hearing loss of unknown aetiology. Patients were randomised to receive valacyclovir 1g po tds for 10 days and prednisolone (80mg po od for 4 days then tapering dose for 8 days) or prednisolone alone.	Randomised, double blind placebo-controlled trial.	Primary outcome: hearing recovery 2 and 6 weeks post treatment.	No significant difference.	No intention to treat analysis. Powered to detect a 30% improvement in the proportion of patients recovering useful hearing. A smaller improvement would still be clinically important. Significant drop out rate (10.5%). Incomplete data reporting (full data only reported the cohort with normal hearing in the unaffected ear (n=68).
			Secondary outcomes: improvement in hearing screening inventory questionnaire and improvement in SF-12 results (a health survey).	No significant difference.
Uri N, Doweck I, Cohen-Kerem R, Greenberg E 2003 Israel	60 patients, presenting with cochlear hearing loss of unknown aetiology. Patients were randomised to receive either acyclovir 15mg/kg iv tds and hydrocortisone 100mg iv tds for 7 days or hydrocortisone alone.	Randomised controlled trial.	Improvement in hearing loss (pure tone audiometry, speech reception threshold and speech discrimination scores) measured at 1, 3 and 12 months after treatment.	No significant difference.	Criteria of SSHL used was different from that provided by US National Institute for Deafness and Communication Disorders [which was used by the other 3 RCTs being evaluated]. Small size study. No power calculation. No blinding. Incomplete data reporting. Unclear whether data was analysed on an intention to treat basis or not.
Westerlaken BO, Stokroos RJ, Dhooge IJ et al 2003 Netherlands	70 patients with sensorineural hearing loss of unknown cause. Patients were randomised to receive either acyclovir 10mg/kg iv tds and 1mg/kg prednisolone iv od for 7 days or prednisolone with placebo.	Randomised double-blind placebo- controlled trial.	Primary outcome: hearing recovery (measured by pure tone & speech audiometry) at 1 week, and at 3,6 and 12 months.	No significant difference.	Large numbers of enrolled patients were not included in final analysis due to administrative problems (n=16%). Failure to control for severity of initial hearing loss between groups (mean hearing loss in the acyclovir group was 62.9 dB HL compared with 83.6 dB HL in the placebo group). The study was underpowered (power calculation required 126 patients but only 91 patients recruited).
			Secondary outcomes: subjective reporting of perceived hearing recovery, tinnitus intensity, pressure sensation and vertigo severity (measured at 1 week and at 3, 6 and 12 months).	No significant difference.
Conlin A E and Parnes L S 2007 Canada	Systematic review of all randomised controlled trials on the treatment of sudden idiopathic sensorineural hearing loss with antivirals. Trials identified by search of MEDLINE between 1996-2006.	Systematic review	Primary outcome: pure-tone average score. Secondary outcome measures: speech reception thresholds, speech discrimination scores and subjective patient reporting of tinnitus, vertigo and perceived hearing improvement.	4 studies identified. No statistically significant results.	Only considered studies published in English language. Limited by quality of RCTs used, all of which had methodological flaws and were of small size.
			Secondary outcome measures: speech reception thresholds, speech discrimination scores and subjective patient reporting of tinnitus, vertigo and perceived hearing improvement.	4 studies identified. No statistically significant results.
Conlin AE, Parnes LS 2007 Canada	Meta-analysis of the results of randomised controlled trials on treatment of sudden sensorineural hearing loss. Trials identified by search of MEDLINE between 1996-2006. Combined data from two trials (performed by Tucci and Westerlaken) across 138 patients. Both trials compared steroids plus antiviral therapy vs. steroid therapy alone.	Meta-analysis	Hearing recovery: measured as 50% improvement from baseline and percentage of improvement in hearing.	No significant difference in outcome between groups (OR, 0.92; 95% CI, 0.29-2.92; p =0.88). No significant heterogeneity (p=0.16).	Only able to use 2 out of 4 RCTs performed (as 2 studies only provided graphical representation of their data). Did not obtain raw data from the authors of the other 2 trials.

Comment(s)

Sudden onset sensorineural hearing impairment (SSHI) is an idiopathic condition of acute hearing loss. The possible association with viral infection has led to the inclusion of antiviral medication in treatment regimes. Evidence to date does not demonstrate any improvement in defined outcomes with the use of antiviral medication. Owing to the weaknesses inherent in the best available evidence, it remains a possibility that in the future more robust trials will identify a benefit. Such trials may be difficult to perform owing to condition incidence (5-20 per 100,000 persons per year) in addition to high rate of spontaneous recovery (around 50% within two weeks in reported series). This is confounded by the lack of concise and agreed outcome measures of what constitutes complete or partial hearing recovery. All RCTs identified were of antivirals and steroids vs steroids alone. Given the lack of lack of definitive evidence to support steroid use in SSHL future studies should consider looking at antivirals in isolation.

Clinical Bottom Line

There is no evidence to support the use of antivirals in sudden onset idiopathic sensorineural hearing loss.

Level of Evidence

Level 2 - Studies considered were neither 1 or 3.

References

1. Stokroos RJ, Albers FWJ, Tenvergert EM Antiviral treatment of idiopathic sudden sensorineural hearing loss: a prospective, randomized, double blind clinical trial Ann Otolaryngol (Stockh) 1998;118:488-495
2. Tucci DL, Farmer JC, Kitch RD, Witsell DL Treatment of sudden sensorineural hearing loss with systemic steroids and valacyclovir. Otol Neurotol 2002; 23: 301-308
3. Uri N, Doweck I, Cohen-Kerem R, Greenberg E Acyclovir in the treatment of idiopathic sudden sensorineural hearing loss. Otolaryngol-Head Neck Surg 2003; 23: 301-308
4. Westerlaken B O, Stokroos R J, Dhooge I J M et al Treatment of Idiopathic Sudden Sensorineural Hearing Loss with Antiviral Therapy: A Prospective, Randomised, Double-Blind Clinical Trial. Ann Otol Rhinol Laryngol 112: 993-1000
5. Conlin A E and Parnes L S Treatment of sudden sensorineural hearing loss, I. A systematic review. Arch Otolaryngol Head Neck Surg 2007; 133: 573-581
6. Conlin AE, Parnes LS Treatment of sudden sensorineural hearing loss, II. A meta-analysis. Arch Otolaryngol Head Neck Surg 2007; 133: 582-586