The authors have no funding, financial relationships, or conflicts of interest to disclose.
Triological Society Best Practice
Does addition of antiviral medication to high-dose corticosteroid therapy improve hearing recovery following idiopathic sudden sensorineural hearing loss?†
Version of Record online: 28 SEP 2011
Copyright © 2011 The American Laryngological, Rhinological, and Otological Society, Inc.
Volume 121, Issue 11, pages 2280–2281, November 2011
How to Cite
Shaikh, J. A. and Roehm, P. C. (2011), Does addition of antiviral medication to high-dose corticosteroid therapy improve hearing recovery following idiopathic sudden sensorineural hearing loss?. The Laryngoscope, 121: 2280–2281. doi: 10.1002/lary.21963
- Issue online: 21 OCT 2011
- Version of Record online: 28 SEP 2011
Idiopathic sudden sensorineural hearing loss (ISSNHL) is defined as an unexplainable decline in hearing that occurs within a short period of time (12–72 hours in most studies). The incidence of ISSNHL is estimated at 5 to 20 cases per 100,000 persons per year.1 In the vast majority of the cases ISSNHL is unilateral, and the prognosis for hearing recovery is good (spontaneous recovery rate 45%–65%). Due to the rare nature of the disease, clinical trials measuring the effectiveness of treatments often have difficulty recruiting sufficient numbers of patients to yield significant results.
Multiple etiologies for ISSNHL have been proposed, including inner ear membrane rupture, obstruction of cochlear vasculature, and new onset or reactivation of viral infection.1 Hypotheses suggesting a viral etiology are supported by the observation that many patients have had recent upper respiratory tract infections within 2 weeks of the onset of ISSNHL, although some authors have noted that this rate is not higher than the general population.2 Some have shown that many patients with ISSNHL have significant levels of antiviral antibodies.2
The appropriate treatment for ISSNHL is still debated despite numerous trials. Many treatment modalities have been used for patients with ISSNHL including vasodilators, hyperbaric oxygen, intravenous contrast agents, antihistamines, corticosteroids, and antiherpetic medications (antivirals, including acyclovir and valacyclovir). Currently, steroid therapy started within 10 days of onset of hearing loss is considered the best supported therapy for ISSNHL.3 Many investigators have suggested that the use of antiviral medications in addition to high-dose steroids might improve patient hearing outcomes by stopping viral replication. Below we examine the evidence regarding the addition of antiherpetic medications to high-dose steroid therapy in the treatment of ISSNHL.
There have been four major randomized controlled trials (RCTs) assessing the efficacy of antiviral therapy combined with high-dose glucocorticoids versus glucocorticoids with placebo for the treatment of ISSNHL. Out of the four, two4, 5 assess similar end points, use similar inclusion and exclusion criteria (i.e., neoplasm, history of autoimmune disease, pregnancy, contraindication to steroid use or antiviral use), and have complete data reporting.3 There is one meta-analysis reviewing RCTs for ISSNHL that focuses on these two RCTs.
In 2002, Tucci et al. conducted a RCT of 105 subjects with ISSNHL. Final data analysis on hearing recovery included the 68 participants with normal contralateral hearing, as presence of contralateral hearing loss complicated the statistical analysis.4 Adult patients (≥18 years of age) were included if they had a hearing loss ≥30 dB in three contiguous frequencies <3 days from onset and showed pronounced hearing loss in comparison with the contralateral ear. All patients had to have had self-reported normal hearing prior to onset of ISSNHL and onset of symptoms within 10 days or less of their enrollment in the trial. Pretreatment evaluation included complete blood count, complete metabolic panel, and fluorescent treponemal antibody (FTA). Imaging studies were performed at the discretion of attending physicians. Of 105 initially recruited patients, 10 did not meet the end-point criteria either due to secondary findings (acoustic neuroma, positive FTA, <30 dB hearing loss on initial evaluation) or noncompliance. All patients were given oral prednisone (80 mg per day for 4 days, then tapered over 8 days) in an outpatient setting. In addition to steroids, 50 patients received oral valacyclovir (1 g three times a day for 10 days), whereas 44 patients were given placebo. There was a 10.5% drop-out rate. Hearing recovery was measured in several ways: improvement of pure-tone average (PTA) to 10 or 20 dB of contralateral PTA; percentage recovery PTA of ≥50%; achievement of final speech discrimination scores (SDS) of 70%, 75%, and 80%; and total percentage improvement in SDS at 2 and 6 weeks. There was no added benefit when patients were treated with valacyclovir in addition to high-dose glucocorticoids (P > .05, Fischer exact test) as measured by change in PTA or SDS (odds ratio [OR], 0.55; 95% CI, 0.21-1.49).3
Westerlaken et al. (2003) conducted a prospective, randomized, double-blind clinical trial of 91 patients age 12 to 80 years (average age, 46 years).5 Inclusion criteria were a sensorineural hearing loss of ≥30 dB for three subsequent frequencies occurring over 24 hours occurring within 14 days of evaluation. Forty-six patients were randomized to acyclovir and prednisolone, and 45 received a placebo. All patients underwent magnetic resonance imaging and laboratory evaluation for discernable causes of hearing loss. Patients were initially given intravenous prednisolone 1 mg/kg on day 1 tapered off over 7 days. Additionally, the experimental group received acyclovir (10 mg/kg intravenously three times a day for 7 days), whereas the steroid-only group was given a placebo. Patients were followed-up on an outpatient basis for the remainder of the study. Of the 91 patients included in the trial, four patients were found to have a discernable, pathologic cause for hearing loss (otosclerosis, vestibular schwannoma, and bleeding cerebral peduncle), and 17 patients had secondary issues that excluded them (documentation issues and refusal to be randomized); analysis was performed on hearing outcomes for the remaining 70 patients. Hearing results were calculated from pure-tone thresholds at 0.5, 1, 2, and 4 kHz, and speech audiometry from audiograms at 1 week, 6 months and 12 months. The authors predicted a 10-dB improvement in the acyclovir group hearing outcomes over an expected recovery in the placebo group of 35 dB. All data were treated with an “intention to treat” principal. Data was analyzed using Mann-Whitney or Fischer exact tests; parametric data was processed by t tests for independent samples and by χ2 analysis (P > .05). The study showed that at 1 year following ISSNHL onset, there was no statistically significant difference in recovery of hearing between the prednisolone plus acyclovir and prednisolone plus placebo groups (OR, 1.83; 95% CI, 0.47-7.17).5
A pooled meta-analysis by Conlin and Parnes (2007) analyzed the data collected from four RCTs on the use of antiviral medications in addition to oral steroids.3 This analysis excluded two studies due to incomplete data reporting that resulted in non-statistically significant results. Hearing recovery was defined as a 50% improvement over baseline in pure-tone audiometry. Analyzing 138 patients reported in the Tucci et al. (2002) and Westerlaken et al. (2003) studies, Conlin and Parnes determined that there was no significant difference between the steroid plus antiviral therapy versus steroid therapy alone (OR, 0.92; 95% CI, 0.29-2.92;). Use of antivirals also had no impact on recovery time or improvement in hearing.
There is insufficient evidence to suggest that the addition of antiviral therapy in addition to corticosteroids will improve hearing recovery for patients with idiopathic sudden sensorineural hearing loss.
LEVEL OF EVIDENCE
Evidence level is 1a (pooled meta-analysis of randomized controlled trials).