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LONDON, Ontario, June 18 -- Although sudden sensorineural hearing loss is typically treated with systemic steroids, little evidence exists to support this or any other treatment, researchers said.

In a meta-analysis and a systematic literature review, both published in the June issue of Archives of Otolaryngology-Head & Neck Surgery, steroids showed only a trend for benefit compared with placebo (odds ratio 2.47, P=0.08), reported Lorne S. Parnes, M.D., of the University of Western Ontario here, and Anne Elizabeth Conlin, M.D., of the University of Ottawa in Ottawa, Ontario.

The wide variety of other treatments studied yielded no significant benefit or had insufficient evidence, they said.

The findings "considerably challenge the conventional view that systemic steroids constitute the gold standard for treatment of sudden sensorineural hearing loss," they wrote.

The researchers searched the English language literature for randomized controlled trials on the treatment of sudden deafness. They found 20 prospective trials published from 1966 through February 2006.

Few of the trials defined sudden sensorineural hearing loss by the National Institute for Deafness and Communication Disorders definition as loss of at least 30 decibels of hearing over three or more contiguous test frequencies within three days.

Outcome measures and evaluation times also varied across trials. The validity scores for the methodological quality of the studies were marginal, ranging from two to eight with a mean of 6.1 on the nine-point scale.

Five of the trials met criteria for meta-analysis.

Eight trials included steroid treatment, two orally in comparison with placebo. One used dexamethasone at twice daily doses of 0.75 mg to 4.5 mg or methylprednisolone at 4 mg a day to 16 mg three times daily. The other used prednisone at a dose of 1 mg/kg daily.

Although the dexamethasone study has been considered the landmark study for the treatment of sudden sensorineural hearing loss, "the methodological validity of this study is significantly limited," the researchers noted.

The study was not described as being randomized, although subsequent review articles have cited it as such, and the time at which outcomes were measured was not specified. The doses of steroids used varied considerably across patients.

The dexamethasone study reported significant benefit for steroids compared with placebo, but the other pseudorandomized controlled trial did not.

In a pooled analysis of these two trials with a total of 88 patients, steroids tended to improve hearing more than placebo, but the difference was not statistically significant (odds ratio 2.47, 95% confidence interval 0.89 to 6.84, P=0.08).

"It is nonetheless interesting," the researchers said, "that, with the addition of some degree of randomization, the positive treatment effect attributed to oral steroids was not reproduced."

"Systemic steroids cannot be considered the gold standard of treatment of sudden sensorineural hearing loss, given the severe limitations of the landmark study supporting their use," they concluded.

Another four studies evaluated antiviral therapy plus steroids (valacyclovir [Valtrex] with prednisone, acyclovir [Zovirax] with prednisolone, or acyclovir with hydrocortisone) compared with placebo plus steroids.

None of these studies found significant benefit for combination therapy over steroids alone. Not surprisingly, in the pooled analysis of the two studies with complete data reporting for 138 patients, the researchers found no benefit to the addition of antiviral therapy (OR 0.92, 95% CI 0.29 to 2.92, P=0.88).

Two trials with a total of 183 patients compared steroids alone to active treatments of carbogen inhalation (5% carbon dioxide and 95% oxygen) or fibrinolysis with the snake venom agent batroxobin or betamethasone. Again, though, the meta-analysis turned up no difference between steroid treatment and other active treatment (OR 1.27, 95% CI 0.64 to 2.55, P=0.50).

These comparisons suggest that targeting one possible cause of sudden sensorineural hearing loss-inflammation-is not more effective than targeting other theoretical causes-disturbances in circulation or viral infection, Drs. Parnes and Conlin said.

"This meta-analysis was unable to definitively support systematic steroids as the gold standard for treatment of sudden sensorineural hearing loss," they wrote.

One trial, however, found significant benefit to intratympanic dexamethasone as salvage therapy for patients who had failed treatment with carbogen, methylprednisolone, nicametate, vitamin B, and fludiazepam.

Significantly more patients randomized to 1 mg/mL weekly intratympanic dexamethasone for three weeks recover at least 30 decibels of hearing compared with those who stayed on nicametate, vitamin B, and fludiazepam (53.3% versus 7.1%, P<0.05).

Mixed results were seen with other types of therapy.

Four trials looked at vasoactive and hemodilution treatments, including pentoxifylline, dextran, Ginkgo biloba, and nifedipine, but none found significant benefit of treatment over control.

Two trials reported significant benefit for the addition of magnesium to standard therapy or steroid therapy, but the methodology of one was poor and the other reported findings in graph form only.

Another two studies found benefit for vitamin E added to steroids, carbogen, and magnesium and for hyperbaric oxygen added to prednisone, dextran 40 (Rheomacrodex), diazepam, and pentoxifylline.

But, fibrinogen, recombinant tissue plasminogen activator, and prostaglandin E₁ -- in three trials separately -- did not improve hearing outcomes.

Overall, "none of these studies was without limitations, and future research is needed to further evaluate the positive findings reported," Drs. Parnes and Conlin concluded.

The researchers reported no conflicts of interest.

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