Salvage Treatment Strategies for Refractory Sudden Sensorineural Hearing Loss: A Comprehensive Review and meta analysis with practical recommendations

Piero Giuseppe Meliante¹Luigi D'Avino²Giuseppe Barba²Edoardo Covelli¹Carla Petrella³Christian Barbato^3*Antonio Minni^4*

• ¹Department of Neuroscience, Mental Health and Sensory Organs (N.E.S.M.O.S.), Faculty of Medicine and Psychology, "Sapienza" University, Rome Italy, ROMA, Italy
• ²Otorhinolaryngology, Head and Neck Surgery, "V. Monaldi" Hospital, A.O.R.N. dei Colli, Naples, Italy, Naples, Italy
• ³Institute of Biochemistry and Cell Biology (IBBC), National Research Council (CNR), Department of Sense Organs DOS, Sapienza University of Rome, Viale del Policlinico 155, 00161 Roma, Italy., ROMA, Italy
• ⁴Department of Sense Organs DOS, Sapienza University of Rome, Viale del Policlinico 155, 00161 Roma, Italy, ROMA, Italy

Background: Sudden sensorineural hearing loss (SSNHL) affects up to 27 per 100,000 individuals annually, with more than half failing to achieve complete recovery following standard therapy. Identifying effective salvage treatments for refractory cases is critical to improve outcomes and reduce long-term auditory disability. This systematic review aims to evaluate the efficacy of current salvage treatment options for SSNHL unresponsive to first-line systemic corticosteroid therapy, and to propose an evidence-based treatment algorithm. Methods: A comprehensive search of PubMed, Embase, and Cochrane Library was conducted for English-language articles published between January 2010 and April 2025. Studies eligible for inclusion were clinical trials and large case series evaluating salvage interventions in patients with SSNHL unresponsive to systemic therapy. Risk of bias was assessed using the ROBINS-I tool. Results: 41 articles met the inclusion criteria. Intratympanic steroids (ITS), both methylprednisolone and dexamethasone, showed consistent efficacy, with methylprednisolone demonstrating superior outcomes (p < 0.05). Hyperbaric oxygen therapy (HY) was also effective, particularly at low frequencies. Combined ITS and HY yielded the best results in terms of word recognition and PTA improvement, although not always statistically superior to monotherapy. Early initiation of ITS correlated with better outcomes, and ITS was especially effective for high-frequency SSNHL and tinnitus (p = 0.002). Non-invasive therapies like constraint-induced sound therapy (CIST) showed promise in improving outcomes by mitigating maladaptive cortical reorganization. Additional emerging treatments (e.g., IGF-1, urokinase, surgical interventions) demonstrated potential but require further validation. Conclusion: ITS and HY, especially in combination, represent the most effective salvage therapies for refractory SSNHL. Methylprednisolone may offer better outcomes than dexamethasone, and early intervention remains a key prognostic factor. CIST demonstrated a promising action for mitigating cortical maladaptation to sound deprivation. Systematic review registration: This review followed PRISMA guidelines and was registered in PROSPERO database (CRD42025645069