Vascular lesions, such as cochlear ischemia or cochlear infarction, are among the most likely causes of SSNHL. The blood vessels in the human ear are terminal blood vessels without collateral circulation (9). Once vasospasm or embolism occurs, blood supply to the nerve cells of the inner ear is compromised, resulting in nutritional depletion. Furthermore, the hair cells of the cochlea have a high oxygen requirement and poor tolerance to hypoxia, making them particularly vulnerable to damage when the microcirculation of the inner ear is impaired. Underlying conditions including hypertension, diabetes and hyperlipidemia can accelerate vascular sclerosis and microcirculatory disorders (10), further increasing disease risk. In addition, studies have shown that hyperfibrinogenemia, antithrombin deficiency and high-factor VIII plasma levels are associated with SSNHL (11–15). These changes lead to hypercoagulability and microthrombosis, which may cause cochlear ischemia and lead to SSNHL.

Certain patients with autoimmune diseases produce specific antibodies against their own inner ear tissues, including anti-inner ear antibodies and anti-heat shock protein (HSP) antibodies (16). In such cases, the immune system mistakenly attacks the inner ear tissues. These antibodies can directly bind to hair cells, the stria vascularis or auditory nerves within the cochlea, leading to cell dysfunction or death. In addition, circulating antigen-antibody complexes may deposit in the blood vessels or basement membrane of the inner ear, activate the complement system and trigger a local inflammatory response. This can lead to microcirculation disorders or thrombosis, ultimately resulting in inner ear ischemia (10,11).

Patients with SSNHL have been found to exhibit elevated levels of circulating immune complexes and HSP70, as well as IgG antibodies against the inner ear-specific proteins cochlin and b-tectorin (15). Upregulated mean erythrocyte sedimentation rate, antinuclear antibody levels, C3, C4 and monocyte counts have also been reported (17). Furthermore, steroid therapy greatly improves hearing recovery in SSNHL (18), likely due to its immunosuppressive and anti-inflammatory effects, which supports the hypothesis that immune-mediated mechanisms contribute to SSNHL.

Common viruses, such as mumps, measles, varicella zoster and influenza, can directly invade the inner ear or auditory nerve, leading to inflammation. Following viral infection, the immune system releases large amounts of pro-inflammatory factors, including TNF-α and IL-6, which can trigger local inflammation in the inner ear, resulting in increased vascular permeability, tissue edema and hair cell dysfunction (4,5). In one case series, sudden hearing loss was reported in a patient with a confirmed severe acute respiratory syndrome-coronavirus-2 infection, suggesting that the infection may have contributed to SSNHL through mechanisms associated with direct damage to the inner ear structure, immune-mediated inflammation and thrombosis (19). In an experimental model, Zhuang et al (20) established cytomegalovirus infection in neonatal mice, and monitored auditory brainstem response tests for 3 consecutive weeks. The study revealed hearing loss, a significant increase in reactive oxygen species (ROS) levels in the inner ear, and activation of the neutrophil/lymphocyte ratio (NLR) family pyrin domain containing 3 inflammasome in the infected mice. These findings suggest that cytomegalovirus infection can induce immune or inflammatory reactions in the inner ear, which are important contributors to hearing loss.

The pathological mechanisms underlying SSNHL may involve ischemia, hypoxia and microcirculatory dysfunction within the inner ear, while HBOT can ameliorate hypoxia in the inner ear, sustain normal metabolic activity in the inner ear microcirculation, induce vasoconstriction and reduce edema by increasing the oxygen partial pressure of the perilymph. Consequently, HBOT improves the permeability of the inner ear and reduces ischemia-related injury, thereby providing therapeutic effects in the treatment SSNHL. The main mechanism of HBOT in SSNHL is shown in Fig. 1.

The cochlea, located within the temporal bone, has a rather limited blood supply, which is mainly provided by the labyrinthine artery. Cochlear potentials play a crucial role in auditory signal conduction, as the cochlea mediates the conversion of sound waves into nerve impulses. This process is dependent on the magnitude of the cochlear potential, which relies on an adequate supply of oxygen. Elevation of the blood oxygen content leads to an increase in the amplitude of the cochlear potential and improves auditory sensitivity, whereas hypoxia results in the loss of intravascular potential, leading to SSNHL (23). Therefore, the correction of inner ear hypoxia is an important component in the treatment of SSNHL. At normal pressure at sea level, ~98% of the oxygen in the blood is complexed with hemoglobin in blood cells, and only a small amount of oxygen is dissolved in the plasma (24). However, inhalation of 100% oxygen at pressures >1.4 ATA significantly increases the diffusion radius of oxygen from capillaries to surrounding tissues (25). Breathing pure oxygen under high pressure increases the partial pressure of oxygen in the lungs and significantly increases the plasma oxygen concentration, enabling the rapid correction of ischemic and anoxic states in the inner ear. This increase in the blood oxygen tension within the inner ear capillaries ensures that sufficient oxygen reaches the auditory cells, thereby maintaining their normal metabolic function (26).

Inflammation of the inner ear has been implicated in the development of sudden deafness (27,28). Toll-like receptor 4 (TLR4), NF-κB and TNF-α levels have been demonstrated to be upregulated in peripheral blood of patients with ISSHL, and to decrease after HBOT. This therapy inhibits the activation of TLR4 and NF-κB, which reduces the release of pro-inflammatory cytokines (4,29). These findings suggest that HBOT may alleviate hearing loss in patients with SSNHL by suppressing TLR4/NF-κB-mediated inflammatory responses (30). In addition, HBOT has been shown to inhibit the expression of TLR4 mRNA, thereby further blocking the transmission of inflammatory signals.

Oxidative stress is a known risk factor for microcirculatory damage (31) and plays a key role in the pathogenesis of SSNHL. It is characterized by alterations in the structure and function of erythrocyte membranes, along with increased levels of membrane lipid peroxidation and intracellular ROS production. HBOT can improve oxygen delivery and reduce the production of inflammatory mediators, including ROS (32), thereby inhibiting oxidative stress and the inflammatory cascade.

The upregulation of insulin-like growth factor-1 (IGF-1) and HSP70 is closely associated with hearing recovery. In particular, IGF-1 has been indicated to alleviate neuroinflammation by inhibiting inflammatory pathways such as TLR4/NF-κB and promoting the polarization of M2-type microglia (33), while the upregulation of HSP70 has been demonstrated to improve the inner ear microenvironment by reducing oxidative stress and inflammatory responses (6). HBOT increases the concentration of IGF-1 and HSP70 in the serum of patients (34), thereby enhancing cellular tolerance to hypoxia and injury, and contributing to improved hearing outcomes in patients with SSNHL.

The NLR is a valuable indicator of inflammatory processes, while the platelet/lymphocyte ratio (PLR) is an important indicator of microcirculatory dysfunction associated with ischemia (35). An elevated NLR may indicate inner ear microvascular inflammation, while an elevated PLR may indicate platelet activation, vascular endothelial injury or atherosclerosis. The NLR and PLR are both significantly upregulated in patients with SSNHL, suggesting the presence of underlying inflammation and vascular ischemia. In addition, a higher NLR and PLR prior to treatment are associated with a poor patient prognosis. Notably, HBOT has been demonstrated to reduce the NLR and PLR (4,36) thereby mitigating local inflammatory responses and improving clinical outcomes (14).

Overall, these findings indicate that HBOT inhibits the inflammatory response through multiple targets and pathways, including suppression of the TLR4/NF-κB signaling pathway, reduction of ROS production, upregulation of IGF-1 and HSP70, downregulation of NLR and PLR, and the enhancement of antioxidant capacity. Together, these mechanisms alleviate inner ear inflammation, protect auditory cells and promote hearing recovery.

HBOT has been shown to significantly reduce whole blood viscosity, plasma viscosity and the blood cell aggregation index by enhancing erythrocyte deformability and reducing platelet adhesion and aggregation (3). These effects improve coagulation function and reduce blood viscosity, thereby helping to alleviate blood hypercoagulability. This promotes the restoration of blood flow and microcirculation in the inner ear, promotes local vasoconstriction, reduces capillary permeability and exudation, diminishes inner ear edema and effectively mitigates cochlear damage caused by microcirculation disorders (24–26).

HBOT can be administered in single- or multi-patient chambers (37). Single-patient chambers accommodate only one patient, and the entire chamber is usually pressurized with 100% oxygen, allowing the patient to breathe directly from the chamber atmosphere. By contrast, multi-patient chambers accommodate several individuals, where each patient breathes ~100% oxygen through a mask, hood or endotracheal tube. For HBOT to be effective in the treatment of SSNHL, the pressure in the hyperbaric chamber should be ≥1.4 ATA to provide an adequate increase in the diffusion radius of oxygen from the capillaries to the surrounding tissues (38). According to European Committee for Hyperbaric Medicine (ECHM) guidelines (39), HBOT is recommended to last for ~90 min and consist of three main phases: i) The first phase lasting ~10 min, with air compressed to 2.0–2.5 ATA and maintained for 70 min; ii) the second phase where the patient breathes pure oxygen through a mask three times for 20 min, interspersed with two 5-min air breaks without the mask; and iii) the final decompression stage. The intermittent oxygen breathing protocol is designed to minimize symptoms of oxygen toxicity.

The optimal treatment strategy for SSNHL varies according to the severity and duration of symptoms and the response to treatment. Most treatments involve an average of 10–20 sessions, with a total HBOT time of ≥1,200 min, and have the greatest effectiveness at a pressure of 2.2–2.5 ATA (40,41).

Age, diabetes, smoking and a history of heart disease have been reported as factors affecting the severity of SSNHL (10,42). An association between metabolic syndrome and SSNHL has also been identified, and the prognosis of SSNHL in patients with metabolic syndrome is poor (43). Early intervention is critical, and studies have emphasized that the optimal effects of HBOT are achieved when this therapy is initiated within 2 weeks of symptom onset (44,45). Generally, earlier treatment initiation leads to improved outcomes (46). Notably, patients with more severe hearing loss tend to experience greater benefits from HBO (47), which may be due to the extent of improvement being more apparent in cases of greater loss. However, the recovery rate of patients with mild hearing loss is higher, whereas the prognosis of patients with severe or total deafness remains poor (48).

The treatment parameters of HBOT can be adjusted based on factors including the age of the patient, the degree of hearing loss and underlying conditions. HBOT is generally considered safe when administered under the guidance of professional doctors (49). The main side effects are barotrauma and oxygen toxicity, which tend to be mild and reversible (50). However, it is necessary to strictly adhere to treatment indications and operating protocols, proactively prevent and manage side effects, assess the potential risks and benefits, and closely monitor patient responses to optimize treatment strategies and maximize treatment safety.

Wilson et al (51) published the findings of a double-blind controlled trial in 1980, which demonstrated that oral steroids effectively improve hearing in patients with SSNHL. Since then, corticosteroids have become the first-line treatment for SSNHL and remain the main treatment option. Although the specific mechanism of steroid action in the inner ear remains unclear, the basic therapeutic effect is the reduction of edema and inflammation (52). Multinational guidelines recommend systemic or local corticosteroid therapy as the initial treatment choice (6,53), which should be initiated within 2 weeks of symptom onset. Systemic administration includes both intravenous and oral administration, while local administration includes intratympanic or retroauricular injections. No difference in efficacy has been detected between the two types of administration (54). Systemic administration is more convenient and does not involve invasive procedures. For patients without contraindications, systemic medication rapidly achieves therapeutic drug concentrations, potentially inhibiting the immune response and improving inner ear microcirculation (55). Conversely, local glucocorticoid therapy offers advantages in safety and targeting, particularly in patients with contraindications to systemic hormone use (18).

HBOT increases the oxygen concentration in the inner ear, elevates the perilymphatic oxygen partial pressure, and promotes the recovery of cochlear function, particularly in patients with severe hearing loss (≥70 dB) (34). The 2019 AAO-HNSF guidelines recommend initiating HBOT and steroids within 2 weeks from symptom onset, or as salvage therapy within 1 month. The efficacy of HBOT is time-dependent, with an optimum benefit within 24–48 h, or at latest within 2 weeks (45,56). Although the recommended timing of treatment varies in different studies, the expert consensus is that earlier intervention achieves improved outcomes (46). The mainstream theory holds that the effect of combined HBOT and glucocorticoids is improved compared with that of drug therapy alone. However, factors including high cost, a dependence on specialized equipment, strict treatment windows and potential delays to treatment may reduce the beneficial effect.

Depending on the condition of the patient, such as elevated initial fibrinogen levels, vasoactive drugs including prostaglandin E1 (PGE1), batroxase and Ginkgo biloba extract may be added to standard corticosteroid therapy. These drugs help to reduce fibrinogen levels and blood viscosity, increase local blood flow, and improve hemorheology (57). Combining vasoactive drugs with conventional treatment has been shown to be more effective in the treatment of SSNHL than conventional treatment alone (58).

Due to insufficient evidence supporting their efficacy, the 2019 AAO-HNSF guidelines explicitly recommend against the routine use of antiviral drugs, thrombolytics, vasodilators and antioxidants (6). Therefore, in clinical practice, the decision to incorporate these into the conventional treatment plan recommended by the guidelines requires careful consideration. Further research is necessary to explore the mechanisms of action of these drugs to establish an accurate and reliable clinical basis for their use.