Adding hyperbaric oxygen therapy (HBOT) to combination treatment for patients with sudden sensorineural hearing loss (SSNHL) consistently led to improved hearing outcomes compared to controls, according to results from a systematic review and meta-analysis published in JAMA Otolaryngology–Head & Neck Surgery.
SSNHL, defined as “a hearing loss of at least 30 decibels (dB) affecting 3 or more contiguous frequencies and occurring during 3 days without a known cause,” is often attributed to inner ear hair cell damage, Temitope G. Joshua, MD, MSc, of the University of British Columbia in British Columbia, Canada, and colleagues explained.
The most common treatment for SSNHL is corticosteroids, but HBOT—a treatment often used for decompression sickness that involves breathing pure oxygen in a pressurized environment to increase oxygen flow to the ears and brain—may also improve outcomes by increasing oxygen supply to the cochlea, thereby potentially improving hearing. The therapy is currently FDA-approved for the treatment of complete SSNHL, and the American Academy of Otolaryngology–Head and Neck Surgery recently determined that HBOT plus a steroid is an option for both acute treatment and salvage therapy for the condition.
However, while previous systematic reviews by Bennett et al and Rhee et al have suggested a potential benefit for HBOT in hearing recovery, the treatment’s actual clinical significance remains unclear.
Joshua and colleagues conducted their review to evaluate current literature on the efficacy of HBOT, alone or as part of a combination treatment, in patients with SSNHL.
“This systematic review and meta-analysis suggests the therapeutic usefulness of HBOT in adult patients with SSNHL,” they found. “In three RCTs, the mean PTA4 change following treatment, final PTA4, and hearing recovery were all associated with significant improvements in patients assigned to the HBOT intervention (a combination treatment regimen) compared with control therapy alone. Further research is required to determine the optimal HBOT protocol.”
In order to track down trial data, Joshua and colleagues searched the Cochrane Central Register of Controlled Trials, PubMed, EMBASE, CINAHL, Web of Science, CAB, ICTRP, Google Scholar, Clinicaltrials.gov, and ISRCTN databases for prospective, randomized clinical trials comparing HBOT, as a single or combination treatment, against control therapies for adults with SSNHL published from Jan. 1, 2000-April 30, 2020. Only trials that used the American Academy of Otolaryngology–Head and Neck Surgery’s diagnostic criteria for SSNHL were included, they noted.
The primary outcome measure was the “mean difference in absolute hearing gain recorded by pure-tone audiometric (PTA) thresholds averaged across four low (0.5, 1, 2, and 3 or 4 kHz [PTA4]) or three high (3 or 4, 6, and 8 kHz) frequencies.” The secondary outcomes were the odds ratio (OR) of hearing recovery—defined as a hearing gain of 10 dB or more in PTA average—and treatment-related adverse events.
“Of the 826 records initially identified, 358 duplicates and 451 articles were excluded based on article type, title, and abstract,” they wrote. “The full texts of 17 articles were reviewed, of which 14 were excluded because they were either not prospective RCTs (11 articles), the participants were less than 18 years old (2 articles), or the PTA was not reported at frequencies of interest (1 article). Three prospective RCTs with a total of 88 participants who received HBOT in the intervention groups and 62 participants who received only medical therapy in the control groups were studied.”
Joshua and colleagues laid out the characteristics for the three included studies:
- Cho et al included patients with SSNHL who had severe to profound hearing loss (≥70 dB); “all patients received oral methylprednisolone 0.8 mg/kg/d) plus IT dexamethasone 0.4 to 0.8 mL (4 mg/mL) for 7 days; the dose of methylprednisolone was then tapered for the next 5 days. The study’s intervention group had daily 60-minute HBOT sessions for 10 days at 2.5 atmospheres absolute (ATA).”
- Krajčovičová et al included patients with SSNHL who had moderate hearing loss (41-60 dB); “all patients received IV methylprednisolone (250 mg daily) for 2 days; the dose was then tapered during 3 days. This was reportedly followed by oral prednisone (400 mg daily, likely typographical error that should have been 40 mg daily) for 5 days and then 20 mg daily for 5 days.17 Pentoxifylline (100 mg, twice daily) and betahistin (16 mg, 3 times daily) were also given to all patients. The intervention group underwent 90-minute daily HBOT sessions for 10 days at 2 ATA.”
- Khater et al did not report recruiting patients with a specific degree of hearing loss, but mean initial PTA4 for the HBOT and control groups was 72.86 (1.43) and 71.94 (2.1) dB, respectively; “all patients received oral prednisolone (1 mg/kg) for 10 days plus an initial dose of IT methylprednisolone 0.4 to 0.6 mL (40 mg/mL); the dose of prednisolone was then tapered during the next 10 days. Patients received an additional dose of IT steroids 1 week later if there had not been any or only partial hearing improvement. All of the patients also received antiviral therapy (acyclovir, 500 mg, 3 times daily) for 1 week. The intervention group underwent 60-minute daily HBOT sessions for 20 days at 2 ATA.”
In all three studies, HBOT was an adjuvant therapy among the intervention groups.
Across the three studies, “The intergroup difference in mean absolute hearing gain (mean difference, 10.3 dB; 95% CI, 6.5-14.1 dB; I2=0%) and the odds ratio of hearing recovery (4.3; 95% CI, 1.6-11.7; I2=0%) favored HBOT over the control therapy,” Joshua and colleagues concluded. Also among the findings:
- A meta-analysis comparing intergroup post-treatment PTA4 found that the HBOT group showed an improvement (mean difference, 9 dB; 95% CI, 4.5-13.6 dB; I2 = 0%) compared to the control group. A further sensitivity analysis excluding the study by Krajčovičová et al still showed a statistically significant improvement favoring HBOT versus controls (mean difference, 10 dB; 95% CI, 5.1-15.0 dB).
- Cho et al had two patients who reported mild otalgia (earache) at HBOT initiation. The other studies did not comment on the adverse effects of treatment, and thus no statistical analysis of these effects could be conducted.
- The studies by Cho et al and Khater et al were both rated as having “some” risk for bias; the study by Krajčovičová et al was rated as being at “high” risk for bias.
“Two prior studies [by Rhee et al and Bennett et al] examined this topic using systematic review and meta-analysis and concluded that HBOT offers potential benefit,” Stephanie A. Moody-Antonio, MD, of Eastern Virginia Medical School in Norfolk, Virginia, Sijana S. Chandrasekhar , MD, of ENT and Allergy Associates, LLP, in New York, and M. Jennifer Derebery, MD, of the House Ear Clinic in Los Angeles, wrote in an editorial accompanying the review. “The current meta-analysis, while evaluating a limited number of participants, provides a statistically superior evaluation of the topic than do previous reports. When considered together with previous meta-analyses, among which there is minimal overlap in the study population, it is reasonable to conclude that HBOT offers potentially beneficial treatment for SSNHL.”
Joshua and colleagues pointed to the small number of included studies and the overall risk of bias in those studies to be important study limitations. However, they also argued that, given that the patients allocated to the intervention and control groups were “similar in age, sex, and the severity of hearing loss across the studies,” it is likely that the study conclusions “are reliable” regardless of concern for bias. “Therefore, because the meta-analysis that excluded the study by Krajčovičová and colleagues identified a greater hearing gain of 10.4 dB associated with HBOT, the risks of bias do not detract from the interpretation of this review’s findings,” they wrote.
They also noted the review’s inability to assess adverse events related to HBOT as another limitation, adding that future studies on the treatment should assess and report adverse effects.
“Weighing the balance of data known thus far, clinicians should consider HBOT in combination with steroid treatment for patients with severe to profound SSNHL,” Moody-Antonio, Chandrasekhar, and Derebery wrote. “It is important for shared decision-making to balance the cost and time commitment for the patient with the potential benefit, acknowledging the limited window of opportunity for effective treatment. Of course, the cost and time must also be weighed against the lifetime negative effects of permanent hearing loss.”
Adding hyperbaric oxygen therapy (HBOT) to combination treatment for patients with sudden sensorineural hearing loss (SSNHL) consistently led to improved hearing outcomes compared to control treatments, according to results from a systematic review and meta-analysis.
Note that HBOT is currently FDA-approved to treat patients with complete SSNHL.
John McKenna, Associate Editor, BreakingMED™
The review authors and editorialists had no relationships to disclose.
Cat ID: 925
Topic ID: 915,925,728,791,730,130,192,925,256