Young Ho Kim Kyung Tae Park Byung Yoon Choi Min Hyun Park Jun Ho Lee Seung-Ha Oh Sun O. Chang

Transcription

1 Eur Arch Otorhinolaryngol (2012) 269: DOI /s OTOLOGY Early combination treatment with intratympanic steroid injection in severe to profound sudden sensorineural hearing loss improves speech discrimination performance Young Ho Kim Kyung Tae Park Byung Yoon Choi Min Hyun Park Jun Ho Lee Seung-Ha Oh Sun O. Chang Received: 19 September 2011 / Accepted: 29 November 2011 / Published online: 8 December 2011 Ó Springer-Verlag 2011 Abstract The objective of the study was to determine the therapeutic efficacy of early combined treatment with intratympanic steroid injection (ITSI) in patients with severe to profound sudden sensorineural hearing loss (SSNHL), who did not respond to initial systemic steroid treatment (SST). The study design included historical controlled trials (retrospective analysis for the SST group). Patients (n = 73; 38 women and 35 men) diagnosed with severe to profound SSNHL at the time of their first visit in tertiary referral centers were recruited. Among these 73 patients, 30 patients who showed no early response within a week after the start of initial SST were prospectively included as the ITSI group. ITSI was performed twice a week for two consecutive weeks. In contrast, 43 patients with the same condition who did not receive ITSI were retrospectively included as the SST group. For each group, pure-tone audiogram (PTA) and speech discrimination score (SDS) tests were performed before SST and more than 2 months after termination of treatment in each group. After termination of each treatment, the final Y. H. Kim (&) M. H. Park Department of Otolaryngology, Head and Neck Surgery, Seoul Metropolitan Government, Seoul National University College of Medicine, Boramae Medical Center, 39, Boramae-Gil, Dongjak-Gu, Seoul , Korea yhkiment@gmail.com K. T. Park J. H. Lee S.-H. Oh S. O. Chang Department of Otorhinolaryngology, Seoul National University College of Medicine, Sensory Organ Research Institute, Seoul National University Medical Research Center, Seoul, South Korea B. Y. Choi Department of Otorhinolaryngology, Head and Neck Surgery, Seoul National University Bundang Hospital, Seongnam, South Korea average gain on PTA showed no significant difference between the two groups; however, the final average gain of SDS demonstrated a significantly better recovery in the ITSI group. ITSI as part of an early combined therapy represents an effective treatment in terms of the improvement of SDS in severe to profound SSNHL showing no early response to initial SST. Keywords Sudden sensorineural hearing loss Intratympanic steroid Combined therapy Systemic steroid Introduction Since the introduction of intratympanic steroid injection (ITSI) approximately 15 years ago, this method of treatment is becoming more popular as an option for the treatment of sudden sensorineural hearing loss (SSNHL) [1]. This therapy has been widely used as a salvage treatment in cases of SSNHL which do not respond to systemic steroid treatment (SST); however, the evidence for its efficacy remains controversial. One of the issues causing controversy regarding the treatment of SSNHL is that it may recover spontaneously, with a recovery rate of 32 70% [2 4]. In addition, the prognosis in patients with hearing loss of less than severe grade of SSNHL, or those who receive prompt SST within 1 2 weeks after onset of sudden hearing loss, is known to be good [5 8]. Although the prognosis is known to be generally favorable, cases with no change in hearing within 2 weeks after onset are likely to show poor recovery [9]. In cases of severe to profound SSNHL nonresponsive to early SST, ITSI may be considered as a useful treatment because there are few effective therapeutic options.

2 2174 Eur Arch Otorhinolaryngol (2012) 269: In the present study, early combined ITSI was performed in patients with severe to profound SSNHL, where poor hearing recovery was expected after early SST. This report merits readers attention, since this is the first report to demonstrate the selective use of ITSI and its effect upon the SSNHL patient group in which poor recovery is expected. The purpose of this study was to determine whether early ITSI combined with early SST may be effective in treating severe to profound SSNHL patients who showed no early response to initial SST. In addition, the usefulness of the criteria used in this study for assessment of hearing recovery was discussed in comparison with previously established criteria from a practical point of view, such as post-treatment auditory rehabilitation. Methods Study design and patients A total of 73 patients diagnosed with severe to profound SSNHL at our tertiary referral centers were enrolled in this study. The patients treated with systemic steroid within a week after the onset of sudden hearing loss were selected. A prospective study was performed for the ITSI group (n = 30), and a retrospective study for the SST group (n = 43). SSNHL was defined as a sensorineural hearing loss of 30 db or more over three contiguous audiometric frequencies occurring in less than 72 h. Patients with other causes of sensorineural hearing loss such as Ménière s disease or autoimmune hearing loss, the presence of any tumorous condition, pregnant patients and patients under 15 years old were excluded in this study. Initially, all subjects of both SST and ITSI groups were treated for 4 days with oral steroids (48 mg/day methylprednisolone or 60 mg/day prednisolone depending upon availability) or intravenous dexamethasone at a dose with the same potency, followed by gradual tapering off of oral steroids over 10 days. The inclusion criteria for each group were the initiation of SST within a week after the onset of hearing loss in severe to profound SSNHL and absence of a gain of more than 20 db on a pure-tone audiogram (PTA, 4-tone average at 0.5, 1, 2 and 3 khz) and a gain of more than 20% on a speech discrimination score (SDS), within a week after initiation of SST. This study was approved by the institutional review board of our centers, and informed consent was obtained from all 30 subjects of the ITSI group before initiation of ITSI. The prospective study for the group treated by ITSI was carried out from October 2008 to October Thirty-one patients whose initial audiological results were more than 70 db on a PTA underwent ITSI, and 30 of those patients who were followed up regularly were enrolled in this study. ITSI was chosen if SST, initiated within a week after onset of hearing loss, did not result in an improvement of more than a PTA gain of 20 db and an SDS gain of 20% within a week after the start of SST. ITSI was performed twice a week for two consecutive weeks, but it was terminated if complete recovery of hearing was identified before completion of the course of treatment. The records of 1,134 patients diagnosed with SSNHL between April 2002 and February 2009 were retrieved. Among them, 43 patients with SSNHL who fitted the audiological criteria mentioned above and who showed no improvement (PTA gain \20 db and SDS gain \20%) within a week after initiation of SST, were identified and chosen as the SST group. Patients in each group were followed for more than 2 months for the final audiological assessment. ITSI technique ITSI was performed as follows. Local anesthesia of the tympanic membrane was achieved using 10% lidocaine spray (Xilonibsa Ò Aerosol 10%, Inibsa, Barcelona, Spain) for approximately 15 min, after confirmation that the tympanic membrane and middle ear were intact. The patient s head was tilted 45 to the opposite side in the supine position. After removal of anesthetic agent and sterilization of the external ear with 70% ethanol, one puncture of the anterosuperior tympanic membrane was made for release of the air in the tympanic space using a 25-gauge spinal needle and a 1-ml syringe under a microscope. Then, ml of dexamethasone (5 mg/ml, Yuhan Corp., Korea) was instilled into the tympanum through the anteroinferior aspect of the tympanic membrane. Patients were instructed not to swallow, talk or change position to prevent spillage of the steroid solution through the eustachian tube for 30 min after the injection. Assessment of hearing improvement and statistical analysis Hearing evaluations, including PTA and SDS, were performed consecutively before SST (on the first visit) and more than 2 months after termination of treatment, in each group to compare mean hearing levels between the two groups. Final hearing outcomes in the two groups were compared with the criteria used in this study (Table 1). We considered a treatment result as successful when the final hearing was better than 40 db of PTA and 75% of SDS (good recovery group), and a recovery rate was calculated accordingly. Mean PTA and SDS were compared between the ITSI and SST groups using Student s t test and the hearing gain of each individual was analyzed using the paired t test. The statistical comparison of the proportion of

3 Eur Arch Otorhinolaryngol (2012) 269: Table 1 Criteria regarding hearing recovery used in this study Type Complete recovery (CR) Good recovery (GR) Fair recovery (FR) Slight recovery (SR) No recovery (NR) successful recovery between the two groups with the criteria used in this study and Siegel s criteria was performed using Fisher s exact test [10]. All statistical analyses were performed using the SPSS statistical software package. The criterion for statistical significance was set at p \ Results Hearing recovery PTA B25 db and SDS C90% Does not satisfy the CR criteria, but PTA B40 db and 75% BSDS Does not satisfy the GR criteria, PTA B55 db and 50% BSDS Does not satisfy the FR criteria, but PTA B70 db and 25% BSDS Does not satisfy the SR criteria PTA pure-tone audiogram (4-tone average), SDS speech discrimination score Patient demographics and initial audiological results for each group are summarized in Table 2. The time interval between onset of hearing loss and initiation of SST, initial PTA result and initial SDS showed no significant difference between the two groups. The age of patients in the ITSI and SST groups ranged from 16 to 74 years (mean age 51.2 years) and from 23 to 77 years (mean age 56.2 years), respectively. The interval of time between onset of hearing loss and initiation of SST in each group was investigated, and the mean time delay was 3.2 and 2.7 days, respectively, in the ITSI and SST group (Table 3). The mean follow-up period in the ITSI and SST group was 5.47 and 4.79 months, respectively. The hearing recovery after treatment in each group is shown in Fig. 1 and Table 4. At more than 2 months after treatment, the improvement of SDS in the ITSI group was significantly greater than that of the SST group, whereas the improvement in PTA in the ITSI group was not (p = 0.01 and 0.25, respectively; Student s t test). In addition, the final gain of SDS after treatment showed a significant difference between the two groups, whereas that of PTA did not (p = 0.02 and 0.19, respectively; Student s t test). On comparing the proportion of successful recovery between the two groups with the criteria used in this study, the recovery rate in the ITSI group was significantly higher, as shown in Fig. 2 (p = 0.01; Fisher s exact test). On comparing the post-treatment outcomes of the two groups using Siegel s criteria, a recovery rate of better than partial recovery, more than 15 db gain and db of final Table 2 Patient demographics and initial audiological results for each group Parameter ITSI group SST group p value No. of patients Sex (M:F) 19:11 16: Mean age (±SD) 51.2 ± ± Affected ear (R:L) 14:16 23: Associated symptoms Tinnitus Dizziness \0.000 Severe: profound SNHL 9:21 17: Delayed days to SST 2.66 ± ± Initial PTA (db) ± ± Initial SDS (%) 4.1 ± ± SST systemic steroid treatment, ITSI intratympanic steroid injection, PTA pure-tone audiogram (4-tone average), SDS speech discrimination score Table 3 Time interval between onset of hearing loss and initiation of systemic steroid treatment Interval (d) ITSI group (n) SST group (n) \ Total Mean 3.2d 2.7d ITSI intratympanic steroid injection, SST systemic steroid treatment hearing, was found to be significantly higher in the ITSI group (p = 0.02; Fisher s exact test), and this showed a statistical similarity when compared with the results using our criteria (data not shown) [10]. Discussion Quite a few studies, prospectively or retrospectively, have reported the positive effectiveness of ITSI in cases of SSNHL [11 14]. This easy and relatively noninvasive therapy seems to have significant advantages, such as avoiding the side effects of systemic steroid treatment, especially in SSNHL cases with various systemic problems. In addition, almost no or only trivial complications have been found in these studies.

4 2176 Eur Arch Otorhinolaryngol (2012) 269: (a) 110 (b) db % * initial PTA ITSI group final PTA SST group 0 initial SDS ITSI group final SDS SST group Fig. 1 Comparison of mean initial and final outcomes of PTA and SDS between ITSI and SST groups. At more than 2 months after treatment, the improvement of SDS in the ITSI group was significantly greater than that of the SST group (b) (*p = 0.01, Student s t test), whereas the improvement on PTA in the ITSI group was not (a) (p = 0.25, Student s t test). ITSI intratympanic steroid injection, SST systemic steroid therapy, PTA pure-tone audiogram (4-tone average), SDS speech discrimination score Table 4 Comparison of initial and final outcomes, and gain of PTA and SDS between the two groups ITSI group (n = 30) SST group (n = 43) p value Initial PTA ± ± Final PTA ± ± Gain PTA ± ± Initial SDS 4.13 ± ± Final SDS ± ± Gain SDS ± ± ITSI intratympanic steroid injection, SST systemic steroid therapy, PTA pure-tone audiogram (4-tone average), SDS speech discrimination score ITSI as a primary therapy, sometimes combined with systemic therapy, was introduced recently [12 17]. However, the application of ITSI should be cautiously considered in some situations such as mild to moderate SSNHL cases, because its application in those cases may not be cost-effective despite its known safety, considering the generally good natural recovery course in untreated SSNHL cases [2, 3, 18, 19]. ITSI may be a useful or an inevitable therapeutic option in SSNHL refractory to SST, since thus far there has been no further solution to SSNHL after failure of primary systemic therapy. ITSI as a salvage treatment of SSNHL seems to have shown some promising results to date [20 26]. However, there has been a report that ITSI as a salvage treatment produced disappointing results, showing a low therapeutic efficacy in cases of delayed treatment [27]. In the present study, the ITSI group demonstrated better SDS improvement compared to the SST group in the final hearing assessment. In addition, when considering the final hearing status corresponding to good recovery, or better based upon the criteria used in this study, as a successful recovery, the ITSI group showed significantly better successful recovery rate. However, this study has some limitations including use of retrospective data in SST group. This study might be slightly biased due to the historical controlled trials. In addition, the SST group in this study (a) NR 53% ITSI group CR/GR* CR 17% GR 13% (b) SST group NR 74% CR 7% GR 0% FR 12% SR 7% FR 7% SR 10% Fig. 2 Comparison of the recovery grades between ITSI and SST groups with the criteria used in this study. When recovery better than good recovery was considered as successful, a recovery in the ITSI group (a) was significantly better when compared to that of SST group (b). ITSI intratympanic steroid injection, SST systemic steroid therapy, CR complete recovery, GR good recovery, FR fair recovery, SR slight recovery, NR no recovery. (*p = 0.01, Fisher s exact test)

5 Eur Arch Otorhinolaryngol (2012) 269: had dizziness at presentation more frequently than the ITSI group did (Table 2). There could be an alternative interpretation that patients with poor prognosis were more recruited in the SST group than in the ITSI group. However, the fact that our ISTI group exclusively consists of patients that went through the systemic steroid treatment and yet not responded to the therapy within a week minimizes the chance. A further randomized prospective controlled study will strengthen the hypothesis in this study. Most studies regarding ITSI have reported no serious complications. However, there are risks of some important complications such as vertigo, tinnitus, aggravation of hearing loss, otitis media and tympanic membrane perforation. In this study, there were tympanic membrane perforations in two patients who showed no improvement in hearing, and transient dizziness in a few patients. One of the two patients with tympanic membrane perforation underwent myringoplasty, and the other did not want further treatment. The ideal goal in the treatment of SSNHL is to achieve a complete recovery of hearing and, if not complete, at least a hearing level that can benefit from auditory rehabilitation. However, previous standards regarding assessment of hearing improvement or treatment success seem to be somewhat generous or frequently do not consider speech discrimination performance, which may not allow a strict comparison of the therapeutic efficacy of treatment for SSNHL among different studies. Given this, the criteria for assessment of post-treatment final hearing recovery were suggested in the present study. In this criteria, the degree of hearing recovered was determined as suggested by ISO 1964, and SDS was added as an additional parameter. The additional and strict consideration of SDS may be more appropriate for a decision regarding auditory rehabilitation as well as assessment of outcomes after the termination of treatment. When comparing our results using the criteria adopted in this study with those using Siegel s criteria, a recovery rate better than good recovery and partial recovery in the two criteria was higher in the ITSI group [10]. There have been some studies that highlighted problems of approach through the round window for local drug delivery [28 31]. One of the possible problems is a false membrane or fibrous plug in the round window [32]. These abnormal findings of the round window niche are estimated to be found in 32% of cases and have the potential to impede access of the drug to the round window membrane by the intratympanic route. Therefore, evaluation of anatomic variations around the round window using high resolution computed tomography (HRCT) may be considered before ITSI. Thirteen patients in the ITSI group of the present study underwent HRCT; however, no specific anatomic variation was found. Further, examination of the round window niche using a fiberoptic mini-otoscope has been suggested [33]. This may be useful in view of the identification and removal of obstacles in the middle ear; however, because it is a form of exploration of the middle ear, the advantages of ITSI as a simple, safe and noninvasive technique may be reduced if this procedure is performed before or after ITSI. In addition, hyaluronic acid hydrogel, which can sustain drug delivery through the round window membrane, has been introduced, and this appears to have advantages as a one-step procedure, except for a minimal invasiveness such as tympanotomy for identification of the round window [34]. 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