European Archives of Oto-Rhino-Laryngology https://doi.org/10.1007/s00405-018-4870-2
OTOLOGY
Inpatient treatment of patients with idiopathic sudden sensorineural hearing loss: a population-based healthcare research study Anne Heuschkel1 · Katharina Geißler2 · Daniel Boeger3 · Jens Buentzel4 · Dirk Esser1 · Kerstin Hoffmann5 · Peter Jecker6 · Andreas Mueller7 · Gerald Radtke8 · Orlando Guntinas‑Lichius2 Received: 24 October 2017 / Accepted: 6 January 2018 © Springer-Verlag GmbH Germany, part of Springer Nature 2018
Abstract Purpose The aim was to determine inpatient treatment rates of idiopathic sudden sensorineural hearing loss (ISSNHL) with focus on diagnostics, treatment, and outcome. Methods A retrospective population-based study in the federal state Thuringia in 2011 and 2012 was performed on all 490 inpatients (51% females, median age: 60 years) treated for ISSNHL (Median duration: 7 days). The association between analyzed parameters and the probability of recovery was tested using univariable and multivariable statistics. Results The inpatient treatment rate for ISSNHL was 11.23 per 100,000. 172 patients (35%) had an outpatient treatment prior to inpatient treatment. For pure-tone audiometry of the three most affected frequencies (3PTAmax), the initial median hearing loss was 66.67 dB, the median absolute hearing gain ΔPTAabs was 10.0 dB, and the median relative hearing gain in relation with the contralateral side ΔPTArel contral was 30.86%. 51% of the patients reached a ΔPTAabs of ≥ 10 dB. About 2 of 5 patients recovered to a ΔPTArel contral ≥ 50% or reached ≤ 10 dB of contralateral ear. The multivariate analysis revealed that an ISSNHL on the left side [Hazard ratio (HR) = 1.6.88; confidence interval (CI) = 1.161–2.454], no down-sloping audiogram type (HR = 2.016; CI = 1.391–2.921), and no prior outpatient prednisolone treatment (HR = 2.374; CI = 1.505–3.745) were independent factors associated with better recovery (ΔPTAabs ≥ 10 dB). Conclusion Inpatient treatment of ISSNHL is variable in daily practice. The population-based recovery rate was worse than reported in clinical trials. More standardization and clearer criteria for outpatient, inpatient, and salvage therapy are needed. Keywords Sudden hearing loss · Sudden sensorineural hearing loss · Risk factors · Healthcare research · Guideline adherence
Introduction
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00405-018-4870-2) contains supplementary material, which is available to authorized users. * Orlando Guntinas‑Lichius
[email protected]‑jena.de 1
Department of Otorhinolaryngology, HELIOS-Klinikum, Erfurt, Germany
2
Department of Otorhinolaryngology, Jena University Hospital, Am Klinikum 1, 07747 Jena, Germany
3
Department of Otorhinolaryngology, Zentralklinikum, Suhl, Germany
4
Department of Otorhinolaryngology, Südharz-Krankenhaus gGmbH, Nordhausen, Germany
There is no international consensus on the treatment of idiopathic sudden sensorineural hearing loss (ISSNHL). The most frequent management recommendations include observation, oral steroids, intravenous steroids, intratympanic 5
Department of Otorhinolaryngology, Sophien/Hufeland-Klinikum, Weimar, Germany
6
Department of Otorhinolaryngology, Klinikum Bad Salzungen, Bad Salzungen, Germany
7
Department of Otorhinolaryngology, SRH Wald-Klinikum, Gera, Germany
8
Department of Otorhinolaryngology, Ilm-Kreis-Kliniken, Arnstadt, Germany
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steroid, or a combination therapy [1–3]. In many countries, ambulatory treatment and, in others, inpatient treatment are preferred. The uncertainty to define an optimal treatment seems to have several reasons: a reported high recovery rate of up to 65%, the still unclear pathological mechanism, the probably multifactorial etiology, and the insufficient evidence to support one treatment against other treatment strategies [4–6]. A relative high incidence for ISSNHL of 5–60 (or even 160 in one study) per 100,000 has been reported [7–10]. Nevertheless, true population-based studies on the incidence on ISSNHL are rare [7, 9]. Regarding the high incidence on the one hand and the uncertainty of the optimal treatment, it is worthwhile to analyze the treatment strategies in clinical routine from a population-based perspective and outcome beyond clinical trials. Thuringia is a territorial state in Germany with approximately 2.2 million habitants. There are only eight hospitals with the departments of otolaryngology. The departments of otolaryngology have built a network primarily to improve health services research in the field of otolaryngology [11, 12]. Use of this network provided an ideal platform for a population-based analysis of the inpatient treatment of unselected patients with ISSNHL in 2011 and 2012 in Thuringia in daily practice with focus on patients’ characteristics, treatment, and outcome.
Methods Study design and patients A standardized retrospective analysis was performed in all eight Thuringian hospitals with a department of otorhinolaryngology. The study protocol was approved by the institutional ethics committee (No. 2726-12/09, 4755-0416). All patients were selected who (1) were treated as inpatients in 2011 or 2012 and (2) were coded for acute hearing loss due to the International Classification of Diseases [ICD], tenth revision, German modification (ICD-10-GM): H91.0, H91.1, H91.2, H91.3, H91.8, and H91.9. The primary data set contained 723 patients. All charts were reviewed. ISSNHL was defined as a sudden unilateral sensorineural hearing loss without recognizable cause in accordance with the German clinical guideline for the treatment of ISSNHL [1]. 196 patients did not have an ISSNHL and were excluded, because a specific disease (for instance, vestibular schwannoma, M. Meniere, otitis media) was responsible for the hearing loss. From the remaining 527 patients, 37 patients with ISSNHL were excluded, because they only had an initial audiogram but no follow-up hearing investigation. Finally, 490 patients were included into the present study. A comparison of the included 490 patients with the excluded 37 patients with
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ISSNHL was performed (Online Resource 1). For some of the excluded patients, it was unknown if they had received an outpatient treatment prior to the inpatient treatment. The group of excluded patients had less frequently vertigo and more often a normal hearing on the contralateral ear. The hearing loss in the excluded patients was less severe than in the included patients. Follow-up of the patients was performed until August 2013. A retrospective analysis of the patients’ charts was performed, and the following variables were obtained: age, sex, physical examinations, all pre-therapeutic investigations, medical treatment, and surgical procedures related to the treatment ISSNHL. Before analysis, data were blinded with respected to the treating hospital. The severity of the hearing loss was described using the pure-tone average [PTA in decibels, dB; always hearing level (HL)]. For PTA calculation, the sum of the hearing level at the respective frequencies was divided by the number of frequencies contributing. Measurement methods for outcome were evaluated with respect to which frequencies were used to calculate the PTA: 10 frequencies (10PTA: 0,125; 0,25; 0,5; 1; 1,5; 2; 3; 4; 6; 8 kHz), 9 frequencies (9PTA: 0.125; 0.25; 0.5; 1; 2; 3; 4; 6; 8 kHz), and 4 frequencies (4PTA: 0.5; 1; 2; 4 kHz): the low-frequency hearing loss (LF-3PTA: 0.125; 0.5; 1 kHz), the middle-frequency hearing loss (MF-3PTA: 2; 3; 4 kHz), the high-frequency hearing loss (HF-2PTA: 6; 8 kHz), and PTA of the three most affected frequencies (3PTAmax). Thresholds that were not measurable because of the limit of the audiometer were dummy coded with 120 dB. The types of initial audiograms were classified as: upwardsloping type (hearing loss more severe in low frequencies), downward-sloping type (hearing loss more severe in high frequencies), flat type (no more than 10 dB deviation on PTA thresholds), and profound type (PTA thresholds worse than 70 dB on all frequencies) [13]. The outcome was measured according to Plontke et al. as absolute improvement ΔPTAabs = PTApre − PTApost in dB; the relative improvement ΔPTArel = 100 × (PTApre − PTApost)/PTApre in percent, and the relative improvement in relation with the contralateral ear (contral) ΔPTArel contral = 100 × (PTApre − PTApost)/ (PTApre − PTAcontral) in percent [14]. Several definitions for a successful improvement were used in dichotomous (yes/ no) outcome variables: ΔPTAabs ≥ 10 dB, ΔPTAabs ≥ 15 dB, ΔPTArel ≥ 50%, ΔPTArel contral ≥ 50%, and PTApost ≤ 10 dB of contralateral ear [14]. In addition, recovery was classified into four groups according to Siegel’s criteria using the 9PTA [15]. The functional disability of the contralateral side was classified according to the World Health Organization (WHO) grades based on the 4PTA: grade 0 = no hearing impairment (≤ 25 dB), grade I: mild impairment (26–40 dB), grade II: moderate impairment (41–60 dB),
European Archives of Oto-Rhino-Laryngology
grade III: severe impairment (61–80 dB), and grade IV profound hearing impairment (≥ 81 dB). The epidemiological calculations were based on the annual mean number of habitants in Thuringia in 2011 and 2012. Population numbers were used that were published in the online database of the Thuringian State Office for Statistics (http://www.tls.thueringen.de). The patients were treated according to the German clinical guideline for the treatment of ISSNHL [1]: All patients received an intravenous prednisolone treatment (already as outpatient treatment or later as inpatient treatment). Prednisolone was administered with an initial dose of 250 mg/day (range: 100–500 mg/day) and was gradually tapered within 12 days. Adjuvant treatment with rheological drugs was optional (not recommended anymore in the actual version of the guideline: [16]). Due to the guideline, treatment of ISSNHL was possible as outpatient or inpatient treatment. Inpatient treatment was recommended for patients with severe ISSNHL, preexisting severe hearing loss on the contralateral side, progression or no decline of the hearing loss under outpatient therapy, ISSNHL with objectifiable vestibular symptoms, relevant comorbidity, or particular occupational concern. The indication for tympanoscopy with round window sealing was unilateral severe hearing loss (4PTA > 80 dB) and no response to inpatient prednisolone treatment within 3 days. The indication for second line intratympanic dexamethasone application (4 mg/0.5 ml) was given in patients with persistent hearing loss (4PTA > 40 dB) after 4 days of inpatient prednisolone treatment.
Statistical analysis If not indicated otherwise, data are presented with mean values ± standard deviation (SD). All statistical analyses were performed using IBM SPSS, version 24.0.0.0. To compare different subgroups of patients, the nonparametric Mann–Whitney U test for independent metric data or the Chi-square test for independent nominal data was applied. The non-parametric Wilcoxon test for dependent metric data was applied to analyze differences between initial hearing loss and final hearing loss on the affected ear at the end of the follow-up. Significant associations (p < 0.05) from these univariate analyses were included into a multivariate binary linear logistic regression for the analysis of potential independent predictors of improvement of the ISSNHL (ΔPTAabs ≥ 10 dB versus ΔPTAabs < 10 dB). Nominal p values of two-tailed tests are reported. The significance level was set at p < 0.05.
Results Subjects and treatment Four hundred and ninety (490) patients were treated as inpatients in Thuringia in 2011 and 2012 (median duration: 7 days) and were included into the study. The patients’ characteristics are presented in Table 1. The median age was 60 years without gender predominance (male-tofemale ratio of 1.03:1). There was no side predominance (left side 53%). 172 patients (35%) had a prior outpatient treatment without improvement. 318 patients were directly treated as inpatients. The reasons were: severe ISSHNL (45%), additional vestibular symptoms (24%), contralateral severe hearing loss (11%), comorbidity (10%), and reason unclear (9%). A minority (18%) presented with a recurrent ISSNHL. A majority complained of tinnitus on the affected ear (62%). About one-third had vertigo as attendant symptom. Two-thirds (66%) had a normal hearing on the contralateral side. Arterial hypertension was the most frequent comorbidity (55%). Compared to patients directly treated as inpatients, patients with prior outpatient treatment had more frequently tinnitus, normal contralateral hearing, and were less comorbid (all p < 0.05; cf. Table 1). The median interval from onset of the symptoms to inpatient treatment was 2 days. In most patients, the inpatient prednisolone treatment was combined with other rheological drugs (Table 2). 17% received a tympanoscopy with sealing of the round window. An additional intratympanic steroid application as salvage therapy was performed in 11%. Patients with prior outpatient treatment had a significant longer interval from onset to inpatient treatment, received more frequently a therapy combining prednisolone with other drugs and an intratympanic steroid application (all p < 0.05), but less frequently a sealing of the sealing of the round window (p > 0.05).
Hearing loss and recovery The data on initial hearing loss, final hearing after treatment, absolute and relative hearing gain for the different PTA outcome measures are summarized in Table 3. For 3PTAmax, the initial median hearing loss was 66.67 dB, the median absolute hearing gain ΔPTA abs was 10.0 dB, the median relative hearing gain ΔPTArel was 21.58%, and the median relative hearing gain in relation with the contralateral side ΔPTA rel contral was 30.86%. On average, hearing improved independent of which PTA measure was used. Initial audiogram showed a flat course, a down-sloping curve, up-sloping curve, or another pattern
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Table 1 Baseline characteristics of patients with idiopathic sudden sensorineural hearing loss (ISSNHL) and inpatient treatment without or with prior outpatient treatment Parameter
Gender Male Female First ISSNHL No Yes Side Left Right Tinnitus No Yes Vertigo No Yes Contralateral normal h earinga No Yes WHO grade contralateral Grade 0 Grade I Grade II Grade III Grade IV Smoking No Yes Arterial hypertension No Yes Coronary heart disease No Yes Diabetes mellitus type II No Yes Hypercholesterolemia No Yes Charlson Comorbidity Index 0 ≥ 1 Age, years
Prior outpatient therapy (N = 172)
N
N
N
%
%
p
%
249 241
50.8 49.2
153 165
48.1 51.9
96 76
55.8 44.2
86 404
17.6 82.4
52 266
16.4 83.6
34 138
19.8 80.2
259 231
52.9 47.1
163 155
51.3 48.7
96 76
55.8 44.2
188 302
38.4 61.6
139 179
43.7 56.3
49 1230
28.5 71.5
342 148
69.8 30.2
217 101
68.2 31.8
125 47
72.7 27.3
166 324
33.9 66.1
124 194
39.0 61.0
42 130
24.4 75.6
324 79 41 20 26
66.1 16.1 8.4 4.1 5.3
194 55 31 16 22
61.0 17.3 9.7 5.0 6.9
130 24 10 4 4
75.6 14.0 5.8 2.3 2.3
417 73
85.1 14.9
273 45
85.8 14.2
144 28
83.7 16.3
219 271
44.7 55.3
132 186
41.5 58.5
87 85
50.6 49.4
432 58
88.2 11.8
272 46
85.5 14.5
160 12
93.0 7.0
415 75
84.7 15.3
259 59
81.4 18.6
156 16
90.7 9.3
427 63
87.1 12.9
269 49
84.6 15.4
158 14
91.9 8.1
354 136
72.2 27.8
210 108
66.0 34.0
144 28
83.7 16.3
SD
Mean
SD
Mean
SD
58.7
16.0
60.6
15.6
55.2
15.5
WHO grade 0 on the contralateral side
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No prior outpatient therapy (N = 318)
Mean
Significant p-values (p < 0.05) in bold a
All patients (N = 490)
0.104
0.343
0.355
0.001
0.307
0.001
0.012
0.528
0.054
0.014
0.007
0.022
< 0.001
< 0.0001
European Archives of Oto-Rhino-Laryngology Table 2 Therapy of patients with idiopathic sudden sensorineural hearing loss (ISSNHL) and inpatient treatment without or with prior outpatient treatment Parameter
Inpatient prednisolone treatment In combination with other drugs Alone Inpatient drug treatment additional to prednisolone: Pentoxifylline No Yes Inpatient drug treatment additional to prednisolone: Hydroxyethyl starch No Yes Inpatient drug treatment additional to prednisolone: Mannitol No Yes Inpatient drug treatment additional to prednisolone: Acetazolamide No Yes Intratympanic steroid application No Yes Sealing of the round window No Yes Interval onset of ISSNHL to inpatient treatment, days Duration of inpatient treatment, days Interval onset of ISSNHL to round window sealing, days Interval onset of ISSNHL to Intratympanic steroids, days
All patients (N = 490)
No prior outpatient therapy (N = 318)
Prior outpatient p therapy (N = 172)
N
%
N
%
N
%
360 130
73.5 26.5
215 103
67.6 32.4
145 27
84.3 15.7
410 80
83.7 16.3
262 56
82.4 17.6
148 24
86.0 14.0
196 294
40.0 60.0
138 180
43.4 56.6
58 114
33.7 66.3
430 60
87.8 12.2
289 29
90.9 9.1
141 31
82.0 18.0
437 53
89.2 10.8
295 23
92.8 7.2
142 30
82.6 17.4
434 56
88.6 11.4
293 25
92.1 7.9
141 31
82.0 18.0
406 84
82.9 17.1
260 58
81.8 18.2
146 26
84.9 15.1
Mean
SD
Mean
SD
Mean
SD
7.7 7.2 7.0 12.6
12.2 1.5 4.8 12.9
4.6 7.2 6.0 8.4
8.4 1.5 3.7 11.7
13.4 7.0 9.3 16.3
15.5 1.4 6.2 12.9
< 0.0001
0.296
0.037
0.001
0.001
0.001
0.381
< 0.0001 0.094 0.006 < 0.0001
Significant p-values (p < 0.05) in bold
in 41, 47, 11, and 2% of the patients, respectively. Table 4 gives an overview about the success rates for the different PTA outcome measures and different success definitions. For 3PTAmax, about half of the patients (51%) reached a ΔPTAabs of ≥ 10 dB. About two of five patients recovered to a ΔPTArel contral ≥ 50% or reached ≤ 10 dB of contralateral ear. If the patients had a prior outpatient treatment before the inpatient treatment, the outcome was worse compared to direct inpatient treatment independent of the PTA outcome measure used (Online Resource 2). The univariate analyses for prognostic factors for a successful recovery defined as ΔPTAabs ≥ 10 dB for the 3PTAmax showed that ISSNHL on the left side (p = 0.033), no down-sloping audiogram type (p < 0.001), no prior outpatient treatment (p < 0.001), no prior outpatient oral prednisolone treatment (p < 0.001), a shorter interval between onset and inpatient treatment start (< 4 days; p = 0.017)
were associated with a higher probability of a recovery of ΔPTAabs ≥ 10 dB for 3PTAmax (Online Resource 3). The multivariate analysis revealed that an ISSNHL on the left side [Hazard ratio (HR) = 1.6.88; confidence interval [CI] = 1.161–2.454], no down-sloping audiogram type (HR = 2.016; CI = 1.391–2.921), and no prior outpatient prednisolone treatment (HR = 2.374; CI = 1.505.-3.745) were independent factors associated with better recovery (ΔPTAabs ≥ 10 dB; Table 5).
Epidemiology The overall inpatient treatment rate for ISSNHL was 11.23 per 100,000 without gender differences (women: 10.87 per 100,000; men: 11.60 per 100,000; Fig. 1). The incidence in adult patients was lowest for the cohort of 31–40-yearold patients (4.31 per 100,000). The incidence was then
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Table 3 Overall absolute and relative improvement of hearing on the affected ear after inpatient treatment without or with prior outpatient treatment Parametera
10PTA, dB All patients No prior outpatient treatment Prior outpatient treatment 9PTA, dB All patients No prior outpatient treatment Prior outpatient treatment 4PTA, dB All patients No prior outpatient treatment Prior outpatient treatment LF-3PTA, dB All patients No prior outpatient treatment Prior outpatient treatment MF-3PTA, dB All patients No prior outpatient treatment Prior outpatient treatment HF-2PTA, dB All patients No prior outpatient treatment Prior outpatient treatment 3PTAmax, dB All patients No prior outpatient treatment Prior outpatient treatment
Pre-treatment (dB) Mean ± SD
Post-treatment (dB) Mean ± SD
p**
Absolute hearing gain ΔPTAabs (dB) Mean ± SD
Relative hearing gain PTArel (%) Mean ± SD
Relative hearing gain, contralateral ΔPTArel contral (%) Mean ± SD
58.0 ± 31.6 62.1 ± 31.8
50.1 ± 33.7 51.4 ± 34.3
< 0.0001 < 0.0001
8.1 ± 16.2 10.7 ± 17.1
14.9 ± 35.9 19.9 ± 36.2
18.0 ± 156.7 26.5 ± 178.6
50.9 ± 29.8
47.5 ± 32.5
0.001
3.2 ± 13.0
5.5 ± 33.2
2.1 ± 103.6
58.1 ± 31.2 61.9 ± 31.6
50.1 ± 33.5 51.4 ± 34.1
< 0.0001 < 0.0001
7.9 ± 16.0 10.5 ± 16.9
14.6 ± 35.1 19.5 ± 35.6
18.3 ± 147.2 27.9 ± 166.6
50.9 ± 29.4
47.8 ± 32.2
0.001
3.2 ± 12.9
5.3 ± 32.2
0.6 ± 100.3
57.8 ± 33.1 61.8 ± 33.2
49.2 ± 35.0 50.8 ± 35.7
< 0.0001 < 0.0001
8.5 ± 17.1 11.3 ± 18.2
13.5 ± 52.6 20.3 ± 41.5
23.0 ± 125.4 26.4 ± 133.5
50.4 ± 31.8
46.9 ± 33.9
0.001
3.5 ± 13.5
1.0 ± 66.7
16.6 ± 108.4
52.8 ± 32.8 57.2 ± 33.0
42.6 ± 34.4 44.1 ± 35.0
< 0.0001 < 0.0001
10.2 ± 18.8 13.1 ± 19.4
18.5 ± 46.8 23.4 ± 48.6
27.6 ± 80.2 31.0 ± 84.1
44.7 ± 31.0
39.8 ± 33.3
< 0.0001
4.9 ± 16.4
9.4 ± 41.7
21.4 ± 72.3
60.8 ± 34.6 64.5 ± 35.0
53.5 ± 36.5 54.7 ± 37.0
< 0.0001 < 0.0001
7.3 ± 17.5 9.8 ± 18.4
11.7 ± 41.9 16.2 ± 43.6
33.1 ± 149.6 46.0 ± 174.8
53.9 ± 32.9
51.1 ± 35.5
0.015
2.7 ± 14.7
3.4 ± 37.0
9.3 ± 80.2
67.6 ± 34.6 70.7 ± 35.1
61.8 ± 36.8 62.8 ± 35.1
< 0.0001 < 0.0001
5.9 ± 17.9 7.8 ± 19.1
8.0 ± 35.9 12.3 ± 35.2
18.0 ± 119.3 25.5 ± 125.6
62.1 ± 33.0
59.8 ± 35.1
0.049
2.6 ± 14.9
0.1 ± 35.9
4.1 ± 106.1
72.9 ± 31.3 76.8 ± 30.7
55.6 ± 34.8 56.5 ± 35.7
< 0.0001 < 0.0001
16.5 ± 21.7 19.7 ± 22.2
25.6 ± 34.1 29.2 ± 35.7
33.7 ± 182.9 37.9 ± 123.9
65.9 ± 31.1
53.8 ± 33.2
< 0.0001
10.6 ± 19.6
18.9 ± 30.0
25.9 ± 259.7
**Wilcoxon test for paired data a
10PTA (0.125; 0.25; 0.5; 1; 1.5; 2; 3; 4; 6; 8 kHz); 9PTA (0.125; 0.25; 0.5; 1; 2; 3; 4; 6; 8 kHz); 4PTA (0.5; 1; 2; 4 kHz); LF-3PTA (0.125; 0.5; 1 kHz); MF-3PTA (2; 3; 4 kHz); HF-2PTA (6; 8 kHz); 3PTAmax = PTA of the three most affected frequencies
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European Archives of Oto-Rhino-Laryngology Table 4 Overall success rate (%) of the treatment with different definitions of success Parametera
ΔPTAabs ≥ 10 dB (%)
ΔPTAabs ≥ 15 dB (%)
ΔPTArel ≥ 50% (%)
ΔPTArel contral ≤ 10 dB of ≥ 50% (%) contralateral ear (%)
Siegel class I complete recovery (%)
Siegel class II partial recovery (%)
Siegel class III slight recovery (%)
Siegel class IV no response (%)
10PTA, dB 9PTA, dB 4PTA, dB LF-3PTA, dB MF-3PTA, dB HF-2PTA, dB 3PTAmax, dB
36.3 36.1 37.8 45.1 31.8
24.9 24.5 26.1 33.7 23.9
14.5 13.9 16.1 22.0 13.5
29.6 30.0 30.4 33.7 29.0
44.1 44.7 43.7 47.6 46.1
– 27.3 – – –
– 6.9 – – –
– 9.8 – – –
– 55.9 – – –
29.6
20.8
10.8
27.3
48.4
–
–
–
–
51.4
43.9
24.1
39.0
41.2
–
–
–
–
ΔPTA = Post-treatment PTA − pre-treatment PTA a
10PTA (0.125; 0.25; 0.5; 1; 1.5; 2; 3; 4; 6; 8 kHz); 9PTA (0.125; 0.25; 0.5; 1; 2; 3; 4; 6; 8 kHz); 4PTA (0.5; 1; 2; 4 kHz); LF-3PTA (0.125; 0.5; 1 kHz); MF-3PTA (2; 3; 4 kHz); HF-2PTA (6; 8 kHz); 3PTAmax = PTA of the three most affected frequencies
Table 5 Multivariable binary logistic regression model of predictors of improvement of the ISSNHL (ΔPTAabs ≥ 10 dB) Parameter
HR
95% CI Lower
Side Right 1 Left 1.688 1.161 Audiogram type down-sloping Yes 1 No 2.016 1.391 Prior ambulant prednisolone treatment Yes 1 No 2.374 1.505 Duration onset to inpatient treatment > median 4 days 1 < median 4 days 1.283 0.871
p Upper
2.454
2.921
3.745
1.889
0.006
< 0.0001
< 0.0001
0.207
ΔPTAabs post-treatment PTA − pre-treatment PTA, HR hazard ratio, CI confidence interval Significant p-values (p < 0.05) in bold
increasing with age. The incidence was highest in the cohort of 71–80-year-old patients (19.83 per 100,000). The treatment incidence was highest for 71–80-year-old men (23.05) and 61–70-year-old women (19.73).
Discussion Population-based studies on incidence and treatment of ISSNHL are rare. Using a medical and pharmaceutical claims database containing information for more than 60 million both outpatients and inpatients in the United States, an
Fig. 1 Incidence per 100,000 population in Thuringia in 2011–2012 in relation with age and gender of the patients
annual incidence of all causes of sudden sensorineural hearing loss of 27 per 100,000 is reported [9]. Data from Taiwanese National Health Insurance program database revealed an annual incidence of 9.23 per 100,000 in 1998–2002 for inpatient treatment of sudden sensorineural hearing loss [7]. This is in the range of the present study (11.23 per 100,000). The US American and the Taiwanese study both suggest that mostly cases of ISSNHL were counted. The treatment is typically performed as outpatient treatment in the United States as outpatient treatment in Taiwan, and in Germany, both is possible. A recent survey-based, i.e., not true populationbased study in Japan, where patients traditionally are treated as inpatients revealed an incidence for ISSNHL of 60.9 per 100,000. Due to the German Federal Health Monitoring System, which allows online data bank searches for ICD codes of inpatient treatments, the age-adjusted incidence
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rates per 100,000 population in 2000–2015 for the ICDcode H81.2 (ISSNHL) declined from 44 in 2000 to 14 in 2015 (http://www.gbe-bund.de). This decline in Germany can be explained by the fact the ISSNHL was treated until 2002 most likely as inpatient treatment and was thereafter slowly replaced by outpatient treatment, leaving inpatient treatment only for selected cases as described in the present study. A recent study in a larger city in Germany analyzed data from about 80% of the otolaryngologists treating ISSNHL as outpatient treatment in 2004 [8]. They revealed an incidence of 151–168 per 100.000. Although this number appears to be too high, it makes clear that the calculated inpatient treatment rate underestimates the true incidence. There are no data available for outpatient treatment of ISSNHL throughout Germany. This is a clear limitation of the present study. There is an unknown rate of patients with ISSNHL treated probably successful as outpatients, and cases probably without accompanying vertigo, normal hearing on the contralateral ear and no relevant comorbidity. Assuming that 20% of the outpatient cases show no improvement, an extrapolation would result in an incidence of about 46 per 100,000 for Thuringia in 2011 and 2012. That in turn is consistent with the data German Federal Health Monitoring System (see above) before 2002 when still most cases were treated as inpatients. In the United States, the incidence was highest in the 65 + year age group and in Taiwan in the 60–64-year age group, i.e., this is in accordance with the present study showing a peak incidence for 60–69-year-old patients. A clear gender predominance is not obvious (male–female ratio; United States: 1.1; Taiwan: 1.2; present study: 1.03; German Federal Health Monitoring System: 0.94–1.07). An advantage of the present study was that it combined populationbased data with hospital-based data. Treatment of SSNHL remains controversial. Although corticosteroids are in most countries the mainstay of treatment for ISSNHL, the benefit still is controversial [4]. Due to the lack of population-based studies, the actual treatment strategies in clinical routine beyond trials remain unclear. In the population-based study of Alexander and Harris, about 25% of the insured US population was included [9]. They showed that in 2007, 41% of the patients with sudden hearing loss received systemic steroids, 1% intratympanic injection, and 4% both treatments in combination. 54%, i.e., the majority received no steroid therapy. In contrast, the present study is showing that probably all patients in Thuringia, and that should be representative for Germany, receive a steroid therapy, at least in 2011 and 2012. The same seems to be true for Spain due to an actually survey (98% systemic steroid treatment; 1.4% intratympanic injections) [17]. The rate of salvage therapy with intratympanic steroid (first line intratympanic injections were not performed yet in 2011 and 2012) was high in the present study with 11%. It has
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to be taken into account that only inpatients and not outpatient (with probably successful recovery) were studied. Most likely, the true rate of intratympanic steroids for all cases of ISSNHL is, therefore, much lower. The other surgical therapy, that was performed frequently, was sealing of the round window. Whereas intratympanic steroid injections was performed mainly after unsuccessful outpatient and inpatient treatment, sealing of the round window was performed mainly when the patients had severe hearing loss and the inpatient treatment showed no improvement within 3 days (cf. Online Resource 4). The rationale behind is that labyrinthine window rupture and the development of a perilymphatic fistula might be the reason for the severe acute hearing loss in these patients [18]. However, for both intratympanic steroid injections and for sealing of the round window, guidelines with clear recommendations are missing. This might explain the variable medication indication in the present study and makes the interpretation of the efficacy difficult (see below). With 490 patients treated within 2-year period, it represents one of the largest cohorts of patient with ISSNHL treated in an actual and short period of time and can also be compared to recent hospital-based studies (cf. Online Resource 5). As in most of the large retrospective studies, the present study could not rule out that some of the hearing gain was spontaneous recovery and not related to the treatment as a placebo group was missing. At least for the patients who had received already an unsuccessful outpatient treatment, this seems to be improbable. In most studies, puretone audiometry is used as primary outcome measure The AAO-HNS also recommends to using the Word Recognition Score (WRS) [2]. For the present study, WRS data were not available. Inpatient treatment refers to negative selection of patients with ISSNHL, either because of baseline risk factors for negative outcome (for instance, severe hearing loss, hearing loss on the contralateral side, vertigo, and comorbidity) or because of prior ineffective outpatient treatment. For the later cases, inpatient treatment was already the first step of salvage therapy. This might explain the worse outcome. Nevertheless, it cannot be ruled out that some patients showed later improvement, but no further audiogram was performed or available. In such a situation, recovery would have been underestimated. The mean absolute hearing gains (ΔPTAabs) for 4PTA for all patients, patients without prior outpatient treatment, with outpatient treatment were 8.5, 11.3, and 3.5 dB, respectively. The mean absolute hearing gains for 3PTAmax for the three categories were 16.5, 19.7, and 10.6 dB, respectively. It might be in the future better for patients who had already unsuccessful outpatient treatment to receive directly intratympanic steroids or in combination with systemic steroids instead of reserving intratympanic steroid as a second step salvage therapy (median time to intratympanic steroid therapy: 7.5 days). This actually
European Archives of Oto-Rhino-Laryngology
second step selvage therapy for patients who did not respond to steroids two times before was not effective. A short interval between onset of ISSNHL and intratympanic steroids seems to be important for the effectiveness of this treatment strategy. Out of the same reasons, the value of sealing of the round window has to be considered critically [18, 19]. In the setting performed in 2011 and 2012 (median time to round window sealing: 6 days), round window sealing was, overall, not effective. However, for both surgical options, absolute hearing gain was significantly higher (data not shown) if the interval to surgery was smaller than the median time. In addition, any adjuvant drug treatment in addition to prednisolone was not effective. Even the actual German guideline and also the U. S American guideline are here not stringent as adjuvant treatment with other drugs (and also hyperbaric oxygen therapy which is not offered in Thuringia) is not excluded. It is only recommended not prescribe other drugs routinely [2, 16]. Looking on the high variability in treatment regimens, four ISSNH in the clinical setting, clearer guidelines, and recommendations for the first and second line treatment are urgently needed. Furthermore, outcome is not satisfactory, especially for patients with risk factors. New treatment strategies beyond corticosteroid treatment would be desirable but not discernable at the moment.
Conclusion The presented population-based study including a cohort of ISSNHL inpatients treated in 2011 and 2012 in a territorial federal state in Germany revealed a high variability in the sequence and extent of treatment decisions. This might reflect the lack of clear guidelines established on evidencebased first and second line treatment strategies. So far, the outcome for patients with ISSNHL and certain risk factors is poor. New treatment concepts are urgently needed. Author contributions OG-L wrote the first draft of the manuscript. No honorarium, grant, or other form of payment was given to anyone to produce the manuscript. Each author listed on the manuscript has seen and approved the submission of this version of the manuscript and takes full responsibility for the manuscript. Funding None.
Compliance with ethical standards Statement of financial interest The authors have no financial interest to declare in relation with the content of this article. Conflict of interest The authors declare that they have no conflict of interest. Ethical approval All procedures performed in studies involving human participants were in accordance with the ethical standards of the insti-
tutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent For this type of study, formal consent is not required.
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