sudden kombinasi th(2) dr.fikri

Steroid intratimpani sebagai salvage therapy

pada Tuli Mendadak

dr.Fikri Mirza Putranto,Sp.THT-KLRS Khusus THT Proklamasi

1

Mekanisme Tuli Mendadak

! Etiologi ◦ Gangguan vaskular ◦ DM, Hipertensi,

Hiperkolesterolemi, Gangguan pembekuan darah

◦ Infeksi virus ◦ Mumps, dll ◦ Autoimun ◦ Kelainan neurologik ◦ Stroke, tumor retrokoklea, ◦ Idiopatik

Patogenesis ◦ Sumbatan pembuluh

darah total dan permanen ◦ Sumbatan pembuluh

darah total dan sementara

◦Stroke Telinga

2

Apa yang terjadi pada koklea yang tersumbat total

60 detik: Gangguan potensial aksi

30 menit: sel rambut, sel ganglion, ligamen spiralis, neuron dan membran tektoria

1 jam: fungsi koklea irreversibel

Aliran darah N potensial aksi tidak dapat kembali N

Penurunan tekanan O2 di perilimfe

6 bulan: invasi jaringan fibrosa dan tulang memasuki telinga dalam

3

Sistem vaskular koklea

4 sudden + kombinasi th - April 4, 2014

Gejala tuli mendadakPembuluh darah Gangguan pendengaran Vertigo

Arteri koklea

Nada tinggi --> berdengingNada rendah --> rasa tertutup + gemuruh

Semua nada --> gangguan dengar

Dengan / tanpa vertigo

Arteri Vestibuler Normal Vertigo

Total Semua nada berat Vertigo berat

5

Faktor prognosisLama onset (terbaik pada onset < 6 hari)

Beratnya ketulian

Bentuk audiogram (paling baik low tone)

Ada/tidaknya vertigo

Usia

6

Prognosis berdasarkan bentuk dan berat audiometri (Kuhn,2011)

7

Imaging vs Recovery

MRI 3T FLAIR High responses No responses

Respons pada MRI 3T FLAIR —> perdarahan

intrakoklea —> prognosis buruk

(Lee 2012)

Kerusakan pembuluh darah

intrakoklea

CR 35 %PR 6.5 %SI 16.1 %NR 41.9 %

CR 47.2 %PR 11.2 %SI 10.1 %NR 31.5 %


Tatalaksana

Prinsip tatalaksana :

Mengurangi efek inflamasi di koklea

Mengembalikan aliran darah ke koklea

Meningkatkan asupan O2 di koklea

9

Rekomendasi tatalaksana terkini

Clinical guideline: Sudden deafness, J Otol Laringol 2012

Tuli mendadak didiagnosis sebagai penurunan audiometri lebih dari 30 dB pada 3 frekuensi berurutan tanpa ditemukan penyebab lainEvaluasi pasien dengan tuli mendadak atas kemungkinan tuli bilateral, tuli episodik berulang, kelainan neurologik

Evaluasi kemungkinan kelainan retrokoklea dengan : MRI, ABR, follow up audiometri

Intratimpanik steroid diberikan pada pasien yang gagal dengan terapi awal

Terapi hiperbarik diberikan pada pasien dengan onset kurang dari 3 bulan

10

Rekomendasi tatalaksana terkini

(Plaza,2011)

150� G.� Plaza� et� al

5 days, 90 mg x 5 days, 60 mg x 5 days, 30 mg x 5 days, 15 mg x 5 days).

-‐� � � If� SD� is� severe� (>� 70� dB),� in� a� single� ear� or� with� severe� associated vertigo (suspected vestibular neuritis), treatment should be offered with intravenous corticosteroids� for� 7� days,� in� a� day� hospital� regime� or through hospital admission, with a dose of 500 mg methylprednisolone per day, slowly passing to one dose in serum in 30 minutes.154,155 Subsequently, the oral regime described above should be reintroduced.

- If there is contraindication for the use of systemic corticosteroids, or if there is no response to treatment with systemic corticosteroids, oral or intravenous, after 7� days� of� its� establishment,� a� rescue� treatment� with�

intratympanic corticosteroids should be offered,121,148 with 1 dose weekly for 3 weeks in outpatient ENT consultation (and maintaining the decreasing oral pattern), with two commonly used guidelines (after topical anaesthesia with phenol on the tympanic membrane, with a no. 22 Abocath needle)150:- Methylprednisolone, 0.9 cc of a 40 mg vial, mixed with

1% lidocaine at 0.1 ml.– Dexamethasone, 0.9 cc of an 8 mg vial.

During systemic steroid treatment, either orally or intravenously, there should be gastro-duodenal prophylaxis with proton pump inhibitors (such as omeprazole) at doses of 40 mg/day, for 1 month.

In patients over 65 years, if glucocorticoid treatment is prolonged beyond 15 days, it will be necessary to associate vitamin D (800 IU/day) and calcium (800-1,000 mg/day) as a preventive regimen of bone loss and osteoporosis (requesting a bone density test is optional).156,157

Moreover, given the relative frequency of adverse effects associated to standard treatments for SD,158-162 this consensus group� suggests� the� use� of� specific� informed� consent,� especially when it uses intravenous corticosteroids at high doses (validated informed consent, which is available from the authors).

In cases of suspected vascular aetiology (known cardiovascular risk factors, etc.), it may be associated with vasodilators,42,163-‐167 such as nimodipine, intravenously (5-15 cc in 500 ml of saline solution, passing slowly, every 8 hours), or such as oral trimetazidine (especially if the patient is already in treatment for hypertension, 1 comp/8 h for 1 month), and then refer the patient to the Internal Medicine Department for evaluation and possible antiplatelet therapy.

- If the diagnosis is late, between 30 days and 90 days after the onset of symptoms, treatment should be with oral corticosteroids for 1 month, following the previous scheme.

- If the diagnosis is very late, more than 90 days from the onset of symptoms, treatment should be discussed individually.

Follow-up

Once the treatment has been established, there should be a� control� after� the� first� week,� including� tonal� and� verbal� audiometry, to assess tolerance to treatment and its results:

- If the patient has fully recovered hearing and presents acusia, the prescribed scheme should be followed (oral corticosteroids in decreasing doses for one month).

- If the patient has regained partial hearing, with an improvement of less than 15 dB, the prescribed scheme should be followed (oral corticosteroids in decreasing doses for one month), and simultaneous intratympanic treatment may be recommended individually.

- If hearing has deteriorated, intravenous rescue treatment will be recommended.

If early diagnosis (<30 days):

If severe SD (>70 dB), in single ear or with intense associated vertigo.

If there is no complete response to systemic corticosteroid treatment,

Figure 3 Diagnostic and therapeutic algorithm for sudden deafness.

aPlease� note� the� equivalence� between� the� two� steroids� in� terms� of� anti-‐inflammatory� effect:� 4� mg� methylprednisolone� equals� 6� mg� deflazacort.

Systematic review 4,180 artikel Oral : Prednison / metil prednisolon 1 mg/kg bb, diturunkan tiap 5 hariSistemik : 500 mg/hari dalam 30 menit 1x dosis, 7 hari —> lanjutkan oralVasodilator —> kelainan vaskular (nimodipine 5 - 15 cc dalam 500 cc saline drip 8 jam, trimetazidine oral/8 jam) + antiplateletIT steroid + oral bila 7 hari tidak ada perbaikan

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Dasar penggunaan steroid IntratimpaniKadar steroid perilimf intratimpani 260 kali lebih tinggi dibandingkan intra vena

Puncak kadar tertinggi dalam 0,5 - 1 jam —> menurun akibat keluarnya obat melalui tuba, resorpsi mukosa telinga tengah

Permeabilitas round window sangat bervariasi

Bird PA, Otol Neurotol 2011


Penelitian IT steroid sebagai salvage therapy

5 tahun terakhir

Nama peneliti Tahun Tipe penelitian Hasil

Dispenza et al 2013 ProspectivePerbaikan pendengaran

pada 20 dari 26 pasien

45 - 55 dB

Lee et al 2011 Case control

Perbaikan pendengaran pada min 10 dB pada

10 dari 22 pasien (6 > 20 dB, 4 10-20 dB)

Li et al 2011 Case control

Perbaikan pendengaran pada min 10 dB pada 10 dari 22 pasien

Hunchaisri et al 2010 Prospective

Perbaikan pendengaran rerata 17.5 + 17 dB & SDS 28.7 + 17 % pada

6 dari 14 pasien

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Teknik IT steroidAnastesi lokal (Xylocaine spray, EMLA)

Spuit 1 cc

Spinal needle No. 25

Metilprednisolone 0.9 cc 40 mg/vial + 0.1 cc lidocaine atau 0.9 cc Dexamethasone 8 mg/vial

Injeksi pada inferior MT (anterior / posterior )

Kepala pasien dimiringkan 45o 20 menit ke sisi kontralateral

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Case 1

Laki-laki, 50 tahun

Gangguan pendengaran tiba-tiba 4 hari

Rasa penuh + tinnitus

Tidak ada vertigo

Tidak ada kelainan pada pemeriksaan lab


Resume terapi

H1 - H4 Steroid i.vVasodilator i.vMeticobalamin Ginko biloba

H5 - H30 Steroid IT/minggu(total 3x) Steroid oralVasodilator oralHiperbaric 10 xMeticobalamin Ginko biloba

Audio 1

Audio pasca th IV

Audio saat terapi kombinasi

Audio akhir terapi

kombinasi

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Case 2Wanita, 37 th

Gangguan dengar tiba-tiba onset hari 1

Tinnitus + berdengung

Vertigo (-)

Laboratorium normal

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Resume terapi

H1 - H7 Steroid i.vVasodilator i.vMeticobalamin Ginko biloba

H8 - H30 Steroid IT/2x minggu (total 5x)Steroid oralVasodilator oralHiperbaric 10 xMeticobalamin Ginko biloba

H30 - Akupunctur

awal masukpasca iv

Kombinasi 1

Kombinasi 2

Kombinasi 3

1 bulan pasca kombinasi

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DiskusiTerapi kombinasi memberikan perbaikan pada pasien yang gagal pada terapi standar

Peningkatan bermakna terutama terjadi pada frekuensi rendah -->

luas area >,

pembuluh darah lokal >

OHC + IHC >

Comparing the present study with many previous

reports, there is one main difference; the timing of ITDI.

The timing of salvage intratympanic therapy was at least3 weeks after initial systemic treatment in most of earlier

reports [4, 7–13]. If 7–14 days are required for initial

systemic steroid therapy, the refractory SSNHL patientsshould have the resting periods of treatment for at least

1 week or more in spite of the half-life of steroids. In theseearlier studies [9], the authors explored whether this effect

of late ITDI (2–3 weeks after initial systemic therapy) was

actually due to intratympanic steroids, and showed thepossibility of its significant role. Therefore, we expected

that early intervention of ITDI could also result in effectivehearing gain in the patients with poor responsiveness or

refractory to initial systemic treatments. Furthermore, to

solve out a remaining question on whether the effect ofITDI was affected by natural pathophysiological course of

the disease and/or the delayed effect of initial systemic

steroids, we compared the effects of sequential ITDI withthe control group, in which the patients did not undergo

any kinds of treatments after initial systemic steroid

therapy.In the present study, there was hearing improvement in

10 (47.6%) of 21 ears in the ITDI group and in only 4

(16.0%) of 25 ears in the control group. The mean PTAimprovement was 11.4 dB in the ITDI group, while 1.7 dB

in the control group. There was statistically significant

hearing recovery in the ITDI group, but it is a level thatmay not be clinically significant due to the standard devi-

ation and the measurement error. Nevertheless, these

results suggest that the sequential ITDI after initial sys-temic steroid therapy may be more effective than a sys-

temic steroid therapy alone for improving hearing in the

patients with SSNHL. When these results were comparedwith our previous study [9] where late ITDI was performed

after 2 weeks after initial systemic steroids, early and

sequential ITDI after initial therapy seemed to have greatereffectiveness as 47.6 versus 39.4% in the proportion of

hearing threshold shift above 10 dB in the PTA and 11.4

versus 9.1 dB in the hearing gain in PTA (Fig. 5). Becauseour two studies were not proceeded at the same time, it is

difficult to compare them directly. But, we think that it ismeaningful to identify their tendencies because their ITDIs

were performed in the same way except for only their

timing.We may be able to use the sequential ITDI in refractory

SSNHL patients regardless of their response to initial

systemic therapy because there was no significant differ-ence in the hearing recovery rates by ITDI between those

who responded at some frequencies to initial systemic

17.1 16.7

10.2

7.46.7 5.7

10.2

3.1

9

3.8 0.6 1.4 1.32.2 2.3

0.60

5

10

15

20

25

30

35

40

45

0.25 0.5 1 2 3 4 6 8

ITDI group (n=21)

Control (n=25)

dB HL

kHz

P=.138 P=.025

P=.080

Fig. 4 Hearing improvementaccording to the frequencybetween in the IDTI group andin the control group. ITDIintratympanic dexamethasoneinjection. The ITDI group hadsignificantly improved hearinggain at 0.5 kHz compared withthe control group (Mann–Whitney U test, P = 0.025)

Table 2 Hearing improvement in the patients treated with sequentialintratympanic dexamethasone injection (ITDI) according to theresponse at initial treatment including oral steroids

[20 dBHearing gain

20–10 dBHearing gain

No gain

Partial responsea (n = 8) 3 (37.5%) 5 (62.5%)

No response (n = 13) 4 (30.8%) 3 (23.1%) 6 (46.1%)

a Patients who showed hearing improvement of 10 dB or more atsome frequencies after initial treatments, including oral steroids, weretreated with a course of ITDI therapy

Table 3 Hearing improvement in the patients treated with sequentialintratympanic dexamethasone injection (ITDI) according to pure-toneaverages before intratympanic injection

[20 dBHearing gain

20–10 dBHearing gain

No gain

26–40 dB (n = 2) 2

41–55 dB (n = 3) 3

56–70 dB (n = 3) 3

71–90 dB (n = 6)a 3 3

91–110 dB (n = 7)a 3 2 2

a Patients with 70 or more dB PTA before ITDI showed significanthearing improvement in the last audiogram compared with otherpatients; Fisher’s exact test (P = 0.038)

Eur Arch Otorhinolaryngol (2011) 268:833–839 837

123

Lee at al 2011, perbaikan pendengaran bermakna pada 500 dan 1 Khz


Peran hiperbarik pada tatalaksana tuli mendadak

Hiperbarik meningkatkan konsentrasi oksigen plasma --> meningkatkan O2 perilimfe bersama dengan steroid memperbaiki inflamasi dan reoksigenisasi jaringan

Alimoglu (2011) : steroid + hyperbaric memberikan hasil lebih baik dari hiperbarik saja (86.88 % vs 46,51 %)

Holy (2011) : hiperbarik yang diberikan kurang dari 10 hari onset memberikan hasil lebih baik dari yang terlambat (65 % vs 38,9%)

Bennet (2011) Cochrane Metaanalysis : 7 RCT mendukung pemberian hiperbarik

Peningkatan 19.3 - 37.7 dB ambang dengar

21 22

Diskusi Pengalaman perbaikan kurang memuaskan pada :

Kasus terlambat

Tidak jelas penyakit penyerta

Kasus anak dengan riwayat parotitis akut (mumps)

on 13 February 2006. Both eardrums were normal.Pure tone audiometry revealed total deafness on theright but normal hearing on the left. Distortion pro-duct otoacoustic emissions were absent on the rightbut normal on the left. The boy felt dizzy around thetime of onset of hearing loss, but did not complain ofdizziness or vertigo when he came to our hospital.The medical interview established that two class-mates had developed mumps in January 2006. Ourpatient’s salivary glands had not been swollen andpalpation of the salivary glands (at interview) wasnormal. Blood examination on 13 February 2006,revealed that mumps IgM was 3.1 U/ml (normalrange: 1.0>) and mumps IgG was 12.0 U/ml (normalrange: 2.0>). 3D-FLAIR MRI taken at 3-tesla (T) with-out gadolinium enhancement on 1 March 2006,revealed high signals in the right cochlea and vesti-bule (Fig. 1A). MRI scans were performed with a 3 TMR (Trio, Siemens, Erlangen, Germany) using areceive-only 8-channel phased-array coil. The MRIprotocols and thefilm settings havebeendescribed indetail in a previous report [5]. The high signal areas in3D-FLAIR were not detected by T1- and T2-weightedMRI in this patient. These results indicated rightlabyrinthitis due to mumps infection (Fig. 1B and C).

3. Discussion

Mumps deafness is suspected in patients with suddenhearing loss, and with high levels of mumps IgMantibody, even if the salivary glands are not swollen[6—9]. Mumps IgM antibody rises after viral infectionsin 1 or 2 days and becomes a peak in 4 or 5 days andgradually falls afterwards while mumps IgG antibody

rises after viral infections since about 1 week andmaintains afterwards a long term. Patients withoutevident clinical signs ofmumps, but have a significantrise in mumps IgM antibody within 3 months after theonset of acute hearing loss are regarded as almostdefinite cases of mumps deafness [6].

The hearing loss may be due to direct viral inva-sion of the cochlea, affecting the stria vascularis,the organ of Corti, the tectorial membrane and/orthe myelin sheath of the eighth nerve [1]. Inhumans, the path of labyrinthine infection has notbeen established, but it is thought to be secondaryto a viremia or to reflect viral spread from infectedcerebrospinal fluid through the labyrinth [10].

Comacchio et al. [10] reported a case of mumpsdeafness in which an abnormal T2-weighted MRI wasfound from the inner ear. Gadolinium enhancementwas not observed in the inner ear, although gadoli-nium enhancement was recognized in the eighth-nerve bundle. Our case revealed that the 3D-FLAIRMRI is superior to T1- and T2-weightedMRI in visualiz-ing abnormality of the inner ear in mumps deafness.Theabnormallyhighsignalweobservedmaybeduetohigh protein concentration in the inner ear fluid. ThisMR imaging is not specific for mumps [11]. But 3D-FLAIR MRI, even without enhancement, can detectthe minor abnormality of the inner ear because of itshigh sensitivity. We assume that all acoustic tumorscan be detected by MRI without enhancement [12].Moreover, 3D-FLAIR MRI may possibly clarify thepathophysiological mechanisms in patients with sen-sorineural hearing loss including mumps deafness.

In conclusion, 3D-FLAIR MRI will help, to demon-strate and define labyrinthitis in mumps deafness, inthe future.

2116 H. Otake et al.

Fig. 1 (A) Axial magnetic resonance imaging using 3D-FLAIR. Bright signals are noted in the right cochlea and vestibularapparatus. High signal areas on 3D-FLAIR MRI were not detected by unenhanced T1-weighted (B) or T2-weighted and (C)MRI. CO: cochlea.

Otaka, 2011MRI 3D FLAIR pada anak dengan tuli mendadak pasca parotitisAdanya enhancement pada koklea & vestibuler kanan —> pelepasan protein dari pembuluh darah intrakoklea

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Kesimpulan

Terapi intratimpani telah diterima secara konsensus sebagai salavage therapy untuk Tuli mendadak

Kombinasi intratimpani dengan terapi oral dan hiperbarik diharapkan memberikan respons yang lebih baik


Terima kasih

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sudden + kombinasi th - April 4, 2014

sudden kombinasi th(2) dr.fikri

Health & Medicine