COMBINED INTRATYMPANIC AND SYSTEMIC

USE OF STEROIDS AS A FIRST-LINE TREATMENT

FOR SUDDEN SENSORINEURAL HEARING LOSS :
A META-ANALYSIS OF RANDOMIZED
CONTROLLED TRIALS

Dosen Pembimbing :
dr. Nur Iman, Sp.THT-KL
Combined Intratympanic And Systemic Use Of
Steroids As A First-line Treatment For Sudden
Sensorineural Hearing Loss : A Meta-analysis
Of Randomized Controlled Trials

Reza Rachman Riski Novian

Omar Basalamah Andreas Tigor
Rohedy Adel Nur Azizah Intan
Ina Marlina Priscilla Jessica
Rizqi Indah Riani Citra Hutami Saraswati
 ABSTRACT

METHOD

OBJECTIVE

An elctronic database searh

To compare the efficacy of (PubMed, Embase, Cochrane
combination therapy (combined Library, and CNKI database)
intratympanic and systemic use
steroid, CT) with systemic steroid Review Manger 5.3 was used
(SST) as a primary treatment for for data synthesis
sudden sensorineural hearing loss
(SSNHL)
 ABSTRACT

Result

◇ A total of 14 RCTs including 756

subjects allocated
to CT and 638 to SST were selected.
he proportion of patients with hearing
improvement as outcome measure was
observed in 13 studies,
Which resulted in an odds ratio (OR) of 2.50
(95% confidence interval [CI]: 1.95–2.1).
 ABSTRACT

Result

The PTA changes (in dB) as

outcome measure was observed in
12 studies, which resulted in mean
difference (MD) 13 (95% CI: 9.24–
16.77).
SDS changes (in %) as outcome
measure were reported in five
studies, which resulted in MD 15.72
(95% CI: 5.11–26.33).
 ABSTRACT

Conclusion Keywords

• CT seems to confer a certain degree of • Key Words : Intratympanic—

benefit as a primary treatment of SSNHL Meta-analysis— Steriod—
as compared with SST. Sudden sensorineural hearing
• Further validation based on high quality loss (SSNHL).
studies is required.
 DEFINITION AND
ETIOLOGY

◇ Definition : Sudden sensorineural hearing loss

(SSNHL) is widely defined as greater than 30dB of
hearing loss across three consecutive frequencies
within 72 hours
◇ Etiologis : the exact underlying mechanisms of SSNHL
remain unclear.
I Introduction
 INDRODUCTION
The aim : to evaluate
Steroid : The most widely
the efficavy of CT
accepted of these is the
compared with SST
use of steroids
as first line therapy
administered systemically.

Use of IT alone :
Clinicians combine IT decrease of leucocytes In recent years,
and systemic use of circulation and inhibition IntraTympanic
steroid. of liberation inflamatory steroid is
Sometimes benefit and mediator increasingly used
unbenefit. Promoted us to comment in SSNHL
that IT may be used as
first line agen treatment
for SSNHL
II Materials and method
 Material and Methods

◇ Search Strategy and selection criteria elektronics search

was performed in the PubMed, embase, cochrane Library
and CNKI database to June 1 st, 2016 for all trials
comparing the effcacy of CT with SST as primary therapy
in the treatment of SSNHL.
◇ All RCT that compared the efficacy of CT with SST
in patients with SSNHL.All RCT fulfilling the
following criteria were included :
1. Conduct of human studies involving subjects
with SSNHL
2. Presence of CT and SST as primary treatment of
SSNHL
3. Steroid treatment

4. The main outcome measures of each arm of the

study was reported at the start and end of the
treatment/ observation period
 Main Outcome Measures

Three main outcome measures :

◇ The proportion of patients with hearing improvement (hearing
improvement was degined by the authors of the included studies)
◇ Pure ton averages changes

◇ Speech discriminationscore changes

 Data Extraction
Years of Number of
Main outcome cases and
publication measures control

Information for Definition of

each study SSNHL

Protocol of Criteria for Follow up

SST and CT improvement period
 Quality Assesment of RCTs
◇ Independently by using
◇ Random sequence generation
◇ Allocation concealment
◇ Blinding of participants
◇ Personnel and outcome assesment
◇ Incomplete outcome data
◇ Selective reporting
◇ Other source of bias
◇ YES if low risk
◇ NO if high risk
◇ UNCLEAR if no explicit information is available on
which to make a judgment
◇ Disagreements were resolved through consensus or
discussed with a third author
 Statistical Analysis
◇ Meta-analyses were conducted regarding the proportion of
patients exhibiting hearing improvement, PTA changes in
decibels and SDS changes in %.

“
◇ The odds ratio and 95% confidence interval were estimated for
the numbers of patients with hearing improvement.
◇ The mean differences (MDs) and 95% CI were estimated for
the PTA and SDS changes. Cochrane’s I2 index was calculated
to asses heterogeneity (I2<50%) the ORs and MDs were
pooled according to the fixed-effect model. Otherwise, the
random-effects model was used.
 ◇ The statistical significance of the pooled OR
and MD was evaluated using the Z test.
Possible publication bias was assessed with
funnel plots.

“
◇ The meta-analyses were performed using
Review Manager Software, version 5.3 from
the Cochrane Collaboration (London, UK).
Significant difference was set at p<0,05 for
all analyses.
III RESULTS
 Results
Study Selection
Records identified through
database searching (n=470)

Records excluded based on

Records after duplicates
removed (n=208) title and abstract review
(n=185)

Records screened (n=23) Publications excluded

based on full text review
(n=9)
Studied included in meta- 1. Abstract, letter (n=2)
analysis (n=14) 2. Not RCT (n=2)
3. Retrospective (n=5)
Characteristics of Studies
◇ The inclusion criteria were all similar
except Arastou -> patients with
poor prognostic factor
◇ Definition
SSNHL
◇ Protocol of SST
and CT
◇ Follow up period
◇ Criteria for
improvement
◇ Audiograms ->
before treatment
◇ Final audiogram
-> follow up
Quality
Assessment
◇ Cochrane Handbook for Systematic Reviews to
asses the risk of bias
￭ Only 7 articles describe the method of
randomization
￭ No trial gave info if concealment of allocation
procedure was used
￭ Only 3 studies report blinding participants
Results of the
Meta-Analysis
◇ 1312 participants reported hearing improvement
◇ There were sifnificant difference when CT compared
with SST
◇ 1192 participants reported PTA changes
◇ The improvement of the PTA was 13.00 dB in
combination therapy
Adverse Effects
◇ Complications of IT steroids reported by five
studies
◇ Minor side effects -> transient vertigo, otalgia
◇ Of 220 patients, two developed tympanic
membrane perforation -> treated with paper
patch and tympanoplasty
◇ A case of otitis media -> oral antibiotics
Publication Bias
◇ There was not significant publication bias in
the meta-analysis
IV Discussion
 Discussion
◇ The first meta-analyses on this topic
◇ Conducted regarding the proportion of patient
with hearing improvement, PTA changes and

“
SDS changes.
◇ Showed CT statistically significant increase
in hearing improvement, PTA and SDS
changes, compared to SST
◇ The combination of IT and systemic steroids
add benefits compared to systemic steroid
alone.
 Discussion
◇ Most likely explanation -> more dose of
corticosteroids delivered to damaged ear

“
◇ Compared to system therapy, IT injection
results higher.
◇ Additional steroids have therapeutic effect :
￭ Preventing hair cell apoptosis
￭ Reestablishing blood flow
￭ Stabilizing endolymph homeostasis
 CT group treated
with IT
dexamethasone Better outcome
(12 and 10

“
mg/ml)
Battalgia et al.
2008 and 2014

CT group treated
with SST high-
dose
 SSNHL treated
with CT
(IT
dexamethasone No Difference

“
5 mg/ml)
Ahn et al. The dose of IT
dexamethasone
SSNHL treated Ahn et al < Battalgia et al
with SST alone
 15 studies
Positive
1 studies used
12mg/ml IT 5 mg/ml of
dexamethasone dexamethasone might

“
not be sufficient to
4 studies using IT achieve benefit with IT
dexamethasone dexamethasone
3 studies used
5 mg/ml IT injection
dexamethasone
Negative
 IT
dexamethason
Better outcome
e (24 mg/ml) +

“
oral prednisone
Compared
taper
outcomes in
Injection of a more
patients treated
concentrated
with different IT dexamethasone solution
concentrations of IT dexamethason into the middle ear may be
dexamethasone e (10 mg/ml) + required in order to
oral prednisone maximize hearing
taper recovery
Limitation
Studies included in this review have certain
degree of risk of bias

Significant variability in trial design

Publication bias cannot be completely ruled

out given the low prevalence of SSNHL
 Implications for
Practice
Patients received CT (Combination Therapy) exhibit
statistically significant increase of hearing
improvement PTA (Pure Tone Averages) changes
and SDS (Speech Discrimination Score) changes
compared with SST (Systemic Steroid Therapy)
group.
 Conclusion
This review support the There is also needed to define
some uncertain aspects such as
benefit of CT
the optimal protocol therapy to be
(Combination Therapy) used and to standardize the
as a primary treatment of outcome measure and criteria of
SSNHL. improvement to allow intertribal
comparability in the fiture
* CRITICAL APPRAISAL
 CRITICAL APPRAISAL

◇ Title
• Interesting
• There is no abbreviation
• Describe the entire contents of the study
 CRITICAL APPRAISAL

◇ Title
• Interesting
• There is no abbreviation
• Describe the entire contents of the study

◇ Abstract
• In the form of a single paragraph which consist of aim of study, method, result,
and conclusion but not background of this study
• Less than 250 words
• There are keywords
 CRITICAL APPRAISAL

◇ Title
• Interesting
• There is no abbreviation
• Describe the entire contents of the study

◇ Abstract
• In the form of a single paragraph which consist of aim of study, method, result,
and conclusion but not background of this study
• Less than 250 words
• There are keywords

◇ Introduction
￭ The introduction title is not mention explicitly, but the contain of
introduction already included in this journal
￭ There is a background underlying the conduct of the research
￭ The aims and objectives of the study were mentioned
￭ Use the relevant literatures known
 CRITICAL APPRAISAL - Methods

◇ Design ◇ Location

◇ Meta-Analysis of Randomized ◇ Medical College of

Controlled Trials Jiangnam University,
◇ Samples of this journal are 14 China
Randomized Controlled Trials

◇ Time ◇ Technique ◇ Method

◇ There is no ◇ Purposive Sampling ◇ Meta-Analysis of

information Randomized
regarding the time of Controlled Trials
this study ◇ Purposive sampling
 CRITICAL APPRAISAL - Result
The Results are presented in Tables

• The title of the table and figure had been written correctly
• Informative
CRITICAL APPRAISAL

◇ Discussion
◇ Conclusion
• The results of research had been explained
￭ Conclusion of this study has
and compared with previous research
been written explicitly and
• The disclaimers from other research with not could be used as
appropriate result had been included recommendation for SSNHL
• The advantages and disadvantages had not treatment in clinical practice.
been explained, but further advice of this
research had been explained.
CRITICAL APPRAISAL

◇ Bibliography

• Referring to the vancouver

system
• Partial of the research from >
5 years before the research
was conducted
* PICO & VIA
 PICO
◇ Population
◇ All RCT comparing the
efficacy of CT with SST as
primary therapy in the
treatment of SSNHL which
fulfil the inclusion criteria
◇ Intervention
◇ There aren’t any intervention in
this study because it is a meta-
analysis
◇ Control
◇ There aren’t any control
group
◇ Outcome
• Patients who received CT demonstrated significant
increase in hearing improvement, PTA changed and
SDS
• Combination of IT and systemic steroids did not have
aditional benefit
• The CT is more successful because more dose of drugs
delivered to inner ear
• IT injection result in higher perilymphatic concetrations
of steroid
 Validity

This review is considered as valid,

◇ How about the validity of considering the multilevel process of
this data? How was the journal selection, from 470 journals
data processed? identified, then being excluded until 14
journals fulfilled the citeria to be
reviewed.
 Importance

• This journal is important because it is

◇ What relevance do the
finding have to clinical
practice?
related to one of emergency cases in
ENT (ear, Nose and Throat)
Department, but there was no
available recommendation on the
therapy before this review being made.
 Availability
◇ Is the treatment provided
easily in my environment?
◇ The result of this journal is not
easily provided specifically in
Indonesia
◇ Are the potential benefits of this
therapy greater than the
potential harm to my patients?
◇ Yes, the potential benefit of the
SSNHL treatment recommended
by this journal is greater to
certain degrees than the
potential harm itself.
Thank You!
Any questions?