1. health and fitness
2. therapy

UHM 2012, Vol. 39, No. 3 – HBO2 AND ISSHL
Hyperbaric oxygen therapy for idiopathic sudden sensorineural
hearing loss
H. Murphy-Lavoie 1, S. Piper 2, R.E. Moon 3, T. Legros 4
1 Associate
Clinical Professor, Section of Emergency Medicine, and Associate Program Director, Louisiana State
University Undersea Hyperbaric Medicine Fellowship, Louisiana State University Medical Center, New Orleans,
Louisiana USA
2 Staff Physician, Van Meter and Associates, Harvey, Louisiana USA
3 Professor and Chief, Division of General, Vascular, and Transplant Anesthesia, and Medical Director of Hyperbaric
Medicine, Duke Medical Center, Durham, North Carolina USA
4 Associate Clinical Professor, Section of Emergency Medicine, and Program Director, Louisiana State University Undersea Hyperbaric Medicine Fellowship, Louisiana State University Medical Center, New Orleans, Louisiana USA
CORRESPONDING AUTHOR: Dr. Heather Murphy-Lavoie – [email protected]
____________________________________________________________________________________________
ABSTRACT
Idiopathic sudden sensorineural hearing loss (ISSHL)
is the newest indication approved by the Undersea
and Hyperbaric Medical Society’s Hyperbaric Oxygen
Therapy Committee. Idiopathic sudden sensorineural
hearing loss appears to be characterized by hypoxia in
the perilymph and therefore the scala tympani and
the organ of Corti. A review of the literature reveals
more than 100 publications evaluating the use of
hyperbaric oxygen (HBO2) for the treatment of
ISSHL, including eight randomized controlled trials.
The best and most consistent results are obtained
when HBO2 is initiated within two weeks of symptom
onset and combined with corticosteroid treatment. The
average hearing gain is 19.3 dB for moderate hearing
loss and 37.7 dB for severe cases. This improvement
brings hearing deficits from the moderate/severe range
into the slight/no impairment range. This is a significant gain that can markedly improve a patient’s quality
of life, both clinically and functionally.
____________________________________________________________________________________________
PROCESS OF ‘NEW INDICATION’ APPROVAL
An individual or group may, after a thorough review
of the literature, request a convening of the Undersea
and Hyperbaric Medical Society’s Hyperbaric Oxygen
Therapy Committee, for consideration of a new indication. If this request is granted, the Committee will ask
for, and assign, two presenters. One side presents the
“pro” argument and the other the “con” argument.
The “pro” argument is usually presented by the individual or group requesting the review. Presentations
are given before the Hyperbaric Oxygen Therapy
Committee at the UHMS Annual Scientific Assembly.
If a quorum is present, the Committee votes on the
proposal following the presentations.
This newest indication, ISSHL, followed this pathway
toward acceptance. It was proposed and presented by
the LSU Undersea and Hyperbaric Medicine Fellowship.
It was favorably voted upon following deliberations at the
UHMS Committee Meeting in Fort Worth in June 2011.
Copyright © 2012 Undersea & Hyperbaric Medical Society, Inc.
It was ratified by the UHMS Executive Board in
October 2011.
The ‘pro’ argument
While there is a large body of literature comparing
therapeutic interventions for the treatment of idiopathic
sudden sensorineural hearing loss (ISSHL), only a small
number of controlled studies have been performed.
Moreover, there has not been a clear consensus for
treatment. More than 60 protocols have been described
[1]. However, when the three most prominent and
efficacious treatments – corticosteroids, vasodilators
and hyperbaric oxygen (HBO2) – were systematically
reviewed by meta-analyses from the Cochrane Collaboration, only the use of HBO2 received multiple,
positive, objective, critical reviews [2-4]. The Cochrane
reviews for the use of HBO2 (2005, 2007 and 2010)
were all conservatively favorable. The 2005 review
found that “HBO2 did improve hearing” [2]. Both the
777
UHM 2012, Vol. 39, No. 3 – HBO2 AND ISSHL
2007 and 2010 updates concluded that “For people with
acute ISSHL, the application of HBO2 significantly
improved hearing, but the clinical significance remains unclear” [3, 4]. The average hearing gains found
to have “unclear clinical significance” are 19.3 dB for
moderate loss (hearing aids recommended) and 37.7
dB for severe loss (hearing aids required, lip-reading
recommended). Importantly, these gains improve
hearing function into the normal range [5].
The World Health Organization lists hearing loss
as the number one cause of disability globally, just
ahead of refractive errors, and well ahead of depression,
cataracts and accidental injuries, which round out the
top five [6]. Acquired hearing loss is also the third
leading cause of years lost due to disability [6]. It stands
to reason that the significant improvements in hearing
gains found with adjunctive HBO2 therapy are functionally important [7]. The reported spontaneous recovery
rate for ISSHL is 65% (Mattox and Simmons, 1977)
[8]. However, this early work regarding the spontaneous
recovery rate is currently contended by most clinical
otolaryngologists as an overestimation [9].
Appropriate patient selection is paramount, and the
literature suggests that these patients benefit the most
from the use of adjunctive HBO2: those with moderate
to profound hearing loss [1, 10-24]; those who receive
early HBO2 therapy [1, 11-17,19-23,25-36]; those who
receive both corticosteroids and HBO2 [1, 11-15, 23, 25,
30, 32; and patients younger than 60 years old [13, 32,
34]. While it is conceded that these studies do not have
sham controls, and many are unblinded, the treatment
of ISSHL with HBO2 does have eight prospective
randomized controlled trials (four in peer-reviewed
journals and four in proceedings) and is the only reviewed
ISSHL treatment found by the Cochrane Collaboration to
be significantly efficacious [2-4].
Multiple controlled studies have demonstrated a
clinically and statistically significant degree of hearing improvement when patients receive early concomitant therapy with HBO2 and oral corticosteroids [1, 1015, 25]. Additionally, the most recent clinical practice
guidelines for sudden hearing loss published by the
778
American Academy of Otolaryngology – Head and Neck
Surgery Foundation gave the use of adjunctive HBO2
a Grade B Level of Evidence (randomized controlled
trials; overwhelmingly consistent evidence from observational studies). This is significant, as there was no
Grade A Level of Evidence for any other diagnostic tests,
treatments, or regimens put forth in these guidelines [9].
The ‘Con’ Argument
The difficulty of establishing efficacy of any treatment
for idiopathic hearing loss is illustrated by a prospective
study, in which 65% recovered completely to functional
hearing levels spontaneously and independent of any type
of medical treatment, with the majority doing so within
14 days [8]. Since then there have been several studies
of the efficacy of corticosteroids (which are the preferred treatment by most otolaryngologists) and HBO2.
Of the studies evaluating HBO2, only four prospective randomized controlled studies have been published
in peer-reviewed journals [13, 16, 17, 37]. In two of these
studies, HBO2 was instituted within 14 days of symptom
onset; in the other study, HBO2 was instituted within
two days. These studies showed some benefit of HBO2.
However, no studies of HBO2 in hearing loss have been
appropriately blinded, and there are no prospective
studies showing benefit when HBO2 is initiated more
than two weeks after symptom onset.
A recent Cochrane Review concluded that there is
limited evidence from methodologically poor studies
that HBO2 improves hearing in patients with ISSHL
who present within two weeks of hearing loss, with no
evidence that any improvement achieved is functionally important [4]. One major weakness of the available
data is that while HBO2 seems to help some patients,
particularly those treated early, there is no useful information to guide patient selection. The perilymph pO2
measurements are at best suggestive that some cases of
ISSHL are associated with lower pO2. However, there
is no definitive evidence to suggest that hypoxia is the
cause. What might be interpreted as intriguing preliminary results should provide the impetus for a definitive
study.
H. Murphy-Lavoie, S. Piper, R.E. Moon, T. Legros
UHM 2012, Vol. 39, No. 3 – HBO2 AND ISSHL
INTRODUCTION
Idiopathic sudden sensorineural hearing loss (ISSHL)
is classically defined as a hearing loss of at least 30 dB
occurring within three days over at least three contiguous frequencies [38]. A common clinical presentation
involves an individual experiencing a sudden unilateral
hearing loss, tinnitus (nearly universal), a sensation of
aural fullness, dizziness and vertigo [9, 39].
The symptoms are often subtle enough, “fullness/
blocked,” that they are overlooked by both the patient
and the clinician until hearing loss becomes severe. The
incidence is estimated at five to 20 cases per 100,000
per year in the United States [40]. This translates into
approximately 4,000 new cases annually in the United
States [41]. However, the incidence may be higher, as
many cases are likely unreported. Additionally, it has
been estimated that as many as 65% of cases may resolve
spontaneously; however, this number has been recently
questioned [8, 9].
The etiologies of ISSHL remain unclear. Several
pathophysiological mechanisms have been described
including: vascular occlusion, viral infections, labyrinthine membrane breaks, immune associated disease,
abnormal cochlear stress response, trauma, abnormal
tissue growth, toxins, ototoxic drugs and cochlear
membrane damage [1].
Hearing loss imposes a heavy social and economic
burden on the individual as well as the community. When
hearing loss is in the slight impairment range (26 dB40 dB), patients are able to hear and repeat spoken
words in a normal voice at 1 meter and may only need
counseling for treatment. However, when hearing loss
is moderate (41 dB-60 dB) or severe (61 dB-80 dB),
hearing aids are usually recommended and when not
available, lip-reading and signing should be taught [7]. Hyperbaric oxygen therapy has been shown to impart
a 37.7 dB improvement in hearing gains to those with
a severe hearing deficit and a 19.3 dB improvement in
those with moderate hearing deficits. This resolves the
impairment toward the normal range, and may dramatically affect quality of life and obviate the need for hearing
aids.
COST IMPACT
There are no formal detailed cost analyses for ISSHL
in the literature. However, the World Health Organization (WHO) has described the cost impact of hearing
loss. Hearing impairment makes it difficult to obtain,
perform and keep jobs, and the hearing-impaired are often stigmatized and socially isolated. The cost of special
H. Murphy-Lavoie, S. Piper, R.E. Moon, T. Legros
education and lost employment due to hearing impairment imposes a heavy social and economic burden [5].
Adult onset hearing loss is the most common cause
of disability globally, and the third leading cause of
years lost due to disability. Moreover, adult onset hearing loss is the 15th leading cause of burden of disease,
and is projected to move up to seventh by the year
2030 [6].
Hearing aids cost between $1,500 and $3,000 per pair,
require replacement every three to five years and they
don’t always give the patient fully functional hearing.
The cost of 10 hyperbaric treatments at an average
outpatient facility ranges between $2,000 and $5,000.
Although additional studies are recommended to
further define the pathology and optimize the treatment
of ISSHL, based on the current medical evidence, the use
of HBO2 outweighs the risk. Furthermore, significantly
improving a patient’s hearing and minimization
of the social and economic burden of this disease
outweighs treatment costs.
RATIONALE
The use of hyperbaric oxygen therapy
in the treatment of ISSHL
The rationale for the use of hyperbaric oxygen to treat
ISSHL is supported by an understanding of the high
metabolism and paucity of vascularity to the cochlea.
The cochlea and the structures within it, particularly the
stria vascularis and the organ of Corti (OOC), require a
high oxygen supply [42]. The direct vascular supply,
particularly to the OOC, is minimal [44]. Tissue oxygenation to the structures within the cochlea occurs via
oxygen diffusion from cochlear capillary networks into
the perilymph and the cortilymph [43]. The perilymph
is the primary oxygen source for these intracochlear
structures.
One study investigated perilymph pO2 in anesthetized humans during surgical exploration of the ear 13
days to 15 years following hearing loss and found that
the perilymph pO2 tended to be lower (8.6 ± 2.8 mm Hg,
range 4.0-12.5 mm Hg) in the seven patients with
ISSHL than those patients with otosclerosis (mean 11.7 ±
10.0 mm Hg, range 2.2 - 27.3 mm Hg), sudden cochleovestibular loss (mean 10.6 ± 9.1 mm Hg, range 3.3 - 23.1
mm Hg), or rapidly progressive sensorineural hearing
loss (16.7 ± 8.2 mm Hg). They observed no correlation
between the degree of hearing loss and perilymph pO2,
but commented that these measurements suggest that
some cases of ISSHL may be due to ischemia [44].
Later animal studies confirmed that normobaric oxygen
779
UHM 2012, Vol. 39, No. 3 – HBO2 AND ISSHL
increases perilymph pO2 3.4-fold, while HBO2 increases
the perilymph pO2 9.4-fold compared to room air [43].
Although normobaric hyperoxygenation increases intracochlear oxygen tensions, only HBO2 achieves the extremely high arterial perilymphatic oxygen concentration
differences [43, 45, 46]. The concept that the efficacy of
HBO2 is related to correction of perilymph hypoxia is
only one theory. Other contributory benefits of HBO2
may be related to its anti-inflammatory effects, as well
as the blunting of ischemia reperfusion injury and
reduction of edema.
The use of corticosteroids in the treatment of ISSHL
Corticosteroids are thought to improve outcomes in
ISSHL by decreasing inflammation and edema. Alexiou
et al. performed a retrospective review that found
patients with lower, middle, or pancochlear hearing loss
had statistically improved outcomes with the administration of corticosteroids and blood flow-promoting
agents [18]. Doyle and colleagues reviewed the literature
on intratympanic (IT) corticosteroids versus systemic
corticosteroids and found similar outcomes in both
groups [47].
Wei et al. performed a Cochrane review in 2006,
analyzing the only two randomized controlled trials.
The results of the trials were conflicting. One showed no
difference between groups. The other showed statistically
better outcome with corticosteroids [48].
In 2009, Plontke et al. performed a Cochrane review
on the use of IT corticosteroids for ISSHL. They found
the treatments equivalent, but of unclear clinical significance [49]. Two years later, Dispenza and co-workers
performed a prospective randomized trial comparing IT corticosteroids to systemic corticosteroids. Both
treatments resulted in hearing gain improvements
above that which is shown without treatment, but there
were no significant differences between groups [50].
In the same year, Alimoglu et al. retrospectively
reviewed their treatment of 217 ISSHL patients. Hearing gains were most statistically significant for those
treated with oral corticosteroids and HBO2. Moreover, the
proportion of those with complete recovery was also
highest in those receiving oral corticosteroids and HBO2.
The oral corticosteroid and HBO2 group also had the
highest mean hearing gain among all groups [1].
IT corticosteroids seem to be less efficacious than
oral corticosteroids, but may be a reasonable alternative
for those patients with contraindications to oral corticosteroid use (e.g., peptic ulcer disease, viral hepatitis
and brittle diabetes) [31].
780
LITERATURE REVIEW
Early investigations
Hyperbaric oxygen therapy has been investigated as a
treatment for hearing loss since the 1970s. Early work
began with a comparative study of acoustic trauma
patients. De Heyn and Van Opstal (1976) compared
acute acoustic trauma (AAT) blast patients treated
with vasodilators with or without HBO2. The addition
of HBO2 improved outcomes, but only if the patients
were treated within 10 days of symptom onset [51].
Lamm and co-workers utilized a guinea pig hypoxia
cochlea model and found HBO2 to be protective [52]. One of the first studies detailing the benefits of
hyperoxygenation in those with ISSHL was the Giger
study (1979) [53]. It was a prospective, randomized
trial in which 55 patients with ISSHL were treated with
either 95% oxygen/5% CO2 (carbogen inhalation) or
intravenous (IV) infusion of papaverin and dextran.
Immediate differences were not found between groups.
However, audiometric testing at one year showed
statistically better results in those treated with carbogen.
The authors opined that carbogen (O2-CO2 mixtures)
therapy may improve the spontaneous recovery rate
inherent with ISSHL [53].
Etiopathogenesis of ISSHL
Human studies: It has been proposed that the high
metabolism and vascular paucity predispose the cochlea
to damage. A number of case reports and series with
human patients have been published focusing on possible
vascular occlusive etiologies such as vertebrobasilar
disease and occlusive carotid disease [54]. However,
few studies have been performed.
Nagahara and colleagues examined perilymphatic
pO2 responsiveness to carbogen patients with either
ISSHL or slowly progressive sensorineural hearing loss.
They found the pO2 readings were initially low, but
responsive to carbogen in those with ISSHL. However,
in those with slowly progressive sensorineural hearing
loss, the pO2 was initially normal and unresponsive to
carbogen [44]. Wilson’s study reiterated the effectiveness
of carbogen in elevating perilymphatic pO2 [55].
Animal studies: There are far more animal studies
related to the pathogenesis of ISSHL. Lamm and coworkers utilized a guinea pig model to evaluate the pO2
in the perilymph and scala tympani under normobaric
and hyperbaric conditions via the insertion of oxygensensitive microcoaxial electrodes. In all animals, the pO2
fell 34% during electrode insertions, and increased after
H. Murphy-Lavoie, S. Piper, R.E. Moon, T. Legros
UHM 2012, Vol. 39, No. 3 – HBO2 AND ISSHL
normobaric and hyperbaric O2 [43]. Lamm et al. used
this same model to evaluate noise stress. They found the
perilymph pO2 of the scala tympani fell 50% to 80%
during noise exposure, the compound action potential
(CAP) latency times were prolonged, and CMs (a measure
of hair cell function) declined by 60% to 70% of
original values.
The authors hypothesized that the decline in perilymph pO2 is indicative of cortilymph hypoxia.
They surmised that during noise exposure, the oxygendependent sodium and potassium pumps of the OOC
decompensate, resulting in intracellular sodium accumulation, which causes microstructural damage. This
damage is manifested in hair cell-cilia fusion; hair cell-,
synaptic- and dendritic swelling; hair cell contraction;
and sustained depolarization [56].
Other animal experiments have shown that occlusion
of the labyrinthine artery results in severe degenerative
changes, fibrosis and new cochlear bone formation. In a
similar manner, the human cochlea, deprived of cochlear
blood supply, results in progressive ossification of the
cochlear spaces, loss of cochlear neurons, labyrinthine
fibrosis, new bone formation and endolymphatic hydrops
[57].
Lamm and Arnold reported their work on guinea
pigs exposed to AAT. They found that AAT induces
cochlear hypoxia in an intensity-dependent fashion
that correlates with hearing loss and precedes the
observed reductions in cochlear blood flow [26].
Kuokkanen et al. evaluated the effect of HBO2 on
hair cell preservation using rats exposed to extreme AAT
daily for 10 days. The AAT caused permanent damage
to the cochlea of all animals, with the most severe lesions in the lower middle coil. In the HBO2-treated
group, there was a significantly less hair cell loss in these
regions [58].
Pilgramm has shown in guinea pig cochlear experiments that HBO2 leads to an increase in perilymph pO2
and a statistically lower number of damaged inner ear
sensory cells 60 hours following AAT [59].
ISSHL pathogenesis theories: Belal discusses the role
that occlusive arterial disease (thrombotic, embolic or
spastic) has in the development of ISSHL and suggests
a vascular etiology of ISSHL [60]. This is the reasoning behind the use of vasodilator drugs, stellate ganglion blocks, anticoagulants and rheological agents in the
treatment of ISSHL. Gloddek and colleagues remarked
upon the differing theories, noting that a viral infection
of the stria vascularis, OOC or spiral ganglion is often
H. Murphy-Lavoie, S. Piper, R.E. Moon, T. Legros
suggested in the American literature, while European
scientists favor a vascular pathology with impaired
inner ear perfusion [61].
These authors aimed to meld competing theories
by offering a theory based on an immunologically
mediated vasculitis resulting in cochlear hypoperfusion.
The basis for this theory is that during viral vasculitis,
circulating immunoglobulins are deposited perivascularly, associated with local decreases in perfusion and
tissue hypoxia [61]. Moreover, in autoimmune disease
perivasculitis is common, with the endothelial cells
promoting the vasculitis by secreting pro-inflammatory
cytokines and adhesion molecules.
The end result of this immunopathological theory
is stenosis, atresia and ischemia [61]. At this time, the
exact etiologies of ISSHL are uncertain. More than
60 protocols for treatment have been proffered [1].
Among them, the use of systemic corticosteroids in
combination with HBO2 has the greatest efficacy.
Acute acoustic trauma and HBO2
Animal studies: A discussion of acute acoustic trauma
(AAT) is appropriate, as a great deal of the early work in
sudden hearing loss and the efficacy of HBO2 involved
the treatment of these patients. Fakhry et al. assessed
AAT in a guinea pig model (extreme exposure of 115 dB
bilaterally for 45 minutes). The combination of HBO2
and corticosteroid therapy provided significant protection, especially when started within a day of insult.
These results correlate with previous literature, although
the hearing loss in this study was considerably greater
[62].
Lamm and Arnold used a guinea pig AAT model
to compare a placebo control group against various
medical treatments, isobaric oxygenation (IBO) and
HBO2. The noise-induced cochlear hypoxia was compensated by IBO. However, HBO2 was much more
effective (with or without supplements). Other treatments
had no sustained effect. The only treatments that
showed efficacy were a combination of HBO2 and
prednisolone, followed by monotherapy with prednisolone or hydroxyethyl starch [63].
Human studies: In human studies, many pharmacological therapies have been used to treat AAT. Pilgramm
and Schumann evaluated eight AAT studies (n=400) comparing rheological, vasoactive and metabolically active
substances with saline-treated controls. All groups
showed superior results, with the rheological agents
showing statistically significant improvement above other
781
UHM 2012, Vol. 39, No. 3 – HBO2 AND ISSHL
agents. Hyperbaric oxygen therapy was found to be
beneficial [64].
These same authors conducted a randomized
controlled study of 122 soldiers with AAT treated with
either betahistine (vasoactive infusion) or HBO2, following the exclusion of those with spontaneous recovery.
Hyperbaric oxygen therapy shortened the recovery of
high-pitch dysacusis (both in the acutely and following a
week of observation) and reduced the relapse frequency
and associated tinnitus that occurs with AAT [65].
Pilgramm reported the results of 10 studies (n=500)
with AAT patients who showed no evidence of spontaneous recovery. The combination of low-molecular
dextran or hydroxyethyl starch and HBO2 produced the
best therapeutic outcome with regard to hearing gain and
reduction of tinnitus, which was statistically significant
[59].
Winiarski et al. evaluated various pharmacological
agents and HBO2 in AAT patients. The HBO2 group
showed statistically significant gains in pure tone audiometry (PTA) compared to pharmacological therapy when
continued over 10 days (p<0.00001) and if started within
five days (p<0.000001) [66].
In 2008, Ylikoski and colleagues also observed an
enhanced recovery rate from AAT with the use of HBO2
compared to normobaric oxygen treatment (p<0.01) [27].
Medical therapies vs. primary HBO2 therapy
To date, HBO2 is generally used as an adjunctive agent
that is most efficacious with systemic corticosteroids.
There is a paucity of literature using HBO2 as a primary
therapy for ISSHL.
In 2001, Fatorri and co-workers reported a prospectively controlled study of patients who presented to
their ENT offices within 48 hours of symptom onset
and were randomly assigned treatment with either
HBO2 or buflomedil. The HBO2 group experienced
a significantly greater response to treatment than the
vasodilator group (73% vs. 55%, respectively). Those
with pantonal hypoacusis responded significantly
better than those with a milder presentation [16].
In 2007, Dundar et al. prospectively compared ISSHL
patients treated with HBO2 versus those treated with
medical therapy. The patients receiving HBO2 had
statistically significant hearing gains across all frequencies, with tinnitus patients showing the greatest hearing improvement [19]. In 2009, Cekin and colleagues
conducted a randomized, prospective and controlled
study evaluating ISSHL patients treated with medical
782
therapy (including corticosteroids) with or without HBO2.
Both groups had success rates above 70% (79.0% HBO2
vs. 71.3% control). However, there was no statistical
difference between groups [37].
The following year, Ohno and colleagues compared
ISSHL patients who had failed four weeks of medical
treatment (and then given HBO2) with ISSHL patients
(controls) treated with medical treatment alone. The mean
hearing gains were not different between groups. However, hearing gains were significantly higher in those
with profound hearing loss than in other patients [20].
Use of HBO2 following medical failures
Two of the difficulties in evaluating the efficacies of
ISSHL treatments are the reportedly high rate of spontaneous improvement and the various pharmacological therapies employed. Recently, the often-quoted
spontaneous recovery rate of 65% has been questioned
[8, 9]. Lamm et al. reported a rate of between 25% 68% for spontaneous full remissions and 47% - 89% for
spontaneous partial remissions [67]. Most authors agree,
however, that a significant number (35% - 39%) of
patients do not respond to medical or placebo therapies.
In 1998, Lamm and colleagues performed a literature
analysis of more than 50 studies utilizing HBO2 as an
adjunctive therapy for ISSHL, acoustic trauma,
noise-induced hearing loss and tinnitus. Corticosteroid therapy was significantly more effective than
placebo or NSAID treatment [67].
They also analyzed the 35% - 39% of patients in
these studies who failed to respond to any medical
therapies. In evaluating these 4,109 refractory patients,
they found that if HBO2 was started between two to
six weeks, 50% showed marked hearing gain (at least
3 frequencies of > 20 dB); 33% showed moderate
improvement (10 dB - 20 dB); and 13% had no improvement [67]. If adjunctive HBO2 was not started within
six weeks but within three months, 13% showed definite
improvement in hearing, 25% moderate improvement,
and 62% had no improvement [67].
In 2000, Marchesi et al. retrospectively studied
95 patients, 80% of whom had previous, ineffective medical treatment, then treated with HBO2 (2.2 atm abs for
75 minutes). The mean age was 45 years and the mean
hearing loss was 76.4 ± 25 dB. Within the HBO2 group,
78.9% had a mean improvement of 38.3 ± 8.3 dB and
41% gained > 20 dB. Complete recovery occurred in
11.6%. HBO2 was effective in those patients treated
within 14 days [68].
H. Murphy-Lavoie, S. Piper, R.E. Moon, T. Legros
UHM 2012, Vol. 39, No. 3 – HBO2 AND ISSHL
Also in 2000, Murakawa and colleagues reviewed
522 cases of ISSHL occurring over a 10-year period in
patients unresponsive to medical therapies. The patients
were treated at 2.5 atm abs for 80 minutes (10 to 15
sessions). Complete recovery occurred in 19.7%, with
significant improvement in 34.9% and slight improvement in 23.2%. Delay in treatment of more than 14 days,
advanced age and vertigo were associated with poorer
outcomes [34].
In 2010, Muzzi and co-workers treated 19 ISSHL
patients who had failed medical therapy with HBO2 (2.5
atm abs for 90 minutes for 30 sessions). Salvage HBO2
improved PTAs, particularly at the low frequencies.
Positive results were more likely in those with reduced
delay in receiving HBO2, but also in older patients
[35].
More recently, the clinical practice guidelines for
sudden hearing loss published by the American Academy of Otolaryngology – Head and Neck Surgery
Foundation have recommended that HBO2 may be considered for use within three months of diagnosis [9].
Chronic hearing loss and HBO2
The strength of evidence for use of HBO2 to treat
chronic hearing loss is far less robust than for the treatment of acute ISSHL. However, there is some evidence
it may be useful. Those patients who have had hearing
loss for longer than three months prior to the initiation of
therapy are the least likely to improve.
In 1990, Schumann and co-workers evaluated 557
patients with chronic hearing loss treated with 10 sessions
of HBO2 and found an improvement of > 10 dB in 27.8%
of cases [69].
In 1997, Kau et al. analyzed 359 patients with refractory hearing loss. Of the patients who had had hearing
loss for more than one month but less than three months,
noticeable improvement or complete recovery was seen
in 13% (20 dB in at least three test frequencies); 25.2%
showed an improvement between 10 dB to 20 dB.
Patients with hearing loss for longer than three months
had markedly less benefit from HBO2. Overall, 30%
had an improvement of > 10 dB, but only 2% regained
normal hearing function [70]. Similar results were
found by Lamm et al. [67].
The efficacy of HBO2 for chronic hearing loss
shows some promise for these patients who have not
responded to other treatments and have chronic loss.
However, further randomized, controlled studies are
required before its use can be routinely recommended.
H. Murphy-Lavoie, S. Piper, R.E. Moon, T. Legros
Medical and HBO2 combination therapies
The effectiveness of HBO2 with various medical and
procedural therapies has been extensively investigated.
These therapies include: vitamins, corticosteroids
(reduction of edema and inflammation), vasodilatory
agents (vasoactive agents and stellate ganglion blocks),
antiviral agents (herpes virus may be a causative agent
for a subset of ISSHL), agents that reduce hematocrit
and improve blood flow (volume expanders, rheological agents and normovolemic hemodilution), antibiotics,
diuretics, osmotic agents, anticoagulants and carbogen.
The results of the most important retrospective, casecontrolled and randomized controlled trials are discussed
below.
ISSHL retrospective and prospective studies
HBO2 and medical therapies: One of the earliest
studies compared medical therapy, stellate ganglion
block (SGB) and HBO2 [25]. Researchers found that
100% of the patients treated with SGB and HBO2
achieved > 10 dB PTA improvement. Moreover, 40%
of these patients recovered to within 20 dB of their
normal hearing levels [25].
The French conducted several studies evaluating the
effectiveness of HBO2 in combination with various
medical therapies. Both studies found HBO2 a useful
synergistic adjunct, with twice-daily sessions reducing
the length of treatment [28, 29].
Aslan and co-workers published a study of patients
treated with medical therapy combined with either
SGB or HBO2 [14]. A significant increase in hearing
gain was found with the addition of HBO2.
Racic et al. compared HBO2 with pentoxifylline
infusions. The HBO2 group showed statistically significant improvement in overall hearing gains, attainment
of physiological hearing values and moderate hearing
gains [21].
Narozny and colleagues reviewed two historical
groups of ISSHL patients treated with combinations
of medical therapy, corticosteroids and HBO2 [12].
Hearing gains were statistically superior for the
HBO2 group over all frequencies and in four ranges
of frequencies for both relative and absolute values
[12]. Moreover, the combination of high-dose corticosteroids and HBO2 resulted in statistically improved
clinical outcomes [12]. Delay to treatment and flat
hearing loss were found to be predictors of poor
clinical outcome. Narozny and co-workers also performed
linear regression analyses of their work to identify
783
UHM 2012, Vol. 39, No. 3 – HBO2 AND ISSHL
prognostic factors related to hearing improvement as
measured by objective change of gain, PTA, high-tone
average and pure middle-tone average. They identified two favorable prognostic factors for ISSHL: treatment with high-dose corticosteroids and HBO2, and
early treatment (within 10 days). A poor prognosis was
found with delayed treatment, labyrinth responsiveness disorders, and decreased TSH levels [30].
Fujimura et al. reported their work with 130 consecutive ISSHL inpatients treated with corticosteroids
(with or without HBO2) [11]. The HBO2 group showed
a statistically superior rate of recovery [11]. Additionally,
a subset analysis of those with severe hearing loss
(> 80 dB) showed that the HBO2 group had a statistically superior rate of hearing improvement.
Dundar et al. prospectively compared patients treated
with HBO2 or medical therapy. The HBO2 group had
statistically significant hearing gains across all
frequencies [19].
Suzuki and colleagues analyzed 196 consecutive
ISSHL patients, comparing corticosteroid or IV PGE1
combined with HBO2 [31]. There were no differences
noted, implying that PGE1 and corticosteroid therapy
are equally effective when combined with HBO2 therapy,
and that PGE1 is a potential alternative in the corticosteroid-intolerant patient (diabetes, peptic ulcer disease,
or viral hepatitis) [31].
Suzuki and co-workers have also compared patients
treated with IV PGE1 or SGB combined with HBO2.
In those with less severe hearing loss (< 80 dB) the outcomes were similar. However, for those with hearing
loss > 80 dB, the hearing rate was statistically superior
in the patients treated with SGB and HBO2 [22].
Ohno and colleagues reported patients treated with
medical therapy or HBO2 and found that while overall
mean hearing gains were not different between groups,
those with profound hearing loss had significantly better
outcomes with the use of HBO2 than other groups [20].
Körpinar and co-workers reviewed the treatment
of patients treated with medical therapy and HBO2 to
identify factors that affect treatment outcomes. The gains
were significant for those with early HBO2; a higher
number of HBO2 treatments; the use of corticosteroids;
low frequency-ascending and total audiogram configuration; and profound hearing loss [23]. The most
important favorable prognosis was found with corticosteroid therapy [23].
Liu et al. reported on patients treated within two
weeks with medical therapy with or without HBO2 [24].
The overall effectiveness was clinically and statistically
784
superior for those treated with HBO2, with the difference being significant and most profound for those with
moderate to severe deafness and those with descending
and flat types of audiograms [24].
Suzuki and colleagues also performed simple and
multiple regression analyses on 174 consecutive ISSHL
patients treated with hydrocortisone and HBO2. Their
aim was to develop a regression model for predicting
hearing outcome in ISSHL patients. They found significant inverse correlations between hearing improvement
rate and days from onset to treatment, patient age and
presence of vertigo [32].
Alimoglu and co-workers reviewed the treatment of
patients receiving various combinations of oral or IT
corticosteroids and HBO2 [1]. Mean hearing gains and
the proportion of patients with complete recovery were
statistically superior for those treated with oral corticosteroids and HBO2.
Hóly and colleagues treated patients with IV vasodilation therapy and HBO2 [33]. Improvement was seen in
59.7% of patients. However, if HBO2 was started within
10 days, significant or complete recovery was noted in
65.9% of patients. In those patients treated with HBO2
after 10 days, improvement was noted in only 38.9%
[33]. Liu and co-workers reported their work on patients
treated with either corticosteroids, corticosteroids plus
dextran, or corticosteroids, dextran and HBO2 [10]. The
addition of HBO2 was found beneficial in those with
initial profound hearing loss. However, the addition of
dextran to corticosteroid therapy was not associated with
improved outcomes [10]. These studies are compared in
Table 1 (Pages 786-787).
ISSHL prospective randomized controlled trials
HBO2 and medical therapies: The earliest randomized
controlled trial was the 1985 study of Pilgramm et al.,
studying patients treated with medical therapy with
or without HBO2. The HBO2 group had statistically
superior outcomes [17].
Ten years later, Hoffman and colleagues performed
a similar study on patients refractory to previous medical therapy. In this study as well, the HBO2 group had
statistically significant improvement [15]. Hoffman and
his co-workers published a second study in the same year,
this time evaluating patients with symptoms occurring
longer than six months. They found no differences
between the HBO2 group and the air control group.
However, in this study, all patients had chronic
symptomatology [71].
H. Murphy-Lavoie, S. Piper, R.E. Moon, T. Legros
UHM 2012, Vol. 39, No. 3 – HBO2 AND ISSHL
Cavallazzi and colleagues reported a study the following
year that also compared medical patients (controls)
treated with or without HBO2. Again, no differences
were found between groups; however, the trend favored
the HBO2 group [72].
In 1998, Schwab et al. reported on patients treated
with either medical therapy or HBO2. They found clinical
and statistical improvement with the use of HBO2 [36].
In 2001, Fatorri et al. studied patients treated within
two days and randomly assigned to treatment with either
buflomedil (vasodilator) or HBO2. The HBO2 group experienced a significantly greater response to treatment
[16]. In 2004, Topuz and colleagues conducted a study
involving patients undergoing dietary and medical treatment with or without HBO2 [13]. The HBO2 group had
statistically significant improvement in hearing gains over
all frequency ranges except 2,000 Hz, and significant
hearing gains in those with initial hearing losses > 60 dB
when compared to lesser hearing losses. Within the HBO2
group, the mean hearing gains for those older than 50 years
was greater than for those younger than 50 years [13].
Most recently, Cekin and colleagues evaluated
patients treated with prednisolone with or without
HBO2. Both groups had success rates above 70%,
with no statistical difference between groups [37].
These studies are compared in Table 2 (Page 788)
ISSHL meta-analyses of treatments
Five treatment modalities for ISSHL have been reviewed
by the Cochrane Collaboration: HBO2 therapy, corticosteroids, vasodilators / vasoactive substances, antivirals
and IT corticosteroids. There are three Cochrane metaanalyses involving the use of HBO2, one reviewing the
use of oral corticosteroids, one reviewing IT corticosteroids and one reviewing the use of vasodilators and
vasoactive substances [2-4, 48, 49, 73]. The antiviral
review has yet to be completed. The IT corticosteroid
treatment was found equivalent to systemic corticosteroids and of unclear clinical significance [49].
The 2006 Cochrane review on the use of oral
corticosteroids for the treatment of ISSHL evaluated
only two studies. One showed significant improvement
in hearing in 61% of patients who received corticosteroids compared to only 32% of controls. The other
study showed a lack of effect of corticosteroids on
hearing improvement. The authors’ conclusions were
that “the value of corticosteroids in the treatment of
ISSHL remains unclear” [48].
H. Murphy-Lavoie, S. Piper, R.E. Moon, T. Legros
The 2009 Cochrane review on the use of vasodilators and vasoactive substances for the treatment of
ISSHL evaluated three trials (n=189) and found that
“the effectiveness of vasodilators in the treatment of
ISSHL remains unproven” [73]. Both the use of cortico-steroids or vasodilator / vasoactive treatments
were found to have “no good evidence to suggest the
effectiveness or lack thereof” in the treatment of
ISSHL [48, 73].
The only reviews that show benefit of therapy
are the HBO2 meta-analyses [2-4]. In the 2005 review,
six trials (n=304) were analyzed and it was reported
that “HBO2 did improve hearing” [2]. The 2007
update by the same authors analyzed six trials
(n=308), and confirmed again that “For people
with early presentation of ISSHL, the application
of HBO2 significantly improved hearing loss” [3].
Additionally, this update defined that the number of
needed to treat (NNT) for one extra good outcome was
5.3. This correlates well with the NNT for diabetic
foot wounds and HBO2 (NNT=4) reported in the 2009
Cochrane review on the use of HBO2 for chronic wounds
[74].
The latest update (2010) for the use of HBO2 for
ISSHL analyzed seven trials (n=392) and reported
the same objective, conservatively positive conclusions
as the 2007 update [74].
LITERATURE CONCLUSIONS
Treatment of ISSHL with Adjunctive HBO2
Many prospective and retrospective studies have shown
significant efficacy utilizing HBO2 as an adjunct to
medical therapy [1, 10-12, 14, 19, 20, 21, 24, 25, 31].
Nine of these 11 studies showed statistically positive
results. These studies are compared in Table 1.
There are also eight randomized, controlled prospective studies (Table 2) [13, 15-17, 36, 37, 71, 72]. Four of
these studies were published in peer-reviewed journal
and four in Proceedings. Five of these eight trials were
positive. Of the remaining studies, one favored the HBO2
group, and two studies (one of which enrolled chronic
hearing loss patients) found no statistical differences
between treatment groups [37, 71, 72]. The best and
most consistent outcomes occur with the use of oral
corticosteroids and HBO2, especially in those with
profound hearing loss treated within two weeks from
symptom onset. The use of HBO2 for the treatment of
ISSHL is Class IIa (AHA Evidence-Based Scoring
System) with an “A” Level of Evidence (data derived
from multiple randomized clinical trials).
n
785
UHM 2012, Vol. 39, No. 3 – HBO2 AND ISSHL
____________________________________________________________________________________________
Table 1 – Retrospective and Prospective Case-Controlled Studies of ISSHL and HBO2
________________________________________________________________________________________________
Study
Patient
groups
HBO2
treatments
Alimoglu1 2011
n = 219
2.5 atm abs
HBO2 (n = 57)
120 minutes
POS (n = 58)
20 sessions
POS + HBO2 (n = 61)
ITS (n = 43)
Concomitant
therapies Hearing gains
oral and intratympanic
corticosteroids as
controls and combined
with HBO2
86.9% POS/HBO2
63.8% POS
46.5% IT
43.9% HBO2
______________________________________________________________________________________________
Complete Recovery
42.6% POS/HBO2
19.0% POS
17.5% HBO2
11.6% ITS
Highest Mean Hearing Gain
POS + HBO2*
______________________________________________________________________________________________
Liu10 2011
n = 465
HBO2 (n = 112)
Corticosteroids (n = 77)
Corticosteroids + Dextran
+ HBO2 (n = 277)
2.5 atm abs
IV and PO
60 minutes
corticosteroids,
10-20 sessions Dextran-40
Liu24 2010
n = 120
treated < 14 d
MT + HBO2 (n = 60)
MT only (n = 60)
2.0 atm abs
60 minutes
HBO2 is beneficial with
profound initial hearing
loss
______________________________________________________________________________________________
Overall Effectiveness
83.3% HBO2*
60% MT
MT as control
type(s) unknown
______________________________________________________________________________________________
Ohno20 2010
n = 92
HBO2 (n = 48)
MT only n = 44)
2.0 atm abs
60 minutes
10 sessions
corticosteroids, vitamins mean hearing gains not
and adenosine
different between groups;
triphosphate
hearing gains for those with
profound loss significantly
higher than other groups*
______________________________________________________________________________________________
Suzuki31 2008
n = 196
loss > 40 dB for < 30 d
unaffected ears
served as controls
POS + HBO2 (n = 101)
PEG1 & HBO2 (n = 95)
Dundar19 2007
n = 80
unavailable
hearing loss > 40 dB
for < 30 days
HBO2 (n = 55)
controls (n = 25)
none;
unaffected ears
served as controls
Fujimura11 2007
n = 130
unavailable
hearing loss > 40 dB
for < 30 days
POS + HBO2 (n = 67)
POS only (n = 63)
PO corticosteroids;
unaffected ears
served as controls
2.5 atm abs
60 minutes
10 sessions
PO corticosteroids,
PGE1
No Difference;
PGE1 as an alternative for
corticosteroid-intolerant
______________________________________________________________________________________________
HBO2 Gains Across
All Frequencies*
______________________________________________________________________________________________
Hearing Rate Improvement
51.1% HBO2*
27.1% controls
Rate of Recovery –
Severe loss (> 80 db)
59.7% HBO2*
39.7% controls
______________________________________________________________________________________________
MT = Medical Therapy
ITS = Intratympanic Corticosteroids
SGB = Stellate Ganglion Block
*(p < 0.05)
POS = PO Corticosteroids
**(p < 0.01)
______________________________________________________________________________________________
Continued on next page
786
H. Murphy-Lavoie, S. Piper, R.E. Moon, T. Legros
UHM 2012, Vol. 39, No. 3 – HBO2 AND ISSHL
____________________________________________________________________________________________
Table 1 – Retrospective and Prospective Case-Controlled Studies of ISSHL and HBO2
________________________________________________________________________________________________
Study
Patient
groups
HBO2
treatments Concomitant
therapies
Hearing gains
Narozny12 2004
n = 133
MT + HBO2 (n = 52)
MT only (n = 81)
2.5 atm abs
60 minutes
MT + HBO2 group =
vasodilators,
high-dose corticosteroids, vitamins and
histamine analog
Hearing Gain Over All
Frequencies* (HBO2)
______________________________________________________________________________________________
% Hearing Gain in All
Frequencies* (HBO2 Group)
MT only = vasodilators,
low-dose corticosteroids and vitamins
______________________________________________________________________________________________
Racic21 2003
n = 115
2.8 atm abs
HBO2 (n = 51)
MT (n = 64)
MT = pentoxifylline
infusion as control
group
Hearing Improvement
46.4 dB HBO2*
21.5 dB MT
Recovery of Physiologic Hearing
47.1 dB HBO2*
6.2% MT
Moderate Hearing Gains
41.2% HBO2*
12.5% MT
______________________________________________________________________________________________
Aslan14 2002
n = 50
2.4 atm abs
MT = betahistine
37.9 dB HBO2*
MT + HBO2 (n = 25)
BID
hydrochloride,
20 dB MT
MT only (n = 25)
90 minutes
prednisone, SGB
20 sessions
effective if treated
______________________________________________________________________________________________
within 60 d
Group 1
25
Goto 1979
n = 91
2.4 atm abs
Treated < 7 d
vasodilators, cortico
Group 1 (n = 22)
90 minutes
PTA > 10 dB
steroids, vitamins
Group 2 (n = 49)
20 sessions
69% Group 1
Group 2
Group 3 (n = 20)
83% Group 2
SGB only
100% Group 3
Group 3
Treated < 14 d
SGB and HBO2
PTA > 10 dB
33% Group 1
69% Group 2
100% Group 3**
______________________________________________________________________________________________
MT = Medical Therapy
ITS = Intratympanic Corticosteroids
SGB = Stellate Ganglion Block
*(p < 0.05)
POS = PO Corticosteroids
**(p < 0.01)
Continued from previous page
______________________________________________________________________________________________
n Acute Acoustic Trauma: Two animal studies utilizing HBO2 and corticosteroids were positive [62, 63]. One
meta-analysis (10 studies) and two more recent human
studies comparing HBO2 with medical therapies were
positive [27, 65, 66]. HBO2 may be beneficial for the
treatment of AAT. However, this will need to be confirmed in appropriately randomized and controlled studies
before the use of for AAT can be routinely recommended.
H. Murphy-Lavoie, S. Piper, R.E. Moon, T. Legros
n
Medical Therapies Versus Primary HBO2 Therapy:
Four studies have prospectively compared medical vs.
HBO2 therapies; three studies were positive, and one
found both treatments resulted in outcomes greater than
that found with spontaneous recovery, but without statistical differences between groups [16, 19, 20, 37]. Although HBO2 has been found more beneficial than
medical therapies in three of these studies, it is not
currently recommended as a primary therapy. There
are a greater number of studies showing the beneficial effects of adjunctive HBO2 therapy.
787
UHM 2012, Vol. 39, No. 3 – HBO2 AND ISSHL
____________________________________________________________________________________________
Table 2 – Randomized Controlled Trials of ISSHL and HBO2
________________________________________________________________________________________________
Study
Patient
groups
HBO2
treatments Concomitant
therapies
Hearing
gains
Cekin37 2009
n = 57
2.5 atm abs
MT = prednisolone, 79.0% HBO2 Presenting < 10 d
90 minutes
famotidine
71.3% Controls
10 sessions
HBO2 + MT (n = 36)
MT alone (n = 21)
Study flaws
______________________________________________________________________________________________
unblinded
no sham controls
no intention-to-treat
analysis
______________________________________________________________________________________________
Topuz13 2004
n = 51
2.5 atm abs
MT = prednisone, Mild Loss
treated within 14 d
90 minutes
diazepam,no difference
no prior therapy
25 sessions
rheomacrodex
Moderate Loss
HBO2 + MT (n = 30)
and pentoxiphylline
35.4 dB HBO2*
controls (MT) (n = 21)
16.2 dB control
Severe Loss
50.7 dB HBO2*
13 dB control
unblinded
no sham controls
randomization unclear
Fattori16 2001
unblinded
no sham controls
randomization unclear
______________________________________________________________________________________________
n = 50
2.2 atm abs
treated within 2 d
90 minutes
HBO2 Group (n = 30)
10 sessions
Vasodilator Grp (n = 20)
vasodilator groupImprovement
received IV61.3 dB HBO2*
buflomedil only24 dB controls
Good Response
73% HBO2*
55% Controls
______________________________________________________________________________________________
Schwab36 1998
n = 75
1.5 atm abs
None
15.6 dB HBO2*
treated within 14 d
45 minutes
10.7 dB controls
no prior therapy
10 - 20 sessions
HBO2 (n = 37)
controls (n = 38)
unblinded
no sham controls
randomization unclear
Proceedings publication
______________________________________________________________________________________________
Cavallazzi72 1996 n = 62
2.5 atm abs
time unknown
90 minutes
HBO2 + MT (n = 32)
15 sessions
controls (MT) (n = 30)
MT = heparin, flunarzine, dextran, betamethasone, vita-
mins, nicotinic acid,
citidinephospho-
choline, antivirals, phosphocholine and neurotropic and anti-
viral agents
Favored
HBO2 Group
(95% vs. 71%)
Improvement in
those with downward configured
audiograms
(80% vs. 33%)
unblinded
no sham controls
randomization unclear
Proceedings publication
______________________________________________________________________________________________
Hoffman71 1995
n = 44
symptoms
for > 6 months
HBO2 (n = 22)
controls (n = 22)
Hoffman15 1995
n = 20
1.5 atm abs
refractory x 14 d
45 minutes
following MT
10-20 sessions
HBO2 (n = 10)
Controls (n = 10)
previous MT = hydroxyethyl starch
pentoxifylline and
cortisone
Pilgramm 1985
n = 37
2.5 atm abs
hearing loss < 14 d
60 minutes
HBO2 + MT (n = 18)
10 sessions
controls (MT) (n = 19)
MT =10% dextran 40, Acute Loss
unblinded
5% sorbitol, vitamin B, 29.2 dB HBO2* no sham controls
and naphtidrofuryl 20.2 controls
hydrogenalalate
1.5 atm abs
NoneFavored Control
HBO2 (100% O2)Group
controls (air)
45 minutes
15 sessions
no sham controls
randomization unclear
Proceedings publication
Chronic hearing loss
______________________________________________________________________________________________
Acute Hearing
Loss
7.5 dB HBO2*
0.7 dB controls
unblinded
no sham controls
randomization unclear
Proceedings publication
______________________________________________________________________________________________
______________________________________________________________________________________________
*p < 0.05; MT = Medical Therapy
788
H. Murphy-Lavoie, S. Piper, R.E. Moon, T. Legros
UHM 2012, Vol. 39, No. 3 – HBO2 AND ISSHL
n HBO2 Following Medical Failures: One literature
analysis of more than 50 studies (n = 4,109) found
that if HBO2 was started two to six weeks following
medical failure, 50% of patients showed marked
hearing gains and 33% showed moderate improvement
[67]. Two other studies were positive. One (n = 95)
showed that 78.9% of patients had a mean improvement
of 38.3 dB and 41% gained > 20 dB. The other study
(n = 522) showed significant improvement in 34.9%,
slight improvement in 23.2% and complete recovery
in 19.7% [34, 68]. Recent otolaryngologist clinical
guidelines recommend HBO2 be considered as a
therapy within three months of diagnosis [9]. HBO2
may be beneficial for the treatment of refractory ISSHL.
However, further studies are needed.
n Chronic Hearing Loss: Three studies have shown
improvements of between 10-20 dB in 27.8% to 30%
of patients [67, 69, 70]. The use of HBO2 for chronic
hearing loss may have some benefit in these recalcitrant patients; however, further studies are required.
TREATMENT GUIDELINES
Patient selection criteria
Patients with moderate to profound ISSHL (≥ 40 dB)
who present within 14 days of symptom onset should
be considered for HBO2. While patients presenting after
this time may experience improvement when treated
with HBO2, the medical literature suggests that early
intervention is associated with improved outcomes.
The American Academy of Otolaryngology recommends
that HBO2 be considered an option for treatment up to
three months after symptom onset [9]. However, the
best evidence supports the use of HBO2 within two
weeks of symptom onset.
Clinical management
Patients who present with ISSHL should undergo a complete evaluation by an otolaryngologist and audiologist,
inclusive of appropriate audiological and imaging studies,
to determine the degree and potential etiology of disease.
Initial management: The clinical practice guidelines
published by the American Academy of Otolaryngology
in March of 2012 strongly recommend the following:
1. Distinguish sensorineural hearing loss from
conductive hearing loss in a patient;
2. Educate patients with ISSHL about the natural history
of the condition, the benefits and risks of
medical interventions, and the limitations of existing evidence regarding efficacy; and
H. Murphy-Lavoie, S. Piper, R.E. Moon, T. Legros
3.Counsel patients with incomplete recovery of hearing
about the possible benefits of amplification and
hearing-assistive technology and other supportive measures.
The panel made recommendations that clinicians should:
1.Assess patients with presumptive SSNHL for bilateral
disease, recurrent episodes of SSNHL, or focal
neurologic findings;
2.Diagnose presumptive ISSHL if audiometry
confirms a 30-dB hearing loss at 3 consecutive
frequencies and an underlying condition cannot
be identified by history and physical examination;
3.Evaluate patients with ISSHL for retrocochlear
pathology by obtaining magnetic resonance imaging,
auditory brainstem response, or audiometric follow-up;
4.Offer intratympanic corticosteroid perfusion when
patients have incomplete recovery from ISSHL
after failure of initial management; and
5.Obtain follow-up audiometric evaluation within six
months of diagnosis for patients with ISSHL [9].
They also recommended that treatment with corticosteroids and hyperbaric oxygen therapy be considered
an option [9].
Corticosteroid therapy: Patients with no known contra-indications to corticosteroid therapy should also be
treated with oral corticosteroids. Several dosing regimens
have been proffered. It is reasonable to begin with an
initial dose of 1 mg/kg/d and taper over two to three
weeks. Intratympanic corticosteroids may be a reasonable
alternative in patients with contraindications to oral
corticosteroids.
Hyperbaric oxygen therapy: Patients determined to
have ISSHL and meet the selection criteria may benefit
from HBO2. The recommended treatment profile consists
of 100% O2 at 2.0 to 2.5 atmospheres absolute for
90 minutes daily for 10 to 20 treatments.
Specialty follow-up: Continued consultation and
follow-up with an otolaryngologist is recommended.
Additional medical therapies may be used at the discretion of the otolaryngologist, and the patient should
continue to be followed by an otolaryngology
specialist during and following HBO2. The American
Academy of Otolaryngology recommends against the
routine use of antivirals, thrombolytics, vasodilators,
vasoactive substances or antioxidants to patients with
ISSHL [9].
789
UHM 2012, Vol. 39, No. 3 – HBO2 AND ISSHL
Utilization review
The optimal number of HBO2 treatments will vary, depending on the severity and duration of symptomatology
and the response to treatment. Utilization review is
recommended after 20 treatments since there is no data
to suggest benefit beyond the 10-20 treatment range.
n
___________________________________________________________________________________________________
REFERENCES
1. Alimoglu Y, Inci E, Edizer DT, Ozdilek A, Aslan M.
Efficacy comparison of oral steroid, intratympanic steroid,
hyperbaric oxygen and oral steroid and hyperbaric oxygen
treatments in idiopathic sudden sensorineural hearing loss
cases. Eur Arch Otorhinolaryngol. 2011 Dec; 268 (12):
1735 - 1741.
2. Bennett MH, Kertesz T, Yeung P. Hyperbaric oxygen
for idiopathic sudden sensorineural hearing loss and tinitus.
Cochrane Database Syst Rev. 2005 Jan 25 (1): CD004739.
3. Bennett MH, Kertesz T, Yeung P. Hyperbaric oxygen
for idiopathic sudden sensorineural hearing loss and tinnitus.
Cochrane Database Syst Rev. 2007 Jan 24 (1): CD004739.
4. Bennett MH, Kertesz T, Matthias P, Yeung P. Hyperbaric
oxygen for idiopathic sudden sensorineural hearing loss
and tinnitus. Cochrane Database Syst Rev. 2010 Jan 20 (1):
CD004739.
5. Deafness and Hearing Impairment. World Health
Organization Fact Sheet. April, 2010. http://www.who.int/
mediacentre/factsheets/fs300/en/index.html
6. The Global Burden of Disease 2004 Update. World Health
Organization. 2008. http://www.who.int/healthinfo/global_
burden_disease/GBD_report_2004update_full.pdf.
7. Grades of Hearing Impairment. World Health
Organization. 2011. http://www.who.int/pbd/deafness/hearing_
impairment_grades/en/index.html.
8. Mattox DE, Simmons FB. Natural history of sudden
sensorineural hearing loss. Ann Otol Rhinol Larnygol. 1977
Jul-Aug; 86: 463 - 80.
9. Stachler R, Chandrasekhar S, Archer S, Rosenfeld R,
Schwartz S, Barrs D, Brown S, Fife T, Ford P, Ganiats T,
Hollingsworth D, Lewandowski C, Montano J, Saunders J,
Tucci D, Valente M, Warren B, Yaremchuk K, Robertson P.
Clinical practice guideline: sudden hearing loss.
Otolaryngology - Head and Neck Surgery 2012 146: S1.
10. Liu SC, Kang BH, Lee JC, Lin YS, Huang KL, Liu DW,
Su WF, Kao CH, Chu YH, Chen HC, Wang CH. Comparison
of therapeutic results in sudden sensorineural hearing loss with
/ without additional hyperbaric oxygen therapy: a retrospective
review of 465 audiologically controlled cases. Clin Otolyarngol. 2011 Apr; 36 (2): 121 - 128.
11. Fujimura T, Suzuki H, Shiomori T, Udaka T, Mori T.
Hyperbaric oxygen and steroid therapy for idiopathic sudden
sensorineural hearing loss. Eur Arch Otorhinolaryngol. 2007
Aug; 264 (8): 861 - 866.
790
12. Narozny W, Sicko Z, Przewozny T, Stankiewicz C, Kot J,
Kuczkowski J. Usefulness of high doses of glucocorticoids and
hyperbaric oxygen therapy in sudden sensorineural hearing loss
treatment. Otol Neurotol. 2004 Nov; 25 (6): 916 - 923.
13. Topuz E, Yigit O, Cinar U, Seven H. Should hyperbaric
oxygen be added to treatment in idiopathic sudden sensorineural hearing loss? Eur Arch Otorhinolaryngol. 2004 Aug; 261
(7): 393 - 396.
14. Aslan I, Oysu C, Veyseller B, Baserer N. Does the
addition of hyperbaric oxygen therapy to the conventional
treatment modalities influence the outcome of sudden deafness?
Otolaryngol Head Neck Surg. 2002 Feb; 126 (2): 121 - 126.
15. Hoffmann G, Bohmer D, Desloovere C. Hyperbaric
oxygenation as a treatment for sudden deafness and acute
tinnitus. Proceedings of the Eleventh International Congress
on Hyperbaric Medicine. Flagstaff, AZ: Best Publishing, 1995:
146 - 151.
16. Fattori B, Berrettini S, Casani A, Nacci A, De Vito A,
De Iaco G. Sudden hypoacusis treated with hyperbaric oxygen
therapy: a controlled study. Ear Nose Throat J. 2001 Sept; 80
(9): 655 - 660.
17. Pilgramm M, Lamm H, Schumann K. Hyperbaric oxygen
therapy in sudden deafness. Laryngol Rhinol Otol (Stuttg).
1985; 64 (7): 351 - 354.
18. Alexiou C, Arnold W, Fauser C, Schratzenstaller B,
Gloddek B, Fuhrmann S, Lamm K. Sudden sensorineural
hearing loss: Does application of glucocorticoids make sense?
Arch Otolaryngol Head Neck Surg. 2001, Mar; 127 (3): 253-258.
19. Dundar K, Gumus T, Ay H, Yetiser S, Ertugrul E.
Effectiveness of hyperbaric oxygen on sudden sensorineural
hearing loss: prospective clinical research. J Otoloaryngol.
2007 Feb; 36 (1): 32 - 37.
20. Ohno K, Noguchi Y, Kawashima Y, Yagishita K,
Kitamura K. Secondary hyperbaric oxygen therapy for
idiopathic sudden sensorineural hearing loss in the subacute
and chronic phases. J Med Dent Sci. 2010; 57 (2): 127 - 132.
21. Racic G, Maslovara S, Roje Z, Dogas Z, Tafra R.
Hyperbaric oxygen in the treatment of sudden hearing loss.
ORL J Otorhinolaryngol Relat Spec. 2003 Nov - Dec; 65 (6):
317 - 320.
22. Suzuki H, Fujimura T, Ikeda K, Shiomori T, Udaka T,
Ohbuchi T, Nagatani G. Prostaglandin E1 in combination with
hyperbaric oxygen therapy for idiopathic sudden sensorineural
hearing loss. Acta Otololaryngol. 2008 Jan; 128 (1): 61 - 65.
H. Murphy-Lavoie, S. Piper, R.E. Moon, T. Legros
UHM 2012, Vol. 39, No. 3 – HBO2 AND ISSHL
23. Korpinar S, Alkan Z, Yigit O, Gor AP, Toklu AS, Cakir B,
Soyuyuce OG, Ozkul H. Factors influencing the outcome
of idiopathic sudden sensorineural hearing loss treated with
hyperbaric oxygen therapy. Eur Arch Otorhinolaryngol. 2011
Jan; 268 (1): 41 -47.
24. Liu Y, Sun D, Shao S, Jiang W, Sun Z, Li Z. The effect of
hyperbaric oxygen therapy to different degree of hearing loss
and types of threshold curve in sudden deafness patients.
Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2010 Oct;
24 (19): 890 - 894.
25. Goto F, Fujita T, Kitani Y, Kanno M, Kamei T, Ishii H.
Hyperbaric oxygen and stellate ganglion blocks for idiopathic
sudden hearing loss. Acta Otolaryngol. 1979; 88 (5 - 6): 335 342.
26. Lamm K, Arnold W. Noise-induced cochlear hypoxia is
intensity dependent, correlates with hearing loss and precedes
reduction of cochlear blood flow. Audiol Neurootol. 1996 May
- Jun; 1 (3): 148 - 160.
27. Ylikoski J, Mrena R, Makitie A, Kuokkanen J, Pirvola U,
Savolainen S. Hyperbaric oxygen therapy seems to enhance
recovery from acute acoustic trauma. Acta Otolaryngol. 2008
Oct; 128 (10): 1110 - 1115.
28. Dauman R, Poisot D, Cros AM, Zennaro O, Bertrand B,
Duclos JY, Esteban D, Milacic M, Boudey C, Bebear JP.
Sudden deafness: a randomized comparative study of 2
administration modalities of hyperbaric oxygenotherapy
combined with naftidrofuryl. Rev Laryngol Otol Rhinol (Bord).
1993; 114 (1): 53 - 58.
29. Zennaro O, Dauman R, Poisot A, Esteben D, Duclose JY,
Bertrand B, Cros AM, Milacic M, Bebear JP. Value of the association of normovolemic dilution and hyperbaric oxygenation
in the treatment of sudden deafness. A retrospective study. Ann
Otolaryngol Chir Cervicofac. 1993; 110 (3):
162 - 169.
30. Narozny W, Kuczkowski J, Kot J, Stankiewicz C, Sicko Z,
Mikaszeweski B. Prognostic factors in sudden sensorineural
hearing loss: our experience and a review of the literature. Ann
Otol Rhinol Laryngol. 2006 Jul; 115 (7): 553 - 558.
31. Suzuki H, Fujimura T, Shiomori T, Ohbuchi T, Kitamura T,
Hashida K, Udaka T. Prostaglandin E1 versus steroid in
combination with hyperbaric oxygen therapy for idiopathic
sudden sensorineural hearing loss. Auris Nasus Larynx.
2008 Jun; 35 (2): 192 - 197.
32. Suzuki H, Mori T, Hashida K, Shibata M, Nguyen KH,
Wakasugi T, Hohchi N. Prediction model for hearing outcome
in patients with idiopathic sudden sensorineural hearing loss.
Eur Arch Otorhinolaryngol. 2011; 268 (4): 497 - 500.
33. Holy R, Navara M, Dosel P, Fundova P, Prazenica P,
Hahn A. Hyperbaric oxygen therapy in idiopathic sudden
sensorineural hearing loss (ISSNHL) in association with combined treatment. Undersea Hyperb Med. 2011 Mar - Apr; 38
(2): 137 - 142.
H. Murphy-Lavoie, S. Piper, R.E. Moon, T. Legros
34. Murakawa T, Kosaka M, Mori Y, Fukazawa M, Misaki K.
Treatment of 522 patients with sudden deafness performed
oxygenation at high pressure. Nihon Jibiinkoka Gakkai Kaiho.
2000 May; 103 (5): 506 - 515.
35. Muzzi E, Zennaro B, Visentin R, Soldano F, Sacilotto C.
Hyperbaric oxygen therapy as salvage treatment for sudden
sensorineural hearing loss: review of rationale and preliminary
report. J Laryngol Otol. 2010; 124 (2): e2.
36. Schwab B, Flunkert C, Heermann R, Lenarz T. HBO in
the therapy of cochlear dysfunctions - first results of a
randomized study. EUBS Diving and Hyperbaric Medicine,
Collected manuscripts of XXIV Annual Scientific Meeting
of the European Underwater and Baromedical Society.
Stockholm: EUBS. 1998: 40 - 42.
37. Cekin E, Cincik H, Ulubil SA, Gungor A. Effectiveness of
hyperbaric oxygen therapy in management of sudden
hearing loss. J Laryngol Otol. 2009, 123: 609 - 612.
38. Haberkamp TJ, Tanyeri HM. Management of idiopathic
sudden sensorineural hearing loss. Am J Otol. 1999 Sep; 20:
587 - 592.
39. Rauch SD. Idiopathic sudden sensorineural hearing loss.
N Engl J Med. 2008 Aug 21; 359 (8): 833 -840.
40. Byl FM Jr. Sudden hearing loss: eight years’ experience
and suggested prognostic table. Laryngoscope. 1984 May; 94
(5 Pt 1): 647 - 661.
41. Hughes GB, Freedman MA, Haberkamp TJ, Guay ME.
Sudden sensorineural hearing loss. Otolaryngol Clin North Am,
1996 June; 29 (3): 393 - 405.
42. Cavallazzi GM. Relations between O2 and hearing
function. Eds: Marroni A, Oriani G, Wattel F. Proceedings of
International Joint Meeting on Hyperbaric and Underwater
Medicine. Milano, Italy. 1996 Sept 4 - 8; 633 – 645.
43. Lamm C, Walliser U, Schumann K, Lamm K. Oxygen
partial pressure measurements in the perilymph and the scala
tympani in normo- and hyperbaric conditions. An animal experiment study. HNO. 1988 Sep; 36 (9): 363 - 366.
44. Nagahara K, Fisch U, Yagi N. Perilymph oxygenation
in sudden and progressive sensorineural hearing loss.
Acta Otolaryngol. 1983 Jul - Aug; 96 (1 - 2): 57 - 68.
45. Tsunoo M, Perlman MB. Temporary arterial obstruction.
Effects on perilymph oxygen and microphonics.
Acta Otolaryngol. 1969; 67: 460 – 466.
46. Lamm H. Der Einfluss der hyperbaren Sauerstofftherapie
auf den tinnitus und den Horverlust bei akuten und chronischen
Innenohrschaden. Otorhinolaryngol Nova. 1995; 5: 161 - 169.
47. Doyle KJ, Bauch C, Battista R, Beatty C, Hughes GB,
Mason J, Maw J, Musiek FL. Intratympanic steroid treatment:
a review. Otol Neurotol. 2004 Nov; 25 (6): 1034 - 1039.
48. Wei BP, Mubiru S, O’Leary S. Steroids for idiopathic sudden sensorineural hearing loss. Cochrane Database Syst Rev.
2006 Jan 25; (1): CD003998.
791
UHM 2012, Vol. 39, No. 3 – HBO2 AND ISSHL
49. Plontke SK, Meisner C, Caye- Thomasen P, Parnes L,
Agrawal S, Mikulec T. Intratympanic glucocorticoids for sudden sensorineural hearing loss. Cochrane Database Syst Rev.
2009 Oct 7 (1): CD008080.
50. Dispenza F, Amodio E, De Stefano A, Gallina S,
Marchese D, Mathur N, Riggio F. Treatment of sudden
sensorineural hearing loss with transtympanic injection of
steroids as single therapy: a randomized clinical study.
Eur Arch Otorhinolaryngol. 2011 Sep; 268 (9): 1273 - 1278.
51. De Heyn G, Van Opstal M. Comparative study of a
coustic trauma caused by blasts, treated by vasodilators or by a
combination of vasodilators and hyperbaric oxygenation.
Acta Otorhinolaryngol Belg. 1976; 30 (3): 251 - 259.
52. Lamm H, Dahl D, Gerstmann W. On the effect of
hyperbaric oxygen (OHP) at the guinea pig’s cochlea insulted
by hypoxia. Arch Otorhinolaryngol. 1977 Oct 31; 217 (4): 415
- 421.
53. Giger HL. Therapy of sudden deafness with O2/CO2 inhalation. HNO. 1979 Mar; 27 (3): 107 - 109.
54. Castro Junior NP, Almeida CI, Campos CA. Sudden
sensorineural hearing loss and vertigo associated with arterial
occlusive disease: three case reports and literature review.
Sao Paulo Med J 2007 May 3; 125 (3): 191 - 195.
55. Wilson WR. Why treat sudden hearing loss. Am J Otol.
1984 Oct; 5 (6): 481 - 483.
56. Lamm K, Lamm C, Lamm H, Schumann K.
Simultaneous determinations of oxygen partial pressure in
the scala tympani, electrocochleography and blood pressure
measurements in noise stress in guinea pigs. HNO. 1988 Sep;
36 (9): 367 - 372.
57. Yoon TH, Paparella MM, Schachern PA, Alleva M.
Histopathology of sudden hearing loss. Laryngoscope. 1990
Jul; 100 (7): 707 - 715.
58. Kuokkanen J, Aarnisalo AA, Ylikoski J. Efficiency of
hyperbaric oxygen therapy in experimental acute acoustic
trauma from firearms. Acta Otolaryngol Suppl. 2000; 543: 132
- 134.
59. Pilgramm M. Clinical and animal experiment studies to
optimise the therapy for acute acoustic trauma. Scan Audiol
Suppl. 1991; 34: 102 - 122.
60. Belal A Jr. Pathology of vascular sensorineural hearing
impairment. Laryngoscope. 1980 Nov; 90 (11 Pt 1): 1831 1839.
61. Gloddek B, Lamm K, Arnold W. Pharmacological
influence on inner ear endothelial cells in relation to the
pathogenesis of sensorineural hearing loss.
Adv Otorhinolaryngol. 2002; 59: 75 - 83.
62. Fakhry N, Rostain JC, Cazals Y. Hyperbaric oxygenation
with corticoid in experimental acoustic trauma. Hear Res. 2007
Aug; 230 (1 - 2): 88 - 92.
792
63. Lamm K, Arnold W. Successful treatment of noiseinduced cochlear ischemia, hypoxia, and hearing loss.
Ann N Y Acad Sci. 1999 Nov 28; 884: 233 - 248.
64. Pilgramm, M, Schumann K. Need for rheologically active,
vasoactive and metabolically active substances in the initial
treatment of acute acoustic trauma. HNO. 1986 Oct; 34 (10):
424 - 428.
65. Pilgramm M, Schumann K. Hyperbaric oxygen therapy
for acute acoustic trauma. Arch Otorhinolaryngol. 1985; 241
(3): 247 - 57.
66. Winiarski M, Kantor I, Smereka J, Jurkiewicz D.
Effectiveness of pharmacologic therapy combined with
hyperbaric oxygen in sensorineural hearing loss following
acute acoustic trauma. Preliminary Report. Pol Merkur
Lekarski. 2005 Sep; 19 (111): 348 - 350.
67. Lamm K, Lamm H, Arnold W. Effect of hyperbaric
oxygen therapy in comparison to conventional or placebo
therapy or no treatment in idiopathic sudden hearing loss,
acoustic trauma, noise-induced hearing loss and tinnitus.
A literature survey. Adv Otorhinolaryngol. 1998; 54: 86 - 99.
68. Marchesi G, Valetti TM, Amer M, Ross M, Tiberti R,
Ferani R. Mauro G Di. The HBO effective in sudden hearing
loss treatment. UHMS Meeting Abstracts, 2000. http://archive.
rubicon-foundation.org/6781.
69. Schumann K, Lamm K, Hettich M. Effect and
effectiveness of hyperbaric oxygen therapy in chronic hearing
disorders. Report of 557 cases 1989. HNO. 1990 Nov; 38 (11):
408 - 411.
70. Kau RJ, Sendtner-Gress K, Ganzer U, Arnold W.
Effectiveness of hyperbaric oxygen therapy in patients with
acute and chronic cochlear disorders. ORL J Otorhinolaryngol
Relat Spec. 1997 Mar - Apr; 59 (2): 79 - 83.
71. Hoffmann G, Bohmer D, Desloovere C. Hyperbaric
oxygenation as a treatment of chronic forms of inner ear
hearing loss and tinnitus. Proceedings of the Eleventh
International Congress on Hyperbaric Medicine. Flagstaff, AZ:
Best Publishing. 1995: 141 - 145.
72. Cavallazzi G, Pignataro L, Capaccio P. Italian experience
in hyperbaric oxygen therapy for idiopathic sudden sensorineural hearing loss. Proceedings of the International Joint
Meeting on Hyperbaric and Underwater Medicine. Bologna:
Grafica Victoria, 1996: 647 - 649.
73. Agarwal L, Pothier DD. Vasodilators and vasoactive
substances for idiopathic sudden sensorineural hearing loss.
Cochrane Database Syst Rev. 2009 Oct 7; (4): CD003422.
74. Kranke P, Bennett MH, Debus SE, Roeckl-Wiedmann I,
Schnabel A. Hyperbaric oxygen therapy for chronic wounds.
Cochrane Database Syst Rev. 2009 Jul 8 (1): CD004123.
u
H. Murphy-Lavoie, S. Piper, R.E. Moon, T. Legros