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Danhong enhances recovery from residual dizziness

after successful repositioning treatment in patients
with benign paroxysmal positional vertigo

Wenting Deng, MD a, 1 , Chuanhong Yang b, 1 , Min Xiong, MD a,, 1 , Xiaoyan Fu, MD a ,

Huangwen Lai, MD b , Weiyi Huang, MD c,
a
Department of Otolaryngology, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou, China
b
Medical Research Center, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou, China
c
Department of Internal Medicine, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou, China

ARTI CLE I NFO A BS TRACT

Article history: Objectives: Although the repositioning maneuvers are usually very effective in patients with
Received 9 May 2014 BPPV, some patients still complain residual dizziness. Danhong injection (DHI), a traditional
Chinese medicine, can effectively dilate blood vessels and improve microcirculation, and has
been proven to be effective in improving cervical vertigo and posterior circulation ischemic
vertigo. The aim of this study was to evaluate the effects of DHI on residual dizziness after
successful repositioning treatment in patients with BPPV.
Methods: Eighty-six patients with BPPV were randomized into two treatment groups, DHI
group and non DHI group. The DHI group received the same repositioning treatment as the
non-DHI group, with the addition of DHI therapy. The durations of residual dizziness of DHI
group and non-DHI group were compared. In addition, the scores of the dizziness handicap
inventory of these two groups were calculated.
Results: The durations of residual dizziness of DHI group were shorter than that of non-DHI
group. There were no significant differences in the scores of dizziness handicap inventory in
the first week between these two groups, and there were much significant differences in the
second, the fourth, the sixth and eighth weeks.
Conclusions: The results demonstrate that DHI can significantly improve the residual
dizziness after successful repositioning treatment in patients with BPPV.
2014 Elsevier Inc. All rights reserved.

1. Introduction vertigo induced by special head position changes, and

accompanied by imbalance and nausea [1,2]. The currently
Benign paroxysmal positional vertigo (BPPV) is the accepted mechanism for the BPPV is that otoconia derived
most common cause for peripheral vestibular vertigo. BPPV from the utricular macula moves to the semicircular canal.
is characterized by short repeated episodes of mild to intense Otoconia is the small crystals of calcium carbonate. These

Correspondence to: M. Xiong, Department of Otolaryngology, Guangzhou General Hospital of Guangzhou Military Command, Liu Hua
Road 111, Guangzhou 510010, China.
Correspondence to: W. Huang, Department of Internal Medicine, Guangzhou General Hospital of Guangzhou Military Command,
Liu Hua Road 111, Guangzhou 510010, China.
E-mail addresses: dr_xiong@163.com (M. Xiong), 18924114669@189.cn (W. Huang).
1
These authors contributed equally to this work.

http://dx.doi.org/10.1016/j.amjoto.2014.07.001
0196-0709/ 2014 Elsevier Inc. All rights reserved.
754 AM ER IC AN JOUR NA L OF OTOLARY NG OLOG Y H EA D A N D N E CK ME D I CI NE AN D SUR G E RY 3 5 ( 2 0 14 ) 75 37 5 7
particles make a change of the endolymph flow in the
semicircular canal and induce the abnormal excitability of
vestibular receptors. About 90% of BPPV patients are affected
in posterior semicircular canal [3]. Most of them often
complain of loss of balance and unstable gait during and
between the paroxysmal vertigo attacks. The diagnosis of
BPPV is confirmed by patient history and provocation
maneuvers, such as the DixHallpike test or the supine
head-turning test. The main treatment of BPPV is to remove
the otoconias by liberating maneuvers [4,5] or BrandtDaroff
exercises [6]. Those are noninvasive procedures for clearing of
otoconias out of the canal and driving them back into the
place where they should belong. Although the repositioning
maneuvers are usually very effective in improving the vertigo,
some patients still complain residual dizziness [7].
Benzodiazepines and antihistamines which are directed to
suppress the vertigo are commonly used for BPPV patients.
Although vestibular suppressants and antiemetic drugs are
useful for acute treatment of vertigo, they are not effective for
BPPV [8,9]. Betahistine dihydrochloride is effective in improv-
ing the recovery rate and life quality of BPPV patients [10]. It is
an affinity for histamine H1 and H3 receptors. In addition,
betahistine dihydrochloride improves the microcirculation
of the labyrinth, and relieves pressure from endolymphatic
fluid [1114]. Danhong injection (DHI), a traditional Chinese
medicine, can effectively dilate blood vessels and improve
microcirculation. DHI has been proven to be effective in
improving cervical vertigo [15] and posterior circulation
ischemic vertigo [16]. The reason that betahistine dihy-
drochloride improves the quality of life (QOL) of patients
with BPPV is partly by dilating the blood vessels and
improving the microcirculation of the labyrinth. In this
study, we aimed to evaluate the effects of DHI on residual
dizziness after successful repositioning treatment in patients
with BPPV.
2. Materials and methods
2.1. Study design
This prospective, randomized, double-blinded study was
performed at the Department of Otolaryngology of Guangzhou
General Hospital of Guangzhou Military Command. The study
was approved by the Institutional Review Board of Guangzhou
General Hospital of Guangzhou Military Command. Eighty six
patients were enrolled between July 2009 and May 2013, and
follow-up was completed by September 2013. All 86 patients
were randomized into two treatment groups, DHI group and
non DHI group, each group contained 43 patients. The
DHI group received the same repositioning treatment as
the non-DHI group, with the addition of DHI therapy. DHI
(Heze Buchang Pharmaceutical Company, Shandong, China;
approved by the Chinese Drug Administration, approved
no. Z20026866) was administered intravenously at the dosage
of 0.33 ml/kg per day for 5 continuous days after successful
repositioning treatment for 1 week. A 20 ml DHI contains
750 g of crude medication Salvia miltiorrhiza and 250 g of crude
medication Flos carthami. Successful repositioning maneuver
was defined as the absence of nystagmus and positional
vertigo, and the success was determined 3 days after the
treatment based on the result of the positioning test. If the
positioning test was negative, we collected information about
any kinds of residual dizziness, and followed up every day.
All of the patients were followed up until complete resolution
of any dizziness via interviews at the outpatient clinic or by
telephone. Additionally, all the patients were asked to give up
smoking and alcohol during the treatment. All patients were
strictly instructed to medical scheme.
2.2. Study procedures
Patients referred to the principal author (otolaryngologist in
the outpatient department) for evaluation of BPPV screened
for eligibility for enrollment. After clinical history and a
thorough physical exam were obtained, DixHallpike test or
supine head-turning test was done. Since 90% of BPPV is
involved with posterior semicircular canal, and canalithiasis
type is in most patients [3]. In this study, only canalithiasis
type of BPPV patients involved with posterior semicircular
were selected. The diagnosis of BPPV was based on the
following criteria: 1. symptoms compatible with BPPV (epi-
sodes of transient attacks of rotational vertigo induced by
sudden head positional changes without auditory symptoms);
2. positional vertigo and positional nystagmus provoked by
DixHallpike maneuver (nystagmus which is vertical with a
torsional component appears after a short latency, the head is
turned toward a side of 45 degrees; it ended after approxi-
mately 30 seconds and decreased when the positioning test
was repeated). The repositioning maneuver described by
Epley [5] was used to remove the otoconias from posterior
semicircular canal. The maneuver was performed only one
time, and only the patients who were with disappearance of
the vertigo and the nystagmus (the negative DixHallpike
positioning test) were chosen in this study. After a successful
physical treatment, patients were requested to stick to
postural restrictions for some days, e.g., to avoid sudden
head movements in the vertical plane. All the Epley reposi-
tioning maneuvers in this study were done by Dr. Min Xiong.
Once a patient was determined to be a candidate for
enrollment, the patient was given a full explanation of the
research protocol, and enrollment into trial was offered.
2.3. Inclusion criteria
Criteria for inclusion in the study were: 1. healthy person age
4164 years and no history of vertigo and vestibular disorders;
2. the first diagnosis of BPPV; 3. time from the onset of vertigo
to the start of treatment 6 days; 4. analithiasis type of BPPV
patients involved with unilateral posterior semicircular canal; 5.
positive symptoms of residual dizziness after successful
repositioning treatment; 6. no diabetes, no hyperlipidemia, no
cerebrovascular disease and other systemic disease. In addition,
the patient should be able to accept follow up.
2.4. Exclusion criteria
1. Concomitant therapy with antivertigo drugs, antihistamines,
calcium antagonists, antiaggregants, thiazide diuretics,
 AM ER IC AN JOUR NA L OF OTOLARY NG OLOG Y H EA D A N D N E CK ME D I CI N E AN D SUR G E RY 3 5 ( 2 0 14 ) 75 37 5 7 755

corticosteroids and benzodiazepines; 2. central disease (includ-
ing central vertigo), terminal disease, medical or surgical
conditions which could interfere with the pharmacokinetics of
DHI used in this study; 3. with history of previous episodes of
vertigo; 4. vascular disorders or cranial traumas; 5. with history of
migraine; 6. with anxiety.
All patients were asked to complete the residual dizziness
survey at the first day after successful repositioning treatment
until the residual dizziness disappeared completely via
telephone or interviews at the outpatient clinic. To determine
if application of DHI resulted in improvement of residual
dizziness, each patient was scheduled for a follow-up until
complete resolution of any residual dizziness. The durations
of residual dizziness of DHI group and non-DHI group were
compared. In addition, we applied the Dizziness Handicap
Inventory, a 25-item questionnaire, which helps patients to
rate dizziness-related physical and emotional impairments,
activity limitations, and restrictions in participation [17]. A yes
response gives a score of 4 points, sometimes 2 points, and no
0 point. The total score ranges from zero (no disability) to 100
(severe disability).
2.5. Statistical analysis
2 And t tests were performed using a commercial statistical
software package (SPSS 19.0) Beijing, China.
3. Results
3.1. Baseline characteristic
Baseline characteristic was presented in Table 1. Table 1
showed that there were no significant differences in baseline
characteristic between these two groups, including age and
gender. All the patients adopted in this study strictly met the
inclusion criteria and exclusion criteria. So the results of these
two groups were comparable.
3.2. Residual dizziness
Residual dizziness after successful repositioning was
characterized by lightheadedness or (and) intermittent
unsteadiness. Some patients showed only symptom of light-
headedness (continuous or intermittent) or intermittent
unsteadiness, and some patients manifested themselves in
both lightheadedness and intermittent unsteadiness. The
durations of residual dizziness which were from successful
repositioning to complete resolution of any residual dizziness
could be precisely quantified. The durations of residual
dizziness of two groups were presented in Table 2. Table 2
showed that there were much significant differences in
the durations of residual dizziness between DHI group
(12.16 5.12 days) and non-DHI group (25.32 8.34 days).
The durations of residual dizziness of DHI group were shorter
than that of non-DHI group (P = 0.0004). The scores of the
dizziness handicap inventory of two groups were showed in
Table 3. Table 3 showed that there were no significant
differences in the scores of the dizziness handicap inventory
in the first week between two groups (P = 0.461), and there
were much significant differences in the second (P = 0.011),
the fourth (P = 0.0023), the sixth (P = 0.0019), and eighth weeks
(P = 0.00017). The results demonstrated that DHI could
significantly improve the residual dizziness after successful
repositioning treatment in patients with BPPV.
4. Discussion
After the successful repositioning Epley maneuver the posi-
tioning vertigo and the typical nystagmus of patients with
BPPV of the posterior semicircular canal disappeared, but the
postural instability remained [18,19]. Patients with BPPV
showed impaired equilibrium and damaged vestibule. The
damaged vestibule is the pathological basis of residual
dizziness after successful repositioning treatment in patients
with BPPV. There may be four reasons for residual dizziness
after successful treatment. The first, the remaining debris is
insufficient to deflect the cupula to a degree sufficient to
provoke overt nystagmus and vertigo [20]. The second, BPPV is
also a disorder of the otoliths, and otolith dysfunction might
account for transient dizziness [21]. The third, some vestibular
lesions that are difficult to identify from the history and clinic
examination might coexist with BPPV. The prevalence of no
specific persistent dizziness was significantly higher in
patients with BPPV who coexisted with additional peripheral or
central vestibular dysfunction [22]. The fourth, central adapta-
tion after particle repositioning might need a longer time.
It reaches a consensus that betahistine dihydrochloride is
effective in the treatment of BPPV patients [10]. Betahistine
dihydrochloride is an affinity for histamine H1 and H3
receptors. Histamine takes an important role in sensory
coding in the vestibular periphery, and increases the spike

Table 1 Baseline characteristics.

Danhong Non-Danhong P value
Table 2 The durations of residual dizziness of the two
injection injection
groups (days).
group (n = 43) group (n = 43)
Danhong Non-Danhong P value
Age (years) 52.45 10.12 51.99 9.43 0.352 a
injection injection
Gender
group (n = 43) group (n = 43)
Male 32 30 0.631 b
Female 11 13 0.631 b The durations of 12.16 5.12 25.32 8.34 0.0004 a
a
residual dizziness
T test.
b
2 test. a
T test.
756 AM ER IC AN JOUR NA L OF OTOLARY NG OLOG Y H EA D A N D N E CK ME D I CI NE AN D SUR G E RY 3 5 ( 2 0 14 ) 75 37 5 7

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