Effect of electroacupuncture combined with toltero

J Wound Ostomy Continence Nurs. 2014;41(3):268-272.
Published by Lippincott Williams & Wilkins
CONTINENCE CARE
Effect of Electroacupuncture Combined
With Tolterodine on Treating Female
Mixed Urinary Incontinence
Chunlan Jin
Xinyao Zhou
Ran Pang
■ ABSTRACT
PURPOSE: To examine the effectiveness of combination
therapy of electroacupuncture and tolterodine in treating
female patients with mixed urinary incontinence.
MATERIALS AND METHODS: Seventy-one women with
mixed urinary incontinence were recruited to receive
electroacupuncture therapy or combination therapy
with electroacupuncture and tolterodine 2 mg orally
twice a day for 8 weeks. In electroacupuncture therapy,
the acupoints, including BL32 (Ci Liao), BL35 (Hui
Yang), SP6 (San Yin Jiao), and ST36 (Zu San Li), were
selected with the stimulation of a low-frequency (20 Hz)
disperse-dense wave. The International Consultation
on Incontinence Questionnaire score, the number of
incontinence episodes, and urine leakage were measured
before and after the treatment to evaluate the effect.
RESULTS: Response rates were 73.5% and 78.4% in
electroacupuncture therapy group and in the combination
therapy group respectively. No significant differences
were found when group outcomes were compared. The
International Consultation on Incontinence Questionnaire
score, the number of incontinence episodes, and urine
leakage improved significantly (P < .001) after 8 weeks
compared with baseline values in both groups. Significantly
more patients in the combination therapy group
experienced more than 50% reduction in the number of
incontinent episodes than in the electroacupuncture group
(75.7% vs 58.8%, P < .01). They also had significantly less
urine leakage than those in electroacupuncture therapy
group (11.2 ± 7.6 g vs 15 ± 9.1 g) (P < .05).
CONCLUSIONS: The effect of electroacupuncture for
female mixed urinary incontinence may be enhanced by
tolterodine.
KEY WORDS: acupuncture, combination therapy,
tolterodine, urinary incontinence.
■ Introduction
The International Continence Society defines mixed urinary incontinence (MUI) as “an involuntary leakage of urine
268 J WOCN ■ May/June 2014
associated with urgency and also with exertion, effort,
sneezing, or coughing.”1 It is more bothersome than stress
urinary incontinence (SUI) or urgency urinary incontinence (UUI) alone.2 An estimated 34.4% of American
women and 9.4% of Chinese women are affected by
MUI.3,4 However, most studies examining urinary incontinence treatments have focused on either SUI or UUI and
not MUI. While there are a few studies that reported that
acupuncture improved MUI,5,6 a literature review found
no studies examining the effects of combined acupuncture
and pharmacotherapy. We therefore elected to evaluate
the effect of combination therapy (CT), electroacupuncture (EA), and tolterodine, in treating women with MUI.
The aims of this study were to compare the effectiveness
of combined EA and tolterodine in (1) reducing MUI and
(2) improving incontinence-specific quality of life in
women compared to EA alone.
■ Methods
Participants were recruited from Guang An Men hospital
and hospital of Acupuncture and Moxibustion, China
The first 2 authors contributed equally to this article.
Chunlan Jin, MD, L.Ac., Attending physician, Institute of
Acupuncture and Moxibustion, China Academy of Chinese Medical
Sciences, and Division of Gynecology, Hospital of Acupuncture and
Moxibustion, China Academy of Chinese Medical Sciences, Dong
Cheng District, Beijing, China.
Xinyao Zhou, MD, Attending physician, Division of Internal
Medicine, Guang An Men Hospital, China Academy of Chinese
Medical Sciences, Xi Cheng District, Beijing, China.
Ran Pang, MD, Attending surgeon, Division of Urology, Guang An
Men Hospital, China Academy of Chinese Medical Sciences, Xi
Cheng District, Beijing, China, and Visiting scientist, Division of
Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota,
USA.
The authors declare no conflict of interest.
Correspondence: Ran Pang, MD, Division of Urology, Guang An
Men Hospital, China Academy of Chinese Medical Sciences, No. 5
Bei Xian Ge Street, Xi Cheng District, Beijing, China 100053
([email protected]).
DOI: 10.1097/WON.0000000000000025
Copyright © 2014 by the Wound, Ostomy and Continence Nurses Society™
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Academy of Chinese Medical Sciences from January 2010 to
September 2012. Inclusion criteria were female, leaking
with urgency and with physical activity, coughing or sneezing (MUI) for more than 1 year, recorded more than
1 incontinent episode per 24 hours in their bladder diary,
and more than 2 g of urine loss based on a 24-hour pad test.
Exclusion criteria were (1) acute urinary tract infection,
(2) bladder outlet obstruction, (3) closed-angle glaucoma,
(4) interstitial cystitis, (5) pelvic organ prolapse more than
stage 2, and (6) previous anti-incontinence surgery or a
post-void residual urine volume more than 100 mL.
Participants were randomly allocated into the EA or CT
group, using a random number generator. The review boards
at all participating institutions approved the study, which
was done according to the Declaration of Helsinki, the
International Conference on Harmonization. All patients
provided written informed consent prior to participation.
Study Procedures
Participants underwent a physical and pelvic examination
including pelvic organ prolapsed quantitative examination, Q-tip test, uroflowmetry, and post-void residual volume measured by ultrasonography on their first visit.
Then they were asked to complete a baseline 24-hour pad
test, a 3-day bladder diary, and the International
Consultation on Incontinence Questionnaire (ICIQ).7
Following randomization, patients underwent EA
therapy 3 times a week for 8 weeks. In addition to EA therapy, patients allocated to CT also received tolterodine
2 mg twice a day orally (SheNiTing, Nanjing Meirui
Pharma Co Ltd, China). At the end of week 8, all patients
were asked to complete the 24-hour pad test, 3-day bladder diary, and ICIQ again. All the posttreatment measurements were collected and compared with the baseline
ones.
To perform the 24-hour pad test, each patient was
given a sealable plastic bag that contained 4 preweighed
pads. Patients could wear them in any 24-hour period but
were not expected to use every pad supplied. Each pad was
placed in a sealable plastic bag after it was used and the
bag was returned at the completion of 24-hour period. The
amounts of urine leakage were calculated based on
the weight of pads.
The ICIQ includes 3 scored items (question 1-3) and an
unscored self-diagnostic item (question 4). Item 1 is
answered using a scale of 0 to 5, where 0 indicates never,
1 indicates about once a week or less often, 2 indicates 2
or 3 times a week, 3 indicates about once a day, 4 indicates
several times a day, and 5 indicates all the time. Item 2
(urinary incontinence [UI] severity) is answered on a scale
from 0 to 6, where 0 = none, 2 = a small amount, 4 = a
moderate amount, and 6 = a large amount. Responses to
item 3 are ranked from 0 (not at all) to 10 (a great deal).
Item 4 is unscored; it was not used as an outcome measure
in this study. The ICIQ has been shown to have reasonable
validity and reliability.7 For example, it discriminates
Jin et al
269
among different groups of individuals, indicating robust
construct validity. In addition, most items show “moderate” to “strong” agreement with other questionnaires,
indicating good convergent validity. Reliability has been
found to be robust as well based on “moderate” to “very
good” stability in test-retest analysis, and a Cronbach
alpha of 0.95,7 indicating good internal consistency.
Intervention
All EA treatments were performed by same acupuncturist.
Sterile disposable, stainless wire acupuncture needles with a
copper wire handle (HWATO, Suzhou medical appliance factory, Suzhou, China), 60 mm long and 0.3 mm in diameter,
were used. The selected acupoints included bilateral BL32
(Ci Liao), BL35 (Hui Yang), SP6 (San Yin Jiao), and ST36 (Zu
San Li). After the acupuncture needles were inserted into
acupoints, a portable EA machine (model HWATO SDZ-II,
electronic acupuncture treatment instrument, Suzhou medical appliance factory, Suzhou, China) was connected to the
handles of acupuncture needles to provide the electrical
stimulation for 30 minutes. A low-frequency (20 Hz) disperse-dense wave stimulation was applied.
■ Data Analyses
Statistical analyses were performed using the JMP 9.0 software package (SAS Institute, Cary, North Carolina).
Descriptive data were expressed as means ± standard deviation or median (interquartile range). All analyses were
based on the intention-to-treat analysis set, which was
defined as patients who have received at least 1 treatment.
Differences between baseline and posttreatment ICIQ
scores and the number of incontinence episodes were analyzed by the Wilcoxon signed-rank test. Each of the scores
for the 3 ICIQ questions, as well as a cumulative score, was
analyzed separately.
Differences between the 2 groups were evaluated by
the Mann-Whitney U test. Baseline and posttreatment
urine leakage (24-hour pad test) amounts were analyzed
by paired t tests and the percent reduction in leakage
between 2 groups was compared using the 2-sample t test.
Patients were considered cured if their symptoms were
eliminated based on bladder diary or urine leakage on the
24-hour pad test was less than 2 g. Patients were considered improved if their 24 hour urine leakage (change in
pad weights) decreased more than 50%. The cure and
response (cured and improved) rates were compared by
the Pearson χ2 test between 2 groups. All reported P values
were 2-sided, and P < .05 was considered statistically
significant.
■ Results
Seventy-one women (34 treated with EA only and 37
treated with CT) participated in our study. However, 2 subjects in the EA group and 1 subject in the CT group missed
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TABLE 1.
■ May/June 2014
TABLE 2.
Summary of ICIQ Score at Baseline and Posttreatmenta
Patient Characteristics
a
Patient Characteristics
EA
CT
Number
34
37
57 ± 8
56 ± 9
23.2 ± 2.7
23 ± 2.8
Length of incontinence, y
5 ± 2.4
4.7± 2.7
PVR, mL
15 ± 14
14 ± 17
Maximal urine flow, mL/s
19 ± 3
20 ± 4
UI frequency
4 ± 2.5
3.8 ± 2.9
Urine leakage, g
30 ± 14.2
29.6 ± 13.7
Number of patients with POP
5 (14.7%)
7 (18.9%)
Age, y
BMI
Abbreviations: BMI, body mass index; CT, combination therapy; EA,
electroacupuncture; POP, pelvic organ proplapse; PVR, postvoid residual
urine volume, UI, urinary incontinence.
aValues are given as mean ± SD.
25% of treatment because of influenza. Another patient in
the CT group missed 50% of treatment due to business
travel. Table 1 summarizes participants’ demographic and
baseline characteristics; no statistically significant differences were found between the groups based on these
characteristics.
After 8 weeks, 97% of patients in the EA group and
97.3% in the CT group experienced a decrease in urinary
incontinence episodes. The median number of incontinence episodes dropped from 4 (range, 1-14) to 1.3 (range,
0-11) (P < .0001) in the EA group. The frequency of UI
episodes decreased from a median of 3 (range, 1-15) to 1
(range, 0-9) (P < .0001) in the CT group. A significantly
higher proportion of women in the CT group experienced
more than a 50% reduction in the number of incontinence episodes as compared to EA group participants
(75.7% vs 58.8%; P < .01).
The mean urine leakage on the 24-hour pad test was
significantly reduced in both groups, decreasing from 30
± 14.2 g to 15 ± 9.1 g (P < .0001) in the EA group and
from 29.6 ± 13.7 g to 11.2 ± 7.6 g (P < .0001) in the CT
group. At the end of 8 weeks, patients with CT showed
significant higher percent reduction in urine loss than
ones with EA (62.9 ± 20.6% vs 51.8 ± 22.5%; P < .05). No
significant differences were found when the proportion of
patients deemed cured was analyzed, or when improved
and cured rates were combined.
The ICIQ scores also diminished after 8 weeks of treatment (Table 2). The median number of total ICIQ score
dropped from 16 to 8 (P < .001) in the EA group and from
16 to 7 (P < .001) in the CT group. The median scores of
each ICIQ question also presented consistent decreases in
each group. No significant difference was found between
2 groups.
Baseline
Question
Posttreatment
EA
CT
EA
CT
How often do you leak urine?
(range, 0–5)
4 (0)
4 (0)
2 (1)b
2 (1)b
How much urine do you
usually leak? (range, 0–6)
4 (0)
4 (0)
2 (0.5)b
2 (0) b
How much does leaking urine
interfere with your
everyday life? (range,
0–10)
8 (2)
8 (1.5)
4 (3)b
4 (3)b
Total (range, 0–21)
16 (3)
16 (2.5) 8 (5.25)b 7 (4)b
Abbreviations: CT, combination therapy; EA, electroacupuncture.
aMeasurements are given as median (interquartile range).
bversus baseline, P < .001.
■ Discussion
Mixed urinary incontinence is the coexistence of SUI and
UUI; it is estimated to affect 33% of women with urinary
incontinence and often responds poorly to pharmacologic
or surgical intervention.8,9 We assessed the effect of EA
alone and CT (EA plus tolterodine) for MUI. We found that
both EA and CT improved incontinence severity and
incontinence-specific quality of life in women with MUI.
However, CT was more effective than EA alone in reducing
the amount of urine leakage as measured by 24-hour pad
test. Nevertheless, no significant differences were found in
cure rate and response rate between 2 groups.
Acupuncture, including EA, has been used in traditional Chinese medicine for the treatment and prevention
of various diseases. Previous studies showed therapeutic
effects on nocturnal enuresis, interstitial cystitis, SUI, UUI,
and MUI.6,10-12 The potential mechanisms for acupuncture’s beneficial effects in treating MUI are shown in
Figure 1. A study suggested that placing acupuncture
needles at ST36 (Zu San Li) might decrease muscarinic
receptor binding capacity in rat’s cerebral cortex, hippocampus, striatum, spinal cord, and spleen13 and another
study showed that placing acupuncture needles at BL32
(Ci Liao) may downregulate VR1 expression in the rat’s
sacral micturition center,14 which could improve the
urgency component of MUI. A recent study demonstrated
that needling SP6 (San Yin Jiao) could downregulate c-Fos
in rat’s brain, which was associated with the enhanced
abdominal leak point pressure.15 Zhang and colleagues16
reported that placing acupuncture needles at BL32 (Ci
Liao) and BL35 (Hui Yang) could increase type I and III
collagen content in pelvic floor supporting tissue in rat
models of SUI. These results suggest that acupuncture
might also benefit the stress component of MUI.
Tolterodine is an antimuscarinic agent that has been
shown to inhibit detrusor overactivity via binding to
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271
FIGURE 1. Potential mechanisms of combination therapy for mixed urinary incontinence (MUI).
muscarinic receptors in the detrusor smooth muscle.17 A
study using an animal model found that low doses of tolterodine exerted an inhibitory effect on C fibers and
increased bladder capacity in rats.18 Its efficacy in treating
UUI and urgency predominant MUI has been confirmed
by some clinical trials.19,20 Our study is the first report of
the effect of EA combined with tolterodine in treating
MUI. At the end of 8 weeks, CT diminished urine leakage
frequency more than EA alone. Moreover, CT reduced
incontinence episodes by 50% in more women than EA
alone. Based on these findings, we hypothesize that synergy of EA and tolterodine may reduce the overactive
detrusor contractions producing UUI symptoms more
effectively than acupuncture therapy alone. Alternatively,
we acknowledged that 8 weeks of tolterodine treatment
may exert an impact on the afferent nerves of the lower
urinary tract in addition to its known motor effects.21
■ Limitations
The important limitations of this study include the lack of
a parallel placebo-control group and nonblind design.
Another limitation is that we did a post hoc power analysis, but not prestudy power analysis in this study.
■ Conclusions
Findings from this study suggest that EA reduces the frequency and severity of UI and improves incontinencespecific quality of life in women with MUI. This effect may
be enhanced by concurrent administration of tolterodine
in some women.
■ ACKNOWLEDGMENTS
This work was supported partly by grant ZZ03087, Institute
of Acupuncture and Moxibustion, China Academy of
Chinese Medical Sciences. The authors are grateful to all
the patients who participated in this study.
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Call for Authors: Continence Care
Original research, case studies and case series addressing, in particular:
• Urinary or fecal stream diversion: indwelling urethral, suprapubic catheters or fecal/bowel management system.
• Pelvic floor muscle rehabilitation protocols for stress, urge and mixed urinary incontinence in men or women.
• Current state of the science presented in systematic reviews and/or meta analyses.
• Evidence based management of incontinence associated dermatitis or moisture associated skin damage.
• Incidence and prevalence of incontinence in understudied populations.
• Quality of life issues associated within continence, care-giving, catheter management, prevention of incontinence.
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