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Transcutaneous electrical acupoint stimulation for preventing postoperative nausea and vomiting after general anesthesia: A meta-analysis of randomized controlled trials
Journal Pre-proof Transcutaneous electrical acupoint stimulation for preventing postoperative nausea and vomiting after general anesthesia: A meta-analysis of randomized controlled trials Jiabao Chen, Qing Tu, Shuai Miao, Zhenfeng Zhou, Shuangfei Hu PII:
S1743-9191(19)30303-6
DOI:
https://doi.org/10.1016/j.ijsu.2019.10.036
Reference:
IJSU 5116
To appear in:
International Journal of Surgery
Received Date: 20 August 2019 Revised Date:
22 October 2019
Accepted Date: 30 October 2019
Please cite this article as: Chen J, Tu Q, Miao S, Zhou Z, Hu S, Transcutaneous electrical acupoint stimulation for preventing postoperative nausea and vomiting after general anesthesia: A metaanalysis of randomized controlled trials, International Journal of Surgery, https://doi.org/10.1016/ j.ijsu.2019.10.036. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2019 Published by Elsevier Ltd on behalf of IJS Publishing Group Ltd.
Title Page Transcutaneous electrical acupoint stimulation for preventing postoperative nausea and vomiting after general anesthesia: A meta-analysis of randomized controlled trials Author list: Jiabao Chen1†, Qing Tu2†, Shuai Miao3, Zhenfeng Zhou1, Shuangfei Hu1* 1
Department of Anesthesiology, Zhejiang Provincial People's Hospital, Hangzhou 310006, China. Department of Anesthesiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China. 3 Department of Anesthesiology, Wuxi People's Hospital, Nanjing Medical University, Wuxi 214000, China.
2
E-mail address: 1. Jiabao Chen, [email protected]; 2. Qing Tu, [email protected]; 3. Shuai Miao, [email protected]; 4. Zhenfeng Zhou, [email protected]; 5. Shuangfei Hu, [email protected] Word Count (including references): Abstract Count: 248 Number of Tables: 4 Number of Figures: 7 References: 37 *
Correspondence: Shuangfei Hu, M.D. Department of Anesthesiology, Zhejiang Provincial People's Hospital, Hangzhou 310006, China E-mail: [email protected] †
J. Chen and Q. Tu contributed equally to the study.
Authors’ contribution J. Chen and Q. Tu collected the data and drafted the manuscript. S. Miao and Z. Zhou performed statistical analyses. S. Hu contributed to study conception. All the authors read the manuscript and approved the final submission.
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1
Manuscript
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Transcutaneous electrical acupoint stimulation for preventing postoperative
3
nausea and vomiting after general anesthesia: A meta-analysis of randomized
4
controlled trials
5 6
Abstract
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Objective: We performed this meta-analysis to evaluate the effectiveness of
8
transcutaneous electrical acupoint stimulation (TEAS) for preventing postoperative
9
nausea and vomiting (PONV) after general anesthesia.
10
Methods: We searched PubMed, EMbase, Ovid, Web of Science for relevant
11
randomized controlled trials (RCTs) about TEAS for the prevention of PONV,
12
published through July 31, 2019. The primary outcome was the incidence of PONV,
13
postoperative nausea (PON) and postoperative vomiting (POV) recorded within 24h
14
after surgery. Secondary outcomes included the numbers of patients needing antiemetic
15
rescue and the incidence of postoperative adverse effects referred to general anesthesia.
16
Data were pooled and analyzed by RevMan 5.3 software.
17
Results: Fourteen RCTs (1653 participants) were included in this meta-analysis. The
18
current results suggested that application of TEAS showed obvious superiority in lower
19
incidence of PONV (relative risk [RR] 0.54, 95% confidence interval [CI] 0.42 to
20
0.68, P < 0.0001), PON (RR, 0.59, 95% CI 0.49 to 0.71, P < 0.0001), POV (RR 0.46;
21
95% CI, 0.33 to 0.65, P < 0.0001), lower numbers of patients needing antiemetic
1
2
1
rescue (RR 0.56, 95% CI 0.40 to 0.78, P = 0.0005), lower incidence of dizziness (RR
2
0.43, 95% CI 0.31 to 0.60, P < 0.0001) and pruritus (RR 0.43, 95% CI 0.31 to 0.58, P
3
= 0.02), compared with controlled intervention.
4
Conclusions: TEAS is a reasonable modality to incorporate into a multimodal
5
management approach for the prevention of PONV, PON, POV and associated with
6
lower numbers needing antiemetic rescue, lower incidence of adverse effects after
7
general anesthesia.
8 9 10
Keywords: transcutaneous electrical acupoint stimulation; postoperative nausea and vomiting; general anesthesia; meta-analysis
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3
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1. Introduction
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Postoperative nausea and vomiting (PONV) are the most common complaints
3
after postoperative pain [1], with the incidence rising to 80% in high-risk groups [2].
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In addition to impairing the patient’s comfort, serious PONV can also result in various
5
complications, such as dehiscence of surgical sutures, bleeding, etc [3]. PONV not only
6
reduces patients' satisfaction about the healthcare system, but also prolongs the length
7
of hospital stay and health care cost [4].
8
Concerns regarding the side effects of the traditional antiemetic drugs have
9
increased the interest in using non-pharmacologic technologies to prevent PONV
10
recently. A meta-analysis suggested that acupuncture on Neiguan (P6) showed
11
evidence in PONV prevention [5], however, the majority included studies'
12
interventions in the analysis were acupuncture, laser acupuncture or transcutaneous
13
electrical nerve stimulation (TENS) and only evaluated the effect of P6. As one of the
14
traditional Chinese acupuncture therapies, transcutaneous electrical acupoint
15
stimulation (TEAS) is widely used in clinic. TEAS imposes an electrical stimulation
16
pulse to target acupoints by using electrodes placed on the acupoints' surface instead
17
of needles, which combines the effects of TENS and acupoint therapy, has the similar
18
effects of electroacupuncture [6]. However, no meta-analysis has assessed of the
19
effectiveness of TEAS for preventing PONV after general anesthesia. Therefore, we
20
performed this meta-analysis to assess the effectiveness of TEAS on prevention of
21
PONV after general anesthesia. The primary outcomes included the incidence of
22
PONV, postoperative nausea (PON) and postoperative vomiting (POV) recorded 3
4
1
within 24 hours after surgery. While secondary outcomes included the numbers of
2
patients needing antiemetic rescue and the incidence of postoperative adverse effects
3
referred to general anesthesia.
4
2. Materials and methods
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2.1 Inclusion and exclusion criteria
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Two authors independently identified the eligibilities of articles for in-depth
7
examination by using the following inclusion: (1) article type of randomized
8
controlled trial (RCT); (2) the intervention in experimental group was TEAS (patients
9
in this group received electrical stimulation on the target acupoints. The stimulation
10
was provided by electrical stimulator through electrode tabs on the target acupoints.
11
The electrical stimulator was set at certain modes, frequency and intensity
12
accordingly), while sham TEAS served as the placebo; (3) articles involved in
13
evaluating the effectiveness of TEAS on prevention of PONV, or PON, or POV after
14
general anesthesia. Exclusion criteria including (1) article type of comments, case
15
reports, crossover studies, letters, editorials, review articles, meta-analysis and
16
retrospective studies; (2) studies of animal experiments; (3) studies involving data that
17
cannot be extracted or lacking of adequate data. If any discrepancies existed on the
18
eligibilities of included articles, the disagreements can be resolved through discussion
19
meeting or by the corresponding author.
20
2.2 Search strategy
21
The meta-analysis was registered in PROSPERO (International Prospective
4
5
1
Register of Systematic Reviews, registration number: CRD42018099275). The work
2
has been reported in line with Preferred Reporting Items for Systematic Reviews and
3
Meta-Analyses (PRISMA) and Assessing the methodological quality of systematic
4
reviews (AMSTAR) Guidelines [7, 8]. We searched PubMed, EMbase, Ovid, Web of
5
Science for relevant papers, about the effect of TEAS for preventing PONV,
6
published through July 31, 2019. The search terms included terms related to TEAS
7
(e.g., ' transcutaneous electrical acupoint stimulation ' OR ' TEAS ' OR '
8
transcutaneous acupoint electrical stimulation ' OR ' TAES ' OR ' acustimulation ') and
9
terms related to postoperative nausea and vomiting (e.g., 'postoperative nausea and
10
vomiting ' OR ' PONV ' OR ' postoperative nausea ' OR ' PON ' OR ' postoperative
11
vomiting ' OR ' POV '). There were no restrictions on dates, sex, or age, type of
12
surgery. We searched these terms in the titles and abstracts of potentially relevant
13
papers. References of the retrieved papers were also reviewed for further relevant
14
studies. Additional studies were also retrieved after reviewing of the reference lists of
15
relevant systemic reviews and meta-analysis.
16
2.3 Quality assessment
17
Two authors independently evaluated the quality of included studies by using
18
Jadad Scale [9]. The following items were evaluated: (1) whether the study followed
19
the principle of randomization; (2) whether the participants and personnel were
20
blinded; (3) whether the study descripted a detailed participant withdrawal or dropout.
21
A Jaded score ≥4 reflected high quality. We also evaluated the risk of bias of included
5
6
1
studies using the Cochrane Risk of Bias Tool [7], based on the following criteria: (1)
2
random sequence generation, (2) allocation concealment, (3) blinding of participants
3
and personnel, (4) blinding of outcome assessment, (5) incomplete outcome, (6)
4
selective reporting.
5
2.4 Data extraction
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The process of data extraction was performed independently by two authors. The
7
following information were extracted from each study: the first author's name,
8
publication year, country, sample size, type of surgery, details of TEAS intervention,
9
outcomes of interest. If a study has insufficient or missing data, we tried to contact the
10
authors for the raw data of the study. Outcomes of interest including the overall
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incidence of PONV, PON and POV within 24h after surgery and the numbers of
12
patients needing antiemetic rescue and the incidence of adverse effects within 24h
13
after surgery. PON was defined as a subjective unpleasant feeling associated with the
14
awareness of vomit urgency, while POV was defined as the forceful expulsion of
15
gastric contents brought about by sustained contraction of abdominal muscles with or
16
without abdominal pain. POV occurs in approximately 30% of patients during
17
surgical period, while the incidence of nausea is around 50% [10]. For PONV, it was
18
an unpleasant complication, which combines PON and POV both.
19
2.5 Statistical Analysis
20
Statistical analyses were performed by using Review Manager version 5.3
21
statistical software (The Cochrane Collaboration, The Nordic Cochrane Centre,
6
7
1
Copenhagen, Denmark). Dichotomous data were assessed using relative risks (RRs)
2
and 95% confidence intervals (CIs). The chi-square test and I2 statistic were used to
3
test the heterogeneity. A P-value of heterogeneity ≤0.10 was regarded as significant
4
heterogeneity existed [11], a Mantel-Haenszel randomized effect model was used.
5
Otherwise, the Mantel-Haenszel fixed effect model was employed. P-values 0.05
6
were regarded as statistically significant. Sensitivity analysis was performed by using
7
method of leave-one-out when individual endpoint resulted in substantial
8
heterogeneity. The effect of a particular statistical method (fixed effect model and
9
randomized effect model) on the variability for the results was also assessed. The risk
10
of publication bias was assessed by Egger test.
11
3. RESULTS
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3.1 Literature Search
13
Base on our search strategy, we identified 263 potential relevant studies in initial
14
search, 208 studies were excluded due to exclusion criteria meet after reading their
15
titles or abstracts. Thirty-four studies were assessed for eligibility and 18 studies were
16
irrelevant to the outcomes of interest. Finally, 14 studies [12-25] were included in this
17
meta-analysis. The flow diagram of the study selection was shown in Figure. 1.
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3.2 Characteristics of included studies
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The 14 studies involved 1653 participants, 835 participants received TEAS in
20
experimental group, while 818 participants received sham TEAS in control group.
21
Among these included RCTs, 9 of them chose combined acupoints as the target
7
8
1
acupoints, while 5 chose single acupoint. Twelve RCTs were conducted in China, 1
2
RCT was conducted in America, as well as Korea. The detailed characteristics of
3
pooled studies were summarized in Table. 1 and 2. List of relevant acupoints was
4
provided in Table. 3.
5
3.3 Risk of bias assessment and sensitivity analysis
6
Of 14 RCTs, 11 RCTs described detailed information of random sequence
7
generation, only 1 RCTs have not mentioned the method of random sequence
8
generation. Ten RCTs described the detailed methods of allocation concealment and
9
10 RCTs were double-blinded by performing rigorous study design, while other 4
10
RCTs have mentioned the adequate method of blinded of participants and personnel
11
unclearly. Six RCTs provided detailed methods of blinded outcomes assessment, only
12
1 RCTs has not mentioned the blinded outcomes assessment. Most of the included
13
studies have low risk bias of attrition and reporting. (Figure. 2) We also conducted a
14
Jadad assessment for the included studies, most of the studies have Jaded scored more
15
than 4 points. (Table. 1) Egger test was performed to assess the publication bias, the
16
results suggested that publication bias was existed based on the outcome of PONV
17
(bias = 0.227, P < 0.05). However, no evidence of significant publication bias existed
18
based on the Egger test of PON (bias = −0.76, P = 0.468) and POV (bias = −0.26, P =
19
0.742). Regardless of different effect model performed, the outcomes of the results
20
remained similar between TEAS and Control group (Table. 4).
21
3.4 TEAS reduces the incidence of PONV, PON and POV
8
9
1
Seven RCTs reported the incidence of PONV within 24h after surgery, there was
2
no evidence of heterogeneity among the studies (P = 0.80, I2 = 0%). A fixed-effects
3
model was performed to analyze the outcome. The meta-analysis found participants in
4
TEAS group had lower incidence of PONV (RR 0.54, 95% CI 0.42 to 0.68, P <
5
0.0001), compered with control group. (Figure. 3)
6
Likewise, 7 RCTs reported the incidence of PON, there was evidence of
7
heterogeneity among the studies (P = 0.22, I2 = 27%). A fixed-effects model was
8
performed to analyze the outcome. The meta-analysis found participants in TEAS
9
group had lower incidence of PON (RR 0.59, 95% CI 0.49 to 0.71, P < 0.0001) than
10
control group. (Figure. 4)
11
In addition, 7 RCTs reported the incidence of POV, there was no significant
12
evidence of heterogeneity among the studies (P = 0.09, I2 = 46%). A randomized
13
effect model was used to analyze the outcome. The meta-analysis also found that
14
TEAS group has lower incidence of POV (RR, 0.46; 95% CI, 0.33 to 0.65, P < 0.0001)
15
than the control group. (Figure. 5)
16
3.5 TEAS reduces the numbers of patients needing antiemetic rescue and adverse
17
reactions
18
Four RCTs reported the numbers of patients needing antiemetic rescue, no obvious
19
evidence of heterogeneity existed among the studies (P = 0.71, I2 = 0%). A
20
fixed-effects model was performed to analyze the outcome. The meta-analysis found
21
TEAS group had less numbers of patients needing antiemetic rescue (RR 0.56, 95%
9
10
1
CI 0.40 to 0.78, P = 0.0005) than control group. (Figure. 6) Dizziness and pruritus
2
were the two commonly adverse effects after general anesthesia. Dizziness was
3
defined as a feeling of spinning or having one’s surroundings spin about, while
4
pruritus was defined as a sensation that causes the desire or reflex to scratch, usually
5
manifested as skin itch. Among the included studies, dizziness and pruritus were the
6
two commonly mentioned adverse effects. Four RCTs reported the incidence of
7
dizziness, no obvious evidence of heterogeneity existed among the studies (P = 0.78,
8
I2 = 0%), a fixed-effects model was performed and the result suggested that the
9
incidence of dizziness in TEAS group was lower than that in the control group (RR
10
0.43, 95% CI 0.31 to 0.60, P < 0.0001). Three RCTs reported the incidence of pruritus,
11
no obvious evidence of heterogeneity existed among the studies (P = 0.16, I2 = 46%).
12
A fixed-effects model was performed and the result suggested that the incidence of
13
pruritus in TEAS group was also lower than that in the control group (RR 0.43, 95%
14
CI 0.31 to 0.58, P = 0.02). (Figure. 7)
15
4. Discussion
16
Finally, a total of 14 RCTs involved included in the study. The obvious
17
heterogeneity (P-value of heterogeneity) was only found in the outcomes of POV. No
18
publication bias was detected. The results of data synthesis suggested that the
19
application of TEAS was associated with lower incidence of PONV, PON, POV,
20
adverse effects and lower numbers of patients needing postoperative antiemetic rescue,
21
suggesting that TEAS provides broadly generalizable benefits during recovery period
10
11
1
and helps to accelerate the progress of enhanced recovery after surgery (ERAS). Our
2
findings are consistent with a previous meta-analysis [5], however, which only
3
included 4 studies with the intervention of TEAS in experimental group. In our
4
meta-analysis, we only included trials with the intervention of TEAS, which provided
5
electrical stimulation on the target acupoints through electrode tabs, and excluded
6
those with interventions of acupuncture, TENS, acupressure, etc.
7
The results of the meta-analysis suggested that TEAS showed effectiveness in
8
preventing PONV. For decades, clinicians have increased their interest in applying
9
non-pharmacologic technologies for preventing PONV recently, such as acupuncture,
10
acupoint massage, or even chewing gum, etc. As a non-invasive approach, TEAS
11
combines the effects of TENS and acupoint therapies, provides multiple effects
12
through stimulating specific acupoints with certain frequency and intensity. While the
13
procedure of acupuncture was accomplished by using invasive needles, operated by
14
professional acupuncture practitioner. In addition, the needles cannot be well
15
protected during the procedure and the overall effects may be minimized. Furthermore,
16
fainting during acupuncture treatment may be occurred for some patients with
17
sensitivities to needles. Some complications may also appear, such as subcutaneous
18
hemorrhage, continued acid bilge feeling and burning sensation of acupuncture sites.
19
However, the use of TEAS has no risks of infection and can potentially be applied by
20
medical personnel with minimal training [26, 27].
21
In terms of physiological mechanism, acupuncture could increase the release of
11
12
1
β-endorphin and promote the secretion of corticosteroids in the brain [10]. In clinical
2
practice, patients were usually proscribed with corticosteroids for preventing PONV
3
[28]. In line with this, the release of endogenous glucocorticoid may be more
4
conducive to reducing the incidence of PONV and mitigate the side effects of
5
exogenous glucocorticoid. As a medical prophylaxis, TEAS are widely used in many
6
Asian countries, such as China, Korea, Japan, etc. Recent guidelines recommended to
7
apply non-drug treatments for the prophylaxis of PONV, such as chewing gum,
8
conventional acupuncture, moxibustion, etc [2]. In China, acupuncture and
9
moxibustion therapy are often used to treat intractable hiccups and cancer vomiting.
10
However, compared with conventional acupuncture, TEAS provided stimulation
11
through electrode tabs instead, which has no risks of infection and can potentially be
12
applied by medical personnel with minimal training [25, 26]. With the master of this
13
technique by clinicians, TEAS becomes one of the most used applications during
14
perioperative period in many clinical centers in China [29]. However, the technique
15
has not been well promoted. The result might be owing to the unclear specific
16
mechanism of TEAS on PONV prevention. Serotonin (5-HT) leads to vomiting reflex
17
by activating 5-HT3 receptors [30]. A research in Chinese suggested TEAS on P6 and
18
Zusanli (ST36) decreased the plasma concentration of 5-HT and resulted in lower
19
incidence of PONV in patients underwent cesarean section [31], but the research did
20
not provide the specific mechanisms. P6 has been confirmed to have an effect of
21
PONV prevention [32, 33]. A meta-analysis of Lee et al suggested that stimulation of
12
13
1
P6 can reduce PONV by 30% [5]. While Chen et al applied TEAS on Jiaji (EX-B2)
2
during colonoscopy presented a downward trend of nausea or vomiting prevalence
3
[34]. In our meta-analysis, 9 of included studies chose combined target acupoints,
4
while another 5 studies chose single acupoint, both of the choice showed superiority
5
for lower incidence of PONV, PON and POV, compared with sham TEAS. However,
6
a recent clinical study by our team member suggested that stimulation on BL13, L14,
7
ST36 during video-assisted thoracic surgical lobectomy have not shown superiority in
8
reducing the incidence of PONV [23], while another study indicated stimulation on
9
BL23, SP9 could help to prevent PONV for patients with ureteroscopic lithotripsy
10
[24]. In line with this, there might still exist certain discrepancies in target acupoints
11
choice. In addition, 12 studies chose the frequency model of dense-disperse, while
12
only 1 chose the frequency model of square-wave and 1 study have not mentioned the
13
choice of frequency mode (Table. 2). Even in the latest guidelines on acupoint
14
stimulation in China, there is no relevant recommendations of frequency model
15
choice [35]. Studies proved that the timing of acustimulation did not impact the
16
incidence of PONV, with similar reductions being achieved with stimulation initiated
17
pre- or post-anesthesia induction [31, 36]. However, results from two meta-analyses
18
suggested that differences in the timing of acupuncture (e.g. pre-, intra- or
19
postoperative) were associated with the observed heterogeneity [5, 37]. So, there is a
20
need for more well design trials to compare the effects of different onset timing of
21
TEAS.
13
14
1
Our findings should be interpreted with cautions because of the limitations in this
2
meta-analysis, although TEAS has obvious advantages in preventing the incidences of
3
PONV, PON, POV and reducing the numbers of patients needing antiemetic rescue, it
4
seems the technique is popular in Asian countries, particularly in China, Korea and
5
some southeast Asian countries for the specific mechanism of TEAS is still
6
incompletely clear, which limits the promotion of this technique in some sense. This
7
limitation also adds bias on our results. In addition, of 14 included studies, 12 were
8
conducted in China, which may play a certain impact on the reliability of the results.
9
In addition, most included RCTs had a simple size of <100 participants, which may
10
also impact the overall results, lead to systematic deviation and reduce the reliability
11
of RCTs to robustly demonstrate efficacy or effectiveness. However, TEAS also have
12
some potential side effects, such as sense of itchiness, skin redness and swelling on
13
the site of target acupoints for long time stimulation. In our study, we mainly choose
14
the incidence of PONV, PON and POV as the primary outcomes. However, the
15
majority of the included studies, the incidences of PONV, PON or POV were only
16
recorded within 24h after surgery. In fact, PONV may persist for several days for
17
some patients with high risks. Therefore, more studies are needed to focus on the
18
long-term effect of TEAS on PONV and relevant outcomes. Since all patients in
19
included studies received general anesthesia during surgery, whether TEAS could
20
prevent PONV secondary to other type of anesthesia, such as spinal anesthesia, still
21
needs more study to prove it.
14
15
1
5. Conclusions
2
TEAS is a reasonable modality to incorporate into a multimodal management
3
approach for the prevention of PONV. Application of TEAS associated with lower
4
incidences of PONV, PON, POV, less numbers of patients needing antiemetic rescue
5
and lower incidences of dizziness and pruritus. Owing to the limitations, more
6
well-designed, involved larger sample size and different races studies are needed to
7
justify the results of this meta-analysis.
8
Funding
9
None.
10
Conflict of interest
11
The authors declare that they have no conflict of interest.
12
Acknowledgements
13
There were no acknowledgements in this study.
14 15
Provenance and peer review
16
Not commissioned, externally peer-reviewed
17 18
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21
22
1
Table legends
2
Table. 1 Characteristic of the included studies
3
Note: TEAS, transcutaneous electrical acupoint stimulation; VATSL Video‐assisted Thoracic
4
Surgical Lobectomy; LC, Laparoscopic Cholecystectomy; LS, Laparoscopic Surgery; SC,
5
Supratentorial Craniotomy; IC, Infratentorial Craniotomy; MBS, major breast surgery; LH,
6
laparoscopic hysterectomy; LAS, lower abdominal surgery; HNTS, head and neck tumor surgery;
7
GLS, gynecological laparoscopic surgery; ABS, ambulatory breast surgery; * 1: postoperative
8
nausea and vomitting; 2: postoperative nausea; 3: postoperative vomitting; 4: number of patients
9
need antiemetic rescue; 5: incidence of adverse effects; ∆Jadad score (range: 0-7) ≥ 4 reflect high
10
quality.
11
Table. 2 Details of interventions
12
Note: TEAS, transcutaneous electrical acupoint stimulation; PACU, Post-anesthesia Care Unit;
13
Hegu, L14; Neiguan, P6; Lieque, LU7; Quchi, LI11; Zusanli, ST36; Sanyinjiao, SP6; Shangwan,
14
CV13; Zhigou ,TE6; Houxi, SI3; ∆each tablet of saridon contains 0.25g acetaminophen, 0.15g
15
propyphenazone, and 0.05g anhydrous caffeine.
16
Table. 3 Description list of acupoints
17
Note: 1 cun ≈ 3.33cm.
18
Table. 4 Sensitivity analysis of outcomes according to different effect models
19
Note: RR, risk ratio; PONV, postoperative nausea and vomiting; PON, postoperative nausea; POV,
20
postoperative vomiting.
22
23
1
Figure legends
2
Figure. 1 Flow diagram of study selection.
3
Figure. 2 Potential risk of bias of each included study.
4
Note: "+" represents low risk; "?"represents unclear risk; "-" represents high risk.
5
Figure. 3 Forest plots comparing the incidence of postoperative nausea and vomiting (PONV)
6
between TEAS and Control group. A Mantel-Haenszel fixed effects model was used. TEAS,
7
transcutaneous electrical acupoint stimulation.
8
Figure. 4 Forest plots comparing the incidence of postoperative nausea (PON) between TEAS and
9
Control group. A Mantel-Haenszel fixed effects model was used. TEAS, transcutaneous electrical
10
acupoint stimulation.
11
Figure. 5 Forest plots comparing the incidence of postoperative vomiting (POV) between TEAS
12
and Control group. A Mantel-Haenszel randomized effects model was used. TEAS,
13
transcutaneous electrical acupoint stimulation.
14
Figure. 6 Forest plots comparing the numbers of patients needing antiemetic rescue between
15
TEAS and Control group. A Mantel-Haenszel fixed effects model was used. TEAS,
16
transcutaneous electrical acupoint stimulation.
17
Figure. 7 Forest plots comparing the adverse effects between TEAS and Control group, including
18
subgroup analysis of dizziness and pruritus. A Mantel-Haenszel fixed effects model was used.
19
TEAS, transcutaneous electrical acupoint stimulation.
23
Table. 1 Characteristic of the included studies Authors, year
Country
Age
Sample size
Type of surgery
Target outcomes*
Jadad score∆
Huang et al, 2017[12]
China
?
60/20
VATSL
1
5
Liu et al, 2008 [13]
China
18~60
48/48
LC
1, 2, 3, 4
5
Wang et al, 2014 [14]
China
29~60
30/30
Sinusotomy
1, 4
6
Wang et al, 2010 [15]
China
20~60
40/40
SC
2, 3, 4
4
Xu et al, 2012 [16]
China
?
60/59
IC
2, 3, 4
5
Gan et al, 2004 [17]
America
?
26/24
MBS
3, 4
5
Kim et al, 2011[18]
Korea
31~67
210/54
LH
1, 2, 3, 4
3
Zheng et al, 2008 [19]
China
39~65
30/30
HNTS
3
3
Yao et al, 2015 [20]
China
18~60
35/36
GLS
2, 3, 5
6
Chen et al, 2015 [21]
China
18~60
41/42
Thyroidectomy
1, 5
6
Zhang et al, 2014 [22]
China
20~50
33/32
ABS
2, 3, 5
7
Tu et al, 2018[23]
China
?
72/72
VATSL
1
7
Tu et al, 2019[24]
China
?
60/60
Ureteroscopic lithotripsy
1, 5
6
Sun et al, 2017 [25]
China
18~70
90/271
LS
2, 3, 4
6
Note: TEAS, transcutaneous electrical acupoint stimulation; VATSL Video-assisted Thoracic Surgical Lobectomy; LC, Laparoscopic Cholecystectomy; LS, Laparoscopic Surgery; SC, Supratentorial Craniotomy; IC, Infratentorial Craniotomy; MBS, major breast surgery; LH, laparoscopic hysterectomy; LAS, lower abdominal surgery; HNTS, head and neck tumor surgery; GLS, gynecological laparoscopic surgery; ABS, ambulatory breast surgery; * 1: postoperative nausea and vomitting; 2: postoperative nausea; 3: postoperative vomitting; 4: number of patients need antiemetic rescue; 5: incidence of adverse effects; ∆Jadad score (range: 0-7) ≥ 4 reflect high quality.
1
Table. 2 Details of interventions Authors, year
Time point
Acupoints
Frequency
Post-operative opioids
Huang et al, 2017[12]
30min before induction,
P6, LI4,
Dense-disperse frequency of
Sufentanil and
throughout the surgery, and
LU7, LI11
2/100 or 2 or 100Hz. intensity of
flurbiprofen i.v.
24, 48h after surgery. Liu et al, 2008 [13]
30~60 min before the
tolerable level. P6
50ms, 2-100Hz, 0.5-4mA
Not mentioned
LI4, P6,
Dense-disperse frequency,
Parecoxib 40 mg i.v.
ST36
2/10Hz, 6~9mA
P6
Dense-disperse frequency,
induction till the end of surgery. Wang et al, 2014 [14] Wang et al, 2010 [15]
30 min before anesthesia 30 min before induction and lasted up to 6h
Not mentioned
2/10Hz , no mentioned of intensity
postoperatively Xu et al, 2012 [16]
30 min before induction of
P6
and up to 24h after surgery Gan et al, 2004 [17]
30 ~ 60 min before induction
Dense-disperse frequency,
Saridon tables∆
2/10Hz , 2mA P6
till the end of surgery
Dense-disperse frequency,
Fentanyl 25µg i.v.
2/10Hz , intensity of feeling de qi sensation.
Kim et al, 2011[18]
During maintenance period
P6
Square-wave pulses of 0.2 ms,
PCIA:fentanyl 50µg and
1Hz, 50mA
ketorolac 30 mg, 60mL
Dense-disperse frequency, 2/100
PCIA:1000mg
Hz, 8-10mA
tramadol/100mL
LI4, P6,
Dense-disperse frequency,
Sufentanil 0.05µg/kg
ST36, SP6
2/10Hz, 6-9mA
i.v.
LI4, P6
Dense-disperse frequency,
Morphine 2mg i.v.
of anesthesia Zheng et al, 2008
30min in the first 2-4h, then
[19]
once more every 3h, 3 times
LI4, P6
in total. Yao et al, 2015 [20] Chen et al, 2015 [21]
30min before induction 30min before induction
2/10Hz, 6-9mA Zhang et al, 2014
30min before induction
[22] Tu et al, 2018 [23]
Tu et al, 2019 [24]
throughout the surgery
4,8,12 h postoperatively and
LI4, P6,
Dense-disperse frequency,
ST36
2/10Hz, 6-9mA
BL13, L14,
Dense-disperse frequency,
ST36
2/10Hz , 5 to 30 mA
BL23, SP9
Dense-disperse frequency,
tramadol hydrochloride
2/10Hz , 5 to 30 mA
tablets if needed
Dense-disperse frequency, 2/100
flurbiprofenaxetil 50 mg
Hz,
i.v.
three times on the next 2
Parecoxib 40 mg i.v. Not mentioned
days after surgery Sun et al, 2017 [25]
30min preoperative, or pre-
LI4, P6
and intra-operative, or pre-
intensity of tolerable level.
and post-operative Note: TEAS, transcutaneous electrical acupoint stimulation; PACU, Post-anesthesia Care Unit; Hegu, L14; Neiguan, P6; Lieque, LU7; Quchi, LI11; Zusanli, ST36; Sanyinjiao, SP6; Shangwan, CV13; Zhigou ,TE6; Houxi, SI3; ∆each tablet of saridon contains 0.25g acetaminophen, 0.15g propyphenazone, and 0.05g anhydrous caffeine.
2
Table. 3 Description list of acupoints Acupoints
Detailed location
Hegu,
On the dorsum of the hand, between the first and second metacarpal bones, approximately in the middle of the
L14
second metacarpal bone on the radial side, line up the position the transverse crease of the first joint of the thumb with the margin of the web between the thumb and the index finger of the other hand. Neiguan, P6
On the palmar side of the forearm and on the line connecting Quze (PC3) and Daling (PC7), 2 cun above the crease of the wrist.
Zusanli, ST36
3 cun below Dubi (S 35), one finger breadth from the anterior crest of the tibia.
Lieque, LU7
On the radial aspect of the forearm, between the tendons of the abductor pollicis longus and the extensor pollicis brevis muscles, in the groove for the abductor pollicis longus tendon, 1.5 cun superior to the palmar wrist crease.
Quchi, LI11
At the midpoint of the line between the radial end of the cubital crease and the external humeral epicondyle.
Sanyinjiao, SP6
On the medial side of the leg, 3 cun above the tip of the medial malleolus, posterior to the medial border of the tibia.
Shangwan,
located in the Conception Vessel Meridian, 1 cun above the mid- point of the line between the xyphisternum and
CV13
the umbilicus.
Zhigou,TE6
On the back of the forearm, 3 cun across the web of the wrist, located on the connecting line between the Yangchi (SJ4) and the elbow tip.
Houxi, SI3
On the ulnar side of the palm, at the junction of the red and white skin posterior to the small finger (the 5th metacarpophalangeal joint).
Jiaji, EX-B2
located on both sides of the spinous column, 0.5 cun lateral to the lower border of each spinous process.
Note: 1 cun ≈ 3.33cm.
3
Table. 4 Sensitivity analysis of outcomes according to different effect models Outcomes of interest
RR
Random effect model
Fixed effect model
PONV
RR
0.56 (0.45 to 0.70)
0.54 (0.42 to 0.68)
PON
RR
0.59 (0.47 to 0.73)
0.59 (0.49 to 0.71)
POV
RR
0.46 (0.33 to 0.65)
0.50 (0.40 to 0.64)
Numbers needing antiemetic rescue
RR
0.56 (0.41 to 0.78)
0.56 (0.40 to 0.78)
Dizziness
RR
0.45 (0.32 to 0.62)
0.43 (0.31 to 0.60)
Pruritus
RR
0.46 (0.14 to 1.49)
0.42 (0.21 to 0.78)
Adverse effects
Note: RR, risk ratio; PONV, postoperative nausea and vomiting; PON, postoperative nausea; POV, postoperative vomiting.
4
Identification
Records identified through database searching (n=246)r
Additional records identified through other resources (n=17)r
Included
Eligibility
Screening
Records after duplicates removed (n=55)r
Records were screened (n=55)r
Full-text articles assessed for eligibility (n=34)r
Studies included in this metaanalysis (n=14)r
Figure. 1 Flow diagram of study selection.
Records excluded: not RCT, no full text reviews, case reports, meeting abstracts, retrospective articles (n=21)r
Records excluded: no outcomes of interest (n=20)r
Figure. 2 Potential risk of bias of each included study. Note: "+" represents low risk; "?"represents unclear risk; "-" represents high risk.
Figure. 3 Forest plots comparing the incidence of postoperative nausea and vomiting (PONV) between TEAS and Control group. A Mantel-Haenszel fixed effects model was used. TEAS, transcutaneous electrical acupoint stimulation.
Figure. 4 Forest plots comparing the incidence of postoperative nausea (PON) between TEAS and Control group. A Mantel-Haenszel fixed effects model was used. TEAS, transcutaneous electrical acupoint stimulation.
Figure. 5 Forest plots comparing the incidence of postoperative vomiting (POV) between TEAS and Control group. A Mantel-Haenszel randomized effects model was used. TEAS, transcutaneous electrical acupoint stimulation.
Figure. 6 Forest plots comparing the numbers of patients needing antiemetic rescue between TEAS and Control group. A Mantel-Haenszel fixed effects model was used. TEAS, transcutaneous electrical acupoint stimulation.
Figure. 7 Forest plots comparing the adverse effects between TEAS and Control group, including subgroup analysis of dizziness and pruritus. A Mantel-Haenszel fixed effects model was used. TEAS, transcutaneous electrical acupoint stimulation.
Highlights:
PONV are the most common complaints after postoperative pain. The meta-analysis to evaluate the effectiveness of TEAS for preventing PONV after general anesthesia. TEAS is a reasonable modality to incorporate into a multimodal management approach for the prevention of PONV, PON and POV after general anesthesia. Application of TEAS also associated with lower numbers needing antiemetic rescue, lower incidence of adverse effects after general anesthesia.
All the data in our manuscript is available to access. Please contact the correspondence, Shuangfei Hu, email: [email protected].
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Author contribution
1
Please specify the contribution of each author to the paper, e.g. study design, data collections, data analysis, writing. Others, who have contributed in other ways should be listed as contributors. Jiabao Chen and Qing Tu collected the data and drafted the manuscript. Shuai Miao and Zhenfeng Zhou performed statistical analyses. Shuangfei Hu contributed to study conception. All the authors read the manuscript and approved the final submission.
Guarantor The Guarantor is the one or more people who accept full responsibility for the work and/or the conduct of the study, had access to the data, and controlled the decision to publish. Shuangfei Hu, M.D. Department of Anesthesiology, Zhejiang Provincial People's Hospital, Hangzhou 310006, China E-mail: [email protected]
2
S1743-9191(19)30303-6
DOI:
https://doi.org/10.1016/j.ijsu.2019.10.036
Reference:
IJSU 5116
To appear in:
International Journal of Surgery
Received Date: 20 August 2019 Revised Date:
22 October 2019
Accepted Date: 30 October 2019
Please cite this article as: Chen J, Tu Q, Miao S, Zhou Z, Hu S, Transcutaneous electrical acupoint stimulation for preventing postoperative nausea and vomiting after general anesthesia: A metaanalysis of randomized controlled trials, International Journal of Surgery, https://doi.org/10.1016/ j.ijsu.2019.10.036. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2019 Published by Elsevier Ltd on behalf of IJS Publishing Group Ltd.
Title Page Transcutaneous electrical acupoint stimulation for preventing postoperative nausea and vomiting after general anesthesia: A meta-analysis of randomized controlled trials Author list: Jiabao Chen1†, Qing Tu2†, Shuai Miao3, Zhenfeng Zhou1, Shuangfei Hu1* 1
Department of Anesthesiology, Zhejiang Provincial People's Hospital, Hangzhou 310006, China. Department of Anesthesiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China. 3 Department of Anesthesiology, Wuxi People's Hospital, Nanjing Medical University, Wuxi 214000, China.
2
E-mail address: 1. Jiabao Chen, [email protected]; 2. Qing Tu, [email protected]; 3. Shuai Miao, [email protected]; 4. Zhenfeng Zhou, [email protected]; 5. Shuangfei Hu, [email protected] Word Count (including references): Abstract Count: 248 Number of Tables: 4 Number of Figures: 7 References: 37 *
Correspondence: Shuangfei Hu, M.D. Department of Anesthesiology, Zhejiang Provincial People's Hospital, Hangzhou 310006, China E-mail: [email protected] †
J. Chen and Q. Tu contributed equally to the study.
Authors’ contribution J. Chen and Q. Tu collected the data and drafted the manuscript. S. Miao and Z. Zhou performed statistical analyses. S. Hu contributed to study conception. All the authors read the manuscript and approved the final submission.
1
1
Manuscript
2
Transcutaneous electrical acupoint stimulation for preventing postoperative
3
nausea and vomiting after general anesthesia: A meta-analysis of randomized
4
controlled trials
5 6
Abstract
7
Objective: We performed this meta-analysis to evaluate the effectiveness of
8
transcutaneous electrical acupoint stimulation (TEAS) for preventing postoperative
9
nausea and vomiting (PONV) after general anesthesia.
10
Methods: We searched PubMed, EMbase, Ovid, Web of Science for relevant
11
randomized controlled trials (RCTs) about TEAS for the prevention of PONV,
12
published through July 31, 2019. The primary outcome was the incidence of PONV,
13
postoperative nausea (PON) and postoperative vomiting (POV) recorded within 24h
14
after surgery. Secondary outcomes included the numbers of patients needing antiemetic
15
rescue and the incidence of postoperative adverse effects referred to general anesthesia.
16
Data were pooled and analyzed by RevMan 5.3 software.
17
Results: Fourteen RCTs (1653 participants) were included in this meta-analysis. The
18
current results suggested that application of TEAS showed obvious superiority in lower
19
incidence of PONV (relative risk [RR] 0.54, 95% confidence interval [CI] 0.42 to
20
0.68, P < 0.0001), PON (RR, 0.59, 95% CI 0.49 to 0.71, P < 0.0001), POV (RR 0.46;
21
95% CI, 0.33 to 0.65, P < 0.0001), lower numbers of patients needing antiemetic
1
2
1
rescue (RR 0.56, 95% CI 0.40 to 0.78, P = 0.0005), lower incidence of dizziness (RR
2
0.43, 95% CI 0.31 to 0.60, P < 0.0001) and pruritus (RR 0.43, 95% CI 0.31 to 0.58, P
3
= 0.02), compared with controlled intervention.
4
Conclusions: TEAS is a reasonable modality to incorporate into a multimodal
5
management approach for the prevention of PONV, PON, POV and associated with
6
lower numbers needing antiemetic rescue, lower incidence of adverse effects after
7
general anesthesia.
8 9 10
Keywords: transcutaneous electrical acupoint stimulation; postoperative nausea and vomiting; general anesthesia; meta-analysis
11
2
3
1
1. Introduction
2
Postoperative nausea and vomiting (PONV) are the most common complaints
3
after postoperative pain [1], with the incidence rising to 80% in high-risk groups [2].
4
In addition to impairing the patient’s comfort, serious PONV can also result in various
5
complications, such as dehiscence of surgical sutures, bleeding, etc [3]. PONV not only
6
reduces patients' satisfaction about the healthcare system, but also prolongs the length
7
of hospital stay and health care cost [4].
8
Concerns regarding the side effects of the traditional antiemetic drugs have
9
increased the interest in using non-pharmacologic technologies to prevent PONV
10
recently. A meta-analysis suggested that acupuncture on Neiguan (P6) showed
11
evidence in PONV prevention [5], however, the majority included studies'
12
interventions in the analysis were acupuncture, laser acupuncture or transcutaneous
13
electrical nerve stimulation (TENS) and only evaluated the effect of P6. As one of the
14
traditional Chinese acupuncture therapies, transcutaneous electrical acupoint
15
stimulation (TEAS) is widely used in clinic. TEAS imposes an electrical stimulation
16
pulse to target acupoints by using electrodes placed on the acupoints' surface instead
17
of needles, which combines the effects of TENS and acupoint therapy, has the similar
18
effects of electroacupuncture [6]. However, no meta-analysis has assessed of the
19
effectiveness of TEAS for preventing PONV after general anesthesia. Therefore, we
20
performed this meta-analysis to assess the effectiveness of TEAS on prevention of
21
PONV after general anesthesia. The primary outcomes included the incidence of
22
PONV, postoperative nausea (PON) and postoperative vomiting (POV) recorded 3
4
1
within 24 hours after surgery. While secondary outcomes included the numbers of
2
patients needing antiemetic rescue and the incidence of postoperative adverse effects
3
referred to general anesthesia.
4
2. Materials and methods
5
2.1 Inclusion and exclusion criteria
6
Two authors independently identified the eligibilities of articles for in-depth
7
examination by using the following inclusion: (1) article type of randomized
8
controlled trial (RCT); (2) the intervention in experimental group was TEAS (patients
9
in this group received electrical stimulation on the target acupoints. The stimulation
10
was provided by electrical stimulator through electrode tabs on the target acupoints.
11
The electrical stimulator was set at certain modes, frequency and intensity
12
accordingly), while sham TEAS served as the placebo; (3) articles involved in
13
evaluating the effectiveness of TEAS on prevention of PONV, or PON, or POV after
14
general anesthesia. Exclusion criteria including (1) article type of comments, case
15
reports, crossover studies, letters, editorials, review articles, meta-analysis and
16
retrospective studies; (2) studies of animal experiments; (3) studies involving data that
17
cannot be extracted or lacking of adequate data. If any discrepancies existed on the
18
eligibilities of included articles, the disagreements can be resolved through discussion
19
meeting or by the corresponding author.
20
2.2 Search strategy
21
The meta-analysis was registered in PROSPERO (International Prospective
4
5
1
Register of Systematic Reviews, registration number: CRD42018099275). The work
2
has been reported in line with Preferred Reporting Items for Systematic Reviews and
3
Meta-Analyses (PRISMA) and Assessing the methodological quality of systematic
4
reviews (AMSTAR) Guidelines [7, 8]. We searched PubMed, EMbase, Ovid, Web of
5
Science for relevant papers, about the effect of TEAS for preventing PONV,
6
published through July 31, 2019. The search terms included terms related to TEAS
7
(e.g., ' transcutaneous electrical acupoint stimulation ' OR ' TEAS ' OR '
8
transcutaneous acupoint electrical stimulation ' OR ' TAES ' OR ' acustimulation ') and
9
terms related to postoperative nausea and vomiting (e.g., 'postoperative nausea and
10
vomiting ' OR ' PONV ' OR ' postoperative nausea ' OR ' PON ' OR ' postoperative
11
vomiting ' OR ' POV '). There were no restrictions on dates, sex, or age, type of
12
surgery. We searched these terms in the titles and abstracts of potentially relevant
13
papers. References of the retrieved papers were also reviewed for further relevant
14
studies. Additional studies were also retrieved after reviewing of the reference lists of
15
relevant systemic reviews and meta-analysis.
16
2.3 Quality assessment
17
Two authors independently evaluated the quality of included studies by using
18
Jadad Scale [9]. The following items were evaluated: (1) whether the study followed
19
the principle of randomization; (2) whether the participants and personnel were
20
blinded; (3) whether the study descripted a detailed participant withdrawal or dropout.
21
A Jaded score ≥4 reflected high quality. We also evaluated the risk of bias of included
5
6
1
studies using the Cochrane Risk of Bias Tool [7], based on the following criteria: (1)
2
random sequence generation, (2) allocation concealment, (3) blinding of participants
3
and personnel, (4) blinding of outcome assessment, (5) incomplete outcome, (6)
4
selective reporting.
5
2.4 Data extraction
6
The process of data extraction was performed independently by two authors. The
7
following information were extracted from each study: the first author's name,
8
publication year, country, sample size, type of surgery, details of TEAS intervention,
9
outcomes of interest. If a study has insufficient or missing data, we tried to contact the
10
authors for the raw data of the study. Outcomes of interest including the overall
11
incidence of PONV, PON and POV within 24h after surgery and the numbers of
12
patients needing antiemetic rescue and the incidence of adverse effects within 24h
13
after surgery. PON was defined as a subjective unpleasant feeling associated with the
14
awareness of vomit urgency, while POV was defined as the forceful expulsion of
15
gastric contents brought about by sustained contraction of abdominal muscles with or
16
without abdominal pain. POV occurs in approximately 30% of patients during
17
surgical period, while the incidence of nausea is around 50% [10]. For PONV, it was
18
an unpleasant complication, which combines PON and POV both.
19
2.5 Statistical Analysis
20
Statistical analyses were performed by using Review Manager version 5.3
21
statistical software (The Cochrane Collaboration, The Nordic Cochrane Centre,
6
7
1
Copenhagen, Denmark). Dichotomous data were assessed using relative risks (RRs)
2
and 95% confidence intervals (CIs). The chi-square test and I2 statistic were used to
3
test the heterogeneity. A P-value of heterogeneity ≤0.10 was regarded as significant
4
heterogeneity existed [11], a Mantel-Haenszel randomized effect model was used.
5
Otherwise, the Mantel-Haenszel fixed effect model was employed. P-values 0.05
6
were regarded as statistically significant. Sensitivity analysis was performed by using
7
method of leave-one-out when individual endpoint resulted in substantial
8
heterogeneity. The effect of a particular statistical method (fixed effect model and
9
randomized effect model) on the variability for the results was also assessed. The risk
10
of publication bias was assessed by Egger test.
11
3. RESULTS
12
3.1 Literature Search
13
Base on our search strategy, we identified 263 potential relevant studies in initial
14
search, 208 studies were excluded due to exclusion criteria meet after reading their
15
titles or abstracts. Thirty-four studies were assessed for eligibility and 18 studies were
16
irrelevant to the outcomes of interest. Finally, 14 studies [12-25] were included in this
17
meta-analysis. The flow diagram of the study selection was shown in Figure. 1.
18
3.2 Characteristics of included studies
19
The 14 studies involved 1653 participants, 835 participants received TEAS in
20
experimental group, while 818 participants received sham TEAS in control group.
21
Among these included RCTs, 9 of them chose combined acupoints as the target
7
8
1
acupoints, while 5 chose single acupoint. Twelve RCTs were conducted in China, 1
2
RCT was conducted in America, as well as Korea. The detailed characteristics of
3
pooled studies were summarized in Table. 1 and 2. List of relevant acupoints was
4
provided in Table. 3.
5
3.3 Risk of bias assessment and sensitivity analysis
6
Of 14 RCTs, 11 RCTs described detailed information of random sequence
7
generation, only 1 RCTs have not mentioned the method of random sequence
8
generation. Ten RCTs described the detailed methods of allocation concealment and
9
10 RCTs were double-blinded by performing rigorous study design, while other 4
10
RCTs have mentioned the adequate method of blinded of participants and personnel
11
unclearly. Six RCTs provided detailed methods of blinded outcomes assessment, only
12
1 RCTs has not mentioned the blinded outcomes assessment. Most of the included
13
studies have low risk bias of attrition and reporting. (Figure. 2) We also conducted a
14
Jadad assessment for the included studies, most of the studies have Jaded scored more
15
than 4 points. (Table. 1) Egger test was performed to assess the publication bias, the
16
results suggested that publication bias was existed based on the outcome of PONV
17
(bias = 0.227, P < 0.05). However, no evidence of significant publication bias existed
18
based on the Egger test of PON (bias = −0.76, P = 0.468) and POV (bias = −0.26, P =
19
0.742). Regardless of different effect model performed, the outcomes of the results
20
remained similar between TEAS and Control group (Table. 4).
21
3.4 TEAS reduces the incidence of PONV, PON and POV
8
9
1
Seven RCTs reported the incidence of PONV within 24h after surgery, there was
2
no evidence of heterogeneity among the studies (P = 0.80, I2 = 0%). A fixed-effects
3
model was performed to analyze the outcome. The meta-analysis found participants in
4
TEAS group had lower incidence of PONV (RR 0.54, 95% CI 0.42 to 0.68, P <
5
0.0001), compered with control group. (Figure. 3)
6
Likewise, 7 RCTs reported the incidence of PON, there was evidence of
7
heterogeneity among the studies (P = 0.22, I2 = 27%). A fixed-effects model was
8
performed to analyze the outcome. The meta-analysis found participants in TEAS
9
group had lower incidence of PON (RR 0.59, 95% CI 0.49 to 0.71, P < 0.0001) than
10
control group. (Figure. 4)
11
In addition, 7 RCTs reported the incidence of POV, there was no significant
12
evidence of heterogeneity among the studies (P = 0.09, I2 = 46%). A randomized
13
effect model was used to analyze the outcome. The meta-analysis also found that
14
TEAS group has lower incidence of POV (RR, 0.46; 95% CI, 0.33 to 0.65, P < 0.0001)
15
than the control group. (Figure. 5)
16
3.5 TEAS reduces the numbers of patients needing antiemetic rescue and adverse
17
reactions
18
Four RCTs reported the numbers of patients needing antiemetic rescue, no obvious
19
evidence of heterogeneity existed among the studies (P = 0.71, I2 = 0%). A
20
fixed-effects model was performed to analyze the outcome. The meta-analysis found
21
TEAS group had less numbers of patients needing antiemetic rescue (RR 0.56, 95%
9
10
1
CI 0.40 to 0.78, P = 0.0005) than control group. (Figure. 6) Dizziness and pruritus
2
were the two commonly adverse effects after general anesthesia. Dizziness was
3
defined as a feeling of spinning or having one’s surroundings spin about, while
4
pruritus was defined as a sensation that causes the desire or reflex to scratch, usually
5
manifested as skin itch. Among the included studies, dizziness and pruritus were the
6
two commonly mentioned adverse effects. Four RCTs reported the incidence of
7
dizziness, no obvious evidence of heterogeneity existed among the studies (P = 0.78,
8
I2 = 0%), a fixed-effects model was performed and the result suggested that the
9
incidence of dizziness in TEAS group was lower than that in the control group (RR
10
0.43, 95% CI 0.31 to 0.60, P < 0.0001). Three RCTs reported the incidence of pruritus,
11
no obvious evidence of heterogeneity existed among the studies (P = 0.16, I2 = 46%).
12
A fixed-effects model was performed and the result suggested that the incidence of
13
pruritus in TEAS group was also lower than that in the control group (RR 0.43, 95%
14
CI 0.31 to 0.58, P = 0.02). (Figure. 7)
15
4. Discussion
16
Finally, a total of 14 RCTs involved included in the study. The obvious
17
heterogeneity (P-value of heterogeneity) was only found in the outcomes of POV. No
18
publication bias was detected. The results of data synthesis suggested that the
19
application of TEAS was associated with lower incidence of PONV, PON, POV,
20
adverse effects and lower numbers of patients needing postoperative antiemetic rescue,
21
suggesting that TEAS provides broadly generalizable benefits during recovery period
10
11
1
and helps to accelerate the progress of enhanced recovery after surgery (ERAS). Our
2
findings are consistent with a previous meta-analysis [5], however, which only
3
included 4 studies with the intervention of TEAS in experimental group. In our
4
meta-analysis, we only included trials with the intervention of TEAS, which provided
5
electrical stimulation on the target acupoints through electrode tabs, and excluded
6
those with interventions of acupuncture, TENS, acupressure, etc.
7
The results of the meta-analysis suggested that TEAS showed effectiveness in
8
preventing PONV. For decades, clinicians have increased their interest in applying
9
non-pharmacologic technologies for preventing PONV recently, such as acupuncture,
10
acupoint massage, or even chewing gum, etc. As a non-invasive approach, TEAS
11
combines the effects of TENS and acupoint therapies, provides multiple effects
12
through stimulating specific acupoints with certain frequency and intensity. While the
13
procedure of acupuncture was accomplished by using invasive needles, operated by
14
professional acupuncture practitioner. In addition, the needles cannot be well
15
protected during the procedure and the overall effects may be minimized. Furthermore,
16
fainting during acupuncture treatment may be occurred for some patients with
17
sensitivities to needles. Some complications may also appear, such as subcutaneous
18
hemorrhage, continued acid bilge feeling and burning sensation of acupuncture sites.
19
However, the use of TEAS has no risks of infection and can potentially be applied by
20
medical personnel with minimal training [26, 27].
21
In terms of physiological mechanism, acupuncture could increase the release of
11
12
1
β-endorphin and promote the secretion of corticosteroids in the brain [10]. In clinical
2
practice, patients were usually proscribed with corticosteroids for preventing PONV
3
[28]. In line with this, the release of endogenous glucocorticoid may be more
4
conducive to reducing the incidence of PONV and mitigate the side effects of
5
exogenous glucocorticoid. As a medical prophylaxis, TEAS are widely used in many
6
Asian countries, such as China, Korea, Japan, etc. Recent guidelines recommended to
7
apply non-drug treatments for the prophylaxis of PONV, such as chewing gum,
8
conventional acupuncture, moxibustion, etc [2]. In China, acupuncture and
9
moxibustion therapy are often used to treat intractable hiccups and cancer vomiting.
10
However, compared with conventional acupuncture, TEAS provided stimulation
11
through electrode tabs instead, which has no risks of infection and can potentially be
12
applied by medical personnel with minimal training [25, 26]. With the master of this
13
technique by clinicians, TEAS becomes one of the most used applications during
14
perioperative period in many clinical centers in China [29]. However, the technique
15
has not been well promoted. The result might be owing to the unclear specific
16
mechanism of TEAS on PONV prevention. Serotonin (5-HT) leads to vomiting reflex
17
by activating 5-HT3 receptors [30]. A research in Chinese suggested TEAS on P6 and
18
Zusanli (ST36) decreased the plasma concentration of 5-HT and resulted in lower
19
incidence of PONV in patients underwent cesarean section [31], but the research did
20
not provide the specific mechanisms. P6 has been confirmed to have an effect of
21
PONV prevention [32, 33]. A meta-analysis of Lee et al suggested that stimulation of
12
13
1
P6 can reduce PONV by 30% [5]. While Chen et al applied TEAS on Jiaji (EX-B2)
2
during colonoscopy presented a downward trend of nausea or vomiting prevalence
3
[34]. In our meta-analysis, 9 of included studies chose combined target acupoints,
4
while another 5 studies chose single acupoint, both of the choice showed superiority
5
for lower incidence of PONV, PON and POV, compared with sham TEAS. However,
6
a recent clinical study by our team member suggested that stimulation on BL13, L14,
7
ST36 during video-assisted thoracic surgical lobectomy have not shown superiority in
8
reducing the incidence of PONV [23], while another study indicated stimulation on
9
BL23, SP9 could help to prevent PONV for patients with ureteroscopic lithotripsy
10
[24]. In line with this, there might still exist certain discrepancies in target acupoints
11
choice. In addition, 12 studies chose the frequency model of dense-disperse, while
12
only 1 chose the frequency model of square-wave and 1 study have not mentioned the
13
choice of frequency mode (Table. 2). Even in the latest guidelines on acupoint
14
stimulation in China, there is no relevant recommendations of frequency model
15
choice [35]. Studies proved that the timing of acustimulation did not impact the
16
incidence of PONV, with similar reductions being achieved with stimulation initiated
17
pre- or post-anesthesia induction [31, 36]. However, results from two meta-analyses
18
suggested that differences in the timing of acupuncture (e.g. pre-, intra- or
19
postoperative) were associated with the observed heterogeneity [5, 37]. So, there is a
20
need for more well design trials to compare the effects of different onset timing of
21
TEAS.
13
14
1
Our findings should be interpreted with cautions because of the limitations in this
2
meta-analysis, although TEAS has obvious advantages in preventing the incidences of
3
PONV, PON, POV and reducing the numbers of patients needing antiemetic rescue, it
4
seems the technique is popular in Asian countries, particularly in China, Korea and
5
some southeast Asian countries for the specific mechanism of TEAS is still
6
incompletely clear, which limits the promotion of this technique in some sense. This
7
limitation also adds bias on our results. In addition, of 14 included studies, 12 were
8
conducted in China, which may play a certain impact on the reliability of the results.
9
In addition, most included RCTs had a simple size of <100 participants, which may
10
also impact the overall results, lead to systematic deviation and reduce the reliability
11
of RCTs to robustly demonstrate efficacy or effectiveness. However, TEAS also have
12
some potential side effects, such as sense of itchiness, skin redness and swelling on
13
the site of target acupoints for long time stimulation. In our study, we mainly choose
14
the incidence of PONV, PON and POV as the primary outcomes. However, the
15
majority of the included studies, the incidences of PONV, PON or POV were only
16
recorded within 24h after surgery. In fact, PONV may persist for several days for
17
some patients with high risks. Therefore, more studies are needed to focus on the
18
long-term effect of TEAS on PONV and relevant outcomes. Since all patients in
19
included studies received general anesthesia during surgery, whether TEAS could
20
prevent PONV secondary to other type of anesthesia, such as spinal anesthesia, still
21
needs more study to prove it.
14
15
1
5. Conclusions
2
TEAS is a reasonable modality to incorporate into a multimodal management
3
approach for the prevention of PONV. Application of TEAS associated with lower
4
incidences of PONV, PON, POV, less numbers of patients needing antiemetic rescue
5
and lower incidences of dizziness and pruritus. Owing to the limitations, more
6
well-designed, involved larger sample size and different races studies are needed to
7
justify the results of this meta-analysis.
8
Funding
9
None.
10
Conflict of interest
11
The authors declare that they have no conflict of interest.
12
Acknowledgements
13
There were no acknowledgements in this study.
14 15
Provenance and peer review
16
Not commissioned, externally peer-reviewed
17 18
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[29]. Y. Hou, Q. Yan, H. An, J. Wang, M. Tian, W. Zhao, A. Wu, Y. Feng Y, The use and protective
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13
21
22
1
Table legends
2
Table. 1 Characteristic of the included studies
3
Note: TEAS, transcutaneous electrical acupoint stimulation; VATSL Video‐assisted Thoracic
4
Surgical Lobectomy; LC, Laparoscopic Cholecystectomy; LS, Laparoscopic Surgery; SC,
5
Supratentorial Craniotomy; IC, Infratentorial Craniotomy; MBS, major breast surgery; LH,
6
laparoscopic hysterectomy; LAS, lower abdominal surgery; HNTS, head and neck tumor surgery;
7
GLS, gynecological laparoscopic surgery; ABS, ambulatory breast surgery; * 1: postoperative
8
nausea and vomitting; 2: postoperative nausea; 3: postoperative vomitting; 4: number of patients
9
need antiemetic rescue; 5: incidence of adverse effects; ∆Jadad score (range: 0-7) ≥ 4 reflect high
10
quality.
11
Table. 2 Details of interventions
12
Note: TEAS, transcutaneous electrical acupoint stimulation; PACU, Post-anesthesia Care Unit;
13
Hegu, L14; Neiguan, P6; Lieque, LU7; Quchi, LI11; Zusanli, ST36; Sanyinjiao, SP6; Shangwan,
14
CV13; Zhigou ,TE6; Houxi, SI3; ∆each tablet of saridon contains 0.25g acetaminophen, 0.15g
15
propyphenazone, and 0.05g anhydrous caffeine.
16
Table. 3 Description list of acupoints
17
Note: 1 cun ≈ 3.33cm.
18
Table. 4 Sensitivity analysis of outcomes according to different effect models
19
Note: RR, risk ratio; PONV, postoperative nausea and vomiting; PON, postoperative nausea; POV,
20
postoperative vomiting.
22
23
1
Figure legends
2
Figure. 1 Flow diagram of study selection.
3
Figure. 2 Potential risk of bias of each included study.
4
Note: "+" represents low risk; "?"represents unclear risk; "-" represents high risk.
5
Figure. 3 Forest plots comparing the incidence of postoperative nausea and vomiting (PONV)
6
between TEAS and Control group. A Mantel-Haenszel fixed effects model was used. TEAS,
7
transcutaneous electrical acupoint stimulation.
8
Figure. 4 Forest plots comparing the incidence of postoperative nausea (PON) between TEAS and
9
Control group. A Mantel-Haenszel fixed effects model was used. TEAS, transcutaneous electrical
10
acupoint stimulation.
11
Figure. 5 Forest plots comparing the incidence of postoperative vomiting (POV) between TEAS
12
and Control group. A Mantel-Haenszel randomized effects model was used. TEAS,
13
transcutaneous electrical acupoint stimulation.
14
Figure. 6 Forest plots comparing the numbers of patients needing antiemetic rescue between
15
TEAS and Control group. A Mantel-Haenszel fixed effects model was used. TEAS,
16
transcutaneous electrical acupoint stimulation.
17
Figure. 7 Forest plots comparing the adverse effects between TEAS and Control group, including
18
subgroup analysis of dizziness and pruritus. A Mantel-Haenszel fixed effects model was used.
19
TEAS, transcutaneous electrical acupoint stimulation.
23
Table. 1 Characteristic of the included studies Authors, year
Country
Age
Sample size
Type of surgery
Target outcomes*
Jadad score∆
Huang et al, 2017[12]
China
?
60/20
VATSL
1
5
Liu et al, 2008 [13]
China
18~60
48/48
LC
1, 2, 3, 4
5
Wang et al, 2014 [14]
China
29~60
30/30
Sinusotomy
1, 4
6
Wang et al, 2010 [15]
China
20~60
40/40
SC
2, 3, 4
4
Xu et al, 2012 [16]
China
?
60/59
IC
2, 3, 4
5
Gan et al, 2004 [17]
America
?
26/24
MBS
3, 4
5
Kim et al, 2011[18]
Korea
31~67
210/54
LH
1, 2, 3, 4
3
Zheng et al, 2008 [19]
China
39~65
30/30
HNTS
3
3
Yao et al, 2015 [20]
China
18~60
35/36
GLS
2, 3, 5
6
Chen et al, 2015 [21]
China
18~60
41/42
Thyroidectomy
1, 5
6
Zhang et al, 2014 [22]
China
20~50
33/32
ABS
2, 3, 5
7
Tu et al, 2018[23]
China
?
72/72
VATSL
1
7
Tu et al, 2019[24]
China
?
60/60
Ureteroscopic lithotripsy
1, 5
6
Sun et al, 2017 [25]
China
18~70
90/271
LS
2, 3, 4
6
Note: TEAS, transcutaneous electrical acupoint stimulation; VATSL Video-assisted Thoracic Surgical Lobectomy; LC, Laparoscopic Cholecystectomy; LS, Laparoscopic Surgery; SC, Supratentorial Craniotomy; IC, Infratentorial Craniotomy; MBS, major breast surgery; LH, laparoscopic hysterectomy; LAS, lower abdominal surgery; HNTS, head and neck tumor surgery; GLS, gynecological laparoscopic surgery; ABS, ambulatory breast surgery; * 1: postoperative nausea and vomitting; 2: postoperative nausea; 3: postoperative vomitting; 4: number of patients need antiemetic rescue; 5: incidence of adverse effects; ∆Jadad score (range: 0-7) ≥ 4 reflect high quality.
1
Table. 2 Details of interventions Authors, year
Time point
Acupoints
Frequency
Post-operative opioids
Huang et al, 2017[12]
30min before induction,
P6, LI4,
Dense-disperse frequency of
Sufentanil and
throughout the surgery, and
LU7, LI11
2/100 or 2 or 100Hz. intensity of
flurbiprofen i.v.
24, 48h after surgery. Liu et al, 2008 [13]
30~60 min before the
tolerable level. P6
50ms, 2-100Hz, 0.5-4mA
Not mentioned
LI4, P6,
Dense-disperse frequency,
Parecoxib 40 mg i.v.
ST36
2/10Hz, 6~9mA
P6
Dense-disperse frequency,
induction till the end of surgery. Wang et al, 2014 [14] Wang et al, 2010 [15]
30 min before anesthesia 30 min before induction and lasted up to 6h
Not mentioned
2/10Hz , no mentioned of intensity
postoperatively Xu et al, 2012 [16]
30 min before induction of
P6
and up to 24h after surgery Gan et al, 2004 [17]
30 ~ 60 min before induction
Dense-disperse frequency,
Saridon tables∆
2/10Hz , 2mA P6
till the end of surgery
Dense-disperse frequency,
Fentanyl 25µg i.v.
2/10Hz , intensity of feeling de qi sensation.
Kim et al, 2011[18]
During maintenance period
P6
Square-wave pulses of 0.2 ms,
PCIA:fentanyl 50µg and
1Hz, 50mA
ketorolac 30 mg, 60mL
Dense-disperse frequency, 2/100
PCIA:1000mg
Hz, 8-10mA
tramadol/100mL
LI4, P6,
Dense-disperse frequency,
Sufentanil 0.05µg/kg
ST36, SP6
2/10Hz, 6-9mA
i.v.
LI4, P6
Dense-disperse frequency,
Morphine 2mg i.v.
of anesthesia Zheng et al, 2008
30min in the first 2-4h, then
[19]
once more every 3h, 3 times
LI4, P6
in total. Yao et al, 2015 [20] Chen et al, 2015 [21]
30min before induction 30min before induction
2/10Hz, 6-9mA Zhang et al, 2014
30min before induction
[22] Tu et al, 2018 [23]
Tu et al, 2019 [24]
throughout the surgery
4,8,12 h postoperatively and
LI4, P6,
Dense-disperse frequency,
ST36
2/10Hz, 6-9mA
BL13, L14,
Dense-disperse frequency,
ST36
2/10Hz , 5 to 30 mA
BL23, SP9
Dense-disperse frequency,
tramadol hydrochloride
2/10Hz , 5 to 30 mA
tablets if needed
Dense-disperse frequency, 2/100
flurbiprofenaxetil 50 mg
Hz,
i.v.
three times on the next 2
Parecoxib 40 mg i.v. Not mentioned
days after surgery Sun et al, 2017 [25]
30min preoperative, or pre-
LI4, P6
and intra-operative, or pre-
intensity of tolerable level.
and post-operative Note: TEAS, transcutaneous electrical acupoint stimulation; PACU, Post-anesthesia Care Unit; Hegu, L14; Neiguan, P6; Lieque, LU7; Quchi, LI11; Zusanli, ST36; Sanyinjiao, SP6; Shangwan, CV13; Zhigou ,TE6; Houxi, SI3; ∆each tablet of saridon contains 0.25g acetaminophen, 0.15g propyphenazone, and 0.05g anhydrous caffeine.
2
Table. 3 Description list of acupoints Acupoints
Detailed location
Hegu,
On the dorsum of the hand, between the first and second metacarpal bones, approximately in the middle of the
L14
second metacarpal bone on the radial side, line up the position the transverse crease of the first joint of the thumb with the margin of the web between the thumb and the index finger of the other hand. Neiguan, P6
On the palmar side of the forearm and on the line connecting Quze (PC3) and Daling (PC7), 2 cun above the crease of the wrist.
Zusanli, ST36
3 cun below Dubi (S 35), one finger breadth from the anterior crest of the tibia.
Lieque, LU7
On the radial aspect of the forearm, between the tendons of the abductor pollicis longus and the extensor pollicis brevis muscles, in the groove for the abductor pollicis longus tendon, 1.5 cun superior to the palmar wrist crease.
Quchi, LI11
At the midpoint of the line between the radial end of the cubital crease and the external humeral epicondyle.
Sanyinjiao, SP6
On the medial side of the leg, 3 cun above the tip of the medial malleolus, posterior to the medial border of the tibia.
Shangwan,
located in the Conception Vessel Meridian, 1 cun above the mid- point of the line between the xyphisternum and
CV13
the umbilicus.
Zhigou,TE6
On the back of the forearm, 3 cun across the web of the wrist, located on the connecting line between the Yangchi (SJ4) and the elbow tip.
Houxi, SI3
On the ulnar side of the palm, at the junction of the red and white skin posterior to the small finger (the 5th metacarpophalangeal joint).
Jiaji, EX-B2
located on both sides of the spinous column, 0.5 cun lateral to the lower border of each spinous process.
Note: 1 cun ≈ 3.33cm.
3
Table. 4 Sensitivity analysis of outcomes according to different effect models Outcomes of interest
RR
Random effect model
Fixed effect model
PONV
RR
0.56 (0.45 to 0.70)
0.54 (0.42 to 0.68)
PON
RR
0.59 (0.47 to 0.73)
0.59 (0.49 to 0.71)
POV
RR
0.46 (0.33 to 0.65)
0.50 (0.40 to 0.64)
Numbers needing antiemetic rescue
RR
0.56 (0.41 to 0.78)
0.56 (0.40 to 0.78)
Dizziness
RR
0.45 (0.32 to 0.62)
0.43 (0.31 to 0.60)
Pruritus
RR
0.46 (0.14 to 1.49)
0.42 (0.21 to 0.78)
Adverse effects
Note: RR, risk ratio; PONV, postoperative nausea and vomiting; PON, postoperative nausea; POV, postoperative vomiting.
4
Identification
Records identified through database searching (n=246)r
Additional records identified through other resources (n=17)r
Included
Eligibility
Screening
Records after duplicates removed (n=55)r
Records were screened (n=55)r
Full-text articles assessed for eligibility (n=34)r
Studies included in this metaanalysis (n=14)r
Figure. 1 Flow diagram of study selection.
Records excluded: not RCT, no full text reviews, case reports, meeting abstracts, retrospective articles (n=21)r
Records excluded: no outcomes of interest (n=20)r
Figure. 2 Potential risk of bias of each included study. Note: "+" represents low risk; "?"represents unclear risk; "-" represents high risk.
Figure. 3 Forest plots comparing the incidence of postoperative nausea and vomiting (PONV) between TEAS and Control group. A Mantel-Haenszel fixed effects model was used. TEAS, transcutaneous electrical acupoint stimulation.
Figure. 4 Forest plots comparing the incidence of postoperative nausea (PON) between TEAS and Control group. A Mantel-Haenszel fixed effects model was used. TEAS, transcutaneous electrical acupoint stimulation.
Figure. 5 Forest plots comparing the incidence of postoperative vomiting (POV) between TEAS and Control group. A Mantel-Haenszel randomized effects model was used. TEAS, transcutaneous electrical acupoint stimulation.
Figure. 6 Forest plots comparing the numbers of patients needing antiemetic rescue between TEAS and Control group. A Mantel-Haenszel fixed effects model was used. TEAS, transcutaneous electrical acupoint stimulation.
Figure. 7 Forest plots comparing the adverse effects between TEAS and Control group, including subgroup analysis of dizziness and pruritus. A Mantel-Haenszel fixed effects model was used. TEAS, transcutaneous electrical acupoint stimulation.
Highlights:
PONV are the most common complaints after postoperative pain. The meta-analysis to evaluate the effectiveness of TEAS for preventing PONV after general anesthesia. TEAS is a reasonable modality to incorporate into a multimodal management approach for the prevention of PONV, PON and POV after general anesthesia. Application of TEAS also associated with lower numbers needing antiemetic rescue, lower incidence of adverse effects after general anesthesia.
All the data in our manuscript is available to access. Please contact the correspondence, Shuangfei Hu, email: [email protected].
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Author contribution
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Please specify the contribution of each author to the paper, e.g. study design, data collections, data analysis, writing. Others, who have contributed in other ways should be listed as contributors. Jiabao Chen and Qing Tu collected the data and drafted the manuscript. Shuai Miao and Zhenfeng Zhou performed statistical analyses. Shuangfei Hu contributed to study conception. All the authors read the manuscript and approved the final submission.
Guarantor The Guarantor is the one or more people who accept full responsibility for the work and/or the conduct of the study, had access to the data, and controlled the decision to publish. Shuangfei Hu, M.D. Department of Anesthesiology, Zhejiang Provincial People's Hospital, Hangzhou 310006, China E-mail: [email protected]
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