A randomized placebo-controlled trial of Chinese medicine acupoint application on gastrointestinal dysfunction after appendectomy

Hong Chen,Yi-Yuan Liu,Yu-Tao Wang,Cheng-Cheng Yang,Xiu-Qin Xu,Hai-Rong Hu,Yun-Lan Jiao,Xing-Tong Bao,Ling Tang

1Department of Second Surgery and Galactophore,Dongfang Hospital Beijing University of Chinese Medicine,Beijing 10078,China;

2Nursing Department, Dongfang Hospital Beijing University of Chinese Medicine, Beijing 10078, China; 3Department of General Surgery, Dongfang Hospital Beijing University of Chinese Medicine, Beijing 10078, China; 4School of Nursing, Beijing University of Traditional Chinese Medicine,Beijing 10002,China.

Abstract

Background: Gastrointestinal dysfunction is one of the common complications of appendectomy,which seriously affects the postoperative recovery and clinical prognosis.Through traditional Chinese medicine acupoint application is suggested for managing postoperative gastrointestinal dysfunction, supporting evidence is weak.Here, the prospective randomized placebo-controlled study was designed to provide high-level evidence regarding whether traditional Chinese medicine acupoint application is effective on the gastrointestinal dysfunction after appendectomy.Methods: A total of 60 patients who underwent appendectomy in Dongfang Hospital Beijing University of Chinese Medicine (Beijing, China) from November 2016 to December 2017 were selected as study objects and randomly divided into control group (n = 30) and observation group (n = 30).Based on routine postoperative care, the acupoints Zusanli (ST36) and Yongquan (KI1) were selected.The control group was given acupoint application of traditional Chinese medicine placebo and the observation group was given acupoint application of clinical empirical Chinese medicine called Wentongliqi prescription.The course of treatment was performed on the 1st, 2nd, and 3rd days after appendectomy, once a day and 4 hours each time.The primary outcome includes the time until the recovery time of bowel sounds (h), the first postoperative flatus (h) and first bowel movement time (h) on the 1st, 2nd, and 3rd days after appendectomy.The secondary outcome includes clinical symptom score,life ability score and adverse reactions were observed and recorded on the 1st,2nd,and 3rd days after appendectomy.Results:After treatment, the recovery time of intestinal sound in the observation group was earlier than that in the control group(P ＜0.05).However,there were no significant difference between the two groups in first anal exhaust time and first bowel movement time, clinical symptom scores and life ability scores between the two groups before and after treatment (P ＞0.05).Conclusion: Acupoint application therapy has limited effect on the recovery of gastrointestinal dysfunction after appendectomy.Further study with large sample size is needed to confirm its therapeutic effects.

Keywords: Appendicitis, Gastrointestinal dysfunction, Acupoint sticking therapy, Randomized controlled clinical trials,Curative effect,Security

Background

Gastrointestinal dysfunction is one of the common complications of appendectomy [1].Its main symptoms include loss of appetite,cessation of exhaust and defecation, accompanied by abdominal distension,abdominal pain, nausea and vomiting, etc.Some patients might even suffer from intestinal obstruction,intestinal adhesion and other complications occur in severe cases [2].How we might to effectively relieve the symptoms of postoperative gastrointestinal dysfunction and promote the recovery of gastrointestinal function has become the focus and difficulty of clinical research.

At present, there are still insufficient measures to manage the postoperative gastrointestinal dysfunction at home and abroad.The main measures include routine treatments such as encouraging patients to get out of bed as soon as possible and applying abdominal hot compress [3] gastrointestinal motility drugs [4].Western medicine such as alvimopan is used to treat postoperative gastrointestinal dysfunction.However,due to the side effects of this drug, including nausea and vomiting, its widespread use is limited [5].Looking for a successful postoperative rehabilitation to promote the early recovery of gastrointestinal function and minimize side effects has gain more and more attention.

According to traditional Chinese medicine, it is necessary to regulate Qi after abdominal operation to help the stomach and intestine recover normal peristaltic function.Traditional Chinese medicine therapy mainly includes oral Qi laxative[6],traditional Chinese medicine enema[7],acupuncture and massage therapy [8–10], traditional Chinese medicine navel application [11, 12], moxibustion [13, 14], acupoint injection [15], etc.Although these therapies can promote the recovery of gastrointestinal function after abdominal surgery, they also have certain limitations.For example, because patients after abdominal surgery should fast, oral drugs have certain restrictions.Chinese medicine enema is not suitable for patients with descending colon and sigmoid colon surgery.Umbilicus application of Chinese medicine is limited by the wound site of abdominal surgery.Moxibustion therapy is limited by the patient's comfort and sensitivity.Acupoint application of Chinese medicine is attracting more and more attention due to its unique treatment, simple method, safe and reliable curative effect.The technology of needling of Zusanli (ST36)acupoint to patients after abdominal surgery has been practiced in clinic for more than 10 years, which has beneficial therapeutic effects on the recovery of gastrointestinal function with less adverse reactions[16–17].

This is the first randomized, double-blind,placebo-controlled clinical study.Through the external application of Chinese medicine called Wentongliqi prescription on acupoints involving Zusanli (ST36)and Yongquan(KI1),we intend to evaluate the efficacy and safety of this therapeutic method in the recovery of gastrointestinal dysfunction after appendectomy.

Methods

Participants

A total of 60 patients diagnosed with appendicitis and scheduled for appendectomy in the surgical ward of Dongfang Hospital of Beijing University of Chinese Medicine (China) from November 2016 to December 2017 were recruited.

Inclusion criteria

(1) Patients aged 18–80 after appendectomy, (2)agreement via written informed consent and (3)diagnosed with appendicitis and scheduled for appendectomy.

Exclusion criteria

Participants who have experienced or have one or more of the following conditions will be excluded: (1)intestinal obstruction;(2) severe basic diseases such as cardiovascular and cerebrovascular diseases, liver diseases and kidney diseases; (3) other postoperative complications affected the observer; (4) allergic constitution.

Ethical standards

The study was planned in accordance with the Helsinki Declaration and was approved by the Ethics Committee of Dongfang Hospital of Beijing University of Chinese Medicine (JDF-IRB-2016034102).All the recruited subjects have signed written informed consent.

Trial design

This study is a randomized placebo-controlled trial conducted in China.According to formula n1=π(1-π)[(u1-α+u1-β)/δ]2(1+c)/c,n1=n2,δ=0.25,α=0.05,β = 0.10, a minimum of 27 patients in each group would be needed.Considering a drop-out rate during study, a total of 60 patients were needed for the study.Then the patients were randomly allocated into the control group or treated group at a 1:1 allocation.

Randomization

Method of random assignment: SAS software was used to generate random sequences, randomly group and encode drugs.Concealment and implementation of allocation scheme: the random sequence is concealed by sealed envelope method.

Blinding

In this trial, subjects and researchers were double blinded.In case of emergency or the patients need to know what kind of treatment they received, the corresponding emergency letters were opened and read by at least two researchers in the presence, and the emergency letters were collected together with the case report form after the end of the trial.

Intervention

Both groups were given routine minimally invasive surgical care, including postoperative fasting water,intravenous fluids and nutritional support.After the operation, the patients were assisted to turn over regularly instructed to do bedside activities and get out of bed early.The control group was given Wentongliqi prescription placebo acupoint application, and the observation group was given Wentongliqi prescription acupoint application.both the placebo and Wentongliqi prescription are uniformly prepared by Beijing Kangrentang Pharmaceutical Co., LTD (Beijing,China).The placebo is made of dextrin, an intermediate product of starch decomposition that has no pharmacological activity.The dosage, color and smell of placebo are the same as those of Wentongqi prescription.The course of treatment was performed on the 1st,2nd,and 3rd days after appendectomy,once a day and 4 hours each time.Apply within 1 hour after appendectomy on 1st day and on 9:00 am on 2nd and 3rd day.

The composition of Chinese medicine experience formula Wentongqi prescription: Gan Jiang (Zingiber oj-jicinale Rosc.) 15 g, Rou Gui (Cinnamomum cassia Presl) 15 g, Ding Xiang (Syzygium aromaticum (L.)Merr.& L.M.Perry) 20 g, Xiang Fu (Cyperus rotundus L.)20 g,Zhi Qiao(Citrus aurantium L.)20 g,Hou Po (Magnolia officinalis Rehd.et Wils.) 20 g, Xie Bai (Allium macrostemon Bunge.) 20 g, Quan Xie(Buthus martensii Karsch)20 g.

Preparation and use of ointment: take 2 pieces of gauze and stack them into the a cross shape,dissemble the prepared sealed bag of Chinese medicine, take one bag of formula granules (68 g) at each point, mix it into paste with 10 mL yellow rice wine and 3 mL honey, then take out the prepared Chinese medicine with iron spoon and place it in the center of the folded cross gauze.The gauze shall be stacked one by one to cover the Chinese medicine, make the poultice into a pancake plaster with a diameter of 10 cm and a thickness of 5 mm by using the puller, put it in the microwave oven and heat it for 5 seconds in high temprature.Clean the skin of the applied area with warm water and apply the ointment to the acupoints of Zusanli (ST36) and Yongquan (KI1).First day: apply within 1 hour after returning to the ward; 2nd and 3rd day:at 9:00 am every day,once a day.

Nursing of application: before application, ask the patient if there is a history of allergy to Chinese medicine and dressing, explain the mechanism,operation method and precautions of application to the patient, and obtain the patient's cooperation.Check if the skin of the applied area is in good condition and clean the skin with warm water.Fix the medicine with dressing and closely observe the patient’s reaction.Prevention and nursing of complications after application[18].

Effectiveness evaluation

Primary outcome.The time until the recovery time of bowel sounds (h), the first postoperative flatus (h) and first bowel movement (h), will be calculated on day 1,2, and 3, which beginning at the time the subject returns to the ward after surgery.The subjects and their family members will be required to keep a record of the time until their first occurrence.

The secondary outcome.Clinical symptom score(Table 1) [19], life ability score, adverse reactionswere observed and recorded on day 1, 2, and 3.The activity of daily living scale was developed by Lawton and Brody in 1969.Adverse reactions were recorded by referring to the NCI classification standard (2009 HHS/NIH/NCI Common Adverse Reaction Terminology Assessment Standard 4.0.3).

Statistical analysis

SPSS 20.0 statistical software was used, and chi-square test was used for counting data such as baseline factors, gender and incidence of adverse events.The measurement data were statistically described by (± s), and the difference before and after treatment was compared byt-test.Bilateral tests were used for all statistical tests, andP＜ 0.05 was considered statistically significant.

Results

Comparison of general information

In this study, there were 6 cases of skin allergy due to local Chinese medicine patch, 3 cases in each of the two groups.The control group included 17 males and 10 females, aged (40.15 ± 14.52) years old, height(170.37 ± 7.60) cm, weight (65.57 ± 12.52) kg.In the treated group, there were 12 males and 15 females,aged(39.41± 13.49)years, height (166.56±7.25)cm,weight (67.24 ± 11.85) kg.The main general information of the patients including gender, age,height and weightwere compared, and the difference was not statistically significant(P＞0.05).

Comparison of postoperative gastrointestinal function recovery

Comparison of postoperative gastrointestinal function recovery between the two groups is shown in Table 2.The time until the first bowel sounds in the observation group was earlier than that in the control group (P＜0.05).However, there was no significant difference between the two groups regarding the time until the first postoperative flatus and first bowel movement(P＞0.05).

Table 1 Clinical symptom rating scale

Table 2 Comparison of postoperative gastrointestinal function between the two groups(±s,h)

Table 2 Comparison of postoperative gastrointestinal function between the two groups(±s,h)

Note:a compared with the control group,P ＜0.05.

Group N The time until the first Bowel sound The time until the first postoperative flatus The time until the first bowel movement The control group 27 22.15±9.45 23.19±9.81 51.33±16.64 Observation group 27 17.41±7.68a 20.30±9.74 45.78±16.39 t 2.023 1.086 1.235 P 0.048 0.282 0.222

Postoperative clinical symptom score

As shown in the Table 3, there was no significant difference in the scores of nausea and vomiting,abdominal distension, abdominal pain, exhaust and defecation between the two groups before treatment(P＞0.05).There was also no significant difference in scores of nausea and vomiting, abdominal distension and abdominal pain between the two groups after treatment (P＞ 0.05).However, the exhaust and defecation were significantly reduced compared with that of the treated group after treatment(P＜0.001).

Comparison of postoperative life ability scores

There was no significant difference in life ability scores between the two groups before and after treatment(P＞0.05)(Table 4).

Table 3 Comparison of postoperative clinical symptom scores(±SD,score)

Table 3 Comparison of postoperative clinical symptom scores(±SD,score)

Note:compared with the treated group after treatment,a:t=-9.35,P ＜0.001.

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Table 4 Comparison of postoperative life ability scores between the two groups(±s,score)

Table 4 Comparison of postoperative life ability scores between the two groups(±s,score)

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Safety evaluation before and after treatment

No obvious adverse reactions were observed before and after local skin application in both groups.

Discussion

After appendectomy and other abdominal operations,some patients will inevitably suffer from postoperative gastrointestinal dysfunction, and even lead to abdominal pain, abdominal distension, intestinal adhesion and other complications,which will seriously affect the postoperative recovery and clinical prognosis of patients.As one of Chinese medicine nursing techniques, a large number of clinical studies have shown that acupoint application of Chinese medicine can significantly promote the recovery of gastrointestinal function after abdominal surgery[20–22].However, there are few randomized placebo-controlled studies of acupoint sticking therapy with Chinese medicine on gastrointestinal dysfunction after appendectomy [23].In this study, a prospective randomized placebo-controlled study was used to investigate the effect and safety of Chinese medicine acupoint application on gastrointestinal function recovery in patients after appendectomy.

The clinical experience Wentongliqi prescription used in this acupoint application therapy is composed ofZingiber oj-jicinale Rosc.,Cinnamomum cassia Presl,Syzygium aromaticum (L.) Merr.& L.M.Perry,Cyperus rotundus L.,Citrus aurantium L.,Magnolia officinalis Rehd.et Wils.,Allium macrostemon Bunge.,Buthus martensii Karsch, which has a good effect on the recovery of gastrointestinal function after abdominal surgery.In this study, yellow rice wine was applied to Zusanli (ST36) and Yongquan (KI1) to promote clinical efficacy, as, with simple clinical acupoint selection, simple operation, and easy to popularize and use the scheme.

The results showed that the time until the first Bowel sound in the treated group was shorter than that in the control group (P＜ 0.05).However, no significant difference was observed regarding the time until the first postoperative flatus, time until the first bowel movement, clinical symptoms scores and life ability scores between the two groups (P＞0.05),which was inconsistent with previous reports [24–26].which may be due to the fact that most of the subjects were young adults (39.78 ± 14.02) and their body functions recovered quickly.Further study with large sample size is needed to confirm its therapeutic effects.

Conclusion

Acupoint sticking therapy has limited effect on promoting gastrointestinal function recovery after appendectomy.In the future, it is necessary to further expand the sample size and study how to effectively screen out the population that can benefit more from this therapy.