A Systematic Review and Meta-analysis for Duhuo Jisheng Decoction Combined with Manipulation in Treatment of Lumbar Disc Herniation

Kai Sun, Li-Gu Zhu o,2, Xu Wei✉, Jie Yu, Min-Shan Feng,2, He Yin, Long Liang, Bin Tang, Bo-Wen Yang

1. Wangjing Hospital of China Academy of Chinese Medical Sciences, Beijing 100102, China

2. Beijing Key Laboratory of Orthopedics of Traditional Chinese Medicine,Beijing 100007,China

Keywords:Duhuo Jisheng decoction lumbar manipulation lumbar disc herniation Systematic review Meta-analysis

ABSTRACT Objective: To systematically evaluate the efficacy and safety of Duhuo Jisheng decoction combined with manipulation in the treatment of lumbar disc herniation. Method:We systematically searched 8 databases at home and abroad. Literature quality of the included studies was evaluated by the bias risk assessment tool of Cochrane collaboration network, and the Meta-analysis was performed by RevMan 5.3 software. Result: A total of 427 related literature were retrieved, and 12 studies were eventually included, involving 1153 patients. All studies were in Chinese. Meta-analysis results showed that the total effective rate of Duhuo Jisheng decoction combined with manipulation in the treatment of LDH was better than that of the control group(RR= 1.23,95% CI [1.17,1.29],P ＜ 0.00001). Subgroup analysis showed that Duhuo Jisheng decoction combined with manipulation had a more significant effect than conventional treatment(RR=1.34,95% CI [1.20,1.50],P＜ 0.00001), nonsteroidal anti-inflammatory drugs(RR=1.24,95% CI [1.12,1.37],P＜ 0.0001), and Yaotongning capsules(RR=1.19,95% CI [1.10,1.29],P＜ 0.0001). It has obvious advantages in improving VAS scores (MD= -1.19,95%CI -1.19 [-1.87,-0.51],P = 0. 0006), but it has no obvious advantages in improving JOA scores(MD= 2.65 95%CI [0.06,5.24]),P=0.05). In terms of safety, Duhuo Jisheng decoction combined with manipulation treatment reported fewer adverse events. Conclusion: The Duhuo Jisheng decoction combined with manipulation treatment can effectively relieve the clinical symptoms of patients with lumbar disc herniation, with obvious clinical efficacy, and fewer adverse events. But in view of the limitations of clinical studies, there are some limitations in this study, and more studies with high quality of evidence are needed to further confirm its efficacy and safety.

1. Introduction

Lumbar disc herniation is a common spinal degenerative disease, and it is one of the important causes of low back pain or sciatica in patients[1, 2]. It has been reported that about 85% of patients with sciatica are associated with lumbar disc herniation [3]. The disease often occurs in young and middle-aged patients, with more men than women. Disc herniation at the L4 / 5 and L5 / S1 segments is more common, up to 90%[4-6]. With the advent of an aging society and the acceleration of the pace of daily life, the number of LDH patients is increasing year by year, bringing a heavy burden on people.

Although surgical technology is developing rapidly, it can effectively reduce the clinical symptoms of patients through the use of fixation, decompression, and fusion techniques. However, there are problems such as wound infection, complications, postoperative recurrence, and high costs [7, 8]. Studies have shown that the prevalence of recurrent lumbar disc herniation is 7 to 24% [9]. In 2017, the guidelines issued by the Rehabilitation Physician Branch of the Chinese Medical Association pointed out [6] that most patients can relieve clinical symptoms through conservative treatment, and only 10% -20% of patients need surgery. Therefore, non-surgical treatments such as spinal manipulation, oral Chinese medicine, acupuncture, and exercise therapy occupy an important position in the prevention and treatment of this disease. Manipulation has the advantages of simple operation and high reproducibility, and many studies at home and abroad have reported that it can effectively alleviate the clinical symptoms of LDH [10, 11]. Traditional Chinese medicine is a unique medical resource in China. The ancient classic recipes represented by Duhuo Jisheng Decoction are often used in the treatment of LDH [12]. Among 15 medicines such as Achyranthes bidentata and Achyranthes bidentata, it has the functions of removing wind and removing paralysis and nourishing liver and kidney. In recent years, the clinical research on the treatment of LDH using manipulation combined with Duhuo Jisheng Decoction has gradually increased, but the relevant evidence summary and systematic review are still lacking, which has limited the promotion and application of this method to a certain extent. Therefore, the purpose of this study is to systematically summarize the results of existing RCT trials using the research methods of evidence-based medicine, analyze the effectiveness and safety of this method in the treatment of LDH, and provide a certain basis and reference for the clinical application of this comprehensive therapy.

2. Materials and methods

2.1Literature search

We searched the eight databases of CNKI, VIP, WanFang, SinoMed, PubMed, Cochrane Library, Embase, and Web of Science. The search time is from the date when the database was established to June 2019. Chinese search terms use “Duhuo Jisheng Decoction”“Live parasitic Decoction”“Protrasion of the lumbar intervertebral disci”, English search terms use "Duhuo Jisheng", "Manipulation", "lumbar disc herniation", "LDH" Combined with the characteristics of each database, subject words and free words are searched together. Taking Weipu database as an example, the retrieval formula is as follows: (((Title or Keyword = Duhuo Parasitic Soup OR Title or Keyword = Duhuo Parasitic Formula) AND Title or Keyword = Technique) AND Title or Keyword = Lumbar Intervertebral Disc Protrusion) , Did not retrieve unpublished papers, etc.

2.2 Inclusion criteria

①The study type is a randomized controlled trial, and the study subject meets the diagnostic criteria for lumbar disc herniation and is treated with a conservative regimen; Intervention: The test group was treated with DuhuoJisheng Decoction combined with manipulation, or the control group was added with DuhuoJisheng Decoction combined with manipulation. The control group was conventional combined Western medicine treatment (non-steroidal anti-inflammatory drugs, neurotrophic drugs, traction, functional exercise) or commonly used proprietary Chinese medicines for the treatment of lumbar disc herniation, and the control group did not include DuhuoJisheng Decoction addition or manipulation treatment. The dose and duration of treatment in both groups are not limited. The methods mainly include lumbar spine manipulation methods or traditional Chinese medicine orthopedic massage methods, and the specific operation methods of the opponent methods are not limited. The primary outcome measure was total effectiveness, and the secondary outcome measures included the Japanese Orthopaedic Association (JOA) score, Visual Analogue Scale (VAS), and adverse events.

2.3 Exclusion criteria

Literatures with errors in data and inappropriate random methods; Literatures with incomplete data not available; Research objectives cannot reflect the literature on the treatment of lumbar intervertebral disc herniation with DuhuoJisheng Decoction combined with manipulation, and interventions include acupoint-oriented therapy, acupuncture, physical therapy, Moxibustion, other decoction treatments, or non-pharmacological treatments were excluded from the literature; duplicate data were retained for the first article only.

2.4 Data extraction and quality evaluation

Two researchers independently performed literature retrieval, screening, data extraction, and evaluation of literature quality. The reasons for the exclusion of the literature were carefully recorded during the literature screening. The data extraction mainly included the investigator's name, the publication year of the literature, the gender, age, and number of cases of the included patients, the intervention measures and observation indicators of the two groups. The study used the bias risk tool provided by the Cochrane Collaboration to evaluate the quality of the included literature. It mainly includes 7 items: Random sequence generation, Allocation concealment, Blinding of participants and personnel, Blinding of outcome assessment, Incomplete outcome data, Selective reporting, and Other bias. Each entry was evaluated from three levels of low risk, high risk, and uncertainty about bias. In the above research process, if there is a dispute on a certain issue or literature, it is determined through mutual discussion or inviting third-party researchers to discuss.

2.5 Statistical analysis

We will use RevMan software (V.5.3) provided by Cochrane Collaboration for data analysis. In view of the characteristics of the previously extracted data, for dichotomous data, we will express the results as a risk ratio (RR) with a 95% confidence intervals (CIs). For continuous data, the mean difference (MD) will be included in the meta-analysis. When I2≤50%, we will choose fixed effect model analysis; when I2＞50%, we will choose random effect model analysis. If the data cannot be analyzed quantitatively, we will perform a qualitative analysis of the data. According to the results of the study, if there are enough studies for the meta-analysis (n≥10), we will evaluate the reporting bias through funnel plots.

3. Results

3.1 Literature screening

A total of 427 articles were retrieved. NoteExpress software was used for document management. After preliminary screening and deduplication, 187 articles were obtained. After reading the title and abstract, 109 articles that were obviously irrelevant were excluded, and then 78 articles were downloaded in full. The criteria and exclusion criteria screened the full text for careful reading, further excluding 66 articles, and finally including 12 articles [13-24] that met the research requirements, all of which were Chinese documents. The screening flowchart is shown in Figure 1.

Fig. 1 Flow chart of literature screening

3.2 Basic information

The total number of cases included in the 12 studies was 1153, including 577 in the test group and 576 in the control group. The maximum sample size of the experimental group and the control group was 70 cases [22, 24], and the minimum sample size was 30 cases [13, 16]. The longest course of medication is 2 months [14], and the shortest is 2 weeks [13, 16, 17]. In terms of efficacy evaluation criteria, 6 studies refer to the “Traditional Chinese Medicine Diagnosis and Efficacy Standards” [16, 17, 19, 20, 22, 24] issued by the State Administration of Traditional Chinese Medicine, and 1 study refers to the “Guidelines for Clinical Research of Traditional Chinese Medicine”. In terms of intervention measures, 10 [13, 16-24] studies in the experimental group used DuhuoJisheng Decoction combined with manipulation, one [14] study used DuhuoJisheng Decoction combined with conventional Western medicine treatment, and one [15] research used DuhuoJisheng Decoction combined with Yaotongning Capsule for treatment. The interventions in the control group mainly included non-steroidal anti-inflammatory drugs [13, 17, 19, 20, 24], conventional Western medicine treatment [14, 16, 22], and the marketed proprietary Yaotongning capsules for the treatment of lumbar disc herniation [ 15, 18, 21, 23]. The main reporting indicators include total effectiveness, JOA score, VAS score, and occurrence of adverse events. Table 1.

3.3 Risk of bias

The Cochrane Collaboration's bias risk tool was used to evaluate the 12 studies included. Three [14, 17, 19] studies used random number tables to generate random sequences. The rest of the studies only mentioned the use of randomness without specifying randomization. the way. All studies did not mention the use of hidden random assignment sequences and blindness in implementation and outcome evaluation. One [21] study reported that the protocol was reviewed by the ethics committee, and the rest of the research did not mention the previous research protocol. Three [13, 22, 24] studies reported followup after treatment, and five [17-19, 21, 23] reported adverse events. It is unclear whether the included studies included selective publications and other biases. Figure 2.

Fig. 2 Percentage of included study that produced the risks of bias

3.4 Evaluation of treatment effect

3.4.1 Total Effectiveness

There are 10 [14-16, 18-24] studies reporting clinical effectiveness. A total of 1003 patients were included in 10 studies, including 502 in the test group and 501 in the control group. The 10 studies included had good homogeneity, and a fixed-effects model was used for meta-analysis (Heterogeneity: Chi2= 15.13, df = 9 (P = 0.09); I2= 41%). The results show that in terms of total effectiveness There is a significant statistical difference between the two groups (RR = 1.23, 95% CI [1.17, 1.29], P ＜0.00001). The combined treatment of Duhuozhitang Decoction and manual manipulation for lumbar disc herniation has obvious advantages in clinical efficacy. Figure 3.

Fig.3 Meta analysis for clinical efficiency(Duhuo Jisheng Decoction combined with manipulation)

A subgroup analysis was performed on the total effectiveness of 10 studies. Three of them [14, 16, 22] studied the intervention of the control group as conventional Western medicine treatment, and the three studies had good homogeneity. A meta-analysis was performed (Heterogeneity: Chi2= 0.16, df = 2 (P = 0.92), I2= 0%), and the difference between the two groups was statistically significant (RR = 1.34, 95% CI [1.20, 1.50], P ＜ 0.00001), indicating that the experimental group has a more obvious effect compared with conventional treatment; two of them [19, 24] study intervention measures are Duhuo Jisheng Decoction combined with non-steroidal anti-inflammatory drugs, and the study has better homogeneity (Heterogeneity: Chi2= 1.79, df = 1 (P = 0.18); I2= 44%), using a fixed-effects model to analyze, the results show that the total effectiveness of the experimental group is better than non-steroidal anti-inflammatory drugs (RR = 1.24 , 95% CI [1.12, 1.37], P ＜0.0001); 4 of them [15, 18, 21, 23] study intervention intervention using Yaotongning capsules, the two groups have better homogeneity (Heterogeneity : Chi2= 4.37, df = 3 (P = 0.22); I2= 31%), analyzed by fixed effect model, and treated with Yaotongning capsules Ratio, combined with a method of treating more significant effect (RR = 1.19,95% CI [1.10, 1.29], P ＜0.0001), Figure 4.

Fig. 4 Subgroup analysis of clinical efficiency

3.4.2 VAS scores

Five [13, 14, 17, 19, 22] studies reported the VAS pain scores. The number of cases in the test group and the control group was 248, and the five data had large heterogeneity (Heterogeneity: Tau2= 0.56; Chi2= 172.52, df = 4 (P ＜0.00001); I2= 98%), so the random effect model was used for analysis. The results show that Duhuo Jisheng Decoction combined with manipulation has obvious advantages in reducing VAS pain score (MD = -1.19, 95% CI -1.19 [-1.87, -0.51], P = 0.006), Figure 5

Fig.5 Meta analysis for VAS scores

3.4.3 JOA scores

Five [13, 15, 17, 20, 22] studies reported JOA scores, but one of them [17] studied the data description problem and was not included in the analysis. Four studies have greater heterogeneity (Heterogeneity: Tau2= 6.62; Chi2= 102.64, df = 3 (P ＜0.00001); I2= 97%). The analysis was performed using a random effects model, and the results showed that Duhuotang Decoction combined with manual therapy There was no significant difference in the JOA score of the improved patients (MD = 2.65 95% CI [0.06, 5.24]), P = 0.05), Figure 6

Fig. 6 Meta analysis for JOA scores

3.4.4 Recurrence rate and adverse events

Two [22, 24] studies reported recurrence within 1 year after treatment, of which one [22] study reported relapses in the test group and 14 in the control group. Another [24] study reported 3 cases of relapse in the experimental group and 11 cases in the control group. Both studies showed that the recurrence rate in the experimental group was significantly lower than that in the control group (P ＜0.05); One [18] study reported one case of drug-induced rash in the experimental group, and three cases of dizziness, two cases of diarrhea, and four drug-induced rashes in the control group; one [19] study showed nine adverse events in the experimental group There were 26 adverse events in the control group; one [21] study showed that 2 patients had diarrhea in the experimental group, 5 had drug-induced rashes in the control group, 3 had dizziness, and 6 had diarrhea; 1 [23] study showed that the experimental group Diarrhea occurred in 2 cases, dizziness occurred in 3 cases in the control group, 5 cases of diarrhea, and 3 cases of drug-derived dermatitis. There were fewer adverse events in the test group than in the control group. Only one [17] study showed that after two weeks of treatment, the liver and kidney function tests were normal in both groups, and no adverse events were found.

3.5 Publication Bias

The total effective rate of the included studies ≥ 10 was analyzed for publication bias. The asymmetry of the figures on the two sides from the funnel chart indicates that there is a greater possibility of publication bias. This may be due to the low quality of the included literature and the large number of small sample studies , Negative research results not published and other reasons. Figure 7.

Fig.7 Total effective rate of funnel plot

4. Discussion

Lumbar disc herniation is a common disease in lumbar degenerative diseases. It has the characteristics of diversified clinical manifestations, recurrent attacks, and difficult to heal, which has brought great trouble to patients' lives [6, 25]. Its pathogenesis is very complicated, and research suggests that it is mainly related to mechanical stress, chemical nerve root inflammation, autoimmunity, biomechanics and other reasons [26, 27]. Manipulation and traditional Chinese medicine are the distinctive treatments currently used in conservative treatment. The main method is to relax the lumbar and back muscles, adjust the disorders of the small joints, and adjust the stress distribution, so as to reduce the mechanical compression and stimulation of the intervertebral disc on the local nerve roots, thereby alleviating the clinical symptoms. Mcmorland G [28] and others confirmed in a RCT study comparing the technique with minimally invasive surgery for lumbar disc herniation that the technique can achieve the same treatment effect as minimally invasive surgery. Duhuo Jisheng Decoction is one of the classic effective prescriptions for treating lumbar disc herniation[29]. Xu Ming [30] showed that Duhuo Shengtang Decoction can significantly improve the efficacy of patients with lumbar disc herniation and improve their ODI function score. The experiment found that Duhuozhitang Decoction has pharmacological effects such as analgesia, anti-inflammatory and regulating immune function. It can affect the degeneration of intervertebral disc tissue by regulating the release of inflammatory mediators and signal pathways such as p38 [31-33]. At present, more and more clinical studies have used Duhuo JishengDecoction combined with manipulation to treat lumbar disc herniation, and have achieved good clinical results, but there is still no systematic summary and evaluation.

From the perspective of the quality of the literature, out of the 12 studies included in this study, only 3 of the research reports used the random number table method, and the remaining 9 studies only mentioned random words. All studies were not clear about the allocation of hidden sequences and blindness. Implementation of the law. All studies did not mention research protocols and registration of clinical trials, and only one [21] study showed that the protocol passed the review of the hospital ethics committee. All of these may affect the reliability of the research conclusions. From the perspective of the design of the study, the outcome indicators selected for the included studies are commonly used indicators of efficacy judgment, such as total effectiveness, JOA score, and VAS score. Three studies compared DuhuoJisheng Decoction combined with conventional treatment, 5 studies compared DuhuoJisheng Decoction combined with non-steroidal anti-inflammatory drugs, 4 studies compared with the marketed proprietary Yaotongning Capsule, but the intervention Measures to market proprietary Chinese medicines may reduce the internal authenticity of the study. After meta-analysis of 10 original studies, it was found that the total effective rate of DuhuoJisheng Decoction combined with manipulation for lumbar disc herniation was significantly better than that of the control group. Subgroup analysis found that it also had significant effects compared with conventional treatment, non-steroidal anti-inflammatory drugs, and Yaotongning capsule treatment, but increased heterogeneity when compared with non-steroidal anti-inflammatory drugs, which may be Because the original study used different types of NSAIDs. However, the total effective rate in the outcome index selected by the study is a composite index. Therefore, in the future research, the efficacy should be judged according to the uniform efficacy standard. In addition, it has obvious advantages in improving the pain VAS score of patients, but the JOA score is not significantly improved, which may be limited by the quality of the original research and needs to be further studied in the future. In terms of safety, fewer adverse events occurred in the experimental group than in the control group, but researchers should also strengthen the management of adverse events / responses throughout the process, including the number of cases, duration, severity, measures and outcomes. Detailed records and reports with objective and real data.

In view of the limitation of the quality of the included literature, this study still has certain limitations: Firstly, the methodological quality of the included studies is low and there are problems with inconsistent reporting standards, so the results may be biased; Secondly, the DuhuoJisheng Decoction and manipulation are two different intervention methods, so they cannot truly reflect the treatment effect of a single treatment method. Third, in terms of intervention measures, the intervention methods of the control group are not exactly the same, which may cause greater heterogeneity. The test group's DuhuoJisheng Decoction is more suitable for patients with liver and kidney deficiency type, but the syndrome factors included in the study were not considered. In addition, it has not standardized the specific operation method of the opponent method, which may have an impact on the research results. Fourth, according to the total effective funnel chart, it is found to have an asymmetric distribution, and this study may have publication bias.

In summary, this study is based on clinical issues and based on existing research data and methods, it has been demonstrated that DuhuoJisheng Decoction combined with manipulation has a good clinical effect in treating lumbar disc herniation with fewer adverse events. However, there are still some limitations in the study. The existing level of evidence is low, and the results obtained are only used as a hint for clinical diagnosis and treatment. In the future, researchers still need to follow the basic principles of clinical research design, fully consider the commonality and personality of traditional Chinese medicine research, strengthen the scientific and reasonable top-level design of research schemes [34, 35], and register the research schemes in time [36], RCT The test report should be based on the requirements of CONSORT [37] to further improve the quality of the evidence of the original research and make the conclusions more standardized.