Recommended methods for professional cure constipation

 

Recommended methods for professional cure constipation

1. Lifestyle adjustments such as increasing dietary fiber and water intake and increasing exercise are the basic treatment measures for chronic constipation. Recommended level: highly recommended.

Chronic constipation is related to the reduction of dietary fiber and fluid intake [69]. Many chronic constipation guidelines and (or) consensus around the world all regard increasing dietary fiber and drinking water as the basic treatment measures for chronic constipation [20,55,70,71 ,72,73,74]. Dietary fiber has an anti-hydrolysis effect on certain enzymes in the small intestine, and will not be absorbed by the colon, so it can retain water in the intestinal lumen and increase stool volume. A number of studies have confirmed that increasing dietary fiber can improve the spectrum of constipation symptoms, including bowel frequency, stool characteristics, bowel pain and colon transit time [75,76,77,78]. The recommended intake of dietary fiber is 20～35 g/d [20,55,70,71,72,73,74], and it is recommended to use soluble dietary fiber[20,75,78]; is there any non-soluble fiber The laxative effect is still controversial, but it should be noted that the increase in dietary fiber in some patients with constipation may aggravate discomfort such as abdominal distension, abdominal pain, and bowel, which is caused by the increased production of intestinal gas due to increased dietary fiber [78,79]. Studies believe that unless the patient is dehydrated, increasing the amount of water consumed will not affect colorectal function and relieve constipation; however, intake of 2 L of water per day will enhance the laxative effect of dietary fiber [80], so a number of constipation guidelines recommend water intake The input volume is 1.5～2.0 L/d[55,70,71]. Regular physical exercise can shorten the intestinal transit time and facilitate laxative. Aerobic exercises such as walking and cycling are effective in improving constipation [70,72,79]. In addition to exercise restriction, there are no strict restrictions on the frequency and extent of constipation patients’ participation in other sports events. Generally, the recommended amount of exercise is 30-60 min/d, at least 2 times/week[55,70,72]. Appropriately increasing the amount of exercise may be more effective for less daily exercise or elderly patients with constipation [70,72,81].

2. Patients with chronic constipation need to establish good bowel habits. Recommended level: highly recommended.

The rising reflex in the morning can promote colon movement and help produce bowel movements. The survey shows that most people’s bowel behavior is in the morning, men generally between 7:00 and 8:00 in the morning, women are about 1 hour later than men [82]. In addition, gastric antrum expansion after a meal, gastric colon reflex and duodenal colon reflex induced by food entering the duodenum can promote colonic peristalsis and produce defecation reflex, which is conducive to successful defecation. Therefore, it is recommended that patients with constipation wake up in the morning And try to defecate within 2 hours after meal. Concentrate when going to the toilet to defecate, avoid being disturbed by factors unrelated to defecation, and develop good defecation habits [55,72,83,84,85]. Studies have confirmed that compared with the sitting position, there is no significant increase in abdominal pressure in the squatting position, and the puborectalis muscle relaxes at this time, and the rectal anal angle during defecation becomes larger (larger than normal sitting position, 126° vs. 100°, P<0.05) , The rectal lumen becomes straight, and the rectal strain required for defecation is small, which is conducive to the discharge of feces[86]; squatting position can shorten the time of defecation, improve the effort of defecation, and improve the satisfaction of patients with defecation[72,87,88,89 ]. Therefore, it is recommended that patients with constipation adopt a squatting defecation posture.

3. Volumetric laxatives and osmotic laxatives are mainly used for patients with mild to moderate constipation. Recommended level: highly recommended.

Volumetric laxatives play a laxative effect by retaining water in the feces, increasing the water content and volume of the feces. Commonly used drugs include psyllium, calcium polycarbophil and wheat bran [55]. The results of the study show that volumetric laxatives are more effective than placebo in alleviating the overall symptoms of chronic constipation patients (remission rate 86.5% vs. 47.4%) and defecation effort (remission rate 55.6% vs. 28.6%), which can increase Complete spontaneous bowel movement (CSBM) times per week (3.9 times vs. 2.9 times), reduce the number of days between bowel movements [75]. The results of a number of clinical studies around the world have shown that taking psyllium can improve the frequency of bowel movements in patients with chronic constipation, and there is no statistically significant difference in adverse drug reactions from the control group, but there is still controversy in improving stool characteristics and intestinal transit time [ 76,90,91,92]. Polycarbophil calcium forms a hydrophilic gel in the intestinal tract, which participates in the formation of stool, making the stool bulky and soft and easy to discharge. The drug is not absorbed in the digestive tract. It is safe for long-term use and helps patients establish good bowel habits [ 93,94,95]. Potential adverse effects of volumetric laxatives include abdominal distension, esophageal obstruction, colonic obstruction, and malabsorption of calcium and iron. Therefore, it is recommended that patients with chronic constipation should drink enough water while taking volumetric laxatives [96].

Osmotic laxatives can form a hypertonic state in the intestine, absorb water, increase stool volume, and stimulate intestinal peristalsis, mainly including polyethylene glycol and unabsorbed sugars (such as lactulose) [55]. A number of large randomized, double-blind, placebo-controlled studies have confirmed that electrolyte-rich polyethylene glycol or electrolyte-free polyethylene glycol is effective in improving weekly bowel frequency, stool characteristics, and constipation-related symptoms. Significantly better than other treatment groups, and its adverse reactions are more acceptable, better tolerated, and easier to control [97,98,99]. The meta-analysis found that polyethylene glycol can increase the number of CSBMs in patients (defecation frequency is 1.98 times/week, P=0.000 3) [100]. Serious adverse reactions of polyethylene glycol are rare and have been recommended by many international guidelines and consensus opinions for the long-term treatment of patients with chronic constipation [20,74,101,102]. Lactulose can be metabolized into lactic acid and acetic acid in the colon to promote the growth of physiological bacteria. At the same time, these relatively low molecular weight organic acids can increase the osmotic pressure in the intestinal cavity, thereby improving the frequency of bowel movements and stool characteristics in patients with chronic constipation. No potential serious adverse reactions were found in patients who received lactulose treatment for more than 4 weeks, suggesting that long-term use of the drug is safe and well tolerated [103,104].

4. As a remedy, stimulant laxatives can be used short-term and intermittently. Recommended level: highly recommended.

Stimulant laxatives (including bisacodyl, phenolphthalein, anthraquinone drugs and castor oil, etc.) act on the enteric nervous system to enhance intestinal motility and stimulate intestinal secretion. The results of a number of randomized, placebo-controlled trials have shown that irritant laxatives such as bisacodyl and sodium picosulfate can increase the number of CSBMs per week in patients with chronic constipation, improve stool characteristics and relieve constipation-related symptoms [105,106]. The meta-analysis found that stimulant laxatives have a good effect on chronic idiopathic constipation (CIC) [relative risk (RR) = 0.54, 95% CI 0.42～0.69], but they need to be taken Patients treated with stimulant laxatives have an increased risk of serious adverse reactions (OR=3.0, 95%CI 2.0～3.5) [107]. Long-term use of stimulant laxatives is prone to drug dependence, malabsorption and electrolyte disturbances, and can also damage the patient’s enteric nervous system, resulting in weakened colonic motility and even melanosis of the colon. A retrospective cohort study found that 34.7% of melanosis patients had at least one adenoma detected, compared with 26.5% in the control group (OR=1.52, 95%CI 1.04-2.24, P=0.03) [108 ]. Therefore, short-term, intermittent use of irritant laxatives is recommended.

5. Guanylyl cyclase-C (guanylyl cyclase-C, GC-C) agonists can improve the symptoms of abdominal pain and constipation in patients with chronic constipation. Recommended level: recommended.

Linaclotide is a 14-amino acid peptide that can bind to and activate the GC-C receptor of intestinal epithelial cells, and significantly increase the intracellular and extracellular cyclic guanosine monophosphate (cGMP) concentration. CGMP activates cystic fibrosis transmembrane conductance regulator (CFTR), which increases the secretion of chloride and bicarbonate and accelerates intestinal peristalsis. Part of cGMP is released into the serosal layer, which can also reduce the intestine. Sensitivity of inner pain peripheral nerves [109]. Phase III clinical trials have confirmed the effectiveness and safety of Linaclotide in patients with chronic constipation. A study included 1 272 patients with chronic constipation, who were randomly divided into placebo group, linaclotide 145 μg/d group or linaclotide 290 μg/d group. After 12 weeks of treatment, the proportion of patients in the linaclotide treatment group who reached the primary endpoint (the number of CSBMs ≥3 times per week, and the number of CSBMs increased by ≥1 times from baseline in at least 9 weeks in 12 weeks) was significantly higher than that in the placebo group . In this study, patients in the linaclotide group of 145 μg/d increased the number of CSBMs by an average of 1.9 and 2.0 times per week, respectively, and patients in the linaclotide group of 290 μg/d increased the number of CSBMs by an average of 2.0 and 2.7 times per week, respectively. Linaclotide can also significantly increase the number of spontaneous bowel movements per week, improve bowel effort and stool characteristics, and can effectively relieve abdominal discomfort such as bloating. Compared with the placebo group, Linaclotide can significantly improve patient satisfaction with treatment and disease-related quality of life. Linaclotide can improve constipation symptoms within the first day of taking the medicine. Compared with placebo, the most common adverse reaction of linaclotide is diarrhea, mostly mild to moderate [110]. Two multicenter, randomized, double-blind, placebo-controlled studies evaluated the effectiveness and safety of IBS-C patients taking 290 μg linaclotide daily for 12 and 26 weeks, and found that linaclotide can significantly increase IBS -C patients with CSBM frequency, improve abdominal discomfort such as abdominal pain and bloating [111,112]. A phase 3 clinical study of linaclotide has been completed in Chinese patients. The results show that taking 290 μg of linaclotide every day can effectively improve the bowel habits, abdominal symptoms and general symptoms of IBS-C patients, and the safety is good [ 113]. In summary, the GC-C agonist Linaclotide can significantly increase the number of CSBMs in patients with chronic constipation, improve bowel movements, stool characteristics, etc., and can effectively relieve abdominal discomfort such as abdominal pain and bloating, and significantly improve the quality of life of patients. Linaclotide is mainly metabolized in the gastrointestinal tract. Linaclotide and its metabolites are rarely absorbed into the blood circulation, and it does not inhibit common drug transporters and metabolic enzymes, so it hardly interacts or interferes with other drugs. Absorption and metabolism of other drugs.

The US FDA approved linaclotide for the treatment of adult CIC and IBS-C in 2012. The 2014 guidelines of the American College of Gastroenterology recommended linaclotide for the treatment of CIC and IBS-C (strong recommendation, high level of evidence) [114]. my country has also approved linaclotide for the treatment of IBS-C.

6. Highly selective 5-hydroxytryptamine 4 (5-hydroxytryptamine 4, 5-HT4) receptor agonists can shorten colonic transit time and increase the number of bowel movements in patients. Recommended level: recommended.

Procapride is a derivative of benzofuran carboxamide compounds. It is a highly selective and high-affinity 5-HT4 receptor agonist. After binding to 5-HT4 receptors in the intestinal myenteric plexus, It can increase the release of cholinergic neurotransmitters, stimulate the colon to produce high-amplitude propulsive contractions, and accelerate gastric emptying, small intestinal transit and colonic transit in constipated patients without anorectal dysfunction [115]. A number of foreign studies have shown that taking 2 mg of prucalopride a day is significantly better than the placebo group in terms of the number of bowel movements, stool characteristics, overall symptoms and quality of life in patients with chronic constipation, and the effect can be as long as 18 months. And it is safe and well tolerated [116,117,118]. Three key European and American studies found that 43.1% of IBS-C patients who received 2 mg of prucalopride daily increased SCBM at least once a week, compared with 24.6% in the placebo group (P<0.001 ); Pracapride also has a significant improvement in treatment satisfaction. The proportion of patients with satisfaction improvement ≥ 1 point in the treatment group and placebo group was 44.0% and 22.2% (P<0.001) [119,120,121]. An Asia-Pacific multi-center, randomized, placebo-controlled Phase 3 clinical study systematically evaluated the efficacy and safety of prucalopride in patients with chronic constipation in Asia-Pacific, and found that 501 patients with chronic constipation were receiving prucalopride 2 During the 12-week treatment with mg or placebo (once a day), prucalopride can significantly improve the patient’s intestinal function and relieve the patient’s constipation symptoms, and the effect is particularly significant during the first week of treatment; The treatment cycles maintained better efficacy than placebo. 33.3% of patients with chronic constipation achieved CSBM frequency ≥3 times/week after drug treatment (the proportion in the placebo group was 10.3%), and 86.4% of patients with chronic constipation could benefit from it Benefit (at least one more spontaneous bowel movement per week) [122]. A domestic multi-center, randomized, double-blind, and placebo-controlled phase 3 clinical study of prucalopride was conducted. The results found that at 12 weeks of treatment, the proportion of patients in the prucalopride group with an average number of CSBMs ≥3 times per week was 39.4%, significantly higher than 12.7% in the placebo group. At 4 weeks of treatment, the proportion of patients in the prucalopride group with an average number of CSBMs ≥3 times per week was 40.0%, which was significantly higher than the 13.3% in the placebo group [123]. The US FDA and European Medicines Agency (European Medicines Agency, EMA) have approved the use of procuracarb for the treatment of chronic primary constipation in adult patients. The recommended dose in many countries is 2 mg/d for adults and 1 mg for the elderly. /d. The main adverse reactions of prucalopride include nausea, diarrhea, abdominal pain and headache. Procapride is recommended for patients whose symptoms of constipation cannot be improved by conventional laxatives. When taking Procapride for 4 weeks and still has no effect, it is necessary to reassess the patient’s condition and whether to continue taking the drug.

 

7. Chloride channel activators can promote intestinal epithelial secretion and increase the number of spontaneous bowel movements in patients. Recommended level: recommended.

Lubiprostone is a bicyclic fatty acid prostaglandin E1 derivative, which can selectively activate the type 2 chloride channel located in the apical membrane of intestinal epithelial cells, promote the secretion of chloride ions from intestinal epithelial cells into the intestinal lumen, and increase the secretion of intestinal juice. Loosen the stool, thereby speeding up the frequency of defecation, changing the characteristics of the stool, reducing the strain of defecation, and alleviating the overall symptoms of defecation [124]. A number of foreign studies have confirmed that lubiprostone can significantly increase the number of spontaneous bowel movements in patients with chronic constipation, and has a dose-response effect on chronic constipation (the dosage is 24 to 72 μg/d); compared with the placebo group, oral Lubiprostone Ketone 24 μg/d, the frequency of spontaneous bowel movements after 1 week was 5.69 times/week, which was significantly higher than 3.46 times/week in the placebo group (P=0.000 1) [125,126,127]. An open study showed that 127 patients with CIC had extended medication for 48 weeks, with good tolerance and continuous improvement in intestinal symptoms [128]. Another study showed that taking lubiprostone had more CSBM times in the first week than placebo; within 24 hours of the initial dose, lubiprostone had a higher CSBM frequency than placebo [129 ]. Animal and human tissue studies have shown that lubiprostone can reverse the inhibition of morphine on mucosal secretion and can effectively treat constipation caused by morphine [130,131,132,133]. In addition, the overall curative effect of oral lubiprostone 8 μg/time and 2 times/d in IBS-C patients is better than placebo, which can significantly accelerate the frequency of spontaneous bowel movements and improve abdominal pain symptoms in IBS-C patients, and the curative effect can last 9-13 Months, and the safety and tolerance are good [134]. In 2006, the US FDA approved the listing of lubiprostone. It is recommended for the treatment of CIC at a dose of 24 μg/time, 2 times/d. Subsequently, in 2008, the US FDA approved it for use in female IBS-C patients over 18 years old, with a dose of 8 μg/time, 2 times/d. In terms of adverse drug reactions, lubiprostone is mainly manifested as nausea, diarrhea, abdominal distension, abdominal pain and headache.

8. Probiotics can be used as one of the treatment options for patients with chronic constipation. Recommended level: recommended.

Existing research data confirm that patients with chronic constipation have intestinal microecological imbalance. Foreign studies have shown that the number of dominant bacterial groups such as Bifidobacterium, Lactobacillus, Bacteroides, Streptococcus faecalis, Clostridium, etc. in the stools of healthy adults with chronic constipation has been significantly reduced. The number of potential pathogenic bacteria such as Staphylococcus aureus, Enterobacteriaceae (Citrobacter, Klebsiella, etc.) and fungi has increased significantly, and this trend is related to the severity of constipation [135]. Domestic scholars have found that chronic constipation patients also have intestinal microecological imbalance, which is manifested as a significant decrease in Bifidobacterium, Bacteroides, and Lactobacillus in the stool of patients with constipation, and a significant increase in Fusobacterium and Enterobacter[136]; refractory constipation The species richness and Shannon diversity index of the colonic mucosa of the patients were significantly lower than those of the healthy control group [137].

At present, the relationship between intestinal microecological imbalance and chronic constipation is not yet fully understood. The possible mechanisms include excessive retention of feces in the intestine, changing the number and types of intestinal flora; the metabolites of the flora (methane and short-chain fatty acids) ), the cellular components of bacteria (lipopolysaccharide) or the interaction between bacteria and the host immune system affect a variety of intestinal functions. Although microecological preparations are not the first-line drugs for the treatment of chronic constipation, they can promote the recovery of intestinal peristalsis and gastrointestinal motility by regulating the imbalance of intestinal flora. More and more researchers recommend them as long-term adjuvant drugs for chronic constipation. Microecological preparations can be divided into three categories: probiotics, prebiotics and synbiotics. Fecal bacteria transplantation treatment also belongs to intestinal microecological treatment in a broad sense.

Probiotics refer to living microorganisms that can have a beneficial effect on the host after ingested in sufficient quantities. The probiotics commonly used to treat chronic constipation are mainly Bifidobacterium and Lactobacillus. A systematic review of 377 patients included in 5 randomized controlled trials showed that Bifidobacterium lactis, Lactobacillus casei and Escherichia coli can relieve chronic constipation in adults, and Lactobacillus casei can relieve chronic constipation in children Symptoms of constipation [138]. Another systematic review of 8 foreign literatures showed that after 2 weeks of ingestion of probiotics, the number of bowel movements per week increased by 1.49 times compared with the baseline (99%CI1.02～1.96, P<0.01)[139]. Many domestic scholars used their own control method and found that the total score of constipation-related symptoms and the total score of fecal traits were significantly reduced after using probiotics for about 1 month [140,141]. The possible mechanism of probiotics to improve the symptoms of constipation: correct microecological disorders, stimulate the nerves of the intestinal wall, change the secretory function of the intestinal cavity, and promote the recovery of intestinal motility.

Prebiotics are fermentable foods that are not digested and absorbed by the host, but can selectively stimulate the growth and reproduction of one or several types of bacteria in the intestinal tract. There are few studies on prebiotics and chronic constipation. A randomized controlled clinical trial showed that after 3 weeks of supplementing with inulin or partially hydrolyzed guar gum mixture to female patients with chronic constipation, the number of bowel movements per week increased, but the difference was not statistically significant with the placebo group[ 142].

Synbiotics are preparations that contain both probiotics and prebiotics. Some studies have applied synbiotic preparations (Plantaria fiber and 5 kinds of probiotics, all belonging to the genus Bifidobacterium and Lactobacillus) to treat patients with chronic constipation after 8 weeks, the patient’s stool characteristics returned to normal levels, and the intestinal transit time was significantly shortened [ 143]. A randomized, double-blind, placebo-controlled clinical trial showed that constipation patients taking a synbiotic preparation containing fructooligosaccharide, bifidobacteria, and lactobacillus for 30 days can significantly increase the number of bowel movements per week, resulting in laborious defecation and incomplete defecation Sensation and fecal traits have also been improved [144].

The application of microecological agents to regulate the intestinal flora can partially relieve the symptoms of constipation. Foreign guidelines and consensus opinions recommend it as one of the treatment options for patients with chronic constipation, but the specific treatment mechanism is still unclear. It is still difficult to draw conclusive opinions on how to choose the appropriate probiotics and the dosage, combination and treatment of the probiotics.

Fecal bacteria transplantation is the transplantation of the flora from the feces of healthy people into the gastrointestinal tract of the patient to rebuild the intestinal flora with normal functions. In recent years, studies have found that the frequency of defecation in STC patients after fecal bacteria transplantation is significantly increased, and the symptom relief rate can reach 71.4% at 4 weeks, but the symptom relief rate at 12 weeks is only 42.9% [145,146]. Fecal bacteria transplantation in the treatment of chronic constipation still has many issues to be studied, such as donor selection, transplant dosage, transplant frequency, etc., and because transplanting other people’s feces has certain risks, such as spreading viruses and pathogenic bacteria in the donor’s body, etc. . In view of this, the treatment of chronic constipation with fecal bacteria transplantation is currently limited to research and should not be used as a routine method for clinical treatment.

9. Chinese medicine has a certain effect on improving the symptoms of chronic constipation. Recommended level: recommended.

A randomized, double-blind, placebo-controlled study on the treatment of chronic constipation with traditional Chinese medicine found that traditional Chinese medicine (including proprietary Chinese medicine preparations and decoctions) can effectively relieve the symptoms of chronic constipation and increase the number of patients with CSBM per week. The safety is similar to that of placebo[147,148 ]. Several meta-analyses have also confirmed this, but the evaluation of its efficacy still needs more evidence-based medical evidence [149,150]. The acupuncture points most commonly used for constipation treatment are Tianshu, Zusanli and Shangjuxu. A number of studies have shown that acupuncture can effectively treat chronic constipation, increase the frequency of bowel movements, improve accompanying symptoms, relieve anxiety and depression, and improve the quality of life of patients [151,152,153]. Massage can promote gastrointestinal peristalsis, stimulate the vagus nerve, promote local blood circulation, etc., and help improve the symptoms of constipation [154,155,156]. Therefore, although traditional Chinese medicine, acupuncture and massage have shown certain clinical efficacy in the treatment of chronic constipation, they still need to be confirmed by large samples and higher-quality studies.

10. Biofeedback therapy is the preferred treatment for patients with functional defecation disorders. Recommended level: recommended.

Biofeedback therapy is a behavioral regulation therapy. When the patient simulates defecation, the abdominal wall electrodes and anorectal baroreceptors can sense and show the patient the state of the muscles of the abdominal wall, rectum, and anal canal, so that the patient can self-regulate and correct uncoordinated defecation. With force, the patient is trained to coordinate the abdominal and pelvic floor muscles to restore normal bowel movements. In the past 10 years, a number of domestic and foreign constipation guidelines or consensus have recommended biofeedback as the preferred treatment for patients with functional defecation disorders [20,55,70,71,74,75]. Many studies have shown that regardless of whether functional defecation disorders are combined with slow intestinal transit, the efficacy of biofeedback is higher than most other therapies [157]. Biofeedback can improve the number of bowel movements, pelvic floor dysfunction, balloon expulsion time, colon transit time in patients with functional defecation disorders, and its curative effect is better than diet, exercise, laxative and other treatment methods [158], and the curative effect can be maintained More than 2 years [159]. Part of the data of Chinese patients with constipation shows that the effective rate of patients with functional defecation disorder after 1 to 6 years after biofeedback treatment is 70.7% [160]. Biofeedback also has a good effect on STC and NTC patients [161], but it is weaker than its effect on patients with functional defecation disorders [162], so it can be used as one of the combined treatment methods for mixed constipation [157 ].

The current clinically used biofeedback methods are mainly divided into abdominal wall myoelectric biofeedback and pressure biofeedback according to different instruments. Abdominal wall myoelectric biofeedback is more widely used, and there is still a lack of large sample data results for the comparison of the efficacy of the two methods. According to the different training places, it is divided into medical institution training and family training. When training in a medical institution, the patient completes each training in a specific treatment place in the hospital under the guidance of medical staff. Home training refers to patients who have received formal treatment training in the hospital and then go home to apply portable biofeedback treatment devices for self-training. Recent studies have shown that family training has similar effects on the recovery of intestinal symptoms and physiological functions of patients with hospital training, but family training has expanded the availability and use of biofeedback therapy [163]. There is no uniform standard for the frequency, single training time, and treatment course of using biofeedback to treat constipation, and there are differences between studies. According to most research methods, some researchers recommend that the frequency of biofeedback treatment is 2 times a week to once every other day, every 30-60 minutes, and each patient completes at least 4-6 times [164,165,166,167].

11. Sacral nerve stimulation can be used for refractory constipation that is ineffective in conventional medical treatment. Recommended level: recommended.

Sacral nerve stimulation, also known as sacral nerve regulation, is one of the neuromodulation treatment methods [168,169,170]. In 2015, the consensus opinions of the American and European Society of Neurogastroenterology and Kinetics and the 2016 Rome IV standard recommended the use of sacral nerve stimulation for refractory constipation that is ineffective in conventional medical treatment [72,171,172]. The exact mechanism of sacral nerve stimulation in the treatment of chronic constipation is still under discussion, but most studies believe that sacral nerve stimulation can regulate the afferent nerves of the vagus and somatic nerves, improve intestinal sensory and motor functions, and affect the pelvic floor organs and lower intestinal segments (mainly Affect the left half of the transverse colon, descending colon and rectum anal canal), promote defecation [172]. The process of sacral nerve stimulation includes two stages: the first stage is a temporary electrode implantation (or called experimental electrode implantation) stage, in which an external regulator is used to test and adjust patients with effective treatment of constipation; the second stage is permanent In the stage of sexual implantation, for patients whose treatment is effective (after a 2- to 3-week screening period, constipation symptoms are improved by more than 50%), a permanent sacral neuromodulator can be implanted [171]. The sacral nerve roots between S2 and S4 are generally selected as the stimulation site [173,174]. The stimulation parameters used in most studies are pulse width 210 μs, frequency 10-15 Hz [175,176], and usually take effect in 2 to 4 weeks [72,171].

The results of the meta-analysis showed that the overall response rate of sacral nerve stimulation for constipation was 56.9%, the overall long-term effective rate was 40.1%, and the long-term effective rate after permanent stimulator implantation was 73.2%. The average follow-up was 31 months. The removal rate of the instrument was 8% to 23%[177], mainly due to adverse reactions and withdrawal of consent by patients. A retrospective study included 61 patients with chronic constipation, 42 of whom were implanted with permanent sacral nerve stimulators (14 STC, 15 constipation with defecation disorder, 13 with mixed constipation), followed up for (51±15) months . The results showed that the patient’s Cleveland constipation score decreased from (17±6) at baseline to (9±6) after implantation of a permanent sacral nerve stimulator (P<0.001); among them, the curative effect of patients with constipation with defecation disorders Significantly more than STC, as measured by the Cleveland constipation score reduced by more than 50%, 60% of patients with dysfunctional constipation and 19% of STC patients reached the standard [178]. Sacral nerve stimulation mainly has complications such as local infection, electrode displacement, and pain at the stimulation site. So far, no life-threatening or irreversible adverse events have been found. A study reported that of 44 patients in the interim treatment stage, 8 had grade 1 complications (electrode site pain, rectal bleeding, urinary retention, abdominal pain, anxiety, lead breakage, and stimulator failure), and 4 had grade 2 complications Complications (increased cramps, increased constipation, hyperglycemia and allergic reactions); out of 15 patients implanted with permanent stimulators, 5 adverse events were recorded, 3 of which were grade 2 (occurrence of superficial infection, hyperglycemia and irritation sites) Pain: 1 case each), 2 cases were grade 3 (1 case each due to severe infection removal of the stimulator and repair surgery) [179]. Severe complications in sacral nerve stimulation require surgical treatment. A retrospective study found that 28.8% (36/125) of the patients who were followed up for 1 to 99 months required surgical treatment. The indications for patients who required surgical treatment included lead injury, intolerable pain, and loss of sacral nerve stimulation. [180].

In addition, acupoint electroacupuncture, rectal and (or) colon electrical stimulation, tibial nerve stimulation, abdominal body surface electrical stimulation and other neuromodulation treatments may all improve the symptoms of constipation, but more evidence-based evidence needs to be improved, and it can be used as a supplement to constipation. Treatment method [72,102,181,182,183,184].