Consensus Recommendations For The Treatment Of Chronic Constipation

Chronic constipation can be divided into primary (or idiopathic, functional) and secondary (secondary to organic diseases or caused by drugs), and the former is mainly discussed here. Constipation is a global problem, and its management is also the focus of clinical work. So what are the "similar views" and what are the "local characteristics" in the guidelines consensus on the treatment of chronic constipation at home and abroad?

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Burden of disease with chronic constipation

Chronic constipation is one of the most common digestive system diseases. According to foreign reports, the prevalence of functional constipation in adults is 14% [3], women are higher than men, and the elderly are higher than young people. The latest meta-analysis in my country shows that the overall prevalence of chronic constipation among Chinese adults is 10.9%, and it is increasing year by year [4].

Functional constipation refers to constipation caused by secondary factors, which is caused by a variety of pathophysiological mechanisms, including intestinal motility disorder, intestinal secretion disorder, changes in visceral sensitivity, pelvic floor muscle dysfunction and enteric nervous system Constipation caused by dysfunction can be divided into normal transit type (NTC), slow transit type (STC), defecation disorder type, and mixed type [1,2], with NTC type being the most common. However, there are overlaps and crossovers between different subtypes of constipation, and transitions may occur in different periods.

Patients with chronic functional constipation are often accompanied by other functional gastrointestinal diseases and have an increased risk of anxiety, depression, obsessive-compulsive disorder, and other psychological disorders. Some patients have unsatisfactory treatment effects, recurrent illnesses, and significant adverse effects on their quality of life. At the same time, chronic constipation also brings a heavy burden to the medical system.

The treatment of chronic constipation leads to the same goal: step-by-step and cascade

When the diagnosis of chronic functional constipation is confirmed and the patient has no alarm symptoms, the current consensus guidelines in various regions follow similar treatment principles and strategies.

A major feature of chronic functional constipation is that family self-medication accounts for a large proportion. Most patients have already adjusted their diet or purchased over-the-counter drug treatment before seeking help from a doctor, and they seek prescription drug treatment after the effect is not good. This "traditional" process is exactly in line with the chronic constipation treatment strategy recommended by the current major guidelines: step-by-step and cascade.

Step 0, Basic Intervention: Starting with diet and lifestyle adjustments, which are the foundation of chronic constipation management

It is generally believed that constipation is related to bad living habits. Therefore, although the conclusions of relevant studies are not completely consistent, various guideline documents and expert consensuses believe that non-drug treatment is the basis and the first step in the treatment of chronic functional constipation. The first step should be implemented before the diagnostic examination. Nonpharmacologic treatment primarily includes patient education and dietary and lifestyle modifications, including:

(1) Increase physical activity. Best done in the morning.

(2) Toilet training. It is recommended that patients with constipation try to defecate in the morning and within 2 hours after meals; do not ignore the desire to defecate; concentrate on defecating in the toilet; adopt a squatting defecation posture; and do not stay in the toilet for more than 5-10 minutes.

(3) Diet. Gradually increase the intake of dietary fiber (especially soluble fiber), the recommended fiber intake is 25-30g per day; drink more water, 1.5-2 L/day. However, increasing dietary fiber is not effective for patients with slow transit constipation or refractory defecation disorders.

Step 1, First-line medical therapy (bulk and osmotic laxatives)

When the general measures are intervened for 4 to 8 weeks and constipation does not improve, specific drugs should be used step by step to promote regular defecation in combination with the patient's condition and type of constipation. The first-line choice is mild and safe laxatives (mostly over-the-counter drugs), such as bulk laxatives and osmotic laxatives. In the constipation treatment cascade process of the WGO guidelines, fiber supplementation is a step following dietary recommendations regardless of the availability of regional resources.

Volumetric laxatives are often called bulking agents in English literature and are divided into soluble fibers (psyllium and semi-synthetic polycarbophil calcium, methylcellulose, etc.) and insoluble fibers (such as wheat bran). These drugs have a laxative effect by retaining water in the stool, increasing the water content and volume of the stool. Among them, soluble fiber, such as polycarbophil calcium, can absorb 60 to 100 times its weight in the weak alkaline environment of the intestinal tract, and form a hydrophilic gel in the intestinal tract to participate in the formation of feces, making the stool loose and soft and easy to pass. In addition, polycarbophil calcium is not absorbed in the digestive tract and is not easily fermented. It is safe for long-term use and helps patients establish good bowel habits [12].

The benefits and harms of insoluble fibers such as wheat bran on constipation are still controversial, especially for IBS-C patients, which may aggravate symptoms and have potentially negative effects.

The principle of action of osmotic laxatives is to form a hypertonic state in the intestinal tract, absorb water, increase the volume of feces, and stimulate intestinal peristalsis. It is the first-line choice for long-term maintenance treatment of functional constipation. These drugs mainly include polyethylene glycol and non-absorbable sugars (such as lactulose). Among them, polyethylene glycol is the first choice recommended by domestic and foreign guidelines. It is better than lactulose in improving the frequency of bowel movements, stool properties, and abdominal pain, and is safe for long-term use. and well tolerated.

Step 2, second-line drug therapy (salvage therapy)

For patients with persistent symptoms after basic intervention and first-line drug treatment, after excluding compliance issues, the specific mechanism and type of constipation need to be explored and identified, and rescue treatment should be targeted. Stimulant laxatives (bisacodyl, phenolphthalein, anthraquinones, castor oil, etc.) were commonly used in the past, but short-term, intermittent use is only recommended because of the potential safety hazards of long-term use of these drugs.

In recent years, a variety of new drugs have been approved at home and abroad for the treatment of functional constipation and constipation-predominant irritable bowel syndrome and have been rapidly promoted in clinical use, mainly including ①secretagogues (linaclotide, lubiprostone, plecanatide), through different mechanisms to promote the secretion of intestinal juice, increase the volume of feces, thereby promoting intestinal transit. ② New prokinetic drug (prucalopride). Prucalopride is a highly selective 5-HT4 receptor agonist, that can promote gastric emptying, small intestinal transit, and colonic transit in patients with constipation without anorectal dysfunction.

According to the severity and type of constipation, other appropriate drugs should be added or replaced based on the original treatment. When one drug is ineffective, other drugs with different mechanisms can be switched or drugs with different mechanisms can be used in combination.

Step 3, multidisciplinary intervention, surgical treatment

Patients with refractory constipation who do not respond to conservative treatment, need to be referred to a higher-level hospital, complete relevant examinations, conduct multidisciplinary consultations, and combine medications if necessary. For patients with refractory constipation who do not respond to drug therapy, neuromodulation therapy such as sacral nerve stimulation can be tried. Surgical treatment should only be considered for patients who are still ineffective after standardized and systematic comprehensive medical treatment, and whose constipation symptoms seriously interfere with their quality of life, and who have clear morphological and/or functional abnormalities indicated by relevant examinations. This is the last "shelter" for functional constipation ".

Seeking common ground while reserving differences in the treatment of chronic constipation: flexible application of different treatment methods

While there are more commonalities than differences among the different guidelines, there are bound to be differences between them. To better guide local clinical practice, guidelines must be adapted and adjusted in light of local characteristics, which is the source of differences.

As mentioned in the AGA2013 guidelines, the fiber in "increasing fiber intake" includes both dietary fiber and fiber supplements (mainly soluble fiber). This reminds us that the timing of the use of psyllium and polycarbophil calcium in volumetric laxatives may be moved forward, integrated into lifestyle adjustments, and become an integral part of the basic treatment of chronic constipation.

For the three types of drugs used as salvage therapy, the ESNM2020 consensus believes that the preferred type should depend on the patient's disease characteristics, cost/efficacy evaluation of the drug, and local preferences; the consensus in my country is "strongly recommended" for stimulant laxatives, and for Lina New drugs such as linaclotide are "recommended", which may be affected by factors such as insufficient experience in the application of new drugs in my country and limited availability of drugs; Linaclotide is recommended as a second-line drug in the Hong Kong consensus in China (accessible sexual causes), while stimulant laxatives are recommended as a co-salvage regimen for non-pharmacological, first- and second-line drug therapy refractory.

Another example is Chinese herbal medicine, moxibustion, acupuncture, etc., which are often sought by patients in Eastern countries. Our country's guidelines recommend that "Chinese medicine has a certain effect on improving the symptoms of chronic constipation." However, given insufficient evidence-based medical evidence, these methods have not been recommended in the consensus of Western guidelines, and large-sample, well-designed, and higher-quality studies are needed to confirm them.

In conclusion, constipation is a heterogeneous, multi-symptomatic, multi-factorial disease. Currently, there is little difference in the guidelines and consensuses of various countries regarding the diagnosis, classification, and treatment of chronic constipation, and they follow similar principles and strategies. However, there are also subtle differences among the guideline consensus in various regions. Some of these differences reflect the differences in medical level, but more are caused by the characteristics of the local population, society, drug supervision, and so on. We need to flexibly apply the guideline recommendations in a reasonable and well-founded way, and tailor "tailor-made" treatment plans according to the specific characteristics of patients. This is the only way to truly understand and use the guidelines.

Natural Herbal Medicine For Relieving Constipation-Cistanche 

Cistanche is a genus of parasitic plants that belongs to the family Orobanchaceae. These plants are known for their medicinal properties and have been used in Traditional Chinese Medicine (TCM) for centuries. Cistanche species are predominantly found in arid and desert regions of China, Mongolia, and other parts of Central Asia. Cistanche plants are characterized by their fleshy, yellowish stems and are highly valued for their potential health benefits. In TCM, Cistanche is believed to have tonic properties and is commonly used to nourish the kidney, enhance vitality, and support sexual function. It is also used to address issues related to aging, fatigue, and overall well-being. While Cistanche has a long history of use in traditional medicine, scientific research on its efficacy and safety is ongoing and limited. However, it is known to contain various bioactive compounds such as phenylethanoid glycosides, iridoids, lignans, and polysaccharides, which may contribute to its medicinal effects.

Wecistanche's cistanche powder, cistanche tablets, cistanche capsules, and other products are developed using desert cistanche as raw materials, all of which have a good effect on relieving constipation. The specific mechanism is as follows: Cistanche is believed to have potential benefits for relieving constipation based on its traditional use and certain compounds it contains. While scientific research specifically on Cistanche's effect on constipation is limited, it is thought to have multiple mechanisms that may contribute to its potential to relieve constipation. Laxative Effect: Cistanche has long been used in Traditional Chinese Medicine as a remedy for constipation. It is believed to have a mild laxative effect, which can help promote bowel movements and induce constipation. This effect may be attributed to various compounds found in Cistanche, such as phenylethanoid glycosides and polysaccharides. Moistening the Intestines: Based on traditional use, Cistanche is considered to have moisturizing properties, specifically targeting the Intestines. Promoting hydration and lubrication of the Intestines, it may help soften tools and facilitate easier passage, thereby relieving constipation. Anti-inflammatory Effect: Constipation can sometimes be associated with inflammation in the digestive tract. Cistanche contains certain compounds, including phenylethanoid glycosides and lignans, that are believed to have anti-inflammatory properties. By reducing inflammation in the intestines, it may help improve bowel movement regularity and relieve constipation.

References:

1. Chinese Consensus Functional Gastroenterology Collaborative Group of Gastrointestinal Dynamics Group, Digestive Diseases Branch of Chinese Medical Association. Consensus Opinion of Chinese Chronic Constipation Experts (2019, Guangzhou). Chinese Journal of Digestion. 2019.39(9):577-598.

2. Chinese Medical Association, Chinese Medical Association Magazine, Chinese Medical Association Gastroenterology Branch, Chinese Medical Association General Medicine Branch, Chinese Medical Association "Chinese Journal of General Practitioners" editorial committee, expert group for compilation of primary diagnosis and treatment guidelines for digestive system diseases.Guidelines for Primary Diagnosis and Treatment of Chronic Constipation (2019). Chinese Journal of General Practitioners, 2020,19(12):1100-1107.

3. Suares NC, Ford AC. Prevalence of, and risk factors for, chronic idiopathic constipation in the community: systematic review and meta-analysis. Am J Gastroenterol. 2011;106(9):1582-1592.

4. Yang Zhi, Wu Chenxi, Gao Jing, et al. Meta-analysis of the prevalence of chronic constipation in Chinese adults. Chinese General Medicine, 2021, 24(16):2092-2097.

5. Camilleri M, Ford AC, Mawe GM, et al. Chronic constipation. Nat Rev Dis Primers. 2017;3:17095. Published 2017 Dec 14. doi:10.1038/nrdp.2017.95

6. WGO World Gastroenterology Organization Practice Guidelines: Constipation. 2007. https://www.worldgastroenterology.org/guidelines

7. AGA American Gastroenterological Association, Bharucha AE, Dorn SD, Lembo A, Pressman A. American Gastroenterological Association medical position statement on constipation. Gastroenterology. 2013;144(1):211-217.

8. ACG Ford AC, Moayyedi P, Lacy BE, et al. American College of Gastroenterology monograph on the management of irritable bowel syndrome and chronic idiopathic constipation. Am J Gastroenterol. 2014;109 Suppl 1:S2-S27.

9. Wu JCY, Chan AOO, Cheung TK, et al. Consensus statements on diagnosis and management of chronic idiopathic constipation in adults in Hong Kong. Hong Kong Med J. 2019;25(2):142-148.

10. Shin JE, Jung HK, Lee TH, et al. Guidelines for the Diagnosis and Treatment of Chronic Functional Constipation in Korea, 2015 Revised Edition. J Neurogastroenterol Motil. 2016;22(3):383-411.

11. Serra J, Pohl D, Azpiroz F, et al. European society of neurogastroenterology and motility guidelines on functional constipation in adults. Neurogastroenterol Motil. 2020;32(2):e13762.

12. Han Zhenjie, Yuan Yaozong. Pharmacological and clinical research of polycarbophil calcium. Chinese Journal of New Drugs and Clinics. 2012.31(6):291-294.