Rehabilitation for Chronic Constipation: Integrative Approaches to Diagnosis and Treatment

Abstract

Background: Chronic constipation is a well-recognized complication which is caused by hard and/or infrequent defecation. According to estimates, constipation presents as a chronic illness affecting 16% of adults globally, who deal with insufficient bowel movements that cause discomfort, bloating, or a sensation of incomplete bowel. Objectives: This review looks at the many local and systemic factors that contribute to the pathogenesis of the causative, including dietary habits, genetic factors, colon function and absorption, social and economic factors, lifestyle, and biological and drug factors. Results: Appropriate diagnostic and management modalities are the cornerstone in the management of patients with chronic constipation. However, there are still controversies regarding the timing of these diagnostic and management approaches. This condition is common and reduces the quality of life of patients and represents a burden on any healthcare system. In clinical practice, it remains problematic, as physicians are most of the time indecisive on which therapy to administer and at what time. Conclusions: Constipation management is a new topic that was introduced over a decade ago and the purpose of this study is to shed some light onto the practice, problems and modern day techniques that can be used to treat constipation in patients, primarily through behavioural, conservative, medical, and surgical means. Additionally, this particular management is to be used in conjunction with an algorithm designed to enhance and support clinical practice.

1. Introduction

Chronic constipation, a growing condition, is a global concern that impacts an estimated 16% of the adult population [1]. It seems to impact the elderly population more (with around 1/3 of the population aged 60 and more feeling some extent of constipation) [2]. In addition to this, over 50% of the inhabitants of nursing homes share the same condition [3]. Apart from this, it is also witnessed in higher rates in females and people of lower economic social status [4]. The most recent research suggests that people with constipation are at risk of heart conditions when compared to those without constipation because constipated individuals have increased cardiovascular strain during bowel movements [5]. This trend is alarming, as NHANES (a national survey conducted by the Centers for Disease Control and Prevention in the United States) found that an association between low frequency of defecation in patients and the onset of heart diseases to be on the rise [6].

Table 1. Rome IV diagnostic criteria for constipation disorders [7].

Category	Criteria
Functional constipation	- Straining during at least 25% of bowel movements. - Hard or lumpy stools (Bristol Stool Scale types 1–2 [8]) in at least 25% of defecations. - Sensation of incomplete evacuation in 25% or more of defecations. - Sensation of anorectal obstruction or blockage in at least 25% of bowel movements. - Manual manoeuvres to facilitate defecation in 25% or more of cases. - Fewer than three spontaneous bowel movements per week. - Loose stools are rarely present unless laxatives are used. - Does not meet criteria for IBS.
IBS-C	- Recurrent abdominal pain, at least one day per week in the last three months, associated with two or more of the following: Pain improves after defecation. Pain associated with changes in stool frequency. Pain associated with changes in stool form (appearance). - Predominantly hard or lumpy stools in more than 25% of bowel movements.
OIC	- New or worsening symptoms of constipation following the initiation of, change in, or escalation of opioid use. - Symptoms include: straining, hard or lumpy stools, sensation of incomplete evacuation, anorectal blockage, or manual manoeuvres during at least 25% of bowel movements. - Does not meet criteria for IBS.
Defecatory disorders	- Difficulty in expelling stool due to dysfunction in the pelvic floor or anorectal muscles. - Diagnostic criteria include the following: Inappropriate contraction of pelvic floor muscles during defecation. Inadequate propulsive forces for defecation. - Associated with prolonged straining, sensation of blockage, or incomplete evacuation.

below includes the Rome IV criteria, which categorizes constipation disorder into four types [7]: (a) functional constipation, (b) constipation due to irritable bowel syndrome (IBS-C), (c) opioid-induced constipation (OIC), and (d) functional defecation disorders (i.e., poor propulsion and dyssynergic defecation).

Of all these, chronic functional constipation is the most common one, which, according to the Rome IV criteria for the diagnosis of the disorder, may be termed chronic constipation because of the presence of specific symptoms [6]. All other symptoms, such as more than three stools a week or feeling of incomplete bowel movement, in combination with two or more hard stools have to be present for a diagnosis of chronic constipation [9].

Barium enemas, CT and MRI scans, defecography, colonoscopy, and plain abdominal radiography are the basic tests that assess the colon and rectal areas in constipation patients [10]. Although these clinical measures provide good substitutes, they still utilize invasive approaches, consume time, and expose patients to radiation [11].

1.1. Incidence and Risk Factors of Constipation

Constipation is experienced differently by individuals, resulting in varying definitions among studies. An Asian study [12] that was conducted recently found that diabetes mellitus, irritable bowel syndrome, and gastroesophageal reflux disease incurred a high health burden of constipation. The US lost approximately 13,000,000 workdays due to constipation. It has also been estimated that, between 2006 and 2011, the number of visits to the emergency department that were due to constipation increased by 41.5% and the related expenditure for such visits increased by 121.4% [13].

More than 30 years ago, Whitehead et al. [14] identified that about 33% of adults over 60 years old suffer from functional constipation. Based on other studies conducted, it has been found that there exists a strong correlation between the quality of life of individuals and the healthcare provisions in terms of the rate of consumption of healthcare resources [15,16,17]. Figure 1 below shows some of the risk factors in constipation.

1.2. Age and Gender Distribution

Compared to younger individuals, constipation is much more frequently seen in older people [19]. Factors such as minimal hydration, reduced or lack of physical activity, poor diet, and medication can all heavily impact an elderly person; thus, constipation can be caused. Due to the aforementioned factors, these people may lack the ability to maintain regular and proper bowel movements [20].

This condition is also widely spread among patients above 65 due to the use of dentures with loose fit or a lack of teeth, which makes it hard to chew [21]. This results in the patient opting for soft and fibrous materials which are then consumed by such people who have lost their interest in food or have difficulty swallowing the food. Moreover, there is a higher prevalence of anatomic abnormalities in elderly patients, especially rectocele, pelvic floor dyssynergia, and prolapse [22].

Regarding gender, constipation is more frequent among the female population than males [23]. Furthermore, due to pelvic organ prolapse, elderly women tend to have marked severe constipation compared to males of the same age [24]. During the last trimester of pregnancy, such women are at a risk of getting constipated due to the enhanced levels of sex hormones which, in turn, tend to lower the intestinal movements and delay the emptying of the intestines due to the external force effect [25].

It has been noted that women tend to experience premenopausal constipation more than other groups, and this may be due to female hormones and associated feelings. In addition, women are much more likely than men to use laxatives when they have a greater need for bowel care for constipation [26].

1.3. Causes of Constipation

Different forms of pathogenesis have highlighted independent determinants such as diet, family history, colonic contractility and absorption, behavioural and biological factors, and medication [27]. In addition, fibrous herb consumption deficit, liquid intake deficit, lack of physical activity, irritable bowel syndrome, inability or unwillingness to defecate, and slow bowel movement have all been found to be linked with genetic susceptibility [28].

1.4. Nutrition

Chronic constipation may come from insufficient fiber or poor water consumption. Typically, in these cases, it is more logical to say that constipation does not pose a threat in such cases, and can be treated with lifestyle or diet changes [29].

Research shows that a high-fiber diet leads to an increase in stool weight, causing colon transit time to decrease as a result of increased straining pressures, while low-fiber diet leads to constipation [30]. Fiber consumption alone has little impact on the colonic motor function. High-fiber diets result in the production of gas and consequent worsening of symptoms due to fiber metabolism [31]. Soluble fiber seems to work in people suffering from IBS and abdominal discomfort by ameliorating constipation and for treating cyclical symptoms including abdominal pain [32].

2. Predisposing Factors for Constipation

According to the medical protocol, the predisposing factors for constipation are gathered by taking a reliable medical history and performing a physical examination [33]. The questions that should be asked involve the stool characteristics, frequency, distention of the abdomen, efforts during defecation, and inadequate attempts to defecate [34].

As per the Rome IV criteria for functional constipation, at least two of the given criteria should be present for a time frame of 3 to 6 months [7]. The Rome IV criteria do include the Bristol Stool Form Scale (BSFS) grades 1 and 2, which means that, in grade 1, the stool may take the form of dry hard lumps/nuts making it quite painful to defecate, while in grade 2 the stool becomes lumpier and can be sausage-shaped [35]. During an abdominal examination, it is also possible to detect intrabdominal tumors or tenderness and stool.

Digital rectal examination (DRE) plays an important role in the physical assessment. Sadeghi et al. established that pelvic floor dyssynergia is diagnosed during DRE with 87% specificity and 75% sensitivity in the presence of standard manometry as reference, while the specificity and sensitivity of rectal balloon expulsion are 56% and 80%, respectively [36]. In addition, rectal examination shows polyps or masses, hemorrhoids, anatomic anomalies, excoriation or rectal prolapse [37]. Also, a sharp pain during the procedure points towards injury to mucosa, inflammation, ulcer, or fissure and is believed to be acute [38]. It is advised clinically that an adult with constipation who manages to respond well to OTC laxatives or appropriately to fiber supplements does not need further investigations. Alternatively, a colonoscopy is recommended for individuals who are of screening age for colon cancer or exhibit warning signs [39].

The American College of Gastroenterology recommends that blood tests should not be performed routinely on patients with chronic constipation [40].

Figure 2 provides a clinical pathway for a patient who presents with the complaint of constipation. This approach starts with a comprehensive medical history of the patient, proceeding to the relevant symptom as well as investigative procedures, such as a digital rectal examination, colonoscopy, or manometry, as appropriate to alarm symptoms or dyssynergic defecation. Clinical laboratory tests are then performed; deviations from normal results may call for further investigations to rule out certain fundamental diseases. In the absence of such abnormalities, the first-line of treatment includes changes in lifestyle (diet, exercise, reduction in stress). If the above attempts fail, then a step-wise approach is followed starting with laxatives and progressing with other medications, biofeedback, and transanal irrigation in that order. The last treatment approach for intractable constipation is surgical.

3. Rehabilitation in Chronic Constipation

3.1. Nonpharmacologic Rehabilitation

Patients suffering from constipation can first be treated by using nonpharmacologic measures involving diet changes and sports [41]. As previously mentioned, research suggests that a lower intake of dietary fibers correlates with a high incidence of constipation. Dietary fibers are polymer carbohydrates which are digested in the colon and can be further divided into soluble and insoluble fibers [42]. Psyllium is one of the most recommended medications, as research has shown a higher vitamin level, which helps patients defecate more, and lowers pain when doing so, even though it does not enhance colon mobility since its effectiveness remains unproven. Insoluble fiber supplements can speed up colonic transit [43]. Gradually raising daily fiber consumption to 25 to 30 g per day is recommended when dealing with constipation since it helps to maintain fiber [44].

Most patients respond positively to physical exercise, and moderate and vigorous physical exercise have been shown to improve the quality of life in individuals with IBS [45]. A recent study conducted by Johnson-Martínez et al. established an association between increased physical activity and more frequent bowel movements in a one-week span [46]. In addition to this, Chang et al. found being physically active to be positively associated with a reduced risk of constipation [47].

Moreover, Özkütük et al. concluded that biofeedback therapy shows good results in patients with defecatory disorders [48]. The authors of this research highlighted that the primary goal is to normalize the reflex and override the dyssynergia that exists between the abdominal rectal and anal sphincter muscles and to enhance rectal perception [48].

3.2. Pharmacological Rehabilitation

3.2.1. Laxatives

Laxatives are the most common and efficacious medication for constipation due to their ease of use and effectiveness. If nonpharmacological management fails, laxatives are the next medications to use [49].

Osmotic laxatives change the osmotic gradient across the intestinal wall. This leads to an increase in water and electrolyte content in the intestinal tract, resulting in a change in stool volume and consistency [50]. In addition, they are generally safe for prolonged use.

An example of an osmotic laxative that is frequently used is polyethylene glycol (PEG). PEG, in comparison to a placebo, is more effective at engendering more bowel movements while reducing strain and the use of prednisone [51]. Comparison of PEG vs. lactulose indicated that PEG is more effective for constipation with fewer side effects. The recommended dose of PEG per day is 10–20 g [52]. But, there are also negative effects of PEG, for example diarrhea or bloating. Lactulose, like PEG, is an osmotic laxative. Lactulose is not absorbed in the small intestine, but instead fermented by bacteria in the lower intestine, which can cause flatulence [53].

Magnesium citrate, magnesium sulphate, Epsom salt, and sodium phosphate, which are in the same category as saline laxatives, are often used as osmotic laxatives because they aid in transporting water into the lumen of the small and large intestines [54]. It is especially important to mention that natural mineral water rich in magnesium sulphate should be consumed due to its effectiveness, low cost, and naturalness, with a minimum magnesium sulphate daily dose of 20 mmol for at least a week [55].

Another category consists of stimulant laxatives which act on the Auerbach and myenteric plexus by directly stimulating intestinal motility. In the management of functional constipation, these laxatives are usually given as a second line of treatment as these laxatives are recommended for use as a rescue therapy when there is no bowel movement after 3 days [56].

Common examples of this group are sodium picosulfate, senna and cascara (the latter two being components of the tea), with the best known being bisacodyl. In a randomized clinical trial conducted by Alsalimy et al., bisacodyl was found to be superior to sodium picosulphate and a placebo [57]. The most frequent adverse effects are cramping and diarrhea. As time goes by, the side effects of bisacodyl do tend to be lessened [58].

Another category of laxatives includes docusate, lubricants, which include prokinetic cascade emollient liquid paraffin, and prokinetic agents [56]. Lubricant laxatives, such as mineral oils, allow for stool to become softer which, in turn, leads to water absorption reduction [59].

The main pharmaceutical agents are included in

Table 2. Summary of pharmacological agents for constipation.

Agent	Mechanism of Action	Clinical Effects
Lubiprostone	ClC-2 activator, EP4 receptor agonist	Improves transit, relieves discomfort and bloating, and lessens the intensity of constipation [60].
Misoprostol	Synthetic prostaglandin E2 analogue	Increases frequency of bowel movements, transit time, and releases fluids and bicarbonate [61].
Linaclotide	Guanylate cyclase-C (GC-C) agonist	Increases the frequency of bowel movements and transit [62].
Plecanatide	Guanylate cyclase-C (GC-C) agonist	Taken once a day, it has localised intestinal activity and extremely powerful activity [63].
Sodium chenodeoxycholate	Bile acid analogue	Increases mucus secretion, improves mucosal permeability and intestinal motility [64].
Elobixibat	Ileal bile acid transporter (IBAT) inhibitor	Alters the circulation of bile acids and promotes the motility and production of colonic fluid [65,66].
Polyethylene glycol (PEG)	Osmotic laxative	Retains water in the intestine, softens stools, and improves stool frequency [67].
Lactulose	Osmotic laxative	Fermented in the colon to increase osmotic pressure, soften stool, and reduce strain [68].
Bisacodyl	Stimulant laxative	Stimulates intestinal motility and alters electrolyte secretion, effective for acute constipation [69].
Sodium picosulfate	Stimulant laxative	Stimulates peristalsis and promotes bowel emptying, commonly used in bowel preparation [70].
Prucalopride	5-HT4 receptor agonist	Enhances colonic motility, promotes spontaneous bowel movements, and is effective in refractory constipation [71].
Methylnaltrexone	Peripheral μ-opioid receptor antagonist	Relieves opioid-induced constipation without affecting central analgesia [72].
Naloxegol	PEGylated μ-opioid receptor antagonist	Effective for opioid-induced constipation in non-cancer patients [73].
Tegaserod	Partial 5-HT4 receptor agonist	Enhances intestinal motility and reduces visceral hypersensitivity, approved for IBS-C [74].
Colchicine	Anti-inflammatory	Increases intestinal motility as a secondary effect, useful in refractory constipation [75].
Alvimopan	Peripheral μ-opioid receptor antagonist	Accelerates recovery of bowel function after surgery, particularly postoperative ileus [76].
Glycerin suppositories	Hyperosmotic laxative	Rapidly softens stool and provides relief for rectal constipation [72].
Mineral oils	Lubricant	Lubricates the intestinal lining and softens stool, reducing water absorption [55].

[60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76].

3.2.2. Prosecretory Agents

As they undergo a treatment for constipation, prosecretory agents change the ion channels of the epithelium [77]. The activation of the guanylate cyclase C receptor triggers intracellular production of cGMP, which, in this case, leads C-GMP-dependent protein kinase II to phosphorylate the cystic fibrosis transmembrane conductance regulator, resulting in the increased secretion of chloride ions as well as the paracellular flow of water and sodium ions into the intestinal lumen [78].

Chloride channel protein 2 is being opened by lubiprostone, which has the effect of chloride secretion into the intestine [79].

Linaclotide binds and activates guanylate cyclase-C receptors, which leads to the uptake of sodium and secretions of chloride and bicarbonate [80]. Linaclotide shows good results in the case of achieving any amount of spontaneous bowel movement to complete spontaneous bowel movement with constipated patients to PP patients with IBS-C [81]. Plecanatide might also stimulate guanylate cyclase-C receptors, making its role in gut function similar to that of linaclotide [82].

3.2.3. Serotoninergic Agonists

Serotonin agonists enhance secretion and increase the movement of the intestine by activating the 5-hydroxytryptamine receptor 4 (5-HT4) that is situated in the digestive system [83].

Prucalopride can be termed a highly specific 5-HT4 receptor agonist and does not have adverse effects in patients who have pre-existing cardiovascular ailments. In a paper from 2016, prucalopride was successful in increasing the number of bowel movements per week [63]. In addition, chronic pelvic pain alleviates anorectal and abdominal symptoms which include pain, bloating, distension, etc., while using this medication. The drug is usually prescribed for taking orally, with a normal daily dose between 2 and 4 mg, usually starting with 2 mg and restrictions marked at 4 mg. In general, the side effects are fairly uncommon: headache, abdominal pain, nausea, and diarrhea were slightly detected, to mention a few [84].

Velusetrag is a novel medication, which is a potent and highly effective medicine for the treatment of gastrointestinal motility disorders, including constipation [85]. In this category, Ihara et al. determined that the use of Velusetrag in the treatment of chronic constipation should be kept to a necessary minimum [86]. However, in the latest trials, Velusetrag does not interact with pharmaceuticals and does not negatively affect the cardiovascular system, e.g., hypertension and hypotension, but further trials must still be completed [87,88].

Some of the 5-HT4 agonists (Tegaserod, Cisapride) are currently restricted in constipation due to possible harmful side effects on the cardiovascular system [89].

3.2.4. Probiotics and Prebiotics

So far, several species and strains of probiotics have been proposed to have protective effects against gastrointestinal issues and gut movement. Several studies prove their usefulness in adult patients with constipation, on the basis of improvements in intestinal motility and stool quality, increased frequency of defecation, and reduced bloating [90,91,92]. Furthermore, it has been demonstrated that the beneficial effects of probiotics are specific to a particular species and strain, and their use in combination with Lactobacillus lactis seems to be the most beneficial [93]. In another study, the effectiveness of dietary supplementation with probiotics, prebiotics, and synbiotics in patients with chronic functional constipation was proven after 8 weeks of treatment [94].

3.2.5. Other Interventions

Alongside opioid medications and their possible side effects, patients who are dependent on opioid treatment tend to have persistent constipation as a chronic condition [95]. In one study, the daily administration of opioids resulted in constipation reports from 81% of patients, while only 46% of those utilising opioids two to three times weekly experienced constipation [96].

3.2.6. Differentiation and Appropriate Use of Pharmacological Agents

The selection of pharmacological agents for managing constipation depends on a variety of factors.

Patient-specific factors are age and comorbidities. Osmotic laxatives such as polyethylene glycol are preferred in elderly patients due to their safety profile and efficacy in improving stool consistency [97]. Lactulose and PEG are commonly used in children due to their gentle action and minimal side effects. In cardiovascular diseases it is best to avoid serotonin agonists such as Tegaserod, as they may exacerbate risks [98]. Prucalopride is a safer alternative for these patients [99]. Agents such as magnesium-based laxatives should be avoided in chronic kidney disease due to the risk of hypermagnesemia [100].

When it comes to the mechanism of action, each class of drug acts on specific pathways, and selection depends on the underlying pathology of constipation. Thus, osmotic laxatives (e.g., PEG, lactulose) are best suited for patients with slow transit constipation, as they increase stool water content and soften stools [101]. Bisacodyl and sodium picosulfate are effective for acute relief or as a rescue therapy in patients unresponsive to first-line treatments [102]. Lubiprostone, Linaclotide and Plecanatide are indicated for chronic idiopathic constipation or irritable bowel syndrome with constipation, as they improve intestinal fluid secretion and motility [103].

In Figure 3 it can be seen that the use of peripheral mu-opioid receptor antagonists is an effective means for the management of this complication [104]. They do not interfere with the systemic analgesic action of the opioid drugs but exclusively ameliorate some adverse effects of opioids, especially gastric distress and constipation, vomiting, and nausea, which are often reported [105]. This group is represented by Methylnaltrexone, Alvimopan, and Naloxegol [106]. Methylnaltrexone bromide is intended for palliative care patients with opioid-induced constipation with end-stage disease and who had failed laxative therapy. It has been also recently approved for chronic non-cancer pain in adults under opioid therapy [107].

Elobixibat elevates bile acid concentration in the intestines by inhibiting bile acid transporters, which results in an improvement in gut movement and an increase in the frequency of defecation [108]. Tomie et al. reported that the frequency of spontaneous bowel movements (SBMs) in the week preceding elobixibat was 2.86 ± 1.77 times per week, which increased to 6.08 ± 4.65 times per week subsequent to its administration [109]. Elobixibat is a usually well-tolerated drug; however, it can induce some side effects like diarrhea, abdominal distension, liver enzyme abnormalities, abdominal pain or nausea, that are generally mild [110].

In an open-label trial, Verne et al. concluded that Colchicine is predominantly used for the management of arthritis; however, it has a side effect, which is diarrhea, and may be effective in the management of constipation [111].

Approved for dealing with gastric ulcers caused by anti-inflammatory medications, Misoprostol is also a prostaglandin E2 analog [112]. This substance assists in enhancing the defecation rate, the amount of stools, and the speed at which food passes through the intestines [113].

3.3. Surgical Approach

Surgical interventions should be included in treatment options for patients whose pharmacological treatment is not effective enough. The physicians have authority to make decisions on approaches so long as the least radical approach is being applied, and, as such, the approach becomes rather heterogeneous. Ileostomy, total colectomy with ileorectal anastomosis, and cecostomy are examples of effective treatment procedures which can be administered to patients with slow transit constipation [96]. The pelvic floor disorder needs timely intervention if the patient is on medical or surgical treatment, which has been found to be more useful. Medical treatment is the best option; for a few patients, due to severe disease or colonic inertia, surgical intervention is required [87].

In a study conducted by Beck et al., 81% of patients expressed at least moderate satisfaction with their bowel frequency; however, 41% reported abdominal pain, 21% experienced incontinence, and 46% encountered diarrhoea at least occasionally. Nevertheless, 93% indicated that they would opt for subtotal colectomy again if presented with another opportunity [114].

In another study, with a follow-up of 19.8 years, the median stool frequency rose from one per week at baseline to five per week throughout long-term follow-up [115]. The same research concluded that hemicolectomy for slow transit constipation enhances stool frequency and diminishes laxative consumption. The long-term success rate varied from 34% (17/50) to 70% (35/50) [115].

Moreover, a recent study argues that, based on existing research, sacral nerve stimulation in the slow transit constipation therapeutic approach does not bring any therapeutic benefit [116], although it has previously been claimed that there is long-term success in this treatment for sacral nerve stimulation. Thus, in a study conducted by Ratto et al., 47% of patients had a Cleveland Clinic Constipation score improvement of more than 50% [117].

4. Conclusions

Constipation is a complex and prevalent condition which can be associated with a wide range of symptoms that can have an impact on life satisfaction. The complex and multifactorial nature of the condition means that the underlying pathophysiology can also be difficult to understand.

Nonpharmacological therapies have been found to be the most effective in treating this condition. Once a patient has been trained to understand the significance of a good diet, intake of fiber, and regular exercise, and these do not perform their function, medication should be prescribed to the patient. However, all prescription is best recommended after assessing the pros and cons of certain medications, since there is a vast variety, including but not limited to laxatives, secretagogues, and serotonergic agonists. Refractory constipation might be a rationale for surgery, if other approaches show no result.

Considering the frequency with which this problem is encountered, the economic costs of treating it, and the negative consequences for quality of life, it is evident that many problems make this condition a concern and further engaging efforts into creating more potent drugs with fewer side effects are necessary to improve treatment outcomes.