Constipation Treatment & Management

Manual disimpaction and transrectal enemas may be used after any critical illness associated with constipation has been ruled out. A well-lubricated gloved finger might be required in patients with lower anorectal impactions. Warm water enemas usually are unpopular among the nursing staff and probably are not necessary within the emergency department (ED). These initial measures are then followed by elective evaluation of the causes of the constipation.

Medical care should focus on dietary change and exercise rather than laxatives, enemas, and suppositories, none of which really address the underlying problem. The patient is at a high risk for becoming dependent on laxatives and developing a laxative colon. Potentially helpful measures include initiation of dietary fiber supplementation and stimulant and/or osmotic laxatices, as appropriate; if necessary, these can be followed by intestinal secretagogues and/or prokinetic agents. ^[3] Another option for opioid-induced constipation is peripherally acting mu-opiate antagonists (PAMORAs) (eg, methyltrexone [oral or parenteral], naldemedine [oral], naloxegol [oral]. ^{[3, 23]}  If conservative measures fail and the patient is clearly compliant with the advice, a more detailed evaluation should be performed (see Workup).

In addition, in January 2014, the FDA issued a warning that exceeding one dose of OTC sodium phosphate products for constipation over a course of 24 hours may cause serious harm to the kidneys and heart and, in rare cases, may be fatal. ^{[24, 25]} Using more than the recommended dose of these products can cause severe dehydration and changes in serum electrolyte levels. Individuals who may be at a higher risk for potential adverse events include young children; patients older than 55 years; patients who are dehydrated; patients with kidney disease, bowel obstruction, or inflammation of the bowel; and patients who are using medications that may affect kidney function. ^{[24, 25]}

The key to treating most patients with constipation is correction of dietary deficiencies. Although some controversy exists about the effectiveness of exercise in constipation treatment, encouraging as much aerobic exercise as possible seems reasonable. Even brisk walking may help stimulate bowel motility and, certainly, is unlikely to hurt most patients.

Counsel the patient regarding the appropriate dietary prophylaxis with follow-up visits on an outpatient basis. If the patient experiences further episodes of constipation, a more detailed evaluation may then become appropriate (see Workup).

Surgical care is generally restricted to the evaluation of underlying causes or the management of acute complications of constipation. For children with constipation, operative management includes the use of antegrade continence enemas, sacral nerve stimulation, and colonic resection. ^[20] Surgical intervention for constipation should be avoided in a patient with an underlying psychiatric cause.

Once acute constipation has resolved and the associated medical or surgical conditions have been ruled out, additional inpatient care is rarely indicated. Patients requiring surgical intervention for acute conditions require postoperative care; however, that is beyond the scope of this article.

Generally, transfer to another facility is not required unless that there is uncertainty about the diagnosis or the underlying cause and more aggressive medical evaluation is deemed necessary. Such an eventuality might occur in patients institutionalized in nursing homes or in chronic care facilities who require medical consultations to rule out conditions that are more serious. The following factors may warrant a transfer:

• Uncertain diagnosis

• Evidence of intra-abdominal catastrophe

• Acute abdominal pain

• Fever

• Lower gastrointestinal (GI) bleeding

• Chills

• Instability of vital signs

• Absence of bowel sounds

• Acute recent change in bowel habits

• Unsuccessful or inadequate treatment offered at the local facility

An international expert consensus (Delphi Survey) established five symptoms and their severities to define treatment failure to provide adequate relief in patients with chronic constipation. ^[26] They indicated that if any one of the following five statements is applicable to a patient, their current therapy has failed to provide adequate relief. ^[26]

• The patient reports an inadequate number of bowel movements most of the time in addition to having complete bowel movements occur on fewer than 3 days per week.
• Straining is required on most occasions or is becoming worse.
• The stool consistency has not improved on the current therapy in addition to having a Bristol Stool Scale Type 1 or Type 2 (ie, lumpy and hard or small and very hard).
• The patient reports inadequate improvement of another symptom/sign of chronic constipation while on the current therapy
• The current therapy is poorly tolerated, such that any relief gained is unacceptable to the patient.

The key to treating most patients with constipation is correction of dietary deficiencies. This generally involves increasing intake of fiber and fluid and decreasing the use of constipating agents, such as milk products, coffee, tea, and alcohol.

Increased fiber intake

Dietary fiber is available in diverse natural sources, such as fruits, vegetables, and cereals. Ingestion of natural fiber sources is nutritionally superior to supplementation with purified fiber. However, advising patients to eat more fruits and vegetables is frequently unsuccessful, at least in American patients. American patients do respond reasonably well to prescriptions and often seek them; accordingly, prescribing a fiber supplement, such as wheat, psyllium, or methylcellulose, is often useful.

Many of the available products vary substantially in their potency. For instance, sugar-free Metamucil (psyllium) has twice the potency of standard Metamucil on a volume basis because the latter is half sugar. Pharmaceutical companies may argue that one type of fiber is better tolerated or more effective than another. This may not make much difference in treatment or in fiber tolerance in most patients as long as the fiber supplementation doses start low and are slowly titrated upward.

Theoretical considerations suggest that the use of a fermentable fiber, which increases short-chain fatty acid concentrations in the colonic lumen, may have other health benefits (as opposed to methylcellulose). However, this suggestion remains controversial and awaits further exploration.

Because no convincing reason exists to pick one product over another, a single brand of choice should be prescribed until the patient’s constipation resolves. The patient may then switch to generic or other brands with appropriate dose adjustments.

The author’s experience has been that some patients have preferences based on the taste of the product or other subjective reasons. In particular, those rare patients who cannot tolerate fermentable fiber supplementation because of resulting gas or bloating may do better with methylcellulose, whereas others may find that the quality of the stool, taste preferences, or both favor psyllium supplementation.

To prevent patient noncompliance resulting from the cramping and bloating that may accompany changes in dietary fiber, fiber supplementation should be started at a low subtherapeutic dose and titrated upwards on a weekly basis until the desired effect is achieved. Patients should continue to increase the dose on a weekly basis until they experience daily bowel movements with no straining or until they reach the maximum dose.

Patients should be cautioned that these products are not laxatives, will not induce a bowel movement, and must be taken daily regardless of their perceived need.

Patients may increase or decrease their dose on a week-to-week basis. In particular, the author advises patients who have arrived at what they believe to be an appropriate and successful dose to increase the dose one additional step for at least a week and then back down if they wish. Some patients find that they actually prefer the higher dose. To ensure long-term compliance, the author believes that patients should titrate the doses in case of changes in potency between fiber supplement brands or changes in diet, fluid intake, or exercise.

Patients should be cautioned that, although various stool softeners, such as docusate sodium, appear much more palatable than fiber, they are not suitable for long-term use. Tachyphylaxis to stool softeners develops over time.

Increased fluid intake

Fluid intake is the key to treatment. Patients should be advised to drink at least 8 glasses of water daily. Counseling may be required to achieve this goal.

Milk and milk products should be minimized if these prove constipating.

In some patient populations, coffee, tea, and alcohol account for the majority of the fluid volume consumed. Patients should be made to understand that because of the diuretic effects of these products, this state of affairs is counterproductive. The author usually recommends that patients decrease their consumption of coffee, tea, and alcohol as much as possible and that they make a point of consuming an extra glass of water for every drink of coffee, tea, or alcohol.

Failure of high-fiber, high-water regimen

Failure to control constipation on a regimen of fiber supplementation and increased water intake should prompt an analysis of patient compliance and a search for other physical causes (eg, altered colonic transit time, outlet obstruction, and psychological causes). The author’s experience is that early failures usually reflect inadequate water intake, whereas recidivism months to years later usually reflects a patient’s decision that fiber supplementation is no longer necessary. Counsel patients in advance to encourage them to avoid these inappropriate decisions.

In selected patients who comply with a trial of a high-fiber, high-water diet but find that this approach does not successfully treat their constipation, a trial of a very-low-residue diet, or even a liquid diet, may be appropriate.

Such a regimen is most successful in patients with an outlet obstruction who are not candidates for surgical correction and in patients whose presentation is more characteristic of IBS with a chief complaint of abdominal pain. A low-residue diet may be effective in the latter group of patients if thorough mechanical cleansing of the bowel, such as is done for diagnostic endoscopy or barium enema, temporarily relieves their symptoms.

Medications to treat constipation include bulk-forming agents (fibers), emollient stool softeners, rapidly acting lubricants, prokinetics, laxatives, osmotic agents, and prosecretory drugs.

Use sodium phosphate products with precaution, particularly in young children; patients older than 55 years; patients who are dehydrated; patients with kidney disease, bowel obstruction, or inflammation of the bowel; and patients who are using medications that may affect kidney function. ^{[24, 25]} According to an FDA warning, exceeding one dose of OTC sodium phosphate products for constipation over the course of 24 hours may cause serious renal and cardiac damage (and, in rare cases, may be fatal) as a result of severe dehydration and changes in serum electrolyte levels. ^{[24, 25]}

Fiber is arguably the best and least expensive medication for long-term treatment, although enthusiasm for the use of polyethylene glycol as first-line therapy in chronic constipation is increasing. It is important to convey to patients that bulk-forming agents generally do not work rapidly and must be used on a long-term basis.

Emollient stool softeners are easier to use, but they lose their effectiveness with long-term administration. These drugs are best reserved for prophylaxis in the short-term setting, as in patients receiving a postoperative narcotic prescription.

Rapidly acting lubricants and laxatives, including over-the-counter products, are often used to treat acute and chronic constipation. A meta-analysis affirmed the efficacy of bisacodyl and sodium picosulfate, which share the same active metabolite, in short- to medium-term use in chronic idiopathic constipation. ^[27] However, their use for acute episodes should be limited, because of the long-term risk of habituation or toxicity.

Polyethylene glycol is simple to use and is more effective than placebo in the management of chronic constipation; however, the effects of long-term therapy with polyethylene glycol over decades are still not well studied.

Lactitol (Pizensy), an osmotic laxative, was approved in February 2020 for treatment of adults with chronic idiopathic constipation. Approval was based on data from approximately 800 patients that included a 6-month placebo-controlled trial and a 3-month active-controlled trial with lubiprostone. ^[6]

Chronic constipation that responds poorly to laxatives may be due to the use of drugs such as opioids or from defecation disorders and advanced colonic dysmotility. ^[28]

The FDA approved prucalopride, a serotonin-4 receptor agonist indicated for chronic idiopathic constipation (CIC), in December 2018. ^[29] Approval was based on an integrated analysis of six double-blind, placebo-controlled, randomized, multicenter clinical studies lasting 12 weeks (studies 1-5) or 24 weeks (study 6). An integrated analysis of six main clinical trials (N=2484) found that significantly more patients treated with prucalopride achieved an average of three or more spontaneous, complete bowel movements per week over the 12-week treatment period compared with placebo (27.8% vs 13.2%; P< .001). A rapid response was seen with prucalopride as early as week 1, with improvements maintained throughout 12 weeks of treatment. ^{[30, 31]}

Lubiprostone and linaclotide are FDA approved for chronic idiopathic constipation and constipation caused by irritable bowel syndrome (IBS). Lubiprostone is also approved for opioid-induced constipation in patients with chronic, noncancer pain. Plecanatide is only approved for chronic idiopathic constipation in adults.

A 2013 study illustrated the long-term efficacy of lubiprostone for opioid-induced constipation. ^[32] In a 9-month open-label extension study in 439 patients, lubiprostone treatment (24 μg twice daily) resulted in statistically significant improvements in constipation from baseline determined by monthly assessments. Patients also reported improvements in the average degree of straining, stool consistency, constipation severity, abnormal bloating and discomfort, and bowel habit irregularity (P< .001 at all treatment months). Reliance on rescue medication significantly dropped over the course of the study, from 33% at month 1 to 18.6% at month 9. Treatment-related adverse events were reported by 24.6% of patients, the most common being nausea, diarrhea, and flatulence. ^[32]

Linaclotide was approved by the US Food and Drug Administration (FDA) in August 2012 to treat chronic idiopathic constipation and for IBS with constipation (IBS-C) in adults. Approval was based on randomized controlled trials that showed significant improvement for each indication compared with placebo. ^{[33, 34, 35]}

The FDA approved plecanatide, a GC-C agonist, in January 2017 to treat chronic idiopathic constipation in adults. ^[8] Approval was based on two randomized controlled trials that demonstrated significant improvements in stool frequency, stool consistency, and time of bowel movement compared with placebo. ^{[8, 9]}

These drugs may be useful in chronic constipation when fiber, water, and polyethylene glycol fail, either alone in combination with simpler interventions. When moving a patient to such interventions after failing on fiber, water, and polyethylene glycol, reconsider whether mechanical issues (eg, tumors, pelvic floor problems) have been adequately ruled out.

Other drugs that have been studied include the prokinetic agents, cisapride and tegaserod. ^{[36, 37, 38]} Although significant promise had been shown with this new class of drugs, these two agents were withdrawn from the US market.

Since July 27, 2007, use of tegaserod has been permitted only via an emergency treatment investigational new drug (IND) protocol through the FDA. As of July 16, 2014, this treatment IND program is still active. ^[39] The treatment IND protocol allows tegaserod treatment of IBS-C or chronic idiopathic constipation (CIC) in women younger than 55 years who meet specific guidelines. Its use is further restricted to those in critical need who have no known or preexisting heart disease.

The FDA Gastrointestinal Drugs Advisory Committee reviewed a supplemental new drug application (sNDA) for tegaserod in October 2018 with the proposed indication of treating women with IBS-C who do not have a history of cardiovascular (CV) ischemic disease. Their recommendation was to reintroduce tegaserod to the US market for women with IBS who are at low risk for CV ischemic disease. ^[40]

Renzapride, a mixed 5-HT4 receptor agonist and 5-HT3 receptor antagonist, has been tested to assess its efficacy and safety in the treatment of chronic constipation. ^[41]

Neurotrophin-3 stimulates the development, growth, and function of the nervous system and has been used to treat functional constipation. Stem cells have been suggested as a means of repopulating dysfunctional neurons.

Surgical care is generally restricted to the evaluation of underlying causes, such as large bowel obstruction, volvulus, or intra-abdominal infection or ischemia. Surgical care may also be indicated for the management of acute complications of constipation, such as hemorrhoidal thrombosis.

Surgery may occasionally play a role in the management of rectal outlet obstruction (eg, rectocele, rectal prolapse, internal rectal intussusception) or in patients with a hypomotile (laxative) colon that is refractory to medical treatment.

In the former case, treatment is directed at the cause of the outlet obstruction. In the latter case, total abdominal colectomy may be indicated; the operation may be less morbid if performed laparoscopically. ^{[42, 43]} In both cases, thorough preoperative evaluation is essential to rule out other medically treatable causes or potentiating factors.

These patients may also have an underlying psychological cause for their ailment, and addressing this is important before irreversible surgical interventions are contemplated.

Benign outlet obstruction due to prolapse may be managed by means of stapled transanal rectal resection or anopexy. ^{[44, 45]} Laparoscopic ventral rectopexy has also been advocated for this problem, although this may be more invasive. ^[46]

There is increasing interest in the use of sacral nerve stimulation in carefully selected patients with severe refractory constipation. In such patients, temporary percutaneous stimulation is typically used for 2-3 weeks to seek benefit, but such trials may not always predict success with permanently implanted nerve stimulators. ^{[47, 48]} This technology seems promising, but further experience will be required to clarify its indications, risks, and benefits.

Pregnant women

Pregnant women are frequently constipated because of dietary alterations, anatomic impingement of a large uterus on the rectosigmoid, fluid shifts, decreased exercise levels, and reduced mobility. Typically, these women develop hemorrhoids from passive venous congestion and uterine impingement. Pregnancy-related constipation potentiates the development of symptomatic hemorrhoids, and the resolution of constipation is the only available antihemorrhoidal therapy during pregnancy.

First-line treatment is fiber supplementation, increased water intake, gentle exercise, and occasional laxative use as required. Hemorrhoidal suppositories and sitz baths may offer symptomatic relief.

Attentive management is particularly important to minimize acute and subacute hemorrhoidal complications induced by the straining associated with vaginal delivery.

Elderly persons

Elderly patients appear to be particularly prone to constipation. The rate of self-reported constipation rapidly increases in patients older than 65 years. Careful review of prescribed medications may reveal one or more agents that may potentiate constipation.

Manipulating their diets and encouraging patients to exercise are the cornerstones of treatment. Laxatives may be required, particularly in patients with a history of chronic laxative abuse.

Children

Constipation is frequently diet-related in children, particularly in toddlers who are being switched from formula feeds to milk. Small children are especially liable to experience constipation that is more prolonged. This is associated with painful bowel movements caused by an acute anal fissure, which forces the child to avoid bowel movements. ^[49]

Painful defecation produces a vicious positive feedback cycle in these children. The child suppresses the urge to defecate, and this results in the formation of a larger and harder stool. When the stools eventually emerge, the pain of defecation is worse, encouraging the child to retain the stools further. Thus, the vicious cycle continues.

Prescribing long-term laxatives for a period of several weeks may be necessary in order to force the child to defecate daily until the cause of the anorectal pain is resolved and the fecal retention behavior is unlearned. Once this pattern has been unlearned, usually within several weeks, laxatives should be gradually tapered off while the use of fiber and fluid supplementation should indefinitely continue. Failure to taper the laxatives without the return of constipation indicates the need for a gastroenterologic consultation to rule out an underlying problem.

The first-line therapy remains dietary manipulation, with increased fluid intake and increased ingestion of fiber, whether via natural sources such as fruits and vegetables or via supplements containing more purified forms of fiber (eg, wheat germ, psyllium, methylcellulose, and malted barley extract). These may be mixed with liquids and administered with the help of a child’s feeding bottle. Stool softeners and local care of any anal fissures may be helpful.

Mentally incapacitated individuals

In mentally incapacitated patients with a pattern of bowel retention, resolution of this pattern requires aggressive short-term use of laxatives, stool softeners, and local care of any anal fissures. As with children, once this pattern is unlearned, laxatives should be gradually tapered off while fiber and fluid supplementation continues indefinitely. If the laxatives cannot be tapered without constipation returning, a gastroenterologic consultation is required to rule out an underlying problem.

Opioid-induced constipation

Opioid-induced constipation (OIC) is a common adverse effect of opioid use. An estimated 40%-80% of patients receiving long-term opioid therapy experience OIC, which can be severe enough to cause discontinuation of opioid therapy. The problem is caused by the binding of opioids to peripheral opioid receptors in the gastrointestinal tract, resulting in absorption of electrolytes, such as chloride, with a subsequent reduction in small intestinal fluid. Activation of enteric opioid receptors also results in abnormal gastrointestinal motility.

Medications to treat OIC and provide analgesia have been approved by the FDA. Lubiprostone (Amitiza) was approved in 2013 and is the first oral treatment for OIC in adults with chronic noncancer pain. ^{[50, 51]} The drug is a specific activator of CIC-2 chloride channels in the intestinal epithelium and bypasses the antisecretory action of opiates by activation of apical CIC-2 channels. Approval was based on results from 12-week phase 3 studies in patients taking opioids, including morphine, oxycodone, and fentanyl, for chronic noncancer pain and from a long-term open-label safety study. ^[50]

Naloxegol (Movantik) is a peripherally-acting mu-opioid receptor antagonist (PAMORA) that was approved by the FDA in September 2014 for OIC in adults with chronic noncancer pain. ^{[52, 53]} Approval was based on two randomized, multicenter, placebo-controlled, 12-week studies involving 1352 adult patients.

In the first study, 44% of patients treated with 25 mg of naloxegol and 41% of those treated with 12.5 mg of naloxegol had an increase in the number of bowel movements per week, compared with 29% of patients who received placebo. ^[52] Results were similar in the second study. Common adverse effects included abdominal pain, diarrhea, headache, and excessive gas. The FDA is requiring a postmarketing study to further examine the potential risk for cardiovascular adverse events with naloxegol treatment.

Data from the KODIAC clinical trial program regarding naloxegol consisted of 4 studies: KODIAC-4, -5, -7, and -8. ^{[54, 55]} KODIAC-4 and -5 were placebo controlled, double-blind, 12-week studies assessing safety and efficacy, ^[54] whereas KODIAC-7 was a 12-week safety extension to KODIAC-4, and KODIAC-8 was a 52-week open-label, long-term safety study. ^[55]

Methylnaltrexone (Relistor) is a PAMORA indicated for opioid-induced constipation in adults with chronic noncancer pain. ^[56] It is also indicated for adults with advanced illness who are receiving palliative care when response to laxative therapy has been insufficient. In a randomized, double blind, placebo-controlled trial, patients (n = 312) with chronic noncancer pain were given methylnaltrexone 12 mg SC once daily. A significantly greater portion of patients taking daily methylnaltrexone reported having 3 or more spontaneous bowel movements per week during the 4-week double-blind period compared to those taking placebo (59% vs 38%). Following the first dose, 33% of patients in the treatment group had a spontaneous bowel movement within 4 hours, and approximately half of patients had a spontaneous bowel movement prior to the second dose. ^[56]

Naldemedine (Symproic), another PAMORA, was approved by the FDA in March 2017 for opioid-induced constipation in adults with noncancer pain. ^[57]  Approval was based on the COMPOSE clinical trials. COMPOSE III was a 52-week, randomized, double-blind, placebo-controlled, long-term safety study that included approximately 620 adults with opioid-induced constipation and chronic noncancer pain. The treatment group showed significant improvements in weekly bowel movement frequency compared with placebo at all time points measured (P ≤.0001), and no significant opioid withdrawal signs or symptoms were noted. ^{[57, 58]}

Surgical consultation is indicated when large bowel obstruction or colonic ileus secondary to an acute intra-abdominal process is suspected. It is also indicated for anorectal complications of constipation or for surgical correction of the underlying cause. Symptomatic hemorrhoids and anal fissures represent complications of constipation until proven otherwise. Acute hemorrhoidal thrombosis requires urgent surgical consultation for evacuation of the clot and relief of pain.

For prolonged chronic hemorrhoids, a trial of aggressive medical treatment (fiber supplementation, increased water intake, exercise, decreased coffee and alcohol intake, sitz baths, and local symptomatic treatment) should be carried out before surgical consultation.

Similarly, acute anal fissures should be managed conservatively because most respond well to aggressive programs of sitz baths, stool softeners, and local anesthetic ointment.

Chronic nonhealing fissures may be managed with topical nitroglycerin or botulinum toxin injections with reasonable success. However, the long-term recurrence rate after such therapy has yet to be established. Many of these patients may require surgical sphincterotomy. Uncontrolled anal dilation has become less popular than sphincterotomy because of concerns over an increased risk of sphincter injury. A colorectal surgeon should be consulted for patients with chronic fissures to evaluate the need for surgical intervention and to consider biopsy of the fissure to rule out malignancy.

Perirectal abscess and fistula in ano may be related to chronic constipation. These complications do not respond to medical management and require surgical referral.

A consultation with a gastroenterologist is necessary to rule out other colonic processes and to assist with the long-term program of stool softener and laxative use in patients who do not respond to simple measures.

Either a gastroenterologist or a surgeon may be consulted for lower GI endoscopy, depending on local referral patterns and the availability of expertise, or (in adults) to differentiate benign solitary rectal ulcers from rectal malignancy.

A psychological or psychiatric consultation may be appropriate before surgical intervention to treat patients with potential or identified psychological issues.

After constipation resolves in a patient who was acutely constipated, outpatient care requires the following measures:

• Confirming that the patient is not chronically constipated

• Ruling out colorectal pathology

For a patient who is chronically constipated, outpatient care may include the following:

• Colonic imaging or endoscopic visualization

• Dietary management

• If these measures fail in a compliant patient, further evaluation