Etiology of Constipation
Common factors that contribute to the development of constipation in the general population are diet, altered bowel habits, inadequate fluid intake, and lack of exercise. Constipation can be a presenting symptom of cancer, or it can occur later as a side effect of a growing tumor or treatment of the tumor. For patients with cancer, additional causative factors are the tumor itself, cancer-related problems, the effects of drug therapy for cancer or for cancer pain, and other concurrent processes such as organ failure, decreased mobility, and depression. Physiologic factors include inadequate oral intake, dehydration, inadequate intake of dietary fiber, or organ failure. Any or all of these factors can occur because of the disease process, aging, debilitation, or treatment. (Refer to the Nausea, Vomiting, Constipation, and Bowel Obstruction in Advanced Cancer section in the PDQ summary on Nausea and Vomiting for more information.)Causes of Constipation
- Chemotherapy (e.g., any agent that can cause autonomic nervous system changes such as vinca alkaloids, oxaliplatins, taxanes, and thalidomide).*
- Opioids or sedatives.
- Anticholinergic preparations (e.g., gastrointestinal antispasmodics, antiparkinsonism agents, and antidepressants).
- Calcium- and aluminum-based antacids.
- Vitamin supplements (e.g., iron and calcium).
- Tranquilizers and sleeping medications.
- General anesthesia and pudendal blocks.
- Inadequate fluid intake.*
Altered bowel habits
- Repeatedly ignoring defecation reflex.
- Excessive use of laxatives and/or enemas.
Prolonged immobility* and/or inadequate exercise
- Spinal cord injury or compression, fractures, fatigue, weakness, or inactivity (including bedrest).
- Intolerance with respiratory or cardiac problems.
- Irritable colon, diverticulitis, or tumor.*
Neuromuscular disorders (disruption of innervation leads to atony of the bowel)
- Neurological lesions (cerebral tumors).
- Spinal cord injury or compression.*
- Cerebrovascular accident with paresis.
- Weak abdominal muscles.
- Hypothyroidism and lead poisoning.
- Chronic illness.
Inability to increase intra-abdominal pressure
- Any neuromuscular impairment of the diaphragm or abdominal muscles.
- Massive abdominal hernias.
Atony of muscles
- Cachexia, anemia, or carcinoma.*
- Inability to get to the bathroom without assistance.
- Unfamiliar or hurried environment.
- Excess heat leading to dehydration.
- Change in bathroom habits (e.g., use of a bedpan).
- Lack of privacy.
Narrowing of colon lumen
- Related to scarring from radiation therapy, surgical anastomosis, or compression from growth of extrinsic tumor.
[Note: *Frequently seen in oncology patients.]
Constipation is frequently the result of autonomic neuropathy caused by the vinca alkaloids, taxanes, and thalidomide. Other drugs such as opioid analgesics or anticholinergics (antidepressants and antihistamines) may lead to constipation by causing decreased sensitivity to the defecation reflexes and decreased gut motility. Since constipation is common with the use of opioids, a bowel regimen should be initiated at the time opioids are prescribed and continued for as long as the patient takes opioids. Opioids produce varying degrees of constipation, suggesting a dose-related phenomenon. One study suggests that clinicians should not base laxative prescribing on the opioid dose, but rather should titrate the laxative according to bowel function. Lower doses of opioids or weaker opioids, such as codeine, are just as likely to cause constipation. (Refer to the Side Effects of Opioids section in the PDQ summary on Pain for more information.)
Other diseases, such as diabetes (with autonomic neuropathy) and hypothyroidism, may cause constipation. Metabolic disorders, such as hypokalemia and hypercalcemia, also predispose cancer patients to developing constipation. Once these disorders are corrected, constipation should subside.Assessment of Constipation
A normal bowel pattern is having at least three stools per week and no more than three per day; however, these criteria may be inappropriate for cancer patients.[1,3] Constipation should be viewed as a subjective symptom involving the complaints of decreased frequency with incomplete passage of dry, hard stool. A thorough history of the patient’s bowel pattern, dietary changes, and medications, along with a physical examination, can identify possible causes of constipation. The evaluation should also include assessment of associated symptoms such as distention, flatus, cramping, or rectal fullness. A digital rectal examination should always be done to rule out fecal impaction at the level of the rectum. A test for occult blood will be helpful in determining a possible intraluminal lesion. A thorough examination of the gastrointestinal tract is necessary if cancer is suspected.
The following questions may provide a useful assessment guide:
- What is normal for the patient (frequency, amount, and timing)?
- When was the last bowel movement? What was the amount, consistency, and color? Was blood passed with it?
- Has the patient been having any abdominal discomfort, cramping, nausea or vomiting, pain, excessive gas, or rectal fullness?
- Does the patient regularly use laxatives or enemas? What does the patient usually do to relieve constipation? Does it usually work?
- What type of diet does the patient follow? How much and what type of fluids are taken on a regular basis?
- What medication (dose and frequency) is the patient taking?
- Is this symptom a recent change?
- How many times a day is flatus passed?
Physical assessment will determine the presence or absence of bowel sounds, flatus, or abdominal distention. Patients with colostomies should also be assessed for constipation. Dietary habits, fluid intake, activity levels, and use of opioids in these patients should be assessed. Irrigation of the colostomy should be monitored for proper technique.Management of Constipation
Comprehensive management of constipation includes prevention (if possible), elimination of causative factors, and judicious use of laxatives. Some patients can be encouraged to increase dietary fiber (fruits; green, leafy vegetables; 100% whole-grain cereals and breads; and bran) and to increase fluid intake to one-half ounce per pound of body weight daily (if not contraindicated by renal or heart disease). (Refer to the PDQ summary on Nutrition in Cancer Care for more information.) A study that involved geriatric patients compared the efficacy, cost, and ease of administration of a natural laxative mixture (raisins, currants, prunes, figs, dates, and prune concentrate) with protocols using stool softeners, lactulose, and other laxatives. Results indicated lower costs, more natural and regular bowel movements, and increased ease of administration with natural laxatives. Even though generalization from these findings was limited by small sample size, additional exploration of natural laxatives in cancer patient populations might be useful. A program for prevention of constipation in cancer patients is described below.
- Establish the patient’s normal bowel pattern and habits (time of day for normal bowel movement, consistency, color, and amount).
- Explore the patient’s level of understanding and compliance relating to exercise level, mobility, and diet (fluid, fruit, and fiber intake).
- Determine normal or usual use of laxatives, stimulants, or enemas.
- Determine laboratory values, specifically looking at platelet count.
- Conduct a physical assessment of the rectum (or stoma) to rule out impaction.
Commonly used interventions:
- Record bowel movements daily.
- Encourage patient to increase fluid intake, with a goal of drinking eight 8-oz (240-mL) glasses of fluid daily unless contraindicated.
- Encourage regular exercise, including abdominal exercises in bed or moving from bed to chair if the patient is not ambulatory.
- Encourage adequate fiber intake. Experts recommend that:
- Healthy adults consume 20 g to 35 g of fiber per day (average consumption is 11 g).
- Children and adolescents consume the number of grams of fiber equal to their age plus 5—for example, a 10-year-old should consume 15 g of fiber per day (10 + 5). This guideline applies until age 18 years; at that time, the adult recommendations should be followed.
While there are no specific fiber recommendations for cancer patients, they should also be encouraged to eat more high-fiber foods such as fruits (e.g., raisins, prunes, peaches, and apples), vegetables (e.g., squash, broccoli, carrots, and celery), and 100% whole-grain cereals, breads, and bran. Increased fiber intake must be accompanied by increased fluid intake, or constipation may result. High fiber intake is contraindicated in patients at increased risk for bowel obstruction, such as those with a history of bowel obstruction or status postcolostomy.
- Provide a warm or hot drink approximately one-half hour before time of patient’s usual defecation.
- Provide privacy and quiet time at the patient’s usual or planned time for defecation.
- Provide toilet or bedside commode and appropriate assistive devices; avoid bedpan use whenever possible.
Another approach, shown below in two parts, is adapted from the MD Anderson Cancer Center practice consensus algorithm for the prevention and management of opioid-induced constipation. [Note: Copyright 2008 The University of Texas MD Anderson Cancer Center]
MD Anderson Cancer Center Algorithm for the Prevention of Opioid-induced Constipation
- Unless there are existing alterations in bowel patterns (e.g., bowel obstruction or diarrhea), all patients receiving opioids should be started on a laxative bowel regimen and receive education for bowel management.
- Stimulant laxative plus stool softener (e.g., Senokot-S [senna 8.6 mg plus docusate 50 mg]), two tablets per day and titrate up (maximum nine tablets per day).
- Ensure adequate fluids, dietary fiber, and exercise, if feasible.
- Prune juice followed by warm beverage may be considered.
MD Anderson Cancer Center Algorithm for the Management of Opioid-induced Constipation
- Assess potential cause of constipation (e.g., recent opioid dose increase, use of other constipating medications, or new bowel obstruction).
- Increase Senokot-S (or senna and docusate tablets, if using separately), and add one or both of the following:
- Milk of magnesia oral concentrate (1170/5 mL), 10 mL by mouth 2 to 4 times per day.
- Polyethylene glycol (MiraLAX), 17 g in 8-oz beverage daily.
- If no response to above, perform digital rectal examination to rule out low impaction. Continue above steps AND:
- If impacted, disimpact manually if stool is soft. If not, soften with mineral oil fleets enema before disimpaction. Follow up with milk of molasses enemas until clear with no formed stools.
- Consider use of rescue analgesics before disimpaction.
- If not impacted on rectal examination, patient may still have higher level impaction; if history is appropriate, consider abdominal imaging and/or administer milk of molasses enema with magnesium citrate 8 oz by mouth. Consider bowel management consult.
- If patient is neutropenic or thrombocytopenic, arrange for bowel management consult.
- Start one of the following regimens if the patient has not had a stool in 3 days or on the first day that any patient starts taking drugs associated with constipation:
- Stool softeners (e.g., docusate sodium, one to two capsules per day). For opioid-related constipation, stool softeners should be used in combination with a stimulant laxative. Bulk-producing agents are not recommended in a regimen used to counteract the bowel effects of opioids.
- Two tablets of a senna preparation twice daily.
- One bisacodyl tablet at bedtime.
- Milk of magnesia, 30 to 45 mL, if a bowel movement is not achieved in 24 hours after other methods are instituted.
- If the amount of stool is still inadequate, increase stool softeners up to six capsules per day or a senna preparation (e.g., Senokot) gradually to a maximum of eight tablets (four tablets twice a day); bisacodyl may be increased gradually to three tablets.
- If the amount of stool is still inadequate, a glycerin or bisacodyl suppository or enema (phosphate/biphosphate, oil retention, or tap water) should be used with caution, especially in patients with neutropenia or thrombocytopenia.
Medical management includes the administration of saline or chemical laxatives, suppositories, enemas, or agents that increase bulk.
Rectal agents should be avoided in cancer patients at risk for thrombocytopenia, leukopenia, and/or mucositis from cancer and its treatment. In the immunocompromised patient, no manipulation of the anus should occur, that is, no rectal examinations, no suppositories, and no enemas. These actions can lead to the development of anal fissures or abscesses, which are portals of entry for infection. Also, the stoma of a patient with neutropenia should not be manipulated.Medical Agents for Constipation
- Bulk producers are natural or semisynthetic polysaccharide and cellulose. They work with the body’s natural processes to hold water in the intestinal tract, soften the stool, and increase the frequency of the passage of stool. Bulk producers are not recommended for use in a regimen to counteract the bowel effects of opioids.
- Onset: 12 to 24 hours (may be delayed up to 72 hours).
- Caution: Patients should take with two full 8-oz (240-mL) glasses of water and maintain adequate hydration to avoid the risk of developing a bowel obstruction. Avoid administering psyllium with salicylates, nitrofurantoin, and digitalis because psyllium decreases the actions of these drugs. Avoid use if intestinal obstruction is suspected.
- Use: Effective in managing irritable bowel syndrome.
- Drugs and dosages:
- Methylcellulose (Cologel): 5 to 20 cc 3 times per day with water.
- Barley malt extract (Maltsupex): Four tablets with meals and at bedtime or 2 tbsp powder or liquid 2 times per day for 3 to 4 days, then 1 to 2 tbsp at bedtime.
- Psyllium: Varies from 1 tbsp to one packet, depending on brand, 1 to 3 times per day.
- The high osmolarity of the compounds in saline laxatives attracts water into the lumen of the intestines. The fluid accumulation alters the stool consistency, distends the bowel, and induces peristaltic movement. Cramps may occur.
- Onset: 0.5 to 3 hours.
- Caution: Repeated use can alter fluid and electrolyte balance. Avoid magnesium-containing laxatives in patients with renal dysfunction. Avoid sodium-containing laxatives in patients with edema, congestive heart failure, megacolon, or hypertension.
- Use: Mostly as a bowel preparation to clear the bowels for rectal or bowel examinations.
- Drugs and dosages:
- Magnesium sulfate: 15 g in a glass of water.
- Milk of magnesia: 10 to 20 cc if concentrated, 15 to 30 cc if regular.
- Magnesium citrate: 240 cc.
- Sodium phosphate: 4 to 8 g dissolved in water.
- Monobasic and dibasic sodium phosphate (Fleet Phospho-soda): 20 to 40 mL mixed with 4 oz cold water.
- Stimulant laxatives increase motor activity of the bowels by direct action on the intestines.
- Onset: 6 to 10 hours.
- Caution: Prolonged use of these drugs causes laxative dependency and loss of normal bowel function. Prolonged use of danthron discolors rectal mucosa and discolors alkaline urine red. Bisacodyl must be excreted in bile to be active and is not effective with biliary obstruction or diversion. Avoid bisacodyl with known or suspected ulcerative lesions of the colon. These medications may cause cramping.
- Drug interactions: Avoid taking bisacodyl within 1 hour of taking antacids, milk, or cimetidine because they cause premature dissolving of the enteric coating, which results in gastric or duodenal stimulation. There is an increased absorption of danthron when it is given with docusate.
- Use: To evacuate bowel for rectal or bowel examinations. Most of the stimulant laxatives act on the colon.
- Drugs and dosages:
- Danthron: 37.5 to 150 mg with evening meal or 1 hour after evening meal.
- Calcium salts of sennosides: 12 to 24 mg at bedtime; senna: Senolax, Seneson, or Black-Draught (two tablets); Senokot (two tablets or 10–15 cc at bedtime).
- Bisacodyl: 10 to 15 mg swallowed whole, not chewed, or a 10-mg suppository.
- Lubricant laxatives lubricate intestinal mucosa and soften stool.
- Caution: Administer on empty stomach at bedtime. Mineral oil prevents absorption of oil-soluble vitamins and drugs. With older patients, aspiration potential suggests that mineral oil should be avoided because it can cause lipid pneumonitis. It can interfere with postoperative healing of anorectal surgery. Avoid giving with docusate sodium. Docusate sodium causes increased systemic absorption of mineral oil.
- Use: Prophylactically to prevent straining in patients for whom straining would be dangerous.
- Drugs and dosages:
- Mineral oil: 5 to 30 cc at bedtime.
- Fecal softeners promote water retention in the fecal mass, thus softening the stool. Up to 3 days may pass before an effect is noted. Stool softeners and emollient laxatives are of limited use because of colonic resorption of water from the forming stool.
- Fecal softeners should not be used as the sole regimen but may be useful given in combination with stimulant laxatives.
- Caution: May increase the systemic absorption of mineral oil when administered together.
- Use: Prophylactically to prevent straining. Most beneficial when stool is hard.
- Drugs and dosages:
- Docusate sodium: 50 to 240 mg taken with a full glass of water.
- Docusate calcium: 240 mg each day until bowel movement is normal.
- Docusate potassium: 100 to 300 mg each day until bowel movement is normal; should increase daily fluid intake.
- Poloxamer 188: 188 mg (480 mg at bedtime).
Lactulose (Cholac, Cephulac)
- Lactulose is a synthetic disaccharide that passes to the colon undigested. When it is broken down in the colon, it produces lactic acid, formic acid, acetic acid, and carbon dioxide. These products increase the osmotic pressure, thus increasing the amount of water held in the stool, which softens the stool and increases the frequency of passage.
- Onset: 24 to 48 hours.
- Caution: Excessive amounts may cause diarrhea with electrolyte losses. Avoid giving to patients with acute abdomen, fecal impaction, or obstruction.
- Dosage: 15 to 30 cc each day (contains 10–20 g of lactulose).
Polyethylene glycol and electrolytes (Golytely, Colyte)
- Five packets are mixed with 1 gallon (3.785 L) of tap water and contain the following: polyethylene glycol (227.1 g), sodium chloride (5.53 g), potassium chloride (2.82 g), sodium bicarbonate (6.36 g), and sodium sulfate (anhydrous, 21.5 g). Do not add flavorings. Serve chilled to improve palatability. Can be stored up to 48 hours in the refrigerator.
- Use: To clear bowel with minimal water and sodium loss or gain.
Opioid antagonists (naloxone, methylnaltrexone)
- Caution: Administer only if other drugs have failed.
- Subcutaneous methylnaltrexone, 0.15 mg per kilogram of body weight, can be administered daily or every other day to treat opioid-induced constipation. In a study of palliative care patients, including those with cancer and noncancer etiologies, approximately one-half of patients defecated within 4 hours of receiving the injection, with 30% of patients having a bowel movement within the first 30 minutes.
- In two studies of palliative care patients—one a single-dose trial and the other a 2-week every-other-day-dose trial—there was no evidence of withdrawal or other central effects of the opioid, and pain scores remained unchanged.[6,7]
- Caution: This drug is contraindicated in patients with bowel obstruction.
- The most common side effects are dizziness, nausea, abdominal pain, flatulence, and diarrhea.
- A study of prolonged-released naloxone in an oxycodone:naloxone ratio of 2:1 (average results of 40:20 mg, 60:30 mg, and 80:40 mg oxycodone:naloxone combination relative to placebo) demonstrated improved bowel function without reversal of analgesia.
Check NCI’s list of cancer clinical trials for U.S. supportive and palliative care trials about constipation, impaction, and bowel obstruction that are now accepting participants. The list of trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.References
- Portenoy RK: Constipation in the cancer patient: causes and management. Med Clin North Am 71 (2): 303-11, 1987. [PUBMED Abstract]
- Bennett M, Cresswell H: Factors influencing constipation in advanced cancer patients: a prospective study of opioid dose, dantron dose and physical functioning. Palliat Med 17 (5): 418-22, 2003. [PUBMED Abstract]
- McShane RE, McLane AM: Constipation. Consensual and empirical validation. Nurs Clin North Am 20 (4): 801-8, 1985. [PUBMED Abstract]
- Bruera E, Suarez-Almazor M, Velasco A, et al.: The assessment of constipation in terminal cancer patients admitted to a palliative care unit: a retrospective review. J Pain Symptom Manage 9 (8): 515-9, 1994. [PUBMED Abstract]
- Beverley L, Travis I: Constipation: proposed natural laxative mixtures. J Gerontol Nurs 18 (10): 5-12, 1992. [PUBMED Abstract]
- Thomas J, Karver S, Cooney GA, et al.: Methylnaltrexone for opioid-induced constipation in advanced illness. N Engl J Med 358 (22): 2332-43, 2008. [PUBMED Abstract]
- Portenoy RK, Thomas J, Moehl Boatwright ML, et al.: Subcutaneous methylnaltrexone for the treatment of opioid-induced constipation in patients with advanced illness: a double-blind, randomized, parallel group, dose-ranging study. J Pain Symptom Manage 35 (5): 458-68, 2008. [PUBMED Abstract]
- Meissner W, Leyendecker P, Mueller-Lissner S, et al.: A randomised controlled trial with prolonged-release oral oxycodone and naloxone to prevent and reverse opioid-induced constipation. Eur J Pain 13 (1): 56-64, 2009. [PUBMED Abstract]