Spring 2015

Constipation is the difficulty or infrequent passage of stool. Normal frequency ranges from 2-3 times daily to 2- 3 times weekly. Patients may experience abdominal bloating, headaches or a sense of rectal fullness from incomplete evacuation of feces. The normal frequency of bowel movements varies with age. Newborn infants frequently defecate an average of two to 2.9 times a day. This frequency gradually declines over time, and the average number of stools is 1.8 in children who are one to three years of age and 1 stool per day in children who are older than three years of age. However, there is wide variation in these numbers. 2

Although there is no universally accepted definition of constipation in clinical practice, the following have been proposed: difficulty in passing feces or fewer than three evacuations per week. The Rome III classification refers to functional constipation when patients have no organic causes but present with two or more of the symptoms listed in the following table. 3

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Usually, constipation is not a sign of serious illness but rather “functional constipation” or “withholding constipation.” Functional constipation is constipation without an organic cause. More than 95% of children over the age of one year with constipation have functional constipation. Most commonly, it is due to a painful bowel movement which then leads to voluntary withholding. However, a small percentage may have a more serious illness such as gastrointestinal diseases (e.g., Hirschsprung’s disease), metabolic causes (e.g., electrolyte abnormalities), diabetes mellitus or insipidus, cystic fibrosis, or neurological diseases 6

PATHOPHYSIOLOGY The primary action of the muscles within the gut wall is to mix bowel contents, enhancing enzymatic and bacterial breakdown of food into reabsorbable nutrients and water and to propel the contents (peristalsis) towards the anus. In the large bowel, mass movements of peristalsis last 10–30 minutes and occur only 1–3 times a day, particularly during the first hour after breakfast. They are triggered by gastric distension, i.e. meals and physical activity 7

The propulsion of feces into the rectum brings about the desire to defecate and stimulates defecation reflexes. These reflexes act both locally in the nerves of the bowel wall (mysenteric plexus) and also via the spinal cord. They lead to distal colonic as well as rectal peristalsis. Hence, once defecation is initiated with the aid of abdominal muscle contraction, peristalsis in the rest of the colon brings more stool to the rectum to be expelled 8

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Common Causes of Constipation. Insufficient dietary fibers. Lack of exercise. Poor bowel habits. Medications. Organic problems such as IBS, hypothyroidism, Parkinson’s disease, intestinal obstruction and tumors. 10

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Non-Pharmacological.  The key to treating most patients with constipation is correction of dietary deficiencies. These generally involve increasing fiber and fluid intake and decreasing the use of constipating agents, such as milk products, coffee, tea, and alcohol.  Increase exercise.  Bowel training to increase regularity. 13 Treatment.

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Dietary fiber is available in diverse natural sources, such as fruits, vegetables, and cereals. It 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. Conversely, American patients respond reasonably well to prescriptions and often seek them. Prescribing a fiber supplement, such as wheat, psyllium, or methylcellulose, is often useful. 15

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, most consumed fluids consist of coffee, tea, and alcohol. Patients should understand that this practice is counterproductive because of the diuretic effects of these products. The author usually recommends that patients decrease consumption of coffee, tea, and alcohol as much as possible, and they should consume an extra glass of water for every drink of coffee, tea, or alcohol. 16

Pharmacological treatment for functional constipation can be divided into disimpaction and maintenance treatment. Disimpaction, if necessary, can be performed manually (physical removal of stool) or pharmacologically. In children, disimpaction is most often performed with medication so as to avoid traumatizing the child. The goals in treating constipation are to produce soft, painless stools and to prevent the reaccumulation of feces. These outcomes are achieved through a combination of education, behavioural modification, daily maintenance stool softeners and dietary modification. Fecal disimpaction may be necessary at the outset of treatment. 17

Disimpaction can be achieved by either oral or rectal medication. In a double-blind uncontrolled study, it was shown that the three-day administration of polyethylene glycol (PEG) 3350 at a dose of 1 g/kg/day to 1.5 g/kg/day (maximum dose 100 g/day) successfully disimpacted 95% of children, and was well tolerated. Another study showed that a regimen of daily enemas for six days was equally as effective as PEG 3350 (1.5 g/kg/day) in relieving disimpaction, but may be less well tolerated. High-dose mineral oil has also been shown to be effective. 18

Children with severe impaction may need to be admitted to hospital or an outpatient medical unit for nasogastric lavage with PEG solution if the volume required is intolerable orally. This is usually continued until the rectal effluent is clear. Digital disimpaction cannot be recommended based on available information, and may have harmful effects 19

Pharmacologic Treatment. Laxatives are classified based on their mechanisms of action into: 1) Bulk-forming laxatives. These are natural or synthetic polysaccharide derivatives that adsorb water to soften the stool and increase bulk, which stimulates peristalsis. They work in both small and large intestines. The onset of action is slow (12 up to 72 hrs). Used to prevent rather than treat acute constipation. Must be given with at least 8 oz water. Shouldn’t be given to patients with obstructive bowel lesions or Crohn’s disease. 20

1) Natural bulk-forming laxatives. a) Psyllium. Adult dose is 3.5g in 8 oz water 1-3 times daily. Child dose is half the adult dose. b) Malt soup extract g 2-4 times daily. Child dose is 16 g 1-2 times daily. Synthetic bulk forming laxatives. a) methylcellulose. 1-2 g given 1-3 times daily. b) Polycarbophil. 1g given 1-4 times daily. Ca-polycarbophil may interact with tetracyclines and fluoroquinolone antibiotics. 21

 Many of the available products vary substantially in their potency. For instance, sugar-free Metamucil 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 remains controversial and awaits further exploration. 22

 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. Some patients have preferences based on the taste of the product or other subjective reasons. In particular, rare patients who cannot tolerate fermentable fiber supplementation because of resulting gas or bloating may do better with methylcellulose, while others find the quality of the stool, taste preferences, or both favoring psyllium supplementation. 23

 To avoid patient noncompliance due to the development of cramping and bloating that 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 achieve 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. 24

2) saline and osmotic laxatives. Work by creating an osmotic gradient to pull water into the small and large intestines which leads to distention of the intestinal lumen and increase in peristalsis. They also increase the activity of cholecystokinin- pancreozymin, an enzyme that increases the secretion of fluids into the GI tract. Onset of action varies depending on the ingredient and dosage form; rectal formulations (suppositories and enemas) have an onset of action of 5-30 minutes. Oral preparations work within 3-6 hrs. a) Saline laxatives. Include sodium and magnesium salts. About 20% of magnesium may be absorbed so should use cautiously in pts with renal impairment. 25

Use cautiously in pts with hypertension or heart failure. Magnesium citrate: adult ½ bottle, children 6-12 years ¼ bottle taken at once. Magnesium hydroxide. Adults 30 ml. children 6-12 years 15 ml. children 2-6 years 5-15 ml taken at once. Magnesium sulfate. Adults 5-10 ml with 8 oz water. Sodium phosphate. Adults mls. b) Osmotic laxatives. Glycerin: through rectal route. Adults 3 g suppositories. Children 1.5 g suppositories. Lactulose. Also used to decrease blood ammonia levels in patients with hepatic encephalopathy. May cause flatulence and cramping and should be taken with fruit juice or milk to improve palatability. Adult dose is ml given 1-2 times daily. 26

Sorbitol. A nonabsorbable sugar, similar in efficacy to lactulose. Administeredd orally (70% solution) or rectally (25% solution). Adult dose is 15 ml orally or 120 ml rectally. Polyethylene glycol more effective than lactulose and sorbitol. Used if other treatments failed. Can be used for more than one week. 27

3) stimulant laxatives. Oral preparations have an onset of action of 6-10 hrs. rectal minutes. Should not be used for more than a week. Can cause cathartic colon if used regularly which resembles symptoms of ulcerative colitis. Sennosides. Adults mg twice daily. Cascara anthraquinones Bisacodyl. Enteric coated tablets. Should not be taken within 1 hr of milk or antacid. Oral dose is 5-15 mg daily. Rectal dose is 10 mg (1 suppository) daily. Castor oil. Onset of action 2-6 hrs. strong cathartic action. Adult dose is ml. Pregnancy Risk Category X 28

4) emollient laxatives. Act as surfactants by allowing absorption of water into the stool, which makes the softened stool easier to pass. Have slow onset of action (24-72 hrs). Laxatives of choice for post MI patients. They are salts of docusate. Na, K and Ca salts. Dose for Na docusate is 50 mg twice daily. May increase the absorption of mineral oil. 5) Lubricant laxatives. Mineral oil works by increasing water retention in the stool to soften the stool. Onset of action is 6-8 hrs. adult dose is ml daily. Can decrease absorption of fat soluble vitamins. Shouldn’t be given to elderly, children less than 6 or pts with rectal bleeding or appendicitis. 29

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Summary of Guidelines: Adults The first step to treat most cases of constipation is to provide more fiber, either as a high-fiber diet or as supplements. Fiber laxatives increase the frequency of bowel movements by one to two per week. Fiber intake should be increased gradually over seven to ten days, starting with twice daily administration. The Institute of Medicine recommends total daily fiber intake of 38 grams for men and 25 grams for women under the age of 50, and 30 grams for men and 21 grams for women over the age of

In most patients, the next step is to add an inexpensive saline laxative such as milk of magnesia. Stimulant laxatives, lactulose, and polyethylene glycol are recommended if these interventions fail. Sorbitol and lactulose have similar efficacy, but their use is limited because they cause gas. 32

Some experts are recommending polyethylene glycol (available OTC) as an alternative to saline laxatives such as milk of magnesia or before stimulants such as senna or bisacodyl for its benign side-effect profile. Long term use of milk of magnesia has been associated with electrolyte imbalances and should be avoided in patients with renal dysfunction. 33

For chronic constipation, psyllium, polyethylene glycol, lactulose, or lubiprostone (Amitiza ® ) are recommended. Amitiza should be reserved for individuals with chronic constipation who don’t respond to or tolerate laxatives. There is not enough evidence to support the use of stool softeners, stimulant laxatives (e.g., senna, bisacodyl), milk of magnesia, calcium polycarbophil, methylcellulose, or bran in chronic constipation. Both polyethylene glycol and lactulose have sufficient evidence to support their use in chronic constipation. 34

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36 Canadian Paediatric Society, Paediatr Child Health 2011;16(10):661-5

CONSTIPATION IN INFANTS In infancy, constipation is mostly functional, but a heightened vigilance for identifying red flags suggestive of an organic disorder in this age group is necessary. It is known that breastfed infants can have greater variability than formula-fed infants in stool frequency. (Some normal breastfed newborns may stool with each feeding or may not have a bowel movement any more often than every seven to 10 days.). Mineral oil is contraindicated in infants because of uncoordinated swallowing and the risk of aspiration and subsequent pneumonitis. Increased intake of fluids and reducing excess cow’s milk intake may be helpful for constipation in older infants. 37

Recommendations to add brown sugar to formula or water for infant constipation are anecdotal and not evidence based, as well as pose a risk of caries development. Lactulose and glycerin suppositories may be used. Two retrospective chart reviews examining the safety of PEG 3350 in infants have been reported. Both showed that at doses of 0.8 g/kg/day, PEG was well tolerated, effective and safe in the management of constipation in infants younger than 18 months of age. 38

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