A thorough history and physical examination is generally sufficient to allow the practitioner to establish whether the child requires further evaluation (Fig. 1, box 4) or has functional constipation (Fig. 1, box 5).
MANAGEMENT OF CHILDREN WITH FUNCTIONAL CONSTIPATION
The general approach to the child with functional constipation includes the following steps: determine whether fecal impaction is present (Fig. 1, box 6), treat the impaction if present (Fig. 1, box 7), initiate treatment with oral medication, provide parental education and close follow-up, and adjust medications as necessary (Fig. 1, box 10).
The education of the family and the demystification of constipation, including an explanation of the pathogenesis of constipation, are the first steps in treatment. If fecal soiling is present, an important goal for both the child and the parent is to remove negative attributions. It is especially important for parents to understand that soiling from overflow incontinence is not a willful and defiant maneuver. Parents are encouraged to maintain a consistent, positive, and supportive attitude in all aspects of treatment. It may be necessary to repeat the education and demystification processes several times during treatment (16).
Fecal impaction is defined as a hard mass in the lower abdomen identified during physical examination, a dilated rectum filled with a large amount of stool found during rectal examination, or excessive stool in the colon identified by abdominal radiography (17). Disimpaction is necessary before initiation of maintenance therapy. It may be accomplished with either oral or rectal medication (Fig. 1, box 7). In uncontrolled clinical trials, disimpaction by the oral route, the rectal route, or a combination of the two has been shown to be effective (Table 7) (18). There are no randomized studies that compare the effectiveness of one with the other. The oral approach is not invasive and gives a sense of power to the child, but adherence to the treatment regimen may be a problem. The rectal approach is faster but is invasive. The choice of treatment is best determined after discussing the options with the family and child.
Disimpaction with oral medication has been shown to be effective when high doses of mineral oil, polyethylene glycol electrolyte solutions, or both are used (18-20). Although there are no controlled trials demonstrating the effectiveness of high-dose magnesium hydroxide, magnesium citrate, lactulose, sorbitol, senna, or bisacodyl for initial disimpaction, these laxatives have been used successfully in that role (21,22). It is recommended that mineral oil, oral electrolyte solutions, or the listed laxatives be used alone or in combination for initial disimpaction when the oral route is selected.
Rectal disimpaction may be performed with phosphate soda enemas, saline enemas, or mineral oil enemas followed by a phosphate enema (23,24). These enemas are widely used and are effective. The use of soapsuds, tap water, and magnesium enemas is not recommended because of their potential toxicity. Rectal disimpaction has also been effectively performed with glycerin suppositories in infants (25) and bisacodyl suppositories in older children.
The Subcommittee discussed the use of digital disimpaction in chronic constipation in the primary care setting. However, there was insufficient literature on the subject, and the Subcommittee could not reach consensus on whether to discourage or recommend its use.
Once the impaction has been removed, the treatment focuses on the prevention of recurrence. In the child who has no impaction (Fig. 1, box 9) or after successful disimpaction, maintenance therapy is begun. This treatment consists of dietary interventions, behavioral modification, and laxatives to assure that bowel movements occur at normal intervals with good evacuation.
Dietary changes are commonly advised, particularly increased intake of fluids and absorbable and nonabsorbable carbohydrate, as a method to soften stools. Carbohydrates and especially sorbitol, found in some juices such as prune, pear, and apple juices, can cause increased frequency and water content of stools (26-27). No randomized controlled studies were found that demonstrated an effect on stools of increasing intakes of fluids, nonabsorbable carbohydrates, or dietary fiber in children (28). A balanced diet that includes whole grains, fruits, and vegetables is recommended as part of the treatment for constipation in children. Forceful implementation of diet is undesirable.
An important component of treatment includes behavior modification and regular toilet habits (29,30). Unhurried time on the toilet after meals is recommended. As part of the treatment of constipation, with or without overflow incontinence, it is often helpful to have children and their caregivers keep diaries of stool frequency. This can be combined with a reward system. For example, a child can use a calendar with stickers to record each stool that is passed in the toilet. The calendar can then be taken on visits with the health-care provider and can serve as both a diary and a point for positive reinforcement. In cases in which motivational or behavioral problems are interfering with successful treatment, referral to a mental health-care provider for behavior modification or other intervention may be helpful.
The successful treatment of constipation, especially with overflow incontinence, requires a family that is well organized, can complete time-consuming interventions, and is sufficiently patient to endure gradual improvements and relapses. Close follow-up by telephone and by office visit is recommended. Some families may need counseling to help them manage this problem effectively.
It is often necessary to use medication to help constipated children achieve regular bowel movements (Table 7). A prospective, randomized trial showed that the addition of medications to behavior management in children with constipation is beneficial (31). Children who received medications achieved remission significantly sooner than children who did not. The use of laxatives was most advantageous for children until they were able to maintain regular toilet habits.
When medication is necessary in the daily treatment of constipation, mineral oil (a lubricant) or magnesium hydroxide, lactulose, sorbitol (osmotic laxatives), or a combination of lubricant and laxative is recommended. At this stage in the treatment of constipation, the prolonged use of stimulant laxatives is not recommended. Extensive experience with long-term use of mineral oil (32), magnesium hydroxide (33), and lactulose or sorbitol (33) has been reported. Long-term studies show that these therapies are effective and safe (33,34). The doses and potential adverse effects of these medications are found in Table 7. Because mineral oil, magnesium hydroxide, lactulose, or sorbitol seem to be equally efficacious, the choice among these is based on safety, cost, the child's preference, ease of administration, and the practitioner's experience (Fig. 1, box 14).
A stimulant laxative may be necessary intermittently, for short periods, to avoid recurrence of an impaction (Fig. 1, box 15) (35). In this situation the use of stimulant laxatives is sometimes termed rescue therapy.
Maintenance therapy may be necessary for many months. Only when the child has been having regular bowel movements without difficulty is discontinuation considered. Primary care providers and families should be aware that relapses are common and that difficulty with bowel movements may continue into adolescence. Long-term follow-up studies have demonstrated that a significant number of children continue to require therapy to maintain regular bowel movements (36,37).
CONSULTATION WITH A SPECIALIST
Consultation with a pediatric gastrointestinal specialist becomes necessary when the therapy fails, when there is concern that an organic disease exists, or when management is complex (Fig. 1, box 20). A consultant can reevaluate the child with nonresponding constipation, exclude an underlying organic process, perform specialized tests, and offer counseling. The pediatric gastroenterologist (Fig. 1, boxes 21-23) can review previous therapies, consider using different or additional medications or higher doses of the current medications, and reassess previous management before performing additional studies (Fig. 1, box 23).
A careful review by the primary care practitioner of the differential diagnosis (Table 4) of the organic causes of constipation may be helpful at this time to determine which laboratory tests are indicated before referral to a specialist. It is recommended that the primary care physician consider whether the children who require evaluation by a specialist should have blood tests to identify evidence of hypothyroidism, hypercalcemia, celiac disease, and lead toxicity (Fig. 1, box 16). By having these tests ordered by the primary care provider just before referral to a pediatric gastroenterologist, patients who are found to have a medical problem that requires evaluation by a different subspecialist can be referred directly to the appropriate subspecialist. For example, a child with hypothyroidism can be referred directly to a pediatric endocrinologist.
Abdominal Radiograph and Transit Time
An abdominal radiograph is not indicated to establish the presence of fecal impaction if the rectal examination reveals the presence of large amounts of stool. A retrospective study in children manifesting encopresis showed that a moderate to large amount of stool found on rectal examination has high sensitivity and positive predictive value (greater than 80%) for fecal retention determined by abdominal radiograph, even using the radiologist's subjective interpretation (38). However, the specificity and negative predictive value were 50% or less. When the systematic scoring system developed by Barr et al. (17) was used for the presence of fecal retention on radiograph, the sensitivity of moderate to large amounts of stool on rectal examination improved to 92%, and the positive predictive value was 94%. However, the specificity remained at only 71%, and the negative predictive value was only 62% (39).
This suggests that, when there is doubt about whether the patient is constipated, a plain abdominal radiograph is reliable in determining the presence of fecal retention in the child who is obese or refuses a rectal examination, or in whom there are other psychological factors (sexual abuse) that make the rectal examination too traumatic. It may also be helpful in the child with a good history for constipation who does not have large amounts of stool on rectal examination (Fig. 1, box 23). In a recent study the value of the Barr score was compared with the colonic transit time. The Barr score was shown to be poorly reproducible, with low interobserver and intraobserver reliability, and there was no correlation with measurements of transit time (39).
Some patients have a history of infrequent bowel movements but have no objective findings of constipation. The history obtained from the parents and child may not be entirely accurate (40). In these patients an evaluation of colonic transit time with radiopaque markers may be helpful (Fig. 1, box 25) (41). The quantification of transit time shows whether constipation is present and provides an objective evaluation of bowel movement frequency. If the transit time is normal, the child does not have constipation. If the transit time is normal and there is no soiling, the child needs no further evaluation (Fig. 1, box 30). In children who have soiling without evidence of constipation, the best results have been achieved with behavior modification, but in some instances psychological evaluation and treatment may be necessary (Fig. 1, box 29). If the transit study is abnormal or fecal impaction is present, further evaluation is needed (Fig. 1, box 26). When there is objective evidence of constipation and it is refractory to treatment, it is important to consider Hirschsprung disease (Fig. 1, box 28).
Hirschsprung disease is the most common cause of lower intestinal obstruction in neonates and is a rare cause of intractable constipation in toddlers and school-aged children (42-44). It is characterized by absence of ganglion cells in the myenteric and submucous plexuses of the distal colon, resulting in sustained contraction of the aganglionic segment. The aganglionic segment begins at the internal anal sphincter, extending orad in a contiguous fashion. In 75% of cases, the disease is limited to the rectosigmoid area. The bowel proximal to the aganglionic zone becomes dilated because of the distal obstruction.
The incidence of Hirschsprung disease is approximately 1 in 5000 live births. The most common associated abnormality is trisomy 21. More than 90% of normal neonates and less than 10% of children with Hirschsprung disease pass meconium in the first 24 hours of life (45,46). Thus, a delayed passage of meconium by a full-term infant raises the suspicion of Hirschsprung disease. Hirschsprung disease can have symptoms of bilious vomiting, abdominal distension, and refusal to feed, all of which are suggestive of intestinal obstruction. Short-segment Hirschsprung disease may go undiagnosed until childhood. Affected children have ribbon-like stools, a distended abdomen, and, often, failure to thrive. In rare cases constipation is the only symptom. Fecal soiling is even more rare and occurs only when the aganglionic segment is extremely short.
Enterocolitis, the most feared complication of Hirschsprung disease, may be its initial manifestation. Enterocolitis has initial symptoms of sudden onset of fever, abdominal distension, and explosive and at times bloody diarrhea (47,48). Occurring most often during the second and third months of life, it is associated with a mortality of 20%. The incidence of enterocolitis can be greatly reduced by a timely diagnosis of Hirschsprung disease.
The mean age at diagnosis decreased from 18.8 months in the 1960s to 2.6 months in the 1980s because of physicians' vigilance, anorectal manometry, and early biopsy. However, in 8% to 20% of children, Hirschsprung disease remains unrecognized after the age of 3 years (49,50). Physical examination reveals a distended abdomen and a contracted anal sphincter and rectum in most children. The rectum is devoid of stool except in cases of short-segment aganglionosis. As the finger is withdrawn, there may be an explosive discharge of foul-smelling liquid stools, with decompression of the proximal normal bowel. In the older child with constipation, a careful history and a thorough physical examination are sufficient to differentiate Hirschsprung disease from functional constipation in most cases.
Once Hirschsprung disease is suspected (Fig. 1, box 28), it is recommended that the patient be evaluated at a medical center in which a pediatric gastroenterologist and a pediatric surgeon are available and where diagnostic studies can be performed. Delay in diagnosis increases the risk of enterocolitis. Rectal biopsy with histopathologic examination and rectal manometry are the only tests that can reliably exclude Hirschsprung disease. Rectal biopsies demonstrating the absence of ganglion cells in the submucosal plexus are diagnostic of Hirschsprung disease (51). The biopsies, obtained approximately 3 cm above the anal verge, must be deep enough to include adequate submucosa. Confirmation is obtained when special staining shows hypertrophied nerves. However, in total colonic aganglionosis there is both an absence of ganglion cells and an absence of hypertrophied nerves. Occasionally, suction biopsies are not diagnostic, and a full-thickness biopsy is necessary.
Anorectal manometry (Fig. 1, box 31) evaluates the response of the internal anal sphincter to inflation of a balloon in the internal anal sphincter (52). When the rectal balloon is inflated, there is normally a reflex relaxation of the internal anal sphincter. In Hirschsprung disease this rectoanal inhibitory reflex is absent; there is no relaxation, or there may even be paradoxical contraction, of the internal anal sphincter. In a cooperative child, anorectal manometry represents a sensitive and specific diagnostic test for Hirschsprung disease. It is particularly useful when the aganglionic segment is short and results of radiologic or pathologic studies are equivocal. If sphincter relaxation is normal, Hirschsprung disease can be reliably excluded. In the presence of a dilated rectum, it is necessary to inflate the balloon with large volumes to elicit normal sphincter relaxation. In the child with retentive behavior, there may be artifacts caused by voluntary contraction of the external anal sphincter and the gluteal muscles. Sedation, which does not interfere with the rectoanal inhibitory reflex, may be used in newborns and uncooperative children. If manometry results are abnormal, diagnosis should be confirmed with a biopsy.
Although a barium enema is often performed as the initial screening test to rule out Hirschsprung disease, it is usually unnecessary beyond infancy (53). When stool is present in the rectum to the level of the anus, the barium enema provides no more useful information than can be obtained with a plain radiograph. However, after the diagnosis of Hirschsprung disease has been made, the barium enema may be useful in identifying the location of the transition zone, provided that laxatives or enemas have not been administered before the study to clean out the colon. The barium enema may not show a transition zone in cases of total colonic Hirschsprung disease, or may be indistinguishable from cases of functional constipation when ultra-short-segment Hirschsprung disease is present.
Other Medications and Testing
If constipation is not resolved with the treatments outlined above, and Hirschsprung disease has been excluded, other therapies may be considered (Fig. 1, box 34). Clearly, treatment may be necessary for an extended period-months or years. Stimulant laxatives can be added for short periods. There is extensive experience with senna, bisacodyl, and phenolphthalein (54,55). However, phenolphthalein is no longer available in the United States because of concerns about its carcinogenic potential.
The effectiveness of cisapride for the treatment of constipation is controversial. In some open-label studies and placebo-controlled trials, it appeared to be effective, but in another placebo-controlled study cisapride had no effect (23,56-59). Polyethylene glycol electrolyte solutions have been used to achieve bowel clean-out (20-61), and it has been suggested recently that the administration of lower doses may be useful in long-term therapy.
Biofeedback therapy has been evaluated in multiple open-label studies in which it was found to be efficacious (62). Results in some recent controlled studies, however, did not demonstrate long-term efficacy. Biofeedback may be beneficial for the treatment of a small subgroup of patients with intractable constipation (63-65). At times intensive psychotherapy may be needed. On rare occasion, hospital admission with behavioral therapy may be necessary.
Many conditions can cause constipation (Table 4). For children who remain constipated despite conscientious adherence to the treatments outlined, other tests may be indicated (Fig. 1, box 38). Magnetic resonance imaging (MRI) of the lumbosacral spine can demonstrate intraspinal problems, such as a tethered cord, tumors, or sacral agenesis. Other diagnostic tests such as anorectal manometry, rectal biopsy, colonic manometry, barium enema, and a psychological evaluation can be helpful. Colonic manometry, by providing objective evidence of colonic function, can exclude the presence of underlying neuropathy or myopathy (66). Barium enema can be useful to exclude the presence of anatomic abnormalities or of a transition zone. Full-thickness rectal biopsy can be useful to detect neuronal intestinal dysplasia or other myenteric abnormalities, including Hirschsprung disease. Metabolic tests, such as serum calcium level, thyrocalcitonin concentration, or thyroid function tests, can detect metabolic causes of constipation (67).
ALGORITHM FOR INFANTS LESS THAN 1 YEAR OF AGE
The evaluation of infants differs in some aspects from that of older children. Even in infancy, most constipation is functional. However, when treatment fails, when there is delayed passage of meconium (Fig. 2, box 4), or when red flags are present (Fig. 2, box, 8), particular consideration of Hirschsprung disease and other disorders is necessary. Hirschsprung disease has been described in detail. In a constipated infant with delayed passage of meconium, if Hirschsprung disease has been excluded, it is recommended that a sweat test be performed to rule out cystic fibrosis (Fig. 2, box 6). Constipation can be an early manifestation of cystic fibrosis, even in the absence of failure to thrive and pulmonary symptoms.
Special consideration should also be given to breast-fed infants in the first year of life. Greater variability in stool frequency occurs among breast-fed infants than in formula-fed infants (4,68,69). Unless suspicion of Hirschsprung disease is present, management of a breast-fed infant requires only reassurance and close follow-up if the infant is growing and breast-feeding normally and has no signs or symptoms of obstruction or enterocolitis.
Some important differences in treatment of constipation in infants include increased intake of fluids, particularly of juices containing sorbitol, such as prune, pear, and apple juices, which is recommended within the context of a healthy diet. Barley malt extract, corn syrup, lactulose, or sorbitol can be used as stool softeners. Light and dark corn syrups are not considered to be potential sources of Clostridium botulinum spores (70). Mineral oil and stimulant laxatives are not recommended. Because gastroesophageal reflux and incoordination of swallowing are more common in infants, there is a greater risk of aspiration of mineral oil, which can induce severe lipoid pneumonia (71-73). Glycerin suppositories can be useful, and enemas are to be avoided.
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