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Correspondence: Allison Blackmer, PharmD, BCPS, Clinical Assistant Professor, Clinical Pharmacy Specialist, University of Michigan College of Pharmacy, University of Michigan, 428 Church St, Ann Arbor, MI 48109-1065
Eshelman School of Pharmacy and North Carolina Children’s Hospital
Chapel Hill, North Carolina
Brady S. Moffett, PharmD, MPH
Clinical Pharmacy Specialist-Pediatric Cardiology
Texas Children's Hospital, Department of Pharmacy
Houston, Texas
Objectives
1.
Review the definitions and complications of chronic constipation in the pediatric population.
2.
Examine the common causes of constipation and assess the evaluation and diagnosis of constipation in children.
3.
Evaluate the current literature, clinical practice guidelines, and pharmacology that direct therapeutic decisions made in the management of constipation in children.
4.
Describe the three-step process for managing constipation in the pediatric patient: complete bowel evacuation, maintenance of bowel evacuation, and weaning of medications.
5.
Appraise novel and alternative pharmacologic agents in the management of constipation in children.
A 10-year-old African American boy presents to your clinic with a history of constipation, encopresis, nausea, and vomiting. Last month he was hospitalized for a 7-day “GoLytely clean-out” for fecal impaction and was discharged with a prescription for MiraLax, 1 capful twice daily. Until 5 days ago, he had been having three to four large stools per week. He states that he involuntarily soils his pants two to three times per day, which requires him to wear special diapers. For the past 5 days he has been completely unable to defecate and has had severe abdominal pain, nausea, and vomiting. This morning his mother gave him eight capfuls of MiraLax in 32 oz of fluid twice, which caused him to have a “large blow out” that relieved his nausea and pain, although he is anxious about this happening again and expresses fear of another hospital admission.
He reports significant anxiety related to accidents and soiling. His accidents occur without the feeling of having a bowel movement coming, and he has had to wear diapers for the past 2 years, which he states is very embarrassing because he is a 4th grader. He reports having “hot flashes” related to nervousness about his constipation and encopresis and wishes he could wear normal underwear and “be normal.” He has been the subject of bullying at school, and as a result he was home-schooled at various points throughout the past year. He states that in the past his family members punished him for soiling his clothing, so he attributes this to bad behavior, although he cannot control it. He wants to “be good” for his family and stop soiling his pants. Additionally, he wants to be able to return to school, but he is quite fearful about his social safety, which is a direct outcome of teasing and cruelty in the past.
Background
This case is a classic example of the manifestations of constipation in children. Constipation has been reported to account for nearly 5% of all pediatric outpatient visits and more than 25% of referrals to gastroenterology specialists (
). In 2009 it was noted that functional constipation had a worldwide prevalence of 7% to 30%, with approximately 30% to 75% of cases of chronic constipation in children resulting in rectal fecal impaction (
). Of these children, up to 90% will experience fecal incontinence. As can be imagined, chronic functional constipation with or without additional complications such as encopresis is a distressing problem for children and their families (
). Despite its prevalence and the physical and emotional severity of the problem, good clinical trial data guiding the management of constipation in children are scarce. Thus the treatment of pediatric constipation is primarily based on clinical experience as opposed to strong clinical trial data (
). This article reviews the basic definitions and complications of constipation in children along with the current literature, clinical guidelines, and pharmacology that direct the management of chronic constipation in the pediatric population.
Definition of Constipation
Constipation can be defined three ways: a stool that is hard, pain associated with defecation, or the passage of fewer than three stools per week (
University of Michigan Health System Functional Constipation and Soiling in Children Guideline Team UMHS functional constipation and soiling guideline.
University of Michigan Health System,
Ann Arbor, MI2003
). For example, a patient who has three or more small stools per week but does not fully empty the colon may have constipation, whereas a child who passes two large, soft stools, entirely emptying the colon, may not fit the definition or diagnosis for constipation.
When assessing constipation, it also is important to consider the normal frequency and stooling patterns in children.
When assessing constipation, it also is important to consider the normal frequency and stooling patterns in children. During the first week of life, neonates defecate an average of four times per day, whereas by 2 years of age, the average number of bowel movements per day is 1.7 (
North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) Constipation Committee Clinical practice guideline: evaluation and treatment of constipation in infants and children: Summary of updated recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.
Journal of Pediatric Gastroenterology and Nutrition.2006; 43: 405-407
). With this physiologic decrease in the number of bowel movements per day comes an increase in the stool volume. It is important for parents and caregivers to understand these physiologic changes and to recognize that stool frequency and consistency may change throughout a child’s life and may not represent constipation. Because stool frequency also varies between individuals, assessments of constipation must address what is normal for each individual child.
Physiologically, continence is maintained through resting tonicity of the internal anal sphincter (
). When more than 15 mL of stool is in the rectum, nerves as well as stretch receptors are activated, the resting tone in the involuntary smooth muscle of the internal anal sphincter is decreased, and stool is able to reach the external anal sphincter, which is made up of voluntary smooth muscles. Once stool reaches the external sphincter, children feel the urge to defecate. At this point, the rectum can be evacuated of stool should the child initiate defecation through squatting and increasing intra-abdominal pressure with the Valsalva maneuver. However, the child also may choose to tighten the muscles of the external anal sphincter and the gluteal muscles, an action that causes stool to re-enter the rectal vault, thus subsiding the urge to defecate. If a child repeatedly tightens these muscles, eventually the rectum and the lower colon stretch, muscle tone is reduced, and the child will begin to retain stool. As stool retention time increases, so does water absorption. While the normal water content of stool is approximately 75%, when stool is cyclically retained in the rectum and/or colon, water absorption increases, and the stool becomes hard and may even reach the point of impaction. Fecal impaction can be defined as a large fecal mass found upon rectal evaluation or abdominal palpation that is unlikely to be passed on command (
). One definition of soiling proposed by the UMHS includes the involuntary passage of stool and/or the voluntary or involuntary passage of stool (formed, semi-formed, or liquid) into a place other than the toilet after the age of 4 years (
University of Michigan Health System Functional Constipation and Soiling in Children Guideline Team UMHS functional constipation and soiling guideline.
University of Michigan Health System,
Ann Arbor, MI2003
). Soiling occurs when overflowing and leaking of loose stool occurs around retained, hard, and sometimes impacted stool in the distended rectum. Encopresis appears more commonly in male children and also appears to occur more frequently among younger children. Encopresis is usually associated with functional fecal retention (90%); however, it also may be caused by organic incontinence in children with damaged corticospinal pathways or in patients with anorectal dysfunction or pelvic floor muscle fatigue. Additionally, in some cases, children exhibit functional encopresis as a form of severe passive-aggressive or oppositional defiant behavior. This phenomenon is not a traditional form of constipation, however, and in these cases conventional treatment approaches for constipation will not be effective.
Another complication of constipation includes enuresis, involuntary urination, or bed-wetting, which occurs in up to 40% of children (
). The large, dilated colon contributes to enuresis, and therefore this complication often resolves with the alleviation of any impaction and the passage of stool. Further urologic concerns include recurrent urinary tract infections secondary to a dilated colon and retained stool. Additionally, a largely dilated colon may eventually lead to prolapse, intussusceptions, rectal ulceration, and even protein-losing enteropathy.
Beyond physical complications, chronic constipation also has social ramifications. Children often are not aware of the soiling until it is nearly complete, a complication that can affect a child’s sense of self, and his or her emotional as well as social development. A child with encopresis and soiling must face the social stigma associated with flatulence and soiling. The child may be required to wear special underwear or diapers, which may cause social exclusion, teasing, and bullying, often leading to social exclusion, anxiety, and depression (
). Some children may experience devastating social and emotional difficulties that cause the child to lose friendships and perform poorly in school, and in some cases, children with constipation may have to switch schools because of these social implications. Furthermore, in severe cases, recurrent hospital admissions are required to entirely clean out the bowel; hospitalizations may further exacerbate problems faced at school, affect the parents’ or caregivers’ ability to hold employment, and disrupt the family’s social situation. Children also face significant anxiety related to hospital admission, often resulting from invasive procedures such as the placement of a nasogastric tube.
Causes of Constipation
Constipation may have functional, anatomic, neurologic, obstructive, endocrine, metabolic, and medicinal causes; however, to examine all of them in depth is outside of the scope of this review. A brief overview of the causes of constipation will follow, with an emphasis on functional constipation.
Neurologic causes of chronic constipation include Hirschsprung’s disease or aganglionosis, which occurs in approximately 1 in 5000 births (
). A lack of ganglion cells in the myenteric and submucosal plexus of the bowel characterize this disorder. Difficulty with evacuation is seen immediately at birth in persons with this disorder, and often there is failure of early passage of meconium. These patients often have severe abdominal distension, nausea, and emesis, as well as a failure to thrive. Hirschsprung’s disease is a heterogeneous genetic disorder that may be associated with several syndromes, including trisomy 21 and the deletion of chromosome 13q. Other causes of neurologic constipation may include neuronal dysplasia, hypoganglionosis, spinal cord dysplasia, and botulism.
Obstructive conditions also may be the cause of constipation. Such conditions as anterior ectopic anus, congenital or acquired anal ring stenosis, meconium ileus, cystic fibrosis, adenocarcinoma, or a pelvic mass may be implicated (
). Endocrine and metabolic causes of constipation include motility disorders such as delayed gastric emptying and small bowel stasis. Some endocrine and metabolic causes may include visceral myopathy, diabetes, hypothyroidism, and porphyria.
Functional constipation, the passage of less than two large-diameter stools per week with or without the presence of retentive posturing or behaviors, is defined as constipation in the absence of genetic, structural, endocrine or metabolic disorders (
). In neonates and infants, functional constipation is considered to be normal because it is difficult for babies to coordinate pelvic floor relaxation and the Valsalva maneuver (
). In older babies, toddlers, and preschool children, functional constipation is pathogenic and is described as the presence of pebble-like, hard stools for the majority of stools or hard stools two or fewer times per week (
). For toddlers and older children, functional constipation is commonly a result of the child’s desire to obtain control over stooling. This functional constipation may be a result of difficulty in toilet training, painful passage of stools, perianal infection, and anxiety related to defecation outside of the home or out of fear of defecation entirely. Functional constipation also may be a result of changes in routines. For example, constipation may occur when a child first attends day care or starts school for the first time or after a summer vacation. It may be a result of a stressful situation or time. Alternatively, in younger children constipation may be a product of hyperactivity or distraction; a child may become too busy with child’s play to stop to empty his or her bowels. In some older children, irritable bowel syndrome may be an additional cause of functional constipation.
… most investigators agree that maintaining a good balance of hydration, fiber intake, and physical activity is important for normal stool formation and bowel motility.
Is functional constipation associated with fiber intake? A study published in 2009 that assessed dietary fiber, fluids, and physical activity in relation to constipation found that fluid and fiber intake was not significantly different among children presenting with constipation; however, children with constipation did report a higher level of physical activity and a lower water intake, indicating that constipation may be correlated to dehydration (
). Despite these data, many practitioners believe that an adequate amount of dietary fiber is necessary to maintain healthy stooling patterns. Overall, although it is not entirely known what role fiber plays in constipation, most investigators agree that maintaining a good balance of hydration, fiber intake, and physical activity is important for normal stool formation and bowel motility.
Functional Constipation—A Cyclical Process
Regardless of the previously described causes, functional constipation is described as a cyclical process, as depicted in Figure 1 (
). This cycle escalates because the next passed stool is even harder and more painful to pass because of the previous retention. This pain may eventually lead the child to be determined to avoid defecation altogether, which eventually leads to fecal impaction, bowel dilation, and the complications previously described (
North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) Constipation Committee Clinical practice guideline: evaluation and treatment of constipation in infants and children: Summary of updated recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.
Journal of Pediatric Gastroenterology and Nutrition.2006; 43: 405-407
North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) Constipation Committee Clinical practice guideline: evaluation and treatment of constipation in infants and children: Summary of updated recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.
Journal of Pediatric Gastroenterology and Nutrition.2006; 43: 405-407
). In addition to family history, the historical bowel patterns, including the time after birth of the first bowel movement, dietary history, and social situations such as day care attendance and toilet training efforts should be included. A detailed description of the character of the stools as well as any presence of blood is essential. If encopresis exists, the age of onset as well as the frequency should be documented. A medical history should address history of physical or emotional abuse, prior surgeries, neonatal complications, and medication use. A dietary intake history should be assessed.
The physical examination should include an assessment of weight, height, and growth velocity (
). The abdomen is assessed for the degree of abdominal distension, bowel sounds, and palpable stool, and the perineum is inspected for evidence of encopresis, infection, hemorrhoids, and fissures. In about 50% of patients, the abdominal examination is positive for palpable stool, and the presence of firm, packed stool in the rectum has a positive predictive value of more than 84% for impaction (
University of Michigan Health System Functional Constipation and Soiling in Children Guideline Team UMHS functional constipation and soiling guideline.
University of Michigan Health System,
Ann Arbor, MI2003
). Guidelines recommend that at least one rectal examination should be performed to assess the sphincter tone, the size of the rectal vault, and to detect any physical abnormality that may lead to diagnosis of an organic disorder (
North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) Constipation Committee Clinical practice guideline: evaluation and treatment of constipation in infants and children: Summary of updated recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.
Journal of Pediatric Gastroenterology and Nutrition.2006; 43: 405-407
University of Michigan Health System Functional Constipation and Soiling in Children Guideline Team UMHS functional constipation and soiling guideline.
University of Michigan Health System,
Ann Arbor, MI2003
). Laboratory testing for hypothyroidism and electrolyte abnormalities as well as a urinalysis also should be performed to rule out or rule in alternative causes for constipation. Radiographs as well as anorectal manometry may be a part of the initial or ongoing evaluation of a child with constipation. To rule out certain neurologic conditions (e.g., Hirschsprung’s disease), rectal biopsies also may be necessary.
Signs and Symptoms
Children demonstrate a wide variety of signs and symptoms related to constipation. For example, a child may have certain rituals such a gluteal tightening and posturing (
). The child may rock back and forth while standing on their tiptoes; they may wiggle or become excessively fidgety, or assume quite unusual positions (
North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) Constipation Committee Clinical practice guideline: evaluation and treatment of constipation in infants and children: Summary of updated recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.
Journal of Pediatric Gastroenterology and Nutrition.2006; 43: 405-407
). These rituals are sometimes mistaken for an attempt to defecate, but they usually represent an effort to retain stool and avoid defecation. Children also may demonstrate early fullness after meals and/or the desire to eat smaller amounts as a result of fecal accumulation in the colon. Complaints of gastrointestinal spasms and abdominal pain, nausea, vomiting, or unusual irritability are also common. Furthermore, with the passage of very large, hard stools, rectal bleeding may be present.
Management
The management of functional constipation will be reviewed and differences between age groups emphasized. Functional constipation is rarely a short-term process and requires a prolonged treatment plan, family compliance, and multidisciplinary support (
). The treatment of nonfunctional constipation is beyond the scope of this article.
Neonates/Infants Younger Than 1 Year
The frequency of bowel movements is quite variable among neonates and infants younger than 1 year. For example, it is not uncommon for breastfed infants to have multiple stools per day, most commonly ranging between three to five stools per day. For formula-fed babies, the average number of stools most commonly ranges between two to four stools per day. Therefore, dietary and stooling histories are of the greatest importance in this age group. If a child presents with constipation within the first year of life, treatment differs from that of older children and adolescents. Constipation during infancy should be evaluated for structural and congenital causes such as anal atresia with or without a fistula, an anteriorly displaced anus, or a tethered spinal cord. In addition, disorders such as Hirschsprung’s disease, neuronal intestinal dysplasia, pseudo-obstruction, or cystic fibrosis should be ruled out (
). Once medical causes of constipation have been excluded and functional constipation has been diagnosed, it is reasonable to insert a glycerin suppository or perform occasional rectal stimulation to induce rectal reflexes; however, routine rectal manipulation is discouraged (
North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) Constipation Committee Clinical practice guideline: evaluation and treatment of constipation in infants and children: Summary of updated recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.
Journal of Pediatric Gastroenterology and Nutrition.2006; 43: 405-407
). Glycerin suppositories help to soften and ease the passage of stool that is in the rectum. If used on an outpatient basis, glycerin should not be used for more than 3 days without a medical evaluation. Alternatively, if stool is very firm, barley cereal can be substituted for rice, and vegetables that contain higher levels of fiber along with nondigestible sugar such as sorbitol, fructose, or lactose (e.g. prune juice) can be incorporated into the diet in patients older than 6 months of age. It is reasonable to increase the fluid intake in all children who are younger than 1 year. The use of mineral oil, stimulant laxatives, and phosphate enemas should be avoided in this age group because of potential toxicity (
North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) Constipation Committee Clinical practice guideline: evaluation and treatment of constipation in infants and children: Summary of updated recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.
Journal of Pediatric Gastroenterology and Nutrition.2006; 43: 405-407
). The use of honey in home remedies should be avoided because it may contain botulinum spores.
Older Children/Adolescents
The remainder of this review will focus on the management of constipation in older children and adolescents. In 2006, NASPGHAN developed a clinical practice based guideline to help health care professionals make clinical decisions with regard to the treatment of functional constipation (
North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) Constipation Committee Clinical practice guideline: evaluation and treatment of constipation in infants and children: Summary of updated recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.
Journal of Pediatric Gastroenterology and Nutrition.2006; 43: 405-407
). The UMHS also has published treatment guidelines for functional constipation and soiling, which overall are very similar to those published by NASPGHAN (
University of Michigan Health System Functional Constipation and Soiling in Children Guideline Team UMHS functional constipation and soiling guideline.
University of Michigan Health System,
Ann Arbor, MI2003
). The management of chronic constipation in children has three phases: complete evacuation if impaction is present, sustained evacuation of impaction, and weaning from intervention through adjustment of medications if necessary (
North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) Constipation Committee Clinical practice guideline: evaluation and treatment of constipation in infants and children: Summary of updated recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.
Journal of Pediatric Gastroenterology and Nutrition.2006; 43: 405-407
University of Michigan Health System Functional Constipation and Soiling in Children Guideline Team UMHS functional constipation and soiling guideline.
University of Michigan Health System,
Ann Arbor, MI2003
). In all phases of management, education is extremely important for the family as well as the patient. Education should include an explanation of the pathogenesis of constipation to help families and patients better understand the problem and the treatment approach (
North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) Constipation Committee Clinical practice guideline: evaluation and treatment of constipation in infants and children: Summary of updated recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.
Journal of Pediatric Gastroenterology and Nutrition.2006; 43: 405-407
University of Michigan Health System Functional Constipation and Soiling in Children Guideline Team UMHS functional constipation and soiling guideline.
University of Michigan Health System,
Ann Arbor, MI2003
). Families should be counseled on the following topics: normal toileting patterns, both the physical and psychological components of chronic constipation, and the role of diet. Additionally, a strong support network is paramount, and realistic expectations must be set. A positive attitude and a strong supportive nature are necessary. Negative associations of fecal soiling need to be removed and punishments should be avoided (
). Reward systems such as sticker charts, toileting calendars, and rewards for successes play a key role in the management of constipation. Additionally, every effort should be made to make the child comfortable during defecation; for example, a footstool may help a child successfully perform the Valsalva maneuver. Steps should be taken to make the bathroom an enjoyable place for the child to be; for instance, many families will place a radio or books in the bathroom.
From a dietary perspective, constipating foods should be reduced or eliminated completely from the child’s diet (
). Examples of constipating foods include meat, bread, pasta, potatoes, fried greasy foods, corn, foods that contain a high level of sugar (e.g., cookies and pies), and dairy products (ice cream, cheeses, and milk). Once constipation resolves completely and rectal tone begins to improve, additional fiber can be added to the diet to improve the efficiency of bowel evacuation. Dietary fiber increases water retention and increases colonic flora by providing substrate for bacterial growth (
). Table 1 contains a list of foods high in water-soluble and water-insoluble fiber. Although the subject is still somewhat controversial, most practitioners agree that once initial bowel evacuation has been accomplished and bowel habits have returned to normal, increasing dietary fiber is an effective and achievable task.
The following recommendations are from guidelines and expert opinions rather than from randomized clinical trial data. Complete bowel evacuation is necessary as the first step in treating chronic constipation because if initial disimpaction is omitted, maintenance therapy with oral stool softeners and laxatives may initially result in worsening of incontinence (
). In older children, hypertonic phosphate enemas (occasionally in combination with mineral oil) are used, and usually are administered at home in the evenings. Saline solution enemas also may be chosen (
North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) Constipation Committee Clinical practice guideline: evaluation and treatment of constipation in infants and children: Summary of updated recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.
Journal of Pediatric Gastroenterology and Nutrition.2006; 43: 405-407
University of Michigan Health System Functional Constipation and Soiling in Children Guideline Team UMHS functional constipation and soiling guideline.
University of Michigan Health System,
Ann Arbor, MI2003
). The mineral oil enema acts to soften and lubricate the stool. Hypertonic enemas directly stimulate contraction in the colon, thus emptying of a fecal mass with a lower incidence of fecal incontinence. For children who are preschool aged or older, an adult-sized enema is required to relieve impaction, and one to three enemas may be required within a 12- to 24-hour period (
University of Michigan Health System Functional Constipation and Soiling in Children Guideline Team UMHS functional constipation and soiling guideline.
University of Michigan Health System,
Ann Arbor, MI2003
). If relief is not achieved in 7 days, continued home use is not recommended because of the potential for electrolyte disturbances. Children often do not tolerate enemas because of the discomfort of placement as well the associated abdominal pain and cramping due to pulsatile contractions. Enemas can be traumatic for children; however, results are seen rapidly (
). Home remedies such as tap water, herbal concoctions, and soap suds enemas should not be used as a substitute because of the potential for toxicity (
North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) Constipation Committee Clinical practice guideline: evaluation and treatment of constipation in infants and children: Summary of updated recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.
Journal of Pediatric Gastroenterology and Nutrition.2006; 43: 405-407
Oral therapies, such as polyethylene glycol solutions, have been suggested as an option for outpatient management of fecal impaction. Oral therapies are not as invasive as enemas; however, adherence to these regimens is often quite poor, because palatability may be problematic for children. If an oral route of administration is chosen, effective use of high doses of mineral oil, polyethylene glycol solutions, or a combination of the two, in addition to other agents such as magnesium hydroxide, magnesium citrate, lactulose, sorbitol, senna, and/or bisacodyl, has been demonstrated in practice. Data to help guide the decision between the use of enemas and oral solutions has historically been lacking, and the choice of treatment is commonly determined after in-depth discussions with the family and the child. Allowing the child to have choice and some amount of control in the decision may improve adherence and lead to more successful disimpaction outcomes (
University of Michigan Health System Functional Constipation and Soiling in Children Guideline Team UMHS functional constipation and soiling guideline.
University of Michigan Health System,
Ann Arbor, MI2003
North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) Constipation Committee Clinical practice guideline: evaluation and treatment of constipation in infants and children: Summary of updated recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.
Journal of Pediatric Gastroenterology and Nutrition.2006; 43: 405-407
In a 2009 published clinical trial, enemas and oral administration of high-dose polyethylene glycol (PEG) (MiraLax) were compared to assess their efficacy in removing a fecal impaction as well as overall tolerability in children with functional constipation and rectal fecal impaction (RFI) (
). A secondary goal of the study was to evaluate the effect of disimpaction on overall bowel habits and colonic transit time (CTT). Ninety patients between the ages of 4 and 16 years of age with demonstrated evidence of RFI and who were diagnosed with functional constipation were randomly assigned to receive rectal enemas (dioctylsulfosuccinate sodium) once daily (n = 46) or PEG 3350 with electrolytes at a dose of 1.5 g/kg per day (n = 44), each for 6 consecutive days. Maintenance therapy was initiated 6 days after disimpaction; maintenance therapy consisted of orally administered PEG 3350 with electrolytes at a dose of 0.5 g/kg/day for at least 2 weeks. Behavioral questionnaires and bowel diaries were filled out throughout the study period, and CTT was assessed through the use of a radio opaque marker. A total of 41 patients in the enema group and 39 in the PEG group completed the study and had complete follow-up data. Successful disimpaction was achieved for 37 patients (80%) from the enema group and 30 patients (68%) from the PEG group (P = .28); this result was not statistically significant. For patients in whom successful disimpaction was not achieved, a second attempt to achieve disimpaction was successful in a total of eight patients with combination enema and PEG therapy. The remainder of the patients (n = 5) were admitted to the hospital for colonic lavage. Bowel movement frequency was increased during the disimpaction period in both groups; however, more patients reported fecal incontinence and watery diarrhea in the PEG group. No differences were elucidated in CTT between the two groups. Tolerability was nearly equally between the two groups, but patients reported a greater degree of abdominal pain in the enema group. This study is the first prospective randomized clinical trial that has evaluated rectal enema versus oral PEG use for the initial treatment of RFI. This study found that no statistically or clinically significant difference exists between the two treatment options, suggesting that both agents can be considered as first-line therapy.
If disimpaction is not achieved through the previously described methods, patients are admitted to the hospital for oral lavage with polyethylene glycol electrolyte solution. Administration via an oral or nasogastric tube at a rate of 25 mL/kg/h for 6 hours is one example. Adding a flavor packet such as Crystal Light may enhance the palatability of the solution. Disimpaction frequently requires the placement of a nasogastric tube and the administration of larger volumes of solution, however. Volumes of 10 to 40 mL/kg/h (maximum 1000 mL/h) may be necessary (
). Evacuation often takes 8 to 24 hours; however, in more severe cases of impaction, oral/nasogastric lavage may be continued for several days. Because the polyethylene glycol-electrolyte lavage solution results in no net absorption or secretion of electrolytes, large amounts can be administered without an associated risk of fluid or electrolyte disturbances. One study noted that an average of approximately 575 mL/kg total was required to achieve disimpaction during a period of nearly 24 hours (
). Nausea and vomiting may result because of the large volumes of polyethylene glycol-electrolyte lavage solution administered, and thus supportive care with antiemetics may be required. Promotility agents such as metoclopramide (0.1 mg/kg/dose, with a maximum 10 mg/dose administered intravenously or by mouth every 6 hours) also are commonly used during “clean-out” regimens. Figure 2 depicts a few common approaches to the acute management and initiation of disimpaction in pediatric patients.
Figure 2Acute management—constipation “clean out” suggested treatment options. This figure is available in color online at www.jpedhc.org.
North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) Constipation Committee Clinical practice guideline: evaluation and treatment of constipation in infants and children: Summary of updated recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.
Journal of Pediatric Gastroenterology and Nutrition.2006; 43: 405-407
). This phase of treatment relies on education, dietary interventions, behavioral modifications, and the use of stool softeners and laxatives. The goal of this phase is to allow the colon and the musculature of the rectum to return to normal and for functional fecal retention and encopresis to resolve. This process may take several months, and thus educating families on the importance of long-term treatment is essential for success. Achieving a regular stool pattern may entail setting a goal of one to two soft stools per day; a mushy consistency aids in more complete evacuation of the bowel (
University of Michigan Health System Functional Constipation and Soiling in Children Guideline Team UMHS functional constipation and soiling guideline.
University of Michigan Health System,
Ann Arbor, MI2003
North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) Constipation Committee Clinical practice guideline: evaluation and treatment of constipation in infants and children: Summary of updated recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.
Journal of Pediatric Gastroenterology and Nutrition.2006; 43: 405-407
). Scheduled “toilet time” for a period of 5 to 10 minutes after meals is encouraged to take advantage of the physiologic gastrointestinal reflex and to establish a regular bowel pattern. Making scheduled “toilet time” more enjoyable by allowing the child to listen to music and/or read a book may further encourage regular bowel movements (
North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) Constipation Committee Clinical practice guideline: evaluation and treatment of constipation in infants and children: Summary of updated recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.
Journal of Pediatric Gastroenterology and Nutrition.2006; 43: 405-407
). As mentioned earlier, calendars with stickers and reward systems can act as motivational tools and have been linked to success.
For babies, stool softening may be achieved through dietary modification. Barley cereal, barley malt extract, and certain juices can be administered after 6 months of age (
). Dietary changes also are commonly advised in older children and include suggestions such as the addition of absorbable and nonabsorbable carbohydrates, especially sorbitol, which is found commonly in prune, apple, and pear juices, as well as the foods listed in Table 1 (
North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) Constipation Committee Clinical practice guideline: evaluation and treatment of constipation in infants and children: Summary of updated recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.
Journal of Pediatric Gastroenterology and Nutrition.2006; 43: 405-407
). Overall, a well-balanced diet is encouraged, including fruits and vegetables. It is not advised, however, to force a child to eat foods that do not appeal to that particular child. Increasing the amount of fiber in a child’s diet may be recommended once the colon and the rectum have returned to normal.
In addition to education and dietary changes, medications are usually necessary to help children with chronic constipation achieve regular bowel patterns (
North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) Constipation Committee Clinical practice guideline: evaluation and treatment of constipation in infants and children: Summary of updated recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.
Journal of Pediatric Gastroenterology and Nutrition.2006; 43: 405-407
). Indeed, studies have noted that children treated with medications in combination with behavioral modifications have achieved remission earlier than do children who do not receive medications. Toddlers present a particularly challenging age group to treat because they are resistant to medications and often are also under-medicated because of parental concerns. Additionally, toilet training is more challenging in this particular age group. If a child has not yet been toilet trained, this should not be attempted until constipation has resolved and the child is passing two soft stools per day (
). Often during this phase, dose reductions of medications previously prescribed for constipation are needed after bowel clean-out to avoid excessive or loose stooling.
At the maintenance phase of treatment, routine use of stimulant laxatives is not recommended because of the increased likelihood of the development of bowel dependence.
The choice of medication, much like in step 1 of treatment, is directed by clinical guidelines only. Oral laxatives with or without the addition of a lubricant can be used (
North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) Constipation Committee Clinical practice guideline: evaluation and treatment of constipation in infants and children: Summary of updated recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.
Journal of Pediatric Gastroenterology and Nutrition.2006; 43: 405-407
). Commonly recommended agents include mineral oil (lubricant), magnesium hydroxide, lactulose, sorbitol, and PEG (MiraLax). Early reports indicate that PEG may be more efficacious than other osmotic laxatives; however, the other aforementioned agents appear to be equally efficacious to one another. Therefore, the choice of these agents relies on the ability of the family to obtain the medication, along with the cost, taste, ease of administration, and personal preference. At the maintenance phase of treatment, routine use of stimulant laxatives is not recommended because of the increased likelihood of the development of bowel dependence. However, stimulants may be used intermittently for short periods as necessary to avoid the recurrence of impaction. For example, if a child has not defecated in 3 days, it is advisable to administer a stimulant laxative for a period of 1 to 3 days to avoid impaction and the necessity of returning to step 1 of treatment. In a study published in Pediatrics in 2005 that assessed the treatment of childhood constipation by primary care physicians, 87% of physicians prescribed some form of laxative or stool softener (
). Magnesium hydroxide was the most commonly prescribed laxative (77%), followed by senna (23%), mineral oil (8%), and lactulose (8%), and combination therapy was prescribed 15% of the time. This study demonstrated that the choice of agent, the number of agents used, or the number of times per day that medication was administered did not influence outcome. However, children who underwent disimpaction prior to maintenance therapy achieved greater success. In another study published in Clinical Pediatrics in 2006, polyethylene glycol was reported to be the most commonly prescribed agent (
). Overall, despite the NASPGHAN and UMHS guidelines, variability still exists among providers in the treatment of childhood constipation.
Polyethylene glycol has become an increasingly appealing agent for the management of constipation in children. Numerous successful reports as well as unblinded trials have been performed, as summarized in
, and support its use. While additional controlled trials are needed, polyethylene glycol appears to be a safe and efficacious agent at a starting dose of 0.5 g/kg/day titrating up to 1.5 g/kg/day if necessary. One major issue that may be present with the choice of polyethylene glycol is cost. When using over-the-counter polyethylene glycol, MiraLax doses are often rounded to 1 capful (17 g) or measurable portions of a capful (i.e., ½ cap or ¼ cap). Additionally, large amounts of fluid volume are required.
Table 2 outlines medications commonly used in the management of constipation in children including mechanism of action, onset of action, common doses, and potential adverse effects. Figure 3 provides a summary of the general classes of laxatives and their mechanisms of action. Figure 4 outlines one strategy suggested to sustain complete bowel evacuation.
Table 2Medications commonly used for the management of constipation in children
North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) Constipation Committee Clinical practice guideline: evaluation and treatment of constipation in infants and children: Summary of updated recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.
Journal of Pediatric Gastroenterology and Nutrition.2006; 43: 405-407
University of Michigan Health System Functional Constipation and Soiling in Children Guideline Team UMHS functional constipation and soiling guideline.
University of Michigan Health System,
Ann Arbor, MI2003
Rectal: Neonates: 0.5 mL/kg/dose of rectal solution as enema <6 y: 1 infant suppository or 2-5 mL of rectal solution as enema >6 y: 1 adult suppository or 5-15 mL of rectal solution as enema
N/A
Magnesium citrate
Citroma
Osmotic laxative
Oral: <6 y: 2-4 mL/kg/dose given once or divided 6-12 y: 100-150 mL/dose given once or divided >12 y: 150-300 mL/dose given once or in divided doses OR 1-3 mL/kg/day
Risk of hypermagnesemia, hypophosphatemia, and secondary hypocalcemia Poor palatability
Dose based on regular strength liquid: 400 mg/5 mL; if using concentrated solution, reduce dose by half.
<2 y: 0.5 mL/kg/dose 2-5 y: 5-15 mL/day once or divided 6-11 y: 15-30 mL/day once or divided >12 y: 30-60 mL/day once or divided OR 1-3 mL/kg/day divided BID
Risk of hypermagnesemia, hypophosphatemia or secondary hypocalcemia if overdosage and/or renal dysfunction; chalky taste
Oral: 5-9 y: 5 mL 10-12 y: 10 mL ≥12 y: 20-30 mL Rectal enema: 2-11 y: 2.25 oz pediatric enema >12 y: 4.5 oz enema
Rectal enemas may cause rectal wall trauma; oral administration may lead to abdominal distension and vomiting; may cause hyperphosphatemia, hypocalcemia, or tetany in overdose situations
Sorbitol
N/A
Hyperosmotic laxative
Oral: 6.4-8.48 h
Oral: 2-11 y: 2 mL/kg (as 70% solution) ≥12 y: 30-150 mL (as 70% solution) OR 1-3 mL/kg/day in 2 divided doses Rectal enema: 2-11 y: 30-60 mL (as 25%-30% solution) ≥12 y: 120 mL (as 25%-30% solution)
Flatulence; abdominal cramping
Effective
Bisacodyl
Bisco-Lax; Correctol; Dulcolax
Stimulant laxative
Oral: 6-10 h Rectal: 15-60 min
Oral: 3-12 y: 5-10 mg or 0.3 mg/kg/day as a single dose >12 y: 5-15 mg/day as a single dose (max: 30 mg) Rectal: <2 y: 5 mg/day as a single dose 2-11 y: 5-10 mg/day as a single dose >12 y: 10 mg/day as a single dose
Possibility of permanent gut, nerve, or muscle damage (i.e., “bowel dependence”).
; not recommended for impaction; not indicated for long-term use
Gentle
Mineral oil
Fleet; Kondremul; Liqui-Doss
Lubricant laxative
6-8 h
Oral: Children: 1-3 mL/kg/day once daily or in divided doses OR 5-11 y: 5-15 mL once daily or in divided doses ≥12 y: 15-45 mL once daily or in divided doses Rectal: 2-11 y: 30-60 mL as a single dose ≥12 y: 60-150 mL/day as a single dose
University of Michigan Health System Functional Constipation and Soiling in Children Guideline Team UMHS functional constipation and soiling guideline.
University of Michigan Health System,
Ann Arbor, MI2003
North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) Constipation Committee Clinical practice guideline: evaluation and treatment of constipation in infants and children: Summary of updated recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.
Journal of Pediatric Gastroenterology and Nutrition.2006; 43: 405-407
). Relapse is common, and thus an individualized tapering schedule should be designed based on the length of time a patient has used maintenance doses of stool softeners and laxatives. In addition to the weaning of medication, at this point in the treatment algorithm, dietary fiber, both soluble and insoluble, should be increased and behavioral therapy should continue. The amount of daily dietary fiber that is recommended for all children is 5 g plus the child’s age in years (
University of Michigan Health System Functional Constipation and Soiling in Children Guideline Team UMHS functional constipation and soiling guideline.
University of Michigan Health System,
Ann Arbor, MI2003
). Although its effects are not clinically proven, some practitioners recommend a higher amount of fiber in the diets of children who are recovering from functional constipation. With an increase in fiber intake, an associated increase in fluid is also recommended. In general, 2 oz of fluid are recommended for each gram of fiber intake. Long-term follow up is required to maintain regular bowel movements. It is recommended that follow-up intervals be as frequent as once per week during clean-out and the initial maintenance periods and then reduced to monthly and then 3-month intervals until weaning from medication is completed (
University of Michigan Health System Functional Constipation and Soiling in Children Guideline Team UMHS functional constipation and soiling guideline.
University of Michigan Health System,
Ann Arbor, MI2003
University of Michigan Health System Functional Constipation and Soiling in Children Guideline Team UMHS functional constipation and soiling guideline.
University of Michigan Health System,
Ann Arbor, MI2003
). Other definitions of successful recovery include three or more bowel movements per week, fewer than two soiling episodes per month, no complaints of abdominal pain, and no use of medications for at least 1 month (
). However, successful recovery is often met with bumps along the road and episodes of impaction or rectal withholding. If this occurs and if defecation has not occurred for more than 3 days, a stimulant suppository should be given to prevent the recurrence of constipation and colonic distension (
). Despite the best treatments, however, multiple cohort studies have demonstrated that recurrence can be as high as 50%. Specifically, after 1 year of treatment, persistent constipation was seen in 53% of children, with 51.6% of children still maintaining constipation at 5 years (
). Treatment failure is more likely to be seen in patients who are not yet toilet trained and in those who have a history of both constipation and encopresis (
). Treatment failure may be a result of lack of adherence to treatment recommendations or a lack of recognition of suboptimal treatment or untreated small impactions along the way (
University of Michigan Health System Functional Constipation and Soiling in Children Guideline Team UMHS functional constipation and soiling guideline.
University of Michigan Health System,
Ann Arbor, MI2003
). Treatment failures also coincide with changes in routine such as vacations, holidays, and changes in medications or physical activity. Consultation with a specialist may be recommended if the previously described treatment fails (
North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) Constipation Committee Clinical practice guideline: evaluation and treatment of constipation in infants and children: Summary of updated recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.
Journal of Pediatric Gastroenterology and Nutrition.2006; 43: 405-407
). It may become necessary to evaluate whether any organic disease exists or if an underlying process is occurring outside of functional constipation. The high recurrence rate highlights the need for ongoing education and behavioral modifications as well as close follow-up and continued interventions for acute episodes of retention.
Novel and Alternative Therapies
Several new therapies have been suggested for the treatment of constipation. Although a complete review is outside the scope of this article, it is important to become familiar with some of the options. Substances that bind to the serotonin receptors as well as to chloride channels have been proposed (
). Agents that affect fluid secretion in the intestines may improve constipation. Lubiprostone (Amitiza) increases chloride in the gut, which facilitates an increase in intestinal fluid that may facilitate intestinal transit and the passage of stool. Although it was approved for adult patients in January 2006, no studies in children have been performed to date. Other agents such as alvimopan (Entereg), a peripherally acting mu-opioid receptor antagonist, and prucalopride, a promotility agent that acts in the colon, have been investigated. With all of these agents, pediatric data are lacking and further studies are required that assess safety, efficacy, and tolerability before they enter the armamentarium of medications used for the treatment of constipation in children.
Biofeedback has been proposed and evaluated in multiple open-label studies (
North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) Constipation Committee Clinical practice guideline: evaluation and treatment of constipation in infants and children: Summary of updated recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.
Journal of Pediatric Gastroenterology and Nutrition.2006; 43: 405-407
). Biofeedback has been shown to demonstrate some efficacy; however, long-term success has not been confirmed. Intensive psychotherapy also may be useful in some extreme cases.
Conclusion/Summary
Constipation in the pediatric patient is a problem that occurs commonly and requires prompt attention, education, and acute and long-term management to avoid physical and emotional complications. Constipation may be a difficult problem to treat, often requiring several months of therapy. However, it is important that children with constipation be treated medically as outlined by the three-step management algorithm: complete evacuation, sustained evacuation, and weaning from medications. In addition to medical interventions, education, behavioral modifications, and a strong, positive and supportive environment is necessary for a successful endpoint in a child experiencing chronic functional constipation. Because of the interaction between physical and psychological factors, it is unlikely that one single treatment approach alone will be effective. Ongoing follow-up is necessary, and treatment approaches should be tailored to individual patients.
North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) Constipation Committee
Clinical practice guideline: evaluation and treatment of constipation in infants and children: Summary of updated recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.
Journal of Pediatric Gastroenterology and Nutrition.2006; 43: 405-407
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