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Childhood constipation: Finally some hard data about hard stools!

2000; Elsevier BV; Volume: 136; Issue: 1 Linguagem: Inglês

10.1016/s0022-3476(00)90039-8

1097-6833

Carlo Di Lorenzo,

Congenital gastrointestinal and neural anomalies

See related articles, p. 35 and p. 41 .It is estimated that 55 million adults in the United States, approximately 28% of the population, are constipated.1Stewart WF Liberman JN Sandler RS Woods MS Stemhagen A Farup CE A large US national epidemiological study of constipation [abstract].Gastroenterology. 1998; 114: A44Abstract Full Text PDF PubMed Google Scholar Similar large-scale epidemiologic data are not available in pediatrics, although it has been reported that 34% of toddlers in the United Kingdom and 37% of Brazilian children younger than 12 years of age were considered by their parents to be constipated.2Loening-Baucke V Constipation in children.N Engl J Med. 1998; 339: 1155-1158Crossref PubMed Scopus (60) Google ScholarA disorder of defecation is the chief complaint in 3% to 5% of visits to pediatricians. At Children’s Hospital of Pittsburgh, a review of visits to the gastroenterology clinic during the past year reveals the prevalence of children referred for evaluation and treatment of constipation to be 11%, second only to gastroesophageal reflux.Few benign medical conditions are as distressing as a disorder of defecation. Parents attach great importance to their children’s successful stooling. Anxious caretakers will call the physician in the middle of the night if the child is perceived to be struggling with defecation. Most of us have met parents so focused on their child’s bodily functions that they are able to recall number, timing, and character of each delivery, describing the event with an emphasis similar to the one used to recall the child’s first steps or words. A tremendous amount of frustration and parent-child hostility are generated when children develop fecal soiling as a consequence of chronic constipation. Decreased self-esteem, depression, loss of coping skills, anxiety, and other affective disturbances often follow.What can go wrong in a process that most of us take for granted? Let’s briefly review the physiology associated with defecation. Within 3 to 4 hours of ingestion, food enters the cecum. It then takes several more hours to reach the rectum. There are 2 normal motor patterns responsible for the movement of colonic contents: (1) segmental, non-propagated tonic and phasic contractions, mixing luminal contents and (2) very powerful high-amplitude propagated contractions, which propel stools to the rectum.3Di Lorenzo C Flores AF Hyman PE Age related changes in colon motility.J Pediatr. 1995; 127: 593-596Abstract Full Text Full Text PDF PubMed Scopus (70) Google Scholar Colonic motility increases after a meal (the “gastrocolonic response”) and on awakening. When the rectal wall is distended by stool, there is a reflex contraction of the rectum with relaxation of the internal anal sphincter, pushing fecal material into the anal canal, where it is now in the “firing” position. The sensitive lining of the anoderm perceives the stool, and a decision is made whether to expel it or to postpone defecation by contracting the external anal sphincter and the puborectalis muscle. If defecation is delayed, a voluntary contraction of the abdominal muscles will be needed later to push the stool into the anal canal and once again produce a bowel movement. The basic regulatory mechanisms that control defecation are present in the newborn, with only the ability to make a conscious decision of contracting and relaxing the skeletal muscles (external anal sphincter, puborectalis, and abdominal muscles) developing at the time of toilet training. Any disruption of this sequence of motor events may lead to constipation. The most common cause of constipation in pediatrics is a decision made by the child to delay defecation after experiencing a painful or frightening evacuation. Children, in their very concrete way of thinking, react to unpleasant experiences with repeated, and often successful, attempts to avoid those experiences again. The abstract thought that “hurting a little now” may have long-term benefits is not easily accepted by constipated children who would be just as pleased to postpone defecation forever! Children with this form of functional (or behavioral) constipation have normal colonic motility. When the rectum is empty, stools reach it without difficulty. When the rectum is full of stool, neural reflexes delay gastric emptying and transit in the small bowel and proximal colon, leading to decreased appetite, abdominal pain, and distension. The only abnormal motor activity in most children with chronic constipation is found in the rectum, which may become so dilated that it may not be able to generate enough pressure to propel the stool into the anal canal. Manometric studies have also suggested that some constipated children have “anismus,” a contraction of the external sphincter during an attempt to defecate. It is nothing other than the manometric equivalent of withholding the stool. The response to ignore the defecatory urge was initially a conscious decision and has now become automatic.Treatment of constipation is based on addressing all the factors that have contributed to its development. The evacuations are made more pleasant by administration of stool softeners. After a few painless evacuations, the child realizes that it is actually a relief to “let go.” The fear of defecation is overcome by avoiding anally invasive procedures (here is a revelation: children hate enemas!) and by using positive reinforcement to make the process less intimidating. In more severe cases, the abnormal motility of the dilated rectum is corrected by the use of cathartics. Key to successful treatment is a thorough understanding by the family (and the child, when mature enough) of the pathophysiology of childhood constipation. Myths and fears associated with constipation need to be dispelled. The initial visit of a child with chronic constipation, especially when soiling is present, should not last less than 30 minutes. Most successful treatments reported in the literature (dietary changes, use of different medications, various forms of behavioral treatments) are based on those basic principles.Interestingly, despite the high prevalence of this condition, there have been very few well-designed therapeutic trials for childhood constipation. A careful review of the literature of the last 33 years identified less than a handful of controlled treatment trials of constipation in children.4Baker SS, Liptak GS, Colletti RB, Croffie JM, Di Lorenzo C, Ector W, et al. Constipation in infants and children: evaluation and treatment. A medical position statement of the North American Society for Pediatric Gastroenterology and Nutrition. J Pediatr Gastroenterol Nutr. In press.Google Scholar Such paucity of studies may be due in part to the lack of interest and financial incentive for pharmaceutical companies to study drugs that are sold as over-the-counter remedies. In this issue of The Journal we can finally read about 2 such studies. Was there a need to identify more effective therapies for childhood constipation? Yes! Despite treatment being fairly straightforward and constipation being short-lived in many cases, it has been reported that approximately 30% of children seen in a tertiary referral center continue to be constipated after 4 years. Why do children with disorders of defecation continue to plug the subspecialist clinics? The mounting pressure on primary care physicians to see more patients in an increasingly limited amount of time may not provide an adequate opportunity for an extensive explanation of the pathophysiology of constipation. Poor compliance with the behavioral and medical interventions accounts for many treatment failures. Nevertheless, there is a sizable subgroup of children with constipation that continues to be refractory to treatment despite compliance with all aspects of conventional treatment. Some of these children may have a colonic motility disorder. Delayed colonic transit has been demonstrated in some children with constipation,5Benninga MA Buller HA Tytgat GN Akkermans A Bossuyt PM Taminiau AM Colonic transit time in constipated children: Does pediatric slow-transit constipation exist?.J Pediatr Gastroenterol Nutr. 1996; 23: 241-251Crossref PubMed Scopus (122) Google Scholar although it is unclear whether it is a primary disorder or the delay is secondary to the long-standing colonic distension. Nurko et al6Nurko S Garcia-Aranda JA Worana LB Zlochisty O Cisapride for the treatment of constipation in children: a double-blind study.J Pediatr. 2000; 136: 35-40Abstract Full Text Full Text PDF PubMed Scopus (46) Google Scholar report, in this issue of The Journal, successful use of cisapride, a prokinetic drug, in a double-blind, placebo-controlled, randomized study to treat children with long-standing constipation (average duration of symptoms, 38-47 months). The patients were evaluated in a subspecialty clinic and continued to have symptoms despite an increase in daily fiber intake. The authors do not discuss whether these children had not responded to treatment with other medical or behavioral interventions. After 12 weeks, treatment was considered successful in 76% of cisapride-treated patients compared with 37% of children receiving placebo. The lack of statistical difference between number of bowel movements and fecal soiling episodes in children receiving cisapride and placebo at the end of the study was likely due to the insufficient power of the study. These results support previous reports, which indicate that a subgroup of constipated children might benefit from treatment with cisapride.7Staiano A Cucchiara S Andreotti MR Minella R Manzi G Effect of cisapride on chronic idiopathic constipation in children.Dig Dis Sci. 1991; 36: 733-736Crossref PubMed Scopus (55) Google Scholar How does cisapride work and who should be treated with it? In this and other studies, cisapride decreased the total gastrointestinal transit time. There is clinical and laboratory evidence that cisapride, a drug more known for its effects on esophageal and gastric motility, has a prokinetic action on the colon as well. It may also cause softer stools by accelerating small bowel transit and increasing the amount of fluid entering the colon. In addition, the high sorbitol content of cisapride in the US liquid formulation may also have a role in producing softer stool.8Feldstein TJ Carbohydrate and alcohol content of 200 oral liquid medications for use in patients receiving ketogenic diets.Pediatrics. 1996; 97: 506-511PubMed Google Scholar Choosing whom to treat with cisapride may not be easy. Nurko et al6Nurko S Garcia-Aranda JA Worana LB Zlochisty O Cisapride for the treatment of constipation in children: a double-blind study.J Pediatr. 2000; 136: 35-40Abstract Full Text Full Text PDF PubMed Scopus (46) Google Scholar wisely suggest that cisapride, a compound that has been linked to prolongation of the QT interval, should be considered a “second line” drug for the treatment of childhood constipation. Interestingly, they removed from their study children with “anismus,” likely selecting a subgroup without behavioral disturbance and more likely to have colonic dysmotility.Certain populations, such as the neurologically impaired children reported by Staiano et al9Staiano A Simeone D Del Giudice E Miele E Tozzi A Toraldo C Effect of the dietary fiber glucomannan on chronic constipation in neurologically impaired children.J Pediatr. 2000; 136: 41-45Abstract Full Text Full Text PDF PubMed Scopus (86) Google Scholar in this issue, have different pathophysiologic mechanisms responsible for chronic constipation and are very challenging to treat.10Di Lorenzo C Chronic constipation and fecal incontinence in children with neurological and neuromuscular handicap.J Pediatr Gastroenterol Nutr. 1997; 25: S37-S39Crossref PubMed Scopus (8) Google Scholar It has been reported that 74% of children with cerebral palsy are constipated.11Del Giudice E Staiano A Capano G Romano A Florimonte L Miele E et al.Gastrointestinal manifestation in children with cerebral palsy.Brain Dev. 1999; 21: 307-311Abstract Full Text Full Text PDF PubMed Scopus (165) Google Scholar Immobilization, abnormal colonic motility, inability to contract the abdominal muscles, and inadequate fiber intake contribute to the high prevalence of constipation in this group of patients. Staiano et al9Staiano A Simeone D Del Giudice E Miele E Tozzi A Toraldo C Effect of the dietary fiber glucomannan on chronic constipation in neurologically impaired children.J Pediatr. 2000; 136: 41-45Abstract Full Text Full Text PDF PubMed Scopus (86) Google Scholar demonstrate in a double-blind, placebo-controlled, randomized study that glucomannan, a soluble fiber, increases stool frequency and decreases laxative use in children with severe neurologic damage. Can these data be extrapolated to the treatment of functional constipation? Although insufficient dietary fiber intake is recognized as a contributing factor to the development of childhood constipation12Roma E Adamidis D Nikolara R Constantopoulos A Messaritakis J Diet and chronic constipation in children: the role of fiber.J Pediatr Gastroenterol Nutr. 1999; 28: 169-174Crossref PubMed Scopus (150) Google Scholar and increased fiber intake is the cornerstone of treatment of adults with constipation, there is very little evidence that increasing fiber intake is helpful in the treatment of constipated children without neurologic deficit. In certain situations, increasing the size of the fecal mass may actually be counterproductive in a child struggling with its evacuation. Fiber may have a more important role in preventing reoccurrence of constipation in children who have been successfully treated.In summary, the authors of these 2 articles published in The Journal need to be congratulated for addressing the common but poorly studied subject of childhood constipation in a scientifically sound way. Progress in our understanding of colonic motility disorders and the pathophysiologic mechanisms responsible for treatment failures will help in the selection of patients who may benefit from the use of cisapride and dietary changes. Development of safe prokinetics with a more selective action on colonic motility will undoubtedly facilitate their use in the treatment of childhood constipation. Until that time, the successful treatment of most constipated children will continue to be based on a compassionate approach by health care personnel familiar with the biopsychosocial aspects of this condition. See related articles, p. 35 and p. 41 . It is estimated that 55 million adults in the United States, approximately 28% of the population, are constipated.1Stewart WF Liberman JN Sandler RS Woods MS Stemhagen A Farup CE A large US national epidemiological study of constipation [abstract].Gastroenterology. 1998; 114: A44Abstract Full Text PDF PubMed Google Scholar Similar large-scale epidemiologic data are not available in pediatrics, although it has been reported that 34% of toddlers in the United Kingdom and 37% of Brazilian children younger than 12 years of age were considered by their parents to be constipated.2Loening-Baucke V Constipation in children.N Engl J Med. 1998; 339: 1155-1158Crossref PubMed Scopus (60) Google ScholarA disorder of defecation is the chief complaint in 3% to 5% of visits to pediatricians. At Children’s Hospital of Pittsburgh, a review of visits to the gastroenterology clinic during the past year reveals the prevalence of children referred for evaluation and treatment of constipation to be 11%, second only to gastroesophageal reflux. Few benign medical conditions are as distressing as a disorder of defecation. Parents attach great importance to their children’s successful stooling. Anxious caretakers will call the physician in the middle of the night if the child is perceived to be struggling with defecation. Most of us have met parents so focused on their child’s bodily functions that they are able to recall number, timing, and character of each delivery, describing the event with an emphasis similar to the one used to recall the child’s first steps or words. A tremendous amount of frustration and parent-child hostility are generated when children develop fecal soiling as a consequence of chronic constipation. Decreased self-esteem, depression, loss of coping skills, anxiety, and other affective disturbances often follow. What can go wrong in a process that most of us take for granted? Let’s briefly review the physiology associated with defecation. Within 3 to 4 hours of ingestion, food enters the cecum. It then takes several more hours to reach the rectum. There are 2 normal motor patterns responsible for the movement of colonic contents: (1) segmental, non-propagated tonic and phasic contractions, mixing luminal contents and (2) very powerful high-amplitude propagated contractions, which propel stools to the rectum.3Di Lorenzo C Flores AF Hyman PE Age related changes in colon motility.J Pediatr. 1995; 127: 593-596Abstract Full Text Full Text PDF PubMed Scopus (70) Google Scholar Colonic motility increases after a meal (the “gastrocolonic response”) and on awakening. When the rectal wall is distended by stool, there is a reflex contraction of the rectum with relaxation of the internal anal sphincter, pushing fecal material into the anal canal, where it is now in the “firing” position. The sensitive lining of the anoderm perceives the stool, and a decision is made whether to expel it or to postpone defecation by contracting the external anal sphincter and the puborectalis muscle. If defecation is delayed, a voluntary contraction of the abdominal muscles will be needed later to push the stool into the anal canal and once again produce a bowel movement. The basic regulatory mechanisms that control defecation are present in the newborn, with only the ability to make a conscious decision of contracting and relaxing the skeletal muscles (external anal sphincter, puborectalis, and abdominal muscles) developing at the time of toilet training. Any disruption of this sequence of motor events may lead to constipation. The most common cause of constipation in pediatrics is a decision made by the child to delay defecation after experiencing a painful or frightening evacuation. Children, in their very concrete way of thinking, react to unpleasant experiences with repeated, and often successful, attempts to avoid those experiences again. The abstract thought that “hurting a little now” may have long-term benefits is not easily accepted by constipated children who would be just as pleased to postpone defecation forever! Children with this form of functional (or behavioral) constipation have normal colonic motility. When the rectum is empty, stools reach it without difficulty. When the rectum is full of stool, neural reflexes delay gastric emptying and transit in the small bowel and proximal colon, leading to decreased appetite, abdominal pain, and distension. The only abnormal motor activity in most children with chronic constipation is found in the rectum, which may become so dilated that it may not be able to generate enough pressure to propel the stool into the anal canal. Manometric studies have also suggested that some constipated children have “anismus,” a contraction of the external sphincter during an attempt to defecate. It is nothing other than the manometric equivalent of withholding the stool. The response to ignore the defecatory urge was initially a conscious decision and has now become automatic. Treatment of constipation is based on addressing all the factors that have contributed to its development. The evacuations are made more pleasant by administration of stool softeners. After a few painless evacuations, the child realizes that it is actually a relief to “let go.” The fear of defecation is overcome by avoiding anally invasive procedures (here is a revelation: children hate enemas!) and by using positive reinforcement to make the process less intimidating. In more severe cases, the abnormal motility of the dilated rectum is corrected by the use of cathartics. Key to successful treatment is a thorough understanding by the family (and the child, when mature enough) of the pathophysiology of childhood constipation. Myths and fears associated with constipation need to be dispelled. The initial visit of a child with chronic constipation, especially when soiling is present, should not last less than 30 minutes. Most successful treatments reported in the literature (dietary changes, use of different medications, various forms of behavioral treatments) are based on those basic principles. Interestingly, despite the high prevalence of this condition, there have been very few well-designed therapeutic trials for childhood constipation. A careful review of the literature of the last 33 years identified less than a handful of controlled treatment trials of constipation in children.4Baker SS, Liptak GS, Colletti RB, Croffie JM, Di Lorenzo C, Ector W, et al. Constipation in infants and children: evaluation and treatment. A medical position statement of the North American Society for Pediatric Gastroenterology and Nutrition. J Pediatr Gastroenterol Nutr. In press.Google Scholar Such paucity of studies may be due in part to the lack of interest and financial incentive for pharmaceutical companies to study drugs that are sold as over-the-counter remedies. In this issue of The Journal we can finally read about 2 such studies. Was there a need to identify more effective therapies for childhood constipation? Yes! Despite treatment being fairly straightforward and constipation being short-lived in many cases, it has been reported that approximately 30% of children seen in a tertiary referral center continue to be constipated after 4 years. Why do children with disorders of defecation continue to plug the subspecialist clinics? The mounting pressure on primary care physicians to see more patients in an increasingly limited amount of time may not provide an adequate opportunity for an extensive explanation of the pathophysiology of constipation. Poor compliance with the behavioral and medical interventions accounts for many treatment failures. Nevertheless, there is a sizable subgroup of children with constipation that continues to be refractory to treatment despite compliance with all aspects of conventional treatment. Some of these children may have a colonic motility disorder. Delayed colonic transit has been demonstrated in some children with constipation,5Benninga MA Buller HA Tytgat GN Akkermans A Bossuyt PM Taminiau AM Colonic transit time in constipated children: Does pediatric slow-transit constipation exist?.J Pediatr Gastroenterol Nutr. 1996; 23: 241-251Crossref PubMed Scopus (122) Google Scholar although it is unclear whether it is a primary disorder or the delay is secondary to the long-standing colonic distension. Nurko et al6Nurko S Garcia-Aranda JA Worana LB Zlochisty O Cisapride for the treatment of constipation in children: a double-blind study.J Pediatr. 2000; 136: 35-40Abstract Full Text Full Text PDF PubMed Scopus (46) Google Scholar report, in this issue of The Journal, successful use of cisapride, a prokinetic drug, in a double-blind, placebo-controlled, randomized study to treat children with long-standing constipation (average duration of symptoms, 38-47 months). The patients were evaluated in a subspecialty clinic and continued to have symptoms despite an increase in daily fiber intake. The authors do not discuss whether these children had not responded to treatment with other medical or behavioral interventions. After 12 weeks, treatment was considered successful in 76% of cisapride-treated patients compared with 37% of children receiving placebo. The lack of statistical difference between number of bowel movements and fecal soiling episodes in children receiving cisapride and placebo at the end of the study was likely due to the insufficient power of the study. These results support previous reports, which indicate that a subgroup of constipated children might benefit from treatment with cisapride.7Staiano A Cucchiara S Andreotti MR Minella R Manzi G Effect of cisapride on chronic idiopathic constipation in children.Dig Dis Sci. 1991; 36: 733-736Crossref PubMed Scopus (55) Google Scholar How does cisapride work and who should be treated with it? In this and other studies, cisapride decreased the total gastrointestinal transit time. There is clinical and laboratory evidence that cisapride, a drug more known for its effects on esophageal and gastric motility, has a prokinetic action on the colon as well. It may also cause softer stools by accelerating small bowel transit and increasing the amount of fluid entering the colon. In addition, the high sorbitol content of cisapride in the US liquid formulation may also have a role in producing softer stool.8Feldstein TJ Carbohydrate and alcohol content of 200 oral liquid medications for use in patients receiving ketogenic diets.Pediatrics. 1996; 97: 506-511PubMed Google Scholar Choosing whom to treat with cisapride may not be easy. Nurko et al6Nurko S Garcia-Aranda JA Worana LB Zlochisty O Cisapride for the treatment of constipation in children: a double-blind study.J Pediatr. 2000; 136: 35-40Abstract Full Text Full Text PDF PubMed Scopus (46) Google Scholar wisely suggest that cisapride, a compound that has been linked to prolongation of the QT interval, should be considered a “second line” drug for the treatment of childhood constipation. Interestingly, they removed from their study children with “anismus,” likely selecting a subgroup without behavioral disturbance and more likely to have colonic dysmotility. Certain populations, such as the neurologically impaired children reported by Staiano et al9Staiano A Simeone D Del Giudice E Miele E Tozzi A Toraldo C Effect of the dietary fiber glucomannan on chronic constipation in neurologically impaired children.J Pediatr. 2000; 136: 41-45Abstract Full Text Full Text PDF PubMed Scopus (86) Google Scholar in this issue, have different pathophysiologic mechanisms responsible for chronic constipation and are very challenging to treat.10Di Lorenzo C Chronic constipation and fecal incontinence in children with neurological and neuromuscular handicap.J Pediatr Gastroenterol Nutr. 1997; 25: S37-S39Crossref PubMed Scopus (8) Google Scholar It has been reported that 74% of children with cerebral palsy are constipated.11Del Giudice E Staiano A Capano G Romano A Florimonte L Miele E et al.Gastrointestinal manifestation in children with cerebral palsy.Brain Dev. 1999; 21: 307-311Abstract Full Text Full Text PDF PubMed Scopus (165) Google Scholar Immobilization, abnormal colonic motility, inability to contract the abdominal muscles, and inadequate fiber intake contribute to the high prevalence of constipation in this group of patients. Staiano et al9Staiano A Simeone D Del Giudice E Miele E Tozzi A Toraldo C Effect of the dietary fiber glucomannan on chronic constipation in neurologically impaired children.J Pediatr. 2000; 136: 41-45Abstract Full Text Full Text PDF PubMed Scopus (86) Google Scholar demonstrate in a double-blind, placebo-controlled, randomized study that glucomannan, a soluble fiber, increases stool frequency and decreases laxative use in children with severe neurologic damage. Can these data be extrapolated to the treatment of functional constipation? Although insufficient dietary fiber intake is recognized as a contributing factor to the development of childhood constipation12Roma E Adamidis D Nikolara R Constantopoulos A Messaritakis J Diet and chronic constipation in children: the role of fiber.J Pediatr Gastroenterol Nutr. 1999; 28: 169-174Crossref PubMed Scopus (150) Google Scholar and increased fiber intake is the cornerstone of treatment of adults with constipation, there is very little evidence that increasing fiber intake is helpful in the treatment of constipated children without neurologic deficit. In certain situations, increasing the size of the fecal mass may actually be counterproductive in a child struggling with its evacuation. Fiber may have a more important role in preventing reoccurrence of constipation in children who have been successfully treated. In summary, the authors of these 2 articles published in The Journal need to be congratulated for addressing the common but poorly studied subject of childhood constipation in a scientifically sound way. Progress in our understanding of colonic motility disorders and the pathophysiologic mechanisms responsible for treatment failures will help in the selection of patients who may benefit from the use of cisapride and dietary changes. Development of safe prokinetics with a more selective action on colonic motility will undoubtedly facilitate their use in the treatment of childhood constipation. Until that time, the successful treatment of most constipated children will continue to be based on a compassionate approach by health care personnel familiar with the biopsychosocial aspects of this condition.