Evaluation and Management of Intractable Constipation in Children

Diagnostic Evaluation and Management 

The evaluation and management of intractable constipation in children is depicted as an algorithm in Figure 1. The first step is the clinical evaluation. Although certain symptoms like bloating, soiling, infrequent bowel movements, and softer stools are more common in slow transit constipation (STC) than in FFR,4 clinical features alone are inferior in determining the cause of constipation to objective measures like transit studies and pressure measurement studies, including anorectal manometry and colonic motility. The Rome criteria has been recently validated in children5 but these criteria have shown poor intraobserver and interobserver reliability and fail to include all children with chronic constipation.6, 7 An important concept is the rectosigmoid sensation, which is usually altered in intractable constipation. Studies of rectosigmoid sensation have shown that dilation of those colonic segments may not allow the proper sensation for stimulation of defecation in children.8, 9

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Figure 1. Algorithmic approach to refractory constipation in children.

After a history and examination including a rectal examination to exclude presacral masses, the next step in the evaluation of intractable constipation is to look for conditions that are commonly associated with constipation, as well as rare conditions that may have constipation as a predominant symptom. Those conditions are listed in Table 1. Once these common problems associated with symptoms of severe constipation have been excluded, the evaluation for the cause of the child’s symptoms begins.

Table 1. Causes of Chronic Constipation

	Common causes
	Medications: opioids, antacids containing aluminum and calcium, calcium channel blockers, antiparkinson drugs, antidepressants, anticonvulsants, iron, antispasmodics, diuretics
	Cow’s milk and food allergy
	Cerebral palsy
	Celiac disease
	Hypothyroidism
	Hypercalcemia (hyperparathyroidism)
	Rare causes
	FG syndrome with associated tethered cord74
	Malrotation
	Chilaiditi’s syndrome75, 76
	Diabetes mellitus type I77
	Anogenital lichen sclerosus78, 79
	Solitary rectal ulcer80
	Currarino triad
	Dystrophic epidermolysis bullosa
	Sacral agenesis

Plain abdominal films (Fig. 2) and a contrast enema are simple to obtain and may provide important information. The contrast enema in particular helps to evaluate the presence of a transition zone, colonic dilation, as well as malrotation or abnormal fixation of the colon. This study is useful to determine if a megarectum or megasigmoid configuration is present (Fig. 3). However, in most studies no definite etiology for constipation will be seen.10, 11 Others have used defecography studies but these studies are cumbersome to perform in children and may be impossible in a noncompliant toddler. Recently a radionuclear defecography has shown promising results using low radiation in evaluating children with constipation,12 but more studies are needed before use of isotope defecography can be recommended in children.

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Figure 2. Toxic colonic distention in child with refractory constipation.

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Figure 3. Massive distal colonic distention (megarectum/megasigmoid) on contrast enema.

The anorectal manometry is a simple but invaluable test in the initial evaluation of intractable constipation. This test assesses the internal anal sphincter (IAS) resting pressure and its relaxation to intrarectal distention. Findings on this study can argue against the diagnosis of HD or IAS achalasia and can help evaluate rectal compliance and the presence of a megarectum.

A rectal biopsy is mandatory in patients with abnormal anorectal manometry. The biopsy can be performed using a device with a suction chamber to retrieve rectal mucosa and submucosa or by obtaining a formal surgical biopsy of the anorectal canal including a portion of the underlying internal sphincter complex. The advantage of a suction biopsy is that it does not require analgesia in most cases, but in older children the biopsy is often inadequate. The more formal surgical biopsy provides information of the sphincter complex that is valuable in patients with intractable constipation. Rectal biopsies have been shown to help in identifying patients with previously unidentified neurenteric disorders who may benefit from additional surgery in the treatment of intractable constipation.13 The histological evaluation of these biopsies should not stop with the presence or absence of ganglion cells. Deficiencies in neurotransmitters implicated in colonic function, like substance P or VIP,14, 15, 16, 17, 18, 19 and a paucity of interstitial cells of Cajal (ICC) can be crucial in understanding the pathophysiology of intractable constipation.18, 20, 21, 22 An absence or paucity of ICC has been found in the proximal colon in infants with anorectal malformations and may be responsible for the severe constipation that frequently complicates the postoperative management of those infants and children.23

The diagnosis of IAS achalasia is best determined by anorectal manometry as the absence of rectosphincteric reflex with rectal balloon inflation but the presence of ganglion cells on rectal biopsy. These patients show earlier onset of symptoms, less fecal soiling, and less withholding behavior than functional constipation.24 There is evidence of innervation defects in IAS achalasia with one study reporting decreased or absent PGP 9.5, synapsin 1, and NADPH-diaphorase.25 Medical treatment has been attempted in adult patients with high resting pressure IAS including the application of nitroglycerin preparations to the anal area with some success. In children with elevated sphincter pressure after surgical correction of HD, the use of topical nitric oxide has been successful.26 We do not recommend the use of topical treatment of this problem since the beneficial effect is short-lived and requires daily applications that may predispose the patients to the undesired systemic side effects of the medication.

We believe the first step in the management of patients with IAS achalasia is the intrasphincteric injection of botulinum toxin type A (Botox®, Allergan Inc., Irvine, CA). The usual total dose used in children ranges between 60 and 100 units divided in aliquots and injected in each of the four quadrants. Retrospective studies in children have shown this treatment is safe and effective in most patients.24, 27, 28 The main effect is seen immediately after the injection as measured by a fall in the elevated resting sphincter pressure and a more appropriate relaxation of the IAS with rectal distention.28 Unfortunately, the response may not be sustained, and many children require more than one injection. Larger prospective studies are needed to gather information on clinical efficacy after long-term use of botulinum toxin type A. Iatrogenic botulism is rare, but it has been reported in the treatment of spasticity.29

Evaluation in those children with a poor clinical response to Botox® injection should include colonic manometry. We followed 14 patients for 2 to 6 years and 6 patients were subsequently diagnosed with colonic neuropathy by colonic motility; two of those required antegrade continence enemas and one required a colostomy.28 We do not recommend anal stretching or forceful dilation for IAS achalasia or idiopathic constipation as others have shown that this treatment is ineffective.30

Anorectal sphinctermyectomy or sphinctermyotomy is an alternative when Botox® injection of the internal anal sphincter does not produce the desired effect or if there is diminished effect with repeated injections (tachyphylaxis). The surgical procedure is effective but has a higher incidence of at least temporary incontinence and sometimes long-term stress incontinence.31, 32 However, a long-term follow-up of patients for 2 to 6 years after sphinctermyectomy showed significant improvement in the frequency of bowel movements and the ability to reduce or stop laxatives.25

A lower spine MRI can be important and is recommended in the evaluation of intractable constipation as 9% of children with severe symptoms have abnormalities of the spinal cord.33 An even higher incidence is noted in those children with constipation complicating anorectal malformations.34 It is important to detect these abnormalities to initiate the proper neurosurgical treatment before considering other surgical options to treat what may be secondary constipation.

When treatments addressing the rectal sphincter have failed and HD has been excluded, it is best to evaluate the entire colon for dysmotility. Two types of radiographic transit studies have been useful for the evaluation of constipation in children, using either radiopaque markers or scintigraphic studies. Radiopaque markers (sitz marks) are commonly used in adult patients and in older children to evaluate colonic transit when colonic manometry is not available (Fig. 4).35, 36 It has been useful in adolescents to differentiate between slow transit constipation and defecation disorders.37, 38 Radionuclear colonic transit has been used and validated in adults. Studies in children have shown promising results, particularly to differentiate slow transit constipation from FFR.39, 40, 41 However, further studies are needed before it can be considered a reliable clinical test in pediatric patients. A recent study reported the use of a retrograde colonic washout technique to evaluate various colonic segments and their ability to evacuate the nuclear marker but the study has significant limitations.42

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Figure 4. Sitz mark study in child with slow transit constipation.

The best test for the purpose of evaluating colonic function is the colonic manometry or colonic motility (CM) studies. The other radiographic tests can provide information about the colonic transit but that information is not as specific and clinically relevant as the CM. Colonic manometry, used in conjunction with the anorectal manometry in the evaluation of intractable constipation in children, best differentiates colonic neuromuscular disorders from FFR.43, 44 The colonic manometry catheter is typically placed endoscopically but more recently has been passed by interventional radiology. The test includes a minimum of 1 hour of fasting, observation of 30 to 60 minutes after a test meal, and a challenge with intracolonic bisacodyl. Normal features of the colonic motility include the gastrocolonic response (increase in baseline motility in response to a meal) and the presence of spontaneous or bisacodyl-induced high-amplitude peristaltic contractions (HAPCs) (Fig. 5). Abnormalities in the test will demonstrate no gastrocolonic response and absent, interrupted, or abnormally propagated HAPCs (Figs. 6A and B and 7).

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Figure 5. Normal colonic manometry in child with functional fecal retention.

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Figure 6. A. Left colonic neuropathy in child with constipation. Arrows mark HAPC at proximal transducer without propagation into distal colon. B. Right colonic neuropathy with HAPC and propagation seen in distal colon.

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Figure 7. Total colonic neuropathy.

The most likely diagnosis is a behavioral condition if anorectal and colonic manometry is normal in the evaluation of severe constipation. The treatment for these patients includes aggressive behavioral modification and use of laxatives. Biofeedback has a greater role in treating fecal incontinence, particularly after surgical correction of HD and imperforate anus.45 Manometry helps to guide therapy in patients with constipation and incontinence after surgery for HD, particularly as specific subsets have been identified in this group.46

The abnormalities on the colonic manometry study can be broadly classified as two types: myopathic and neuropathic. The neuropathic type is the most common type and usually carries a better prognosis. The diagnostic criteria of neuropathy include absence of gastrocolonic response, absence of HAPCs in a dilated colon, lack of distal propagation of HAPCs, and the lack of initiation of HAPCs in the right colon. The myopathic type is diagnosed less frequently and includes the presence of low-amplitude contractions or the absence of contractions in a nondilated colon.47 These manometric changes may be present in the entire colon but they can also occur segmentally, in either the right or the left colon. The term colonic inertia is used to describe adult patients with severely prolonged colonic transit time measured by a transit study. The problem often is found in young, otherwise healthy, women. In children, colonic inertia is less well defined and likely includes patients with neuropathic and myopathic enteropathies. For this review we use the term to include patients in whom the colonic transit time is severely delayed and/or the colonic manometry does not show gastrocolonic response and HAPCs.

Among the many medications tried in the treatment of severe constipation, tegaserod (Zelnorm®, Novartis Pharmaceuticals Corp, East Hanover, NJ) has shown a beneficial effect on the treatment of intractable constipation. Tegaserod, a 5-HT4 serotonin receptor agonist, has been recently granted FDA approval for constipation in adults. Unfortunately, there are no randomized clinical trials with the use of tegaserod in the treatment of intractable constipation in children. There is a recent report of successful treatment with tegaserod in four constipated pediatric patients with no identifiable pathological diagnosis (including HD).48 We do not recommend the routine use of tegaserod before a formal evaluation is performed, including an anorectal and a colonic manometry to exclude functional fecal retention. In our experience, tegaserod can be effective in approximately a third of patients with intractable constipation, and we recommend its use in patients diagnosed with either segmental or total colonic neuropathy.

For patients with slow transit constipation in whom tegaserod does not improve the frequency and consistency of bowel movements, the use of antegrade continence enemas has been successful. These enemas administered through an appendicostomy or cecostomy have revolutionized the management and quality of life of patients with intractable constipation, particularly children with complex neurological conditions such as cerebral palsy, spina bifida, and myelomeningocele.49 Reports of antegrade enemas in children and adults with refractory constipation not associated with neurological diseases have shown a similar significant improvement in quantity and quality of bowel movements, quality of life, lessened use of medications for constipation, number of missed school days, and number of visits to a physician’s office.50, 51, 52, 53, 54 Recently, placement of the tube in the left colon has been reported to be successful.55, 56, 57

Patients that do not respond to antegrade enemas are candidates for extirpative surgery. We believe that the most appropriate surgical procedure can be guided by the result of the colonic manometry.58, 59, 60 For patients in whom the manometry showed a partial neuropathy, especially left colonic neuropathy, a left hemicolectomy may be successful, particularly when associated with dilation of that segment. There is less information on neuropathy on the right colon, but the same principles and treatment algorithm as used with left colon dysmotility would be recommended. A study including four pediatric patients with intractable constipation and megarectum on contrast enema has demonstrated the effectiveness of this more aggressive surgical approach. These children underwent resection of the dilated rectum and temporary use of a cecostomy button for antegrade enemas. All of those children had their cecostomies removed and have continued to have do well without return of symptoms of constipation or encopresis.61 Others have reported resection of a dilated sigmoid colon with improvement of constipation symptoms, particularly in children with anorectal anomalies.62, 63, 64, 65

For patients in whom colonic manometry shows a total colonic neuropathy, a severe dilation that renders interpretation of colonic manometry difficult, or a colonic myopathy, a diverting ileostomy is the surgical treatment of choice. Since the natural history of “colonic inertia” in children is unknown, resection is not appropriate as the primary procedure. Based on our experience, we do not recommend the use of antegrade colonic enemas in these cases but instead recommend a diverting ileostomy. Others have recommended a proximal diverting colostomy with success in children with intractable constipation,66 but we consider this a lesser option. The key principle in recommending an ileostomy is to realize total colonic decompression with the hope that, after some period of time (usually 9 to 12 months), colonic motility will improve and a successful closure of the diverting enterostomy can be performed. The treating physicians may need to evaluate the small intestine if the diverting enterostomy does not result in an alleviation of the child’s symptoms. In that instance, it is important to assess the small bowel motility to rule out total intestinal pseudoobstruction.

There is evidence (and it is our experience) that colonic manometry can best guide the decision to close a stoma after diversion. Villarreal and coworkers reported four children with intractable constipation that underwent an ileostomy or colostomy for severe colonic neuropathy. The repeat colonic manometry showed improvement with HAPCs present only in the right colon and a left hemicolectomy and right colon to rectal anastomosis was performed with resolution of their constipation. They also reported four patients with intractable constipation in whom the repeat colonic manometry after diversion was normal and a simple closure of the stoma was performed.59 We recommend repeating the colonic motility after a period of no less than 9 to 12 months and, if that manometry is normal, to close the diverting enterostomy. In the same line, if the colonic manometry is abnormal, the segment (or the entire colon) affected should be resected followed by a primary anastomosis.

Total abdominal colectomy with ileoproctostomy is considered the treatment of choice for colonic inertia in adults, and it has been shown to be effective in improving the symptoms of constipation in most patients.67, 68, 69, 70, 71 Even still, a fair percentage of treated adult patients continue to experience some of the same preoperative symptoms, such as bloating and abdominal pain, despite a technically successful operation.72, 73 The use of this more extensive surgery in children has not been reported, although anecdotally we have had success with total abdominal colectomy and ileorectal anastomosis.

Information in the literature is scant regarding the outcomes in children who have been more aggressively managed in the treatment of intractable constipation. Our own experience complements the available literature. Many of the children and their families experience a benefit by this more aggressive approach. We believe that the use of these functional studies are crucial in avoiding unnecessary surgery in children who will not benefit from surgery. More importantly these studies allow the pediatric surgeon and pediatric gastroenterologist to identify the surgical procedure that will have the best chance of alleviating these debilitating symptoms.