Case Studies in Constipation

At an industry-sponsored symposium held in conjunction with the American College of Gastroenterology’s 2002 Annual Scientific Meeting, a panel of experts discussed the incidence and pathophysiology of constipation and described various diagnostic and
treatment options. The panel also reviewed current studies for new treatment approaches and the evaluation for surgical indication, and discussed the on-going management of constipation in children.

This program was jointly sponsored by Seton Hall University School of Graduate Medical Education and the American Academy of Continuing Medical Education, Inc.

This program was supported by an unrestricted educational grant from Braintree Laboratories, Inc.

Pathophysiology of Constipation

In his overview of the pathophysiology of constipation, Lawrence Schiller, MD, FACP, FACG, Program Director, Gastroenterology Fellowship of the Department of Gastroenterology at Baylor University Medical Center in Dallas, Texas, stated that the colon absorbs fluids, electrolytes, and bacterial fermentation products, and plays a major role in the transit of material to the rectum. Another physiologic characteristic of the colon is its reservoir function.
The anatomy of the distal colon and rectum is very important in terms of function. The rectum is surrounded by muscle layers, including the pelvic floor muscles, and the external and internal anal sphincters. The latter sphincter is responsible for the timely emptying of feces. The puborectalis muscle maintains the right angle between the rectum and anus. For successful defecation, the puborectalis must be relaxed.

Is It Helpful to Categorize the Types of Constipation?
Treatment options vary according to the category of constipation, stated Dr. Schiller. Idiopathic constipation includes slow transit constipation (colonic inertia), functional outlet obstruction, and constipation-predominant irritable bowel syndrome (IBS). Colonic inertia is the most common mechanism of constipation, accounting for approximately 75% of patients with constipation. It is presumed to involve dysfunctional neuromuscular co- ordination of the colon, but also may result from functional outlet obstruction, chronic use of stimulatory laxatives, or be part of a generalized disorder (Table 1).

Functional outlet obstruction has many causes, such as intrarectal intussusception, perineal descent, or spastic pelvic floor or “anismus,” which entails paradoxical contraction of the puborectalis and external anal sphincter during defecation. Spastic pelvic floor syndromes often have psychiatric overtones.
The symptoms of constipation- predominant IBS show considerable overlap between those of normal transit constipation and IBS. Patients exhibit similar psychological profiles and have similar problems with pain.

Table 1. General Characteristics of Slow Transit Constipation

• Presumably a problem with colonic neuromuscular coordination
• Common occurrence
• May be secondary to functional outlet obstruction
• May be due to chronic stimulatory laxative use
• May be part of a generalized disorder

Evaluating Patients Who Have Constipation

Evaluating Patients Who Have Had Constipation for Several Months, Have a Sensation of Incomplete Defecation, Difficulty with Stool Passage, and
Who Are Taking Antihypertensives
First, irritable bowel syndrome must be ruled out, because it requires different management strategies, advised Jack A. Di Palma, MD, FACG, Professor and Director of the Division of Gastro-enterology at the University of South Alabama College of Medicine, in Mobile, Alabama. Dr. Di Palma reported that the Rome II criteria for constipation consider not only the frequency of stools but also factors such as anorectal blockage, incomplete defecation, and the occurrence of loose stools.

More than 900 medications, including analgesics, anticholinergics, antihistamines, and antihypertensives, cause constipation. In one study, 40% of patients screened for constipation were using constipating medications (Adeniji OA, DiPalma JA. Am J Gastroenterol. 2001;96:S140).

A careful physical examination should evaluate for masses, fissures, fistulas, hemorrhoids, and gross puborectalis and anal sphincter contractions. Metabolic profiles, including fasting glucose levels and TSH, should be recorded to rule out endocrinopathic causes. Radio-opaque transit markers with a single KUB for 5 days are useful in defining colonic inertia.

Colon cancer screening, recommended for patients aged >50 years, involves annual fecal occult blood tests and sigmoidoscopy every 5 years or, preferably, colonoscopy every 10 years. Colonoscopy at 40 years is recommended for patients with a family history of colon cancer.

What Are the Available Treatment Options for Patients with Constipation?
Educating patients with constipation is an essential aspect of managing their condition, stated Dr. Di Palma. Patients must have realistic expectations regarding the number and frequency of bowel movements. Dr. Di Palma encourages his patients to respond to the call to defecate, exercise moderately, and to recognize the consequences of disrupting daily routines (eg, by travel).

Bulk-forming laxatives, such as fiber, psyllium, and methylcellulose, reportedly promote peristalsis and reduce transit time (Adeniji OA, DiPalma JA. Am J Gastroenterol. 2001;96:S140). These agents, however, are most effective in patients with normal transit rather than with obstructive defecation. A trial of dietary fiber is recommended before patients undergo diagnostic testing (Voderholzer WA, et al. Am J Gastroenterol. 1997;92(1);95-98).

Lubricating agents (mineral oil) may be used to treat constipation. Stimulant laxatives, such as surface-acting agents, diphenylmethane, ricinoleic acid, and anthraquinones, are widely believed to aggravate slow transit constipation, although evidence to support this claim is lacking.

Osmotic laxatives include magnesium and phosphate salts, lactulose, and polyethylene glycol (PEG). Lactulose is maldigested and transits to the colon, where it serves as a substrate for bacterial fermentation. Lactulose increases the water content of stool and stimulates small bowel activity, but patients may experience bloating, flatus, or diarrhea.

Polyethylene glycol laxatives, such as Miralax®, have high molecular weights, are metabolically inert, and obligate intraluminal water retention. Importantly, PEG laxatives may be administered once daily, unlike lactulose. A randomized, placebo-controlled, multicenter, parallel trial of 151 subjects with fewer than 3 stools daily found that Miralax® increased stool frequency (PEG: 2.7 BM/wk, control 1.5; P<0.01) (Di Palma JA, et al. Am J Gastroenterol. 2000;95:446). The agent was judged by both patients and investigators to be effective and no adverse experiences or laboratory abnormalities were recorded.

Is the Diagnostic Approach for Children Different from that for Adults?

David A. Gremse, MD, Professor and Interim Chair of the Department of Pediatric Gastroenterology and Nutrition, at the University of South Alabama, in Mobile, Alabama, explained that pediatric physical evaluations are similar to those performed in adults. Evaluations should include abdominal palpation for fecal mass, assessment of anal size and position, and inspection of the skin on the lower spine for vascular, pigmented, hairy patches. Neurological examinations also are recommended. The diagnostic evaluations in children are similar to those used in adults, such as stool hemoccult, T4, TSH evaluations, barium enemas, intestinal transit times, and anorectal manometry. For children with growth impairment, Dr. Gremse recommends sweat chloride assessments and screening for celiac disease.

Hirschprung’s disease (HD) is an important condition to rule out when evaluating pediatric constipation. HD often is associated with neonatal constipation, but unlike functional constipation, rarely causes soiling, difficulty with toilet training, stool withholding, or stool accumulation in the vault. Importantly, the ability to pass stools without suppositories usually rules out HD, a condition that necessitates rectal stimulation for defecation. Various techniques, including barium enemas, suction rectal biopsy, or anorectal manometry may be used to confirm HD (Reid JR, et al. Pediatr Radiology. 2000;30:681). Additionally, an MRI may rule out tethered cord.

Treatment options for infant dyschezia may include fruit juices, Karo syrup (1 tbsp/4 oz formula qD to BID), fiber (Maltsupex® 1-2 tsp/4 oz formula or juice BID to QID), osmotic laxatives (eg, lactulose or MOM 1-2 mL/kg/dose qD to BID), and polyethylene glycol 3350 (Miralax®). The safety and efficacy of Miralax® in infants has not yet been studied. Mineral oil should not be used in infants because of aspiration risk.

Effective treatment of painful defecation in infancy may reduce the incidence of fecal impaction and fecal soiling in later childhood. Partin et al found
that 63% of school-age children with encopresis had a history of painful defecation as infants or toddlers (Partin JC, et al. Pediatrics. 1992;89:1007). This underscores the need to treat infant dyschezia, believes Dr. Gremse.

What Treatment Strategy Would You Use for a Child with Functional Fecal Retention?
Functional fecal retention (voluntary stool withholding) is the most common cause of childhood constipation. Symptoms usually peak during toilet training or at school age, and patients have a history of intermittent passage of large, painful stools. Male children often experience fecal incontinence.

Treatment strategies for pediatric constipation comprise three phases. Phase 1 involves disimpaction (3-5 days) using enemas, magnesium citrate, or polyethylene glycol (PEG). Enemas are very unpleasant for children and their parents, and children sometimes have difficulty consuming adequate volumes of oral magnesium citrate. The PEG balanced electrolyte solution Nu-Lytely® has a pediatric indication and can be used for colonic lavage.

Phase 2 involves maintenance therapy (3-12 months) with oral laxatives, mineral oil, lactulose, or PEG. Patients follow a high-fiber diet, with regular toileting and behavioral modifications. Patients are gradually weaned from the laxatives (dose cut 50% for 1 month) in Phase 3.

In a 2-week, randomized crossover trial, Gremse et al found that lactulose and PEG 3350 were similar in terms of stool consistency and ease of stool passage (Gremse DA, et al. Clin Pediatr. 2002;41:225). However, patients expressed a 3 to 1 preference for PEG 3350, because it was easier to use.
In treatment follow-up, laxative doses may be increased if the stool is still hard and the patient is compliant. If the patient is not compliant (eg, taste aversion), the laxative may be changed. If the stool is soft and the bowel movements are infrequent, a stimulant laxative may be added.

What Could Explain a Lack of Response to Lactulose, and Could Higher Doses of PEG Be Used?
Inadequate cleanout before maintenance stool softening therapy is a common cause of treatment failure, as are inadequate doses of stool softener and inadequate duration of stool softening therapy. A lack of response to a laxative highlights the importance of adequate washout and satisfactory disimpaction in management of pediatric constipation. Enemas and PEG electrolyte solutions are most commonly used for this purpose. The use of PEG without electrolytes for disimpaction currently is being studied.

Youssef et al have demonstrated that Miralax® doses of 1 g/kg/day and 1.5 g/kg/day are effective for disimpaction, but not doses of 0.5 g/kg/day (Youssef NN, et al. J Pediatr. 2002; 141:410). The higher doses also did not cause electrolyte complications, suggesting that in children weighing up to 30 kg, doses of 30-50 g may be safe.

Is There a Special Evaluation for Suspected Obstruction Defecation or Pelvic Floor Dysfunction?

In patients with constipation, possible anatomic causes should be determined first, according to David E. Beck, MD, FACS, Chairman of the Department of Colon and Rectal Surgery of the Ochsner Clinic Foundation in New Orleans, Louisiana. After anatomic causes have been ruled out, transit studies with commercial markers may be used to select candidates for surgery and to determine the most appropriate procedure.

Patients may undergo an abdominal x-ray (kidney, ureters, bladder [KUB]) 1, 3, and 5 days after taking a marker capsule. This study also helps to identify patients who may be demanding surgery that is unnecessary. If the patients claim that they did not have a bowel movement but the markers present on day 1 are gone by day 3, then surgery probably should not be considered.

Commercial markers also may function as transit studies of the upper intestine. Retention of the marker in the patient’s stomach 1 to 3 days after the capsule has been taken suggests gastroparesis. If the patient has outlet obstruction, the markers accumulate just above the rectum.

Outlet obstruction also may be detected using a balloon expulsion test (Beck DE. Dis Colon Rectum. 1992; 35:597). The patient is required to pass a balloon that has been inflated in his or her rectum. Successful evacuation of the balloon demonstrates that the patient can empty his or her rectum. A defecogram may be recommended for patients who cannot pass the balloon.

Is Surgery an Option for Patients in Whom Laxatives Have Been Unsuccessful?
In the past, poor patient selection and inadequate surgical procedures resulted in high morbidity. Currently, if the patient’s lifestyle is significantly impaired, surgery can be a treatment option.

Colectomy and ileoproctostomy may be used to treat colonic inertia. Various studies have demonstrated success rates of 65%-100% (average 88%) following this procedure (Pikarsky AJ, et al. Dis Colon Rectum. 2001;44:179). The postoperative frequency of bowel movements ranges from 0.5 to 5/day, but decreases over time, particularly among younger patients and those without symptoms of irritable bowel syndrome (IBS). Patients with IBS who undergo these surgical procedures often continue to have pain and bloating. Approximately 7%-50% of patients who have had a total colectomy experience small bowel obstruction within 2 years, but this rate is expected to decrease with growing use of new products designed to prevent adhesions. Ileostomy without colectomy is an option for patients who have incontinence associated with constipation (i.e., women with childbirth injuries).

In patients with outlet obstruction, rectocele prolapse can be treated with protectomy (Altmeier procedure) or mucosectomy (Delorme procedure). Abdominal fixation or resection with fixation also may be considered. Determining whether a prolapse is causing all of the symptoms is sometimes a problem, therefore obtaining a good history and physical examination are important for patient selection. Rectoceles are common and may be corrected
using transvaginal, transanal, or perineal outpatient procedures.

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