A 27-Year-Old Woman With Constipation: Diagnosis and Treatment

Transcription

1 CLINICAL GASTROENTEROLOGY AND HEPATOLOGY 2010;8: EDUCATION PRACTICE A 27-Year-Old Woman With Constipation: Diagnosis and Treatment ARNOLD WALD Section of Gastroenterology and Hepatology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin This article has an accompanying continuing medical education activity on page e108. Learning Objectives At the end of this activity, the learner should be able to evaluate and manage the patient with chronic constipation. A Clinical Scenario 27-year-old woman has had chronic constipation of several years duration and is referred by her primary care physician to a gastroenterologist for further evaluation and management. For the past 5 years, she has averaged 2 3 bowel movements per week, which are often small and hard (types 1-2 on Bristol Stool Scale) and passed with considerable straining. She often has a sense of incomplete emptying of her bowels, is bloated after meals, and complains of lower abdominal distention. She denies heartburn, early satiety, abdominal cramps, excessive flatulence, weight loss, or episodes of diarrhea. Her menses are regular, and she denies urinary symptoms. She is married with 2 children, ages 7 and 5 years, who are well. There is no family history of gastrointestinal disorders. She is otherwise healthy, exercises several times a week, does not smoke, eats ample portions of vegetables, fruits, and fiber cereals, and drinks at least 8 glasses of water daily. She takes no constipating medications and has been tried on stimulant laxatives, polyethylene glycol (PEG) containing laxatives, and lubiprostone with no success. She appears healthy, with a blood pressure of 110/64 mm Hg, pulse 62 and regular, height 63 inches, weight 115 pounds (body mass index, 22.8). Her thyroid is not enlarged, heart and lungs are normal, and abdomen is soft and nontender with no masses or organomegaly. Rectal exam discloses normal anal sphincter tone and strength and no perianal deformities, prolapse, or hemorrhoids. Stool is firm and hemoccult-negative. The Problem The previous overly narrow medical definition of infrequent defecation has been broadened to encompass difficult defecation, which has aligned physician concepts with those of patients and the general population. Indeed, infrequent defecation is an uncommon complaint among those who are constipated, and there is little evidence that symptoms predict colon and anorectal dysfunction as defined by current diagnostic tests. Several consensus definitions might serve as a guide for practicing physicians, and indeed this patient s symptoms meet the criteria for both guidelines. The American College of Gastroenterology s Definition Constipation is a symptom-based disorder defined as unsatisfactory defecation and is characterized by infrequent stools, difficult stool passage, or both. Difficult stool passage includes straining, a sense of difficulty passing stool, incomplete evacuation, hard/lumpy stools, prolonged time to stool, or need for manual maneuvers to pass stool. Chronic constipation is the presence of these symptoms for at least 3 months. Rome III Criteria for Functional Constipation A. Must include 2 or more of the following: 1. Straining during at least 25% of defecations 2. Lumpy or hard stools in at least 25% of defecations 3. Sensation of incomplete evacuation for at least 25% of defecations 4. Sense of anorectal obstruction/blockage for at least 25% of defecations 5. Manual maneuvers to facilitate at least 25% of defecations (eg, digital evacuation, support of the pelvic floor) B. Loose stools are rarely present without the use of laxatives C. There are insufficient criteria for irritable bowel syndrome (IBS) D. Criteria fulfilled for the last 3 months with symptoms onset at least 6 months before diagnosis Evaluating complaints of constipation involves a careful delineation of its duration and characteristics and with the knowledge of the many potential causes of constipation. A critical question concerns the onset and duration of the complaint. A recent change in bowel habit is of concern, especially in adults, whereas complaints of longer duration, as seen in this patient, are more likely to be caused by functional constipation. The nature of the symptoms helps to address the specific concerns of the patient. However, frequency of defecation and defecatory difficulties such as excessive straining, discomfort, or sense of incomplete evacuation of the rectum do not reliably identify whether the problem is one of colonic dysfunction or a defecation disorder. It might occasionally be helpful to ask the patient to describe a typical stool and an ideal one to determine whether misperceptions exist. The presence of pain or bleeding with defecation should be noted. Abbreviations used in this paper: FDA, Food and Drug Administration; 5-HT, serotonin; IBS, irritable bowel syndrome; PEG, polyethylene glycol by the AGA Institute /$36.00 doi: /j.cgh

2 October 2010 DIAGNOSIS AND TREATMENT OF CONSTIPATION 839 Inquiry concerning constipating medications and laxative use is important, as are questions concerning similar gastrointestinal complaints in other family members. An assessment for evidence of affective disorders, dysphoria, emotional distress (eg, litigation, psychological counseling), and the use of moodaltering drugs helps to establish potential contributing factors to constipation. In many patients, constipation might be associated with disordered movement of stool through the colon or anorectum. The clinical use of colonic transit studies with radiopaque markers has identified subgroups of patients with constipation who have slow or normal transit through the colon or delay confined to the rectosigmoid colon. Slow colonic transit in some patients is associated with neuroenteric changes in the colon, whereas in others it is related to disorders such as anorexia nervosa or to medications. However, many patients have normal colonic transit when tested. This suggests the possibility of a defecation disorder, misperception of normal bowel functions, or perhaps an insensitivity of a single test to detect colonic dysmotility. A major advance has been the characterization of several defecation disorders such as dyssynergic defecation and its functional equivalent, inadequate expulsion. The diagnosis currently depends on physiologic testing that is best done in laboratories experienced with specific diagnostic testing. However, a digital rectal examination might be used to screen for this disorder. With the examining finger oriented posteriorly at the level of the puborectalis muscle, the patient is asked to bear down as if to defecate. Normally, the puborectalis and external anal sphincter relax to widen the anorectal angle and relax the anal canal that leads to perineal descent. In dyssynergia, the opposite occurs, with no relaxation or actual contraction of the muscles and no descent of the perineum. In experienced hands, a normal expulsion effort makes dyssynergia unlikely in my experience. There is a tendency to diagnose patients with constipation and normal colonic transit as having IBS-C, but with little justification. Abdominal pain is an important hallmark of patients with IBS and often requires treatment in conjunction with regulation of bowel habits. Moreover, there are no published studies to show that IBS-C is uniformly characterized by normal colon transit. It is not always possible to distinguish patients with functional constipation from those with IBS. However, clinicians should try to make the distinction in clinical practice in accordance with consensus recommendations. Management Strategies and Supporting Evidence Constipation in the general population is usually mild, intermittent, and often responsive to readily available over-thecounter medications. The initial approach to such patients generally entails empirical treatment with little or no work up. The more problematic patients are those who do not respond to therapy and in whom an explanation should be sought. There is little evidence to support the routine ordering of thyroid studies or serum calcium test. The focus of testing should be on physiologic aspects of colorectal function rather than structural explanations. In general, the use of colonoscopy and imaging studies should be minimized. It is often argued that colon transit studies to measure movement of markers through the colon are unnecessary in patients with unresponsive constipation because treatment will be similar regardless of findings. This point of view is debatable for several reasons. The demonstration of slow colonic transit while consuming a g fiber diet suggests that fiber supplement and osmotic laxatives are unlikely to be effective and are even counterproductive by causing increased bloating and discomfort. Such patients often feel better on less fiber and might respond to stimulant laxatives, enterokinetics or prosecretory agents, although there is little published evidence to support this. Conversely, the demonstration of normal colonic transit suggests either a possible defecation disorder or a misperception by the patient that they have a bowel disorder. Although patterns of slow colon transit do not reliably predict pathophysiology, some patterns might be of practical value. The finding of slow transit in the rectum and sigmoid colon with normal transit proximally suggests either an anorectal dysfunction such as a defecation disorder or a behavioral problem such as withholding. Slow transit in the right colon with normal anorectal testing suggests a neuroenteric disorder in the absence of known conditions that might slow transit. This kind of analysis might help to identify rational treatment options for the refractory patient. Anorectal function studies such as manometry and balloon expulsion provide information on rectal sensation, relaxation of the internal anal sphincter, and anal sphincter patterns on expulsion of the apparatus. During the latter maneuver, the rectal transducer records intra-abdominal pressures generated during expulsion efforts, while pressure recordings of the anal sphincters indicate relaxation or inappropriate contraction of the external anal sphincter. In patients with dyssynergic defecation, there is either an increase or insufficient decrease in anal canal pressures during attempted expulsion of the apparatus. Patients who exhibit this finding are often unable to expel a water-filled or air-filled balloon within 60 seconds while seated on a commode, a test that can be used as an office-based screening method. Anterior rectoceles are outpouchings of the rectovaginal wall into the lumen of the vagina. These can be identified during digital examination and are common in women with and without constipation. The precise relationship between rectoceles and defecation disorders is unknown; for example, does prolonged defecatory straining result in the formation of a rectocele? Does a preexisting rectocele, when it reaches a critical size, result in misdirection of stool expulsion and lead to prolonged straining? What is acknowledged is that most rectoceles are asymptomatic, but that defecation difficulties might occasionally arise when expulsive forces are misdirected into a large pouch. The key to management is to identify the latter when contemplating surgical repair of the rectocele (see Areas of Uncertainty). Choosing a Diagnostic Strategy Most chronically constipated patients do not require diagnostic studies beyond a careful history and a physical examination, especially of the rectum and pelvic floor. Colonoscopy or flexible sigmoidoscopy is indicated only in the presence of alarm symptoms (recent worsening of constipation, blood in the stools, weight loss, anorexia, nausea, or vomiting) or as a screening procedure in patients older than age 50. Because symptoms do not discriminate between physiologic subgroups of patients who do not respond to conservative treatment, the work up is similar regardless of presenting symp-

3 840 ARNOLD WALD CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol. 8, No. 10 Figure 1. Suggested evaluation of patient with chronic constipation who does not respond satisfactorily to conservative treatment. toms (Figure 1). A 1- to 2-week prospectively obtained bowel diary, measurement of colonic transit time, and screening for a defecation disorder by using a simple device to measure the expulsion of a balloon filled with air or water are the most useful studies to obtain. Normal transit studies and balloon expulsion might reassure both physician and patient that colorectal function is not seriously impaired. If the balloon expulsion test is abnormal, the patient should be referred for anorectal manometry. If the patient is seen in a center with high quality anorectal manometry, both balloon expulsion and manometry are better for clinical decision-making. On completion of these studies, 4 patterns of colonic and anorectal function are possible. Treatment Strategies The major recent developments in the treatment of chronic constipation include (1) the reevaluation and reduced availability of stimulant laxatives, (2) the efficacy and widespread availability of PEG laxatives, (3) the development of serotonin agonists and intestinal secretory agents, (4) the demonstration of the efficacy of biofeedback for defecation disorders, and (5) the continued evolution of the role of surgery in selected patients. Representative laxatives for each category including bulk laxatives are shown in Table 1, with typical monthly costs if each were to be used on a daily basis. Bulk laxatives. Many studies support the effectiveness of dietary fiber supplements to improve stool frequency and consistency in chronically constipated persons. Natural fiber products (ie, psyllium, wheat dextrin) and synthetic compounds (ie, methylcellulose, calcium polycarbophil) are available without a prescription. Fiber laxatives might be used as first-line agents in patients with constipation who cannot tolerate or are unable to consume sufficient amounts of dietary fiber. Stimulant laxatives. Many physicians and patients continue to avoid chronic use of stimulant laxatives because of unsubstantiated claims that they harm the colon, promote dependency and habituation, and have the potential for abuse. When used appropriately, stimulant laxatives are not harmful, are often efficacious, and are cost-effective for many patients with chronic constipation. Senna and bisacodyl are the stimulant laxatives currently available in the United States. Although use of chronic anthraquinones causes reversible melanosis coli, there is no evidence that such laxatives, when given in appropriate doses, cause enteric damage in either animals or humans. Osmotic laxatives. Osmotic agents for chronic use contain PEG or nonabsorbable sugars such as lactulose. In contrast to the latter, PEG is not degraded by colonic bacteria, and therefore, increased gas production in the colon is not a problem. PEG-containing solutions have proved effective when taken daily for periods of up to 6 months and are less likely to produce bloating and flatulence. Magnesium salts are best used intermittently in patients without renal disease. Table 1. Available Agents for Treatment of Chronic Constipation Laxative Usual adult dose Onset of action Cost (30 days) a Bulk-forming laxatives Psyllium 14 g 1 2 times daily h $ Methylcellulose 1 g 2 6 times daily h $ Wheat dextrin 14 g 1 2 times daily h $ Osmolar agents PEG g in 240-mL liquids 2 4 d $ Lactulose 20 g (30 ml) daily h $38.40 Stimulant laxatives Bisacodyl 10 mg by mouth daily 6 10 h $ mg suppository daily min Senna Two 5-mg tablets daily 6 12 h $5.40 Other agents Lubiprostone 24 g by mouth twice daily 24 h $ a Available at: Accessed February 2010.

4 October 2010 DIAGNOSIS AND TREATMENT OF CONSTIPATION 841 Evidence supporting the efficacy of PEG and lactulose is strong, on the basis of the quality and number of published trials. Studies have shown that PEG in daily doses of g was more effective than lactulose in comparable amounts. PEG without electrolytes is now available to patients without prescription, on the basis of efficacy and safety. Enterokinetic and secretory agents. Serotonin (5- HT) agonists stimulate intestinal motility, in part by facilitating enteric cholinergic transmission. Tegaserod, a partial 5-HT4 agonist, was withdrawn because of a statistically significant increase in cardiovascular events such as unstable angina, myocardial infarction, and stroke. The Food and Drug Administration (FDA) has approved lubiprostone for treatment of chronic functional constipation. The first drug of its chemical type, lubiprostone increases intestinal fluid secretion by stimulating the intestinal chloride-2 channel. The most important side effects are headache and nausea (reported in more than 25% of patients), which sometimes can be reduced with dose adjustment. Some patients with severe constipation have been treated successfully with misoprostol, with and without PEG. There are no randomized controlled trials, and the number of patients treated is small. In my experience, I have found that a combination of PEG 17 g daily plus misoprostol starting in doses of 200 g twice daily and titrating up on the basis of response and side effects is helpful in about 40% of patients with severe and intractable slow transit constipation with normal anorectal function. This drug is ideally confined to postmenopausal woman or those using birth control measures. Treatment of constipation during pregnancy and breastfeeding. Most laxatives are designated as FDA pregnancy categories B or C, with the exception of misoprostol, which is contraindicated in pregnancy. In pregnant women, osmotic and stimulant laxatives are safe and effective for shortterm use. A consensus panel concluded that PEG (category C) was the optimal laxative in pregnancy because it is effective, minimally absorbed, has few side effects, and carries low risk. Lactulose (category B) and sorbitol are probably safe but are less effective and have more side effects than PEG, whereas senna and bisacodyl (category C) are not recommended for long-term use. Lubiprostone (category C) might be considered in the pregnant woman only if other available laxatives are ineffective. Biofeedback. Biofeedback therapy is an effective and durable treatment in many patients with documented dyssynergic defecation. Candidates should undergo balloon expulsion studies and anorectal manometry to establish the diagnosis before being offered this option, which is time-intensive, requires highly trained and dedicated personnel, and is relatively expensive (average charges from $3000 to $6000 on personal survey of several centers offering biofeedback programs). Biofeedback works to improve coordination of the pelvic floor by using visual feedback in the form of pressure recordings or electromyogram tracings to patients. Training sessions are provided weekly or several times per week until coordination is established. First, patients are taught to strain more effectively and coordinate expulsion efforts. Then they are taught to relax the pelvic floor muscles and sphincter while straining. With visual feedback and practice, the patient is able to master the physical skills of perceiving rectal distention and relaxing pelvic floor muscles while straining to defecate. This behavioral therapy should be the first line of therapy in patients found to have dyssynergic defecation. A possible alternative to biofeedback is the injection of botulinum toxin A into the puborectalis muscle bilaterally by using endoscopic ultrasound guidance. Randomized, controlled, and double-blind studies are needed to confirm these findings before botulinum toxin A treatments are recommended. Surgery. In highly selected and carefully evaluated patients with severely incapacitating slow-transit constipation, colectomy with ileorectal anastomosis can ameliorate incapacitating symptoms. Limited resection of the colon to shorten or remove kinks generally produces unsatisfactory results. Before surgery, studies should establish normal gastroenteric and anorectal function because the presence of a generalized motility disorder is associated with unsatisfactory results. Anorectal dysfunction is a contraindication to ileorectal anastomosis unless it can be corrected. There is also a substantial complication rate with surgery even in centers with expertise. Bloating and abdominal pain are unlikely to improve with surgery. A patient with abdominal pain is not an appropriate candidate for subtotal colectomy because such surgery is highly unlikely to improve pain. The indications for surgical repair of a rectocele remain poorly defined. The size of the rectocele does not seem to influence surgical outcome. Optimally, one should demonstrate improved defecation when pressure is placed on the posterior wall of the vagina during defecation before proceeding with a repair. Reports of outcomes after rectocele repairs are difficult to evaluate because symptoms have been heterogenous and preoperative investigations and surgical techniques variable. All patients should be investigated for dyssynergic defecation before a rectocele repair is undertaken, because the condition might recur if unrecognized dyssynergia is not corrected. Areas of Uncertainty Although chronic constipation is a common disorder that has been studied extensively, our understanding of colonic and anorectal function remains incomplete. Moreover, the treatment of many constipated persons is perceived to be unsatisfactory. Therefore, it is not surprising that many questions concerning the evaluation and management of this condition remain. The characterization of dyssynergic defecation has been a major conceptual advance, but the optimum methods to diagnose this condition in practice remain uncertain. Anorectal manometry, balloon expulsion tests, and defecography have limitations, not the least of which is that they do not test under physiologic conditions. Thus, do our current studies of anorectal function illuminate defecation, or are they largely artificialities in a laboratory setting? Moreover, there is an important need to standardize these tests across all laboratories to determine which test or combination of tests is most predictive of treatment success. Another area of uncertainty is whether slow colonic transit and colonic inertia are separate entities, and if so, whether such a distinction needs to be made for treatment purposes. The clinical utility of colonic manometry to guide decision-making in adults with refractory constipation remains to be established. Similarly, the advantages of capsule motility over radiopaque marker studies remain to be determined in future studies, specifically, whether the addition of colon manometry with this

5 842 ARNOLD WALD CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol. 8, No. 10 device provides additional therapeutic guidance to practicing physicians. Newer agents to enhance laxation by using innovative drugs to enhance secretion and/or motility continue to be introduced or are in development. But do these more expensive agents perform in a superior fashion to relatively inexpensive laxatives that are available without prescription? In view of issues such as cost control in health care, funding for comparison studies of newer agents and traditional laxatives is a priority. Many women continue to undergo rectocele repairs, but selection criteria are relatively undefined. The relationship between rectoceles and dyssynergia should be further explored. For example, the lessons learned from repairing Zenker s diverticula, that is, not addressing upper esophageal sphincter dysfunction, might be equally applicable to rectoceles. Finally, the indications for colectomy and comparisons with specific surgical procedures require further definition. The possible efficacy of spinal cord stimulation for chronic constipation requires further study to define its future role in selected patients with hard to manage constipation. Published Guidelines American Gastroenterological Association guidelines on constipation were published in 2000 after approval by the Clinical Practice Committee in September Although there are new agents for constipation and substantial evidence for the use of biofeedback for dyssynergic defecation, the overall approaches to diagnosis and management remain up-to-date and continue to provide a general framework for the practicing gastroenterologist. The American College of Gastroenterology published an evidence-based review of the evaluation and management of constipation in Although not designated specifically as guidelines, they were adopted as such in the Journal of Family Practice in that same year. The document is somewhat dated by the withdrawal of tegaserod by the FDA, the absence of recommendations for lubiprostone, which was released after the review was published, and new evidence of randomized controlled studies of biofeedback as the primary therapy for dyssynergic defecation. As is the case with any evidence-based review, the American College of Gastroenterology report favors recently developed agents that have been evaluated with more rigorous studies over older, traditional laxatives. The reader should remember that absence of evidence for does not mean evidence against. The standard use of stimulant laxatives as rescue drugs in modern clinical trials of constipation therapies is in keeping with their perceived efficacy in many patients, and there have been few comparison studies between newer laxatives and traditional products now available without prescription. Summary The patient underwent a colon transit study in which 24 markers were given on each of 3 successive days, and an overpenetrated abdominal film was obtained on days 4 and 7. On day 4, 30 markers were present and scattered throughout the colon, whereas on day 7, only 5 markers were seen (transit time, 35 hours; normal, 68 hours). She was unable to expel a rectal balloon filled with 50 ml water within 2 minutes (normal, 60 seconds). She was then referred to a center where anorectal manometry demonstrated a pattern characteristic of anorectal dyssynergia. The patient was referred to a physical therapist with training and experience with instrumental biofeedback. She received 5 training sessions, each lasting minutes, on a weekly basis. In the laboratory, she normalized defecation patterns, first by using visual feedback and then without seeing the tracing. Her complaints resolved, and 3 months after completion of training, she reported an average of 5 bowel movements weekly without laxatives, less bloating, and no sense of incomplete emptying of the rectum. Suggested Reading 1. Locke GR, Pemberton JH, Phillips SF. AGA medical position statement: guidelines on constipation. Gastroenterology 2000;119: Brandt LJ, Schoenfeld P, Prather CM, et al. Systematic review on the management of chronic constipation in North America. Am J Gastroenterol 2005;100(Suppl): S5 S Longstreth GF, Thompson WG, Chey WD, et al. Functional bowel disorders. Gastroenterology 2006;130: Bharucha AE, Wald A, Enck P, et al. Functional anorectal disorders. Gastroenterology 2006;130: Rao SS, Ozturk R, Laine L. Clinical utility of diagnostic tests for constipation in adults: a systematic review. Am J Gastroenterol 2005;100: Diamant NE, Kamm MA, Wald A, et al. AGA technical review on anorectal testing techniques. Gastroenterology 1999;116: Minguez M, Herreras B, Sanchiz V, et al. Predictive value of the balloon expulsion test for excluding the diagnosis of pelvic floor dyssynergia in constipation. Gastroenterology 2004;126: Wald A. Chronic constipation: advances in management. Neurogastroenterol Motil 2007;19: Muller-Lissner S, Kamm MA, Scarpignato C, et al. Myths and misconceptions about chronic constipation. Am J Gastroenterol 2005;100: Scott SM. Current perspectives in chronic constipation. Neurogastroenterol Motil 2009; 21(Suppl 2): Mahadevan U, Kane S. American Gastroenterological Association Institute medical position statement on the use of gastrointestinal medications in pregnancy. Gastroenterology 2006;131: Chiaroni G, Whitehead WE, Pezzo V, et al. Biofeedback is superior to laxatives for normal transit constipation due to pelvic floor dyssynergia. Gastroenterology 2006;130: Reprint requests Address requests for reprints to: Arnold Wald, MD, Section of Gastroenterology and Hepatology, University of Wisconsin School of Medicine and Public Health, 600 Highland Avenue, H6/516, Madison, Wisconsin axw@medicine.wisc.edu; fax: (608) Conflicts of interest The author discloses no conflicts.