Constipation in the Older Adult


Brian E. Lacy, PhD, MD, and Matthew S. Cole, MD


Pages 44 - 54

Accreditation The Johns Hopkins University School of Medicine is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The Johns Hopkins University School of Medicine takes responsibility for the content, quality, and scientific integrity of this CME activity. Credit Designation Statement The Johns Hopkins University School of Medicine designates this educational activity for a maximum of 1.0 category 1 credit toward the AMA Physician’s Recognition Award. Each physician should claim only those hours of credit that he/she actually spent in the educational activity. Valid December 1, 2004 - February 28, 2005. Estimated time: 1 hour FULL DISCLOSURE POLICY AFFECTING CME ACTIVITIES As a provider accredited by the Accreditation Council for Continuing Medical Education (ACCME), it is the policy of Johns Hopkins University School of Medicine to require the disclosure of the existence of any significant financial interest or any other relationship a faculty member or provider has with the manufacturer(s) of any commercial product(s) discussed in an educational presentation. The presenting faculty reported the following: Dr. Cole has indicated that he has not received financial support for consultation, research or evaluation or has a financial interest relevant to this article. Dr. Lacy has indicated that he has received grants/research support from Novartis Phamaceuticals, AstraZeneca, and GlaxoSmithKline. No faculty member has indicated that their presentation will include information on off-label products. DISCLAIMER STATEMENT The opinions and recommendations expressed by faculty and other experts whose input is included in this program are their own. This enduring material is produced for educational purposes only. Use of Johns Hopkins University School of Medicine name implies review of educational format design and approach. Please review the complete prescribing information of specific drugs or combination of drugs, including indications, contraindications, warnings and adverse effects before administering pharmacologic therapy to patients. Educational Objectives 1. To understand the prevalence and natural history of chronic constipation in the older patient 2. To review the current definition of constipation and understand differences in patient and physician perceptions of this disorder 3. To review the common etiologies and the underlying patho- physiologies of constipation in the older patient 4. To review current treatment options using an evidence-based approach Constipation is a heterogeneous disorder with a wide spectrum of symptoms and complaints. Constipation results in 2.5 million office visits each year,1 leads to a significant reduction in quality of life,2 and is expensive to treat.3,4 This review describes the difficulties in defining constipation in clinical practice, the epidemiology and natural history of constipation in the older adult, normal and abnormal colonic physiology, the effects of aging on the colon, and provides recommendations on cost-effective methods of evaluating and treating this common disorder. Definition Physicians and patients differ dramatically in their definition of constipation. Clearly defining what is meant by the term constipation is critical to accurately diagnose the problem, review the natural history, and assess response to treatment. Physicians tend to use objective measures to define constipation, and this typically involves measuring stool frequency. Several large population studies have shown that most individuals have from 3 bowel movements per day to 3 bowel movements per week.5,6 As such, many physicians define constipation as less than 3 bowel movements per week. However, studies have shown that a patient’s definition of constipation agrees with a physician’s definition only 50% of the time,7 and most often focuses on symptoms rather than stool frequency; patients use stool frequency as a measure of constipation only 32% of the time.8 Patients are likely to report that they are constipated if they have straining at stool (52%), hard stools (44%), the urge to pass stool but cannot (34%), or abdominal discomfort (20%). Other complaints include bloating and feelings of incomplete evacuation. Thus, during the interview, it is likely that patients are discussing something very different than their doctors when they say they are constipated. This is an important factor to consider as it significantly affects diagnostic strategies and treatment options. Due to these significant discrepancies in the definition of constipation, it is recommended that the Rome II criteria be used to define constipation (Table I).9 Epidemiology and Natural History Prevalence rates for constipation in the elderly range from approximately 19-40% (Table II).10-15 This wide range occurs for a number of reasons. Some studies were conducted without constipation being adequately defined, and studies were conducted using a variety of instruments. Self-report questionnaires may not be reliable and often correlate poorly with objective measures such as the Rome criteria.16 Further, symptoms of constipation are subjective and are influenced by social customs, which invariably affect study results. Finally, not all studies were limited to the older adult. Data presented in Table II include studies that focused on this age group, although in those studies which included all age groups, data were extracted to focus on the geriatric population. Despite these limitations, what can be confidently stated is that the prevalence of constipation increases significantly in adults over 65 years of age.1 The prevalence of constipation in the elderly can be compared to that of the general population, which is estimated at 2-28%.17 This common problem affects patients on a number of different levels. It leads to an increase in physician visits, especially after the age of 65.18 Constipation in the elderly is expensive to treat; for example, laxative use in the United States is associated with an estimated annual cost of nearly $1 billion. Further, patients with constipation have been shown to have a reduced quality of life compared to other patients without constipation.16 Constipation may lead to complications including fecal impaction, overflow fecal incontinence, solitary rectal ulcer syndrome, diverticulosis, pelvic floor dysfunction, and development of a rectocele, enterocele, rectal prolapse, and intussusception; it may even increase the risk for colorectal cancer. In fact, for most patients, constipation remains a chronic problem, leading to continued expense and reduction in quality of life. For these reasons, an efficient and effective diagnostic and treatment algorithm is needed. Normal Colonic Physiology The colon is often considered nothing more than a conduit for material to pass through from the small intestine to the rectum. However, the normal colon has several different functions: it acts to concentrate stool through its ability to absorb large amounts of water and can absorb electrolytes and some nutrients; it is responsible for the fermentation and absorption of certain carbohydrates; it acts as a reservoir to store stool; and normal colonic motility is responsible for the mixing of liquid effluent from the ileum and for the propagation of material from the right side of the colon to the sigmoid colon and rectum, where it can be stored and then evacuated. Normal transit of material through the colon is about 36 hours, and colonic transit time is equally divided between the right colon, transverse colon, and left colon. Normal colonic motility is a complex and incompletely understood process that relies on intact extrinsic innervation (autonomic nervous system [ANS]), an intact intrinsic nervous system (enteric nervous system [ENS]), and normal muscle function (both the smooth muscle in the colon and the muscles of the pelvic floor). A variety of neurotransmitters (acetylcholine [ACh], nitric oxide [NO], vasoactive intestinal peptide [VIP], substance P) and hormonal factors (estrogen, progesterone) also play a role, although their exact function is not known and clinical data are often contradictory. Normal transit of materials through the colon primarily depends on a functioning ENS. Injury to the ENS or to the pacemaker cells of the colon (interstitial cells of Cajal) may lead to decreased motility, disordered peristalsis, and constipation. Extrinsic input to the colon from the sympathetic, parasympathetic, and pelvic plexus is critical for defecation to occur. The parasympathetic nervous system carries sensory afferents from the colon and provides excitatory (stimulatory) input to the colon. Sympathetic fibers primarily provide inhibitory input to the colon (except for the sympathetic input to the sphincters, which is excitatory and causes tonic contraction); in addition, these fibers carry some sensory afferent information. Prior abdominal surgery (cesarean section, hysterectomy, rectocele repair, bladder suspension, surgery to the colon), previous back surgery, obstetrical injury or trauma (prolonged delivery with stretching of the pudendal nerve), radiation, and trauma to the pelvis are all risk factors for injuring these critical nerves. Colonic motility involves two distinct patterns of activity. Low-amplitude contractions are responsible for the mixing of materials within the colon and for the movement of colonic contents over short distances. These contractions are 5-40 mm Hg in amplitude, more common after meals, and occur about 60 times per day. The local to-and-fro movement of these low-amplitude propagating contractions (LAPCs) exposes the liquid in the right colon to a greater surface area and thus promotes water absorption. Movement of large amounts of material through the colon occurs via high-amplitude propagating contractions (HAPCs) (100 mm Hg) that are most common in the morning on first awakening and after meals. High-amplitude propagating contractions are also called mass movements. Segmenting contractions in the colon, which retard the movement of stool to promote fluid absorption, are nonperistaltic in nature; these are seen on fluoroscopic studies as haustra. Evacuation of stool from the rectum is a complex learned process greatly influenced by societal norms that also requires an intact nervous system and normal muscle function. For defecation to occur, multiple steps are required: stool must first be propelled from the sigmoid colon into the rectum; rectal distention must be properly sensed (defecation generally occurs only if it is a socially appropriate time); by assuming a squatting position, the anorectal angle increases (becomes straighter) to allow increased ease of evacuation; the internal anal sphincter reflexively relaxes on rectal stimulation, and the external anal sphincter must then be voluntarily relaxed; and a valsalva maneuver is employed increasing both intra-abdominal and intra-rectal pressure and facilitating stool evacuation. Abnormal Colonic Physiology Constipation is a symptom rather than a disease. A number of different conditions can cause it in the elderly, including anatomical obstruction, slow transit constipation, pelvic floor disorders, irritable bowel syndrome, medications, metabolic disorders, neurologic/myopathic disorders, and psychiatric problems. These may be classified as structural, mechanical, metabolic, or medication-related. In the colon, a number of different pathophysiologic processes are responsible for the development of constipation. In the elderly, constipation is typically categorized as normal transit constipation, slow transit constipation, obstructed defecation (pelvic floor dysfunction), or irritable bowel syndrome. Normal transit constipation is often a difficult concept for both patients and physicians to understand. Patients complain of constipation (infrequent stools, bloating, fullness, abdominal pressure), although there is no evidence of a mechanical obstruction. When measured, both colonic transit and pelvic floor function are normal. Normal transit constipation is considered a functional gastrointestinal disorder. Slow transit constipation typically develops because of a neuropathic process. In slow transit constipation, the number of HAPCs may be reduced in the postprandial period, leading to slow colonic transit and a reduction in the number of mass movements.19 Alternatively, the number of HAPCs may be normal, although they are uncoordinated. Abnormalities in rectal function may lead to slow transit constipation; for example, abnormally strong rectal contractions can impede the flow of colonic contents distally.20 Constipation may also develop because of injury to the pacemaker cells in the colon, the interstitial cells of Cajal,21,22 or secondary to abnormalities in sensory processing. In the latter situation, injury to rectal sensory afferents prevents the initiation of a normal rectal reflex. Finally, uncommon disorders of smooth muscle (scleroderma, amyloidosis, hollow visceral myopathy) may lead to a myopathic process and loss of contraction within the colon. Defecatory disorders in the elderly encompass a variety of abnormalities that can develop in the pelvic floor. A large rectocele or sigmoidocele, rectal prolapse, or intussusception may all impede normal evacuation of stool. Megarectum, an uncommon condition, can lead to impaired rectal sensation and reduced contractile forces in the rectum. Less commonly, descending perineum syndrome (perineal descent greater than 3 cm below the ischial tuberosities during straining) can develop, or the rectum may have diminished contractile function. Pelvic floor dyssynergia, a condition where the internal anal sphincter fails to relax properly or the external anal sphincter inappropriately contracts during attempted defecation, is most commonly found in women. Physiology of the Colon and Anorectum with Aging It is a common misbelief that the physiology of the colon and anorectum changes significantly with aging. Total gut transit time does not appear to decrease with age in healthy elderly patients,23,24 although some older patients with constipation have significantly prolonged colonic transit times.23,25 Prolonged colonic transit may not only lead to complaints of constipation but also can further exacerbate constipation as slow transit leads to increased absorption of water, producing a harder, more concentrated stool that is even more difficult to evacuate. Mean anal canal pressures are lower in older persons than in younger individuals,26,27 and this reduction is more pronounced in women than in men. These changes are not usually associated with constipation, but they increase the risk of fecal incontinence. Normal rectal sensation plays a critical role in normal defecation. One study has demonstrated that elderly patients with constipation and a history of fecal impaction have impaired rectal and perianal sensation, and require significantly larger volumes of rectal distention to stimulate the normal urge to defecate.28 A second study found that rectal perception of stool is impaired in elderly patients with constipation,26 although sensation appears to remain intact in those patients without constipation. Disordered defecation can develop due to injury to the pudendal nerve. Incidence of pudendal nerve terminal motor latency (PNTML), an indicator of pudendal nerve dysfunction, is increased in older female patients.29 Injury to the pudendal nerves can lead to abnormal perineal descent, which can adversely influence rectal emptying by causing partial prolapse of the anal canal by anterior rectal mucosa. Evaluation for Constipation Diagnosis of constipation in the older adult begins with a good history. The first step is to carefully review the patient’s diet, with an emphasis on caloric intake and fiber content. Adding fiber to the diet is beneficial in those who are fiber-deficient, but is not generally helpful in those patients already taking 25-30 g of fiber each day. Fluid intake should be assessed, although no good scientific studies are available to support the common view that increasing fluid intake improves constipation. Patients should be questioned about their level of activity, as immobile patients with little physical activity are more prone to constipation. Medications, both prescription and over-the-counter, should be carefully reviewed, as many medications commonly used in the elderly increase the risk of constipation, including opioids, anticholinergic agents, tricyclic antidepressants, calcium-channel blockers, aluminum-containing medications, calcium supplements, diuretics, iron salts, antipsychotics, antihistamines, and antiparkinsonian agents. The onset of constipation should be identified. Constipation since childhood suggests Hirschsprung’s disease, whereas constipation that develops after childbirth or back surgery suggests injury to the ANS, ENS, or pelvic nerves. Prior surgery to the abdomen, colon, and anorectum should be noted. A careful family history should be taken with an emphasis on colorectal cancer, and the patient should be questioned about perceived normal bowel habits. Prior diagnostic studies (abdominal x-rays, colonoscopy, barium enema, anorectal manometry, Sitzmark study) and response to previously used medications or therapies should be reviewed. Most importantly, patients should be asked what they mean when they say they are constipated. Stool frequency, stool consistency, straining, ease of evacuation, pain with defecation, and need for manual maneuvers (vaginal splinting, pressure on perineal body) should all be assessed. Stool frequency is not a good indicator of colonic transit, but stool form is (rocky, hard = slow, loose = fast). A careful physical examination should be performed to look for evidence of a systemic disorder such as hypothyroidism, scleroderma, amyloidosis, or the presence of a neurologic disorder such as Parkinson’s disease. Examination of the abdomen begins by looking for evidence of previous surgery that may have affected nerves critical to colonic and pelvic floor function (ie, ANS and pudendal nerves). Bowel sounds should be listened for and palpation of the abdomen should be performed to determine whether a mass is present, or whether there is a significant amount of stool in the sigmoid colon. A careful rectal examination is critical. The patient should be comfortably placed in the left lateral recumbent position. Visual inspection of the perianal area may reveal the presence of fissures, hemorrhoids, masses, or evidence of prior surgery. Excoriation of the perianal skin indicates fecal soiling, which can occur in elderly patients with fecal impaction and overflow incontinence. Stroking of the perianal skin should elicit a reflex contraction of the external anal sphincter. If absent, this may indicate a neurologic defect (ie, nerve injury secondary to prior surgery, spinal stenosis, or spinal cord tumor). During the rectal examination, the strength of the external anal sphincter should be assessed by asking the patient to voluntarily contract the external sphincter. The internal anal sphincter can be palpated and its tone assessed. Elevated tone, or incomplete relaxation of the anal sphincter, may be seen in patients with pelvic floor dyssynergia. Strictures, masses, a rectocele, and hard stool in the rectal vault can be easily felt. During rectal examination, the patient should be instructed to bear down as if to have a bowel movement. The internal anal sphincter should relax during this maneuver; incomplete relaxation of the internal anal sphincter is an indication of pelvic floor dyssynergia. During straining, the perineum should normally descend 1-3 cm. Descending perineum syndrome, with abnormal perineal descent of more than 3 cm, can be visualized during this maneuver. Finally, rectal prolapse can be identified during straining as a fold of tissue strikes the examining finger or as tissue is pushed out through the anus. During the initial evaluation, simple laboratory tests should be ordered, including complete blood count, thyroid-stimulating hormone level, electrolytes, calcium, phosphorous, and magnesium. An abdominal x-ray can be used to look for evidence of impaction or severe obstipation. If the colon has not previously been studied, colonoscopy is warranted. If colonoscopy is normal, empiric therapy should be initiated. If therapy is still ineffective, consider referral to a gastroenterologist with expertise in motility and consider obtaining anorectal manometry with balloon expulsion. This test, performed at most university hospitals, is designed to assess neuromuscular function of the anorectum and pelvic floor. As Hirschsprung’s disease is uncommon in the older adult, colonoscopy and anorectal manometry are best suited to diagnose pelvic floor dyssynergia and to differentiate constipation secondary to slow transit from pelvic floor disorders. If these tests are normal and symptoms persist, a Sitzmark study could be performed. This test, which can be ordered at most x-ray departments, is designed to measure colonic transit. Patients should maintain normal fiber intake during the study period but should not use laxatives or suppositories. Typically, patients take a single capsule on day 0 (often Sunday), and have an abdominal x-ray taken 1, 3, and 5 days later. Each capsule contains 24 radio-opaque markers. As the markers progress through the colon, serial x-rays assess whether the study is normal ( 20% of markers are retained and distributed throughout the colon on day 5), or whether the patient has pelvic outlet obstruction (markers are clustered in the rectosigmoid area). Specialized testing may include video defecography and colonic motility studies with drug challenges to assess neuromuscular function in the colon. Evidence is currently lacking to endorse treatment based on these specialized tests, however, so testing beyond colonoscopy or barium enema with flexible sigmoidoscopy is not recommended for all. Treatment Although surprising to many geriatricians and primary care physicians, the prevalence of laxative use in the elderly is reported to be as high as 50%. This high prevalence may occur because patients appropriately treat symptoms of constipation (straining, infrequent bowel movements); however, many elderly patients take laxatives because they believe that “a bowel movement each day is necessary for good digestive health.”30 After establishing treatment goals and discontinuing medications that may be contributing, consideration must be given to lifestyle factors. High-fiber regimens have been advocated to treat many disorders, especially since Burkitt and coauthors31,32 described the inverse relationship that exists between “Western-risk diseases” and the amount of daily fiber consumed.33 Bulking agents (bran, psyllium, methylcellulose, calcium polycarbophil), which are safe and inexpensive, are typically used first in the treatment of constipation. The addition of extra fiber to the diet increases water absorption, increases stool weight, and accelerates orocecal transit. Fiber supplements are best taken before morning and evening meals so that the fiber is incorporated into the ingested food. Slowly increasing fiber to the maximum recommended dose can help decrease common side effects, which include flatulence, bloating, and abdominal discomfort. Synthetic fiber preparations, such as methylcellulose, may also cause fewer complaints of bloating and distention. Symptoms typically begin to improve within 1-2 weeks, although patients should receive a minimum of 4-6 weeks of therapy to accurately assess treatment response. Several studies using bulking agents revealed benefits as compared to placebo (Table III), especially with respect to improved stool consistency and decreased laxative use.34-43 Although no serious side effects occur with bulking agents, they can reduce the efficacy of other medications taken concomitantly, including warfarin, digitalis medications, potassium-sparing diuretics, salicylates, tetracyclines, and nitrofurantoin. The next most commonly used group of agents includes the surfactants, best characterized by stool softeners. These agents facilitate the mixing of water and fat by reducing the surface tension of the oil-water interface in stool. This results in enhanced incorporation of water and fat, thereby softening stool. The majority of trials in this class have used docusate, the most commonly used laxative. Small studies comparing docusate to placebo have shown a trend toward increasing frequency of bowel movements and reducing the need for breakthrough, or rescue, laxatives (Table III). Although recommended only for short-term use, surfactants are commonly used for prolonged periods despite a lack of evidence. Excessive use can lead to fluid and electrolyte disturbances, including hypokalemia. Other stool softeners, such as mineral oils, are not recommended due to decreased absorption of vitamins, prolongation of the clotting time for patients on warfarin, and the increased risk of aspiration. Osmotic agents are the next group of medications most physicians use to treat constipation. These act by retaining water in the intestinal lumen, thereby accelerating intestinal transit. The most commonly used agents include lactulose, sorbitol, magnesium hydroxide, and polyethylene glycol. Many studies have demonstrated a benefit for osmotic agents in the short-term treatment of constipation (Table III). It should be noted that the synthetic disaccharides (sorbitol, lactulose) often take up to 24-48 hours to achieve the desired effect. Both of these agents can lead to significant abdominal bloating, flatulence, and diarrhea. They should be used with caution in patients with diabetes mellitus, and patients should be monitored for electrolyte disorders, especially with prolonged use. Lactulose is contraindicated in patients on a galactose-restricted diet, while sorbitol should not be used in patients with anuria due to the possibility of exacerbating edema. One of the newer agents, polyethylene glycol, has been shown to be effective in the ambulatory population, although studies focusing on the elderly have not yet been performed. At present, this agent is not approved for use for more than 2 weeks. The next class of agents—the stimulants or irritants—includes bisacodyl and the anthraquinones (eg, senna, cascara sagrada, aloe). These agents stimulate peristalsis by directly irritating the smooth muscle of the intestine and possibly stimulating the colonic intramural plexus. In addition, these agents promote water and electrolyte secretion, which increases orocecal transit. This group of medications has not been well studied in the elderly. Their short-term use, however, has led to an improvement in overall symptoms compared with placebo (Table III). The combination of a stimulant agent with a bulking agent has produced improvement in both stool frequency and stool consistency, and has reduced the need for rescue laxatives when compared to osmotic agents alone.42 Thus, these agents are often used as therapy after more conservative measures have failed. Prolonged use should include monitoring for fluid and electrolyte imbalances. Additionally, bisacodyl has been implicated in decreasing the effect of warfarin. Early studies suggested that stimulant laxative use could possibly damage the enteric nervous system,44 although more recent studies in animals have not confirmed this suspicion and no human studies have confirmed these initial findings. Thus, concerns about the long-term risks remain controversial.45 Enemas (tap water, soapsuds, mineral oil, and phosphate) are often used together with the above agents with varying success, but there are no good data to support their efficacy over other proposed therapies. They are generally considered safe to use, with warm water and soapsuds enemas probably the most benign. The predominant mechanism of action is to soften and lubricate stool, although insertion of the enema may directly stimulate the rectum, thereby initiating rectosigmoid contractions. Biofeedback, using a knowledgeable physical therapist interested in pelvic floor disorders, has proven beneficial in many patients with pelvic floor dyssynergia. Tegaserod, a 5-HT4 receptor agonist, improves constipation in women with irritable bowel syndrome.46 Tegaserod has been shown to be safe in the elderly; however, recent FDA approval (August 2004) for treating chronic constipation was only for patients 65 years of age and younger. Colchicine, a microtubule formation inhibitor, can be helpful in some patients with refractory constipation, but there is concern that long-term use could cause a neuromyopathy, and side effects (nausea, abdominal discomfort) often limit its use. Many physicians use misoprostol, a prostaglandin E1 analog, because one of its side effects is diarrhea; however, misoprostol is expensive and beneficial effects are generally short-lived. Neither colchicine nor misoprostol have been studied in older patients. Ideally, there would be a large number of studies assessing drug efficacy in the elderly so that an evidence-based approach to the treatment of constipation could be provided. However, there are no good long-term studies available regarding medical therapy for constipation in the older person.47 A treatment algorithm, using a graduated stepwise approach, is outlined in the Figure. In general, once the desired effect is achieved, the clinician should reassess the patient and determine whether his or her goals can be obtained with fewer medications or lower doses of medications. This may improve patient compliance and minimize costs, side effects, and potential drug interactions. Finally, for patients with documented slow transit constipation who have failed medical therapy and persist with intractable symptoms (in the absence of pelvic floor dysfunction), total colectomy with ileorectostomy is an option. This should be considered only after a thorough evaluation and extensive testing has been performed, which usually requires referral to a center specializing in motility disorders of the gastrointestinal tract. From the Division of Gastroenterology & Hepatology, Dartmouth-Hitchcock Medical Center, Lebanon, NH.