Constipation in the Hospitalized Older Patient: Part 1
Key words: Acute care, constipation, idiopathic constipation, medication-induced constipation.
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Constipation is one of the most common problems encountered in the care of older patients. In the acute care setting, constipation can affect the outcomes, length of hospital stay, and quality of life of this patient population, and it has been associated with delirium, chronic pain, urinary incontinence, and poor participation in physical activities.1,2 Therefore, the need to address this problem cannot be overemphasized. Every effort should be made to prevent and effectively treat older patients who have constipation and to establish a screening program to better identify those at risk.
There has been no general consensus on a definition for constipation, but it is most commonly considered to be a decrease in the frequency and amount of usual bowel function, typically associated with difficult and sometimes painful passage of hard, dry stool, which may be followed by a feeling of incomplete emptying.3-5 In general, constipation is said to be present if there has been less than one bowel movement in 3 days. In the geriatric patient, however, any change in a preexisting pattern of bowel function needs to be taken seriously and evaluated appropriately, as it may serve as a warning sign of a significant underlying pathology. In this two-part article, we review issues relating to constipation in older patients in the acute care setting.
Pathophysiology and Etiology of Constipation in the Older Patient
The gastrointestinal (GI) tract starts with the mouth; includes the esophagus, stomach, small intestine duodenum, jejunum, ileum, large intestine colon, and rectum; and terminates at the anus. The accessory organs of the GI system—the salivary glands, pancreas, liver, and gallbladder—contribute digestive enzymes to the GI tract. When food is digested, waste products are moved through the intestines by the contraction of smooth muscles. In the large intestine, most of the water and salt from the waste products are reabsorbed and used by the body for everyday functions. Constipation can occur if too much water is absorbed or if waste products move through the bowels too slowly.
As people age, the number of digestive enzymes produced by the body decreases, leading to reduced and slower digestion, slower absorption of nutrients, and increased accumulation of fecal matter in the intestinal tract. Undigested food material and metabolic waste can also accumulate owing to slow elimination, which can cause a series of health problems. Many factors can contribute to constipation, including low-fiber diets, use of certain prescription and over-the-counter medications, inactivity, insufficient fluid intake, and medical conditions that decrease bowel motility (Table). When the cause of a patient’s constipation is unknown, the condition is referred to as idiopathic. This diagnosis should not be used, however, until a thorough investigation has been made for the cause of constipation, as this condition is one of the initial nonspecific symptoms associated with colorectal malignancies in older patients. What follows is a review of several factors that should be considered as part of the evaluation, including function of the small intestine and colon, various medical disorders related to aging, and some drug classes, including anticholinergics, opioid analgesics, and calcium channel blockers.
Small Bowel Motility
Although small bowel motility is essentially unchanged with normal aging,6-8 numerous factors can cause disturbances in small bowel motility, leading to constipation. Such factors may include bacterial overgrowth, use of narcotics and other medications, history of gastric surgery, and presence of an obstruction. Although rare, pytobezoars as a cause of small bowel obstruction may be a consideration in elderly patients who have poor dentition or difficulty masticating food, particularly if they also have a history of gastric surgery or a small bowel disease, such as diverticulosis. Many conditions that impair small bowel motility also cause a variety of other symptoms, such as vomiting, abdominal pain or tenderness, and abdominal distension. Such associated symptoms may help point to the diagnosis, but when they are not present and a small bowel motility disturbance is suspected, a variety of techniques may be used to gauge small intestinal transit times, including breath tests, colonic transit scintigraphy, and esophageal manometry.
Colonic Function
Evidence to support older age as an independent risk factor for impaired colonic function is conflicting. While some studies reported significant prolongation of colonic transit time with advancing age,9,10 more recent studies found no significant age-related impact on colonic function.11,12 A few studies of colonic motor or myoelectric activity have also been performed,13-15 but these have failed to reveal any significant age-related changes. Therefore, at this juncture, clear evidence for a clinically significant effect of age on colonic transit time is lacking. There are, however, many factors that are common among elders that can affect colonic function. These include increased and prolonged intake of constipating drugs or laxatives, reduced intake of dietary fiber and fluids, and relatively low levels of physical activity.
Neurological Disorders
The two predominant neurological disorders associated with constipation in older adults are stroke and idiopathic Parkinson’s disease (PD). Constipation has been reported to affect up to 60% of patients in stroke rehabilitation wards16 and between 50% and 80% of patients with PD.17 Stroke may be associated with constipation and anorectal dysfunction, including fecal incontinence. How stroke leads to constipation and its associated complications is not well understood. Although immobility may play a role, these changes are more likely due to alterations in the cortical regulation of colonic and anorectal physiology.
Idiopathic PD causes widespread and sometimes severe derangements of GI motility.18,19 There are two components to GI dysfunction in PD. First, data suggest striatal muscle dysfunction in the oropharynx, proximal esophagus, and anal canal result from the same neurological abnormalities that cause the cardinal manifestations of PD.10 Second, PD may cause dysfunction in the smooth muscle of the GI tract.20 This mechanism is less well understood, but it may reflect pathology in the autonomic and/or enteric nervous systems. It appears likely that constipation in patients with PD has a multifactorial etiology, with delayed colonic transit, anorectal dysfunction, drug therapies, and reduced physical activity all contributing to the problem.
Neuropsychiatric Disorders
The two major neuropsychiatric disorders of old age that are associated with constipation are depression and dementia. Like other psychological disorders, depression may cause a variety of symptoms and behaviors, some of which may result in constipation (eg, poor appetite, decreased physical activity levels). In addition, patients may be taking antidepressants that have anticholinergic effects, such as tricyclic antidepressants (TCAs), which can lead to similar symptoms (eg, decreased appetite) and to constipation. However, depression has also been correlated with derangements in GI motility that occur independently of the symptoms of depression or of any antidepressant medications used to treat it.19,21
In one study, approximately one-fifth of a group of 51 patients presenting to the hospital with a functional psychiatric disorder (principally depression) had abnormal esophageal motility, as detected by krypton-81m esophageal transit scintigraphy and esophageal manometry.19 In a group of 30 consecutive patients investigated in a referral center, psychopathology was much more prevalent in patients with abnormal rather than normal esophageal manometry (84% vs 31%).21 Whole-gut transit time has also been shown to be significantly prolonged in persons with depression, with transit times correlating directly with the severity of the illness.22 One study that included older persons with constipation found that colonic transit times significantly correlated with the presence and severity of psychopathological symptoms.23 These associations are clinically important, as older patients may become preoccupied and distressed by their constipation, not realizing that depression is their underlying problem. Once the depression is treated, their constipation disappears. It should come as no surprise, therefore, that in large surveys of older people, constipation is consistently and significantly associated with immobility and neurological and psychological diseases.10
There are no published data on the influence of Alzheimer’s disease (AD) and other dementias on gastric or small intestinal motility, despite constipation being a well-known problem among these patients. One large-scale, retrospective survey of the medical records of 4 million patients discharged from US veterans hospitals showed that AD was associated with a significantly increased risk of constipation, megacolon, volvulus, and intestinal impaction, compared with the absence of neurological or psychiatric diseases.24 AD-associated problems that may affect nutritional intake, dietary content, physical activity levels, and use of medications may be coexisting or even causative factors.
Endocrine Disorders
The endocrine system regulates the release of various hormones throughout the body, which requires coordination between numerous different glands, from the pituitary gland, to the adrenal glands, to various male and female sex glands. When one or more of these glands ceases to function properly, an endocrine disorder results, leading to any number of complications. Two major endocrine disorders associated with old age are diabetes mellitus and hypothyroidism. Both of these conditions have also been linked to constipation.
Diabetes. While there are few data available on the prevalence of either GI symptoms or their associated functional abnormalities among community-dwelling patients with diabetes mellitus, surveys performed in diabetes clinics suggest that GI symptoms are common.25 In addition, the prevalence of type 2 diabetes mellitus increases exponentially with age, and this disorder is the most common cause of impaired GI motility in elders. The term diabetic gastroenteropathy is used to refer to the broad range of GI motor abnormalities that may accompany diabetes. Although diabetic gastroenteropathy has traditionally been associated with long-standing type 1 diabetes mellitus, it is now clear that various features of diabetic gastroenteropathy may also be a complication of type 2 diabetes mellitus.26
In patients with diabetes and symptomatic gastroparesis, several motor abnormalities have been documented, including: (1) abnormal intragastric distribution of food; (2) a reduced incidence of the antral component of the migrating motor complex; (3) antral dilation and fasting and postprandial hypomotility; and (4) electrical dysrhythmias.10 Many of these features are consistent with extrinsic autonomic denervation. Several recently developed lines of evidence and previous clinical observations, however, indicate that a number of other factors may be relevant to the pathophysiology of GI symptoms in patients with diabetes, including hyperglycemia and direct involvement of the enteric nervous system and enteric muscle system.27,28
Abnormal small intestinal motility also occurs in patients with diabetes, including both reduced duodenojejunal phasic pressure activity and increased bursts of prolonged, nonpropagated, small intestinal contractile activity; this is more common in patients with gastroparesis. Increased colonic transit time is a common feature in patients with diabetes who have abnormal autonomic function tests. Colonic transit time and duration of diabetes mellitus have been positively correlated.28 These findings indicate that diabetes is an important risk factor for constipation in the older patient.
Hypothyroidism. Hypothyroidism is the second major endocrine disorder associated with old age, and the main GI symptom of this condition at any age is constipation. Although some studies showed thyroid function to have a direct effect on various intestinal myoelectric and manometric events, a study that evaluated orocecal transit time among patients with hypothyroidism, both before and after treatment, revealed neither a significant difference at baseline compared with healthy, age-matched controls, nor any detectable response to treatment.10 In a study of older patients on thyroxine replacement therapy for their hypothyroidism, temporary withdrawal of thyroxine was associated with increased orocecal transit time.29 This transit time was normalized when patients resumed their previous thyroxine regimen. Thus, it remains uncertain whether prolonged colonic transit time is solely responsible for constipation in persons with hypothyroidism or whether other factors may also contribute.
Subclinical hypothyroidism has also been associated with gastric dysmotility.30 Subclinical hypothyroidism is defined as a serum thyroid-stimulating hormone above the defined upper limit of the reference range, with a serum concentration of free thyroxine within the reference range.31 The condition is generally asymptomatic; thus, some clinicians will not treat it, thinking that the expense of treatment and the possibility of adverse effects outweigh any potential benefits. However, no studies have been done to determine whether hormone replacement therapy to bring thyroid-stimulating hormone levels to within normal limits will normalize transit time.
Medication-Induced Constipation
Older people make up 11% to 19% of the total population of Western countries, but they account for 40% to 45% of all prescribed drugs and often receive multiple medications.32 Adverse drug reactions and interactions are particularly prevalent in old age, with GI adverse effects being among the most common. Agents with anticholinergic properties are known to impair GI motility and cause constipation, particularly in elderly persons, which may lead to fecal impaction. A variety of over-the-counter and prescribed drugs have anticholinergic effects, including certain cold remedies, antidepressants, psychotropics, asthma medications, pulmonary disease medications, and antispasmodics. In addition to anticholinergics, particularly antidepressants like TCAs, the principal drug classes that cause disordered GI motility at any age include opioid analgesics and calcium channel blockers. Elderly patients are commonly prescribed agents from these drug classes, which are also more likely to cause iatrogenic morbidity in these patients than in younger adults. These effects are primarily related to a reduction in the amplitude of peristaltic contractions throughout the gut.
Antidepressants. Various antidepressants can cause constipation. The specific effects of TCAs on gastric motility have been studied in some detail. Compared with patients who have idiopathic constipation, patients with TCA-induced constipation have reduced high-amplitude, propagating, colonic contractions, as measured by colonic manometry.33,34 Currently, TCAs are prescribed less frequently to elderly people because of the availability of more selective antidepressant agents.
The most widely prescribed antidepressant drugs worldwide are selective serotonin reuptake inhibitors (SSRIs), which have been available for more than a decade. These agents are commonly prescribed because of their lower risk of drug toxicity than other antidepressants; however, several well-recognized GI adverse effects have been associated with their use, including nausea, cramping abdominal pain, deceased intestinal transit time, diarrhea, and, less commonly, constipation. Their precise effects on GI motility remain unknown.
Opioid analgesics. Opioid analgesics are among the most widely prescribed drugs in older people. For centuries, constipation has been a well-known adverse effect of opioids, mediated principally through reduced colonic propulsive activity. Morphine increases the velocity of primary peristalsis and reduces the duration and magnitude of lower esophageal sphincter (LOS) relaxation, effects that are readily and specifically reversed by naloxone.35 In one study, morphine decreased baseline LOS pressure, whereas naloxone increased it by approximately 20%.36 Therefore, morphine slowed the rate of gastric emptying, whereas naloxone sped it up.
The inhibitory effects of opioids on gastric emptying are an important consideration when prescribing other drugs, particularly those that need a rapid onset of action to be effective (eg, levodopa). Opioids delay small intestinal and colonic transit times, with the latter delay resulting from a combination of increased tonic contractions and decreased propulsive contractions.37 Overall, different opioid drugs have different effects on GI motility. For example, tramadol given to patients with painful osteoarthritis caused no significant increase in colonic transit time, whereas dihydrocodeine has been shown to delay colonic transit time.38 Neither drug increased orocecal transit time, a parameter that incorporates esophageal, gastric, and small intestinal transit times.38
Calcium channel blockers. Elderly people are frequently prescribed calcium channel blocking agents to treat hypertension and ischemic heart disease. The effects of calcium antagonists on GI motility have been well described since they were first introduced into clinical medicine in the 1960s.39 Nifedipine, verapamil, and diltiazem have been the most widely studied. While therapeutic doses of nifedipine reduces LOS pressure and the amplitude of esophageal peristaltic contractions, it has not been shown to significantly affect gastric emptying of solid or liquid meals. Orocecal transit time is significantly increased by nifedipine, with the small intestine being the likely site of this effect. Nifedipine also inhibits colonic motor activity,40 which may be the mechanism by which it causes constipation in some patients.
Verapamil has similar effects to nifedipine on esophageal peristalsis and LOS function. Like nifedipine, verapamil and diltiazem do not significantly delay gastric emptying in healthy patients. Quantification of gastric emptying, small intestinal transit time, and colonic transit time by scintigraphy in healthy men showed a significant inhibitory effect for verapamil only on colonic transit.41 Verapamil, like nifedipine, inhibits the colonic motor response to eating. The clinical impact of these motor effects of calcium antagonists is unclear. Although the net effect in individuals without underlying GI disease appears to be minimal, the colonic effects may have the potential to exacerbate preexisting disease. Newer dihydropyridine drugs, such as nitrendipine and lacidipine,42 do not appear to influence GI motility and may therefore be more suitable choices for older patients who report constipation before or after starting therapy with traditional calcium channel blocking agents.
Conclusion
Normal aging is associated with significant changes in the function of most organs and tissues, of which the GI tract is no exception. Although the effects of age alone on bowel function may not result in constipation, they may lower the threshold for clinically significant problems when coupled with other precipitating factors. A major confounding factor in the interpretation of motor phenomena throughout the GI tract in older patients is the frequent coexistence of neurological, endocrinological, and other disease states, which may be independently associated with dysmotility. In addition, older patients often have atypical signs, symptoms, and diagnostic test results, adding to the diagnostic conundrum. Clinicians must always be mindful of the effects that comorbidities and medications have on the GI tract, as this is imperative to properly identify and prevent iatrogenic disease.
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Disclosures:
The authors report no relevant financial relationships.
Address correspondence to:
Steven R. Gambert, MD, AGSF, MACP
University of Maryland Medical Center N3E09, 22. S. Greene Street
Baltimore, MD 21201
sgambert@medicine.umaryland.edu