CHAPTER
19  
Constipation
ANTHONY J. LEMBO
CHAPTER OUTLINE
Definition and Presenting Symptoms.........................................270
Epidemiology.............................................................................271
Prevalence................................................................................ 271
Incidence.................................................................................. 271
Public Health Perspective.......................................................... 271
Risk Factors..............................................................................271
Gender..................................................................................... 271
Age.......................................................................................... 272
Ethnicity.................................................................................... 272
Socioeconomic Class and Education Level.................................. 272
Diet and Physical Activity........................................................... 272
Medication Use......................................................................... 272
Colonic Function........................................................................272
Luminal Contents...................................................................... 272
Absorption of Water and Sodium............................................... 273
Diameter and Length................................................................. 273
Motor Function.......................................................................... 273
Innervation and the Interstitial Cells of Cajal............................... 274
Defecatory Function................................................................... 274
Size and Consistency of Stool.................................................... 274
Classification.............................................................................274
Pathophysiology.........................................................................275
Normal-Transit Constipation....................................................... 275
Constipation affects a substantial portion of the Western popu-
lation and is particularly prevalent in women, children, and
older adults. Many persons with constipation do not seek
medical attention, but because constipation affects between
3% and 31% of the population, it results in over $6.9 billion in
medical costs annually and is 1 of the most common reasons
for an office visit to a physician.
For most affected persons, constipation is intermittent and
requires no or minimal intervention. For others, constipation
can be challenging to treat and have a negative impact on
quality of life. In these cases, specific causes of constipation
like systemic or structural diseases must be excluded.
DEFINITION AND PRESENTING
SYMPTOMS
It is important to ask patients what they mean when they say
“I am constipated.” Most persons describe perception of dif-
ficulty with bowel movements or a discomfort related to
bowel movements. The most common terms used by young
270
Slow-Transit Constipation.......................................................... 275
Defecatory Disorders................................................................. 275
Causes......................................................................................276
Disorders of the Anorectum and Pelvic Floor.............................. 276
Systemic Disorders.................................................................... 278
Nervous System Disease........................................................... 278
Structural Disorders of the Colon, Rectum, and Anus.................. 279
Medications.............................................................................. 280
Psychological Disorders............................................................. 280
Clinical Assessment...................................................................281
History...................................................................................... 281
Physical Examination................................................................. 281
Diagnostic Tests........................................................................281
Tests for Systemic Disease........................................................ 282
Tests for Structural Disease....................................................... 282
Physiologic Measurements........................................................ 282
Treatment..................................................................................285
General Measures..................................................................... 285
Specific Therapeutic Agents....................................................... 286
Other Forms of Therapy............................................................. 294
healthy adults to define constipation are straining (52%),
hard stools (44%), and inability to have a bowel movement (34%).1
Analysis of the National Health Interview Survey (NHIS)
data found that in 10,875 subjects older than age 60, straining
and hard bowel movements were most strongly associated
with self-reported constipation.2
The definition of constipation also varies among health
care providers. The traditional medical definition of constipa-
tion, based on the 95% lower confidence limit for healthy
adults in North America and the United Kingdom,3 has been
3 or fewer bowel movements per week. Reports of stool fre-
quency, however, are often inaccurate and correlate poorly
with complaints of constipation.4 In an attempt to standardize
the definition of constipation, a consensus definition was ini-
tially developed by international experts in 1992 (Rome I Con-
sensus Committee criteria)5 and was revised in 1999 and 2006
(Rome II and III criteria, respectively [Box 19-1]).6,7
The Rome criteria incorporate the multiple symptoms of
constipation, of which stool frequency is only 1, and require
that a minimum of 2 symptoms be present in at least 25%
of bowel movements. Unlike the Rome I criteria, the Rome
II criteria include symptoms suggestive of pelvic floor

BOX 19-1 Rome III Criteria for Functional Constipation
Two or more of the following 6 must be present*:
Straining during at least 25% of defecations
Lumpy or hard stools in at least 25% of defecations
Sensation of incomplete evacuation for at least 25% of
defecations
Sensation of anorectal obstruction/blockage for at least 25%
of defecations
Manual maneuvers to facilitate at least 25% of defecations
(e.g., digital evacuation, support of pelvic floor)
Fewer than 3 defecations per week
*Criteria fulfilled for the previous 3 months, with symptom onset at least 6
months prior to diagnosis. In addition, loose stools should rarely be present
without the use of laxatives, abdominal pain is not required, and there should
be insufficient criteria for IBS. These criteria may not apply when the patient is
taking laxatives.
dyssynergia or outlet obstruction (e.g., a sensation of anorectal
blockage or obstruction and use of maneuvers to facilitate
defecation). The Rome III criteria allow patients to have rare
episodes of loose stools without the use of laxatives and
require that symptoms be present during the previous 3
months, with an onset at least 6 months earlier. The American
College of Gastroenterology defines constipation as unsatis-
factory defecation characterized by infrequent stools, difficult
stool passage, or both. Difficult stool passage includes strain-
ing, 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
defined as the presence of symptoms for at least 3 months and
should be distinguished from irritable bowel syndrome (IBS
[see Chapter 122]), although the two entities have overlapping
features.8
EPIDEMIOLOGY
Prevalence
The prevalence of constipation ranges from 3% to 31% of the
population in Western countries9-25 and varies depending on
the demographics of the population, definition of constipation
(e.g., self-reported symptoms, fewer than 3 bowel movements/
week, Rome criteria), and method of questioning (e.g., postal
questionnaire, interview). A meta-analysis that included 41
studies with over 261,000 subjects found the pooled preva-
lence of constipation to be 14%.26 In general, the prevalence is
highest when constipation is self-reported9 and lowest when
the Rome criteria for constipation are applied. When the Rome
II criteria are used to diagnose constipation, the effects of
gender, race, socioeconomic status, and level of education on
the prevalence of constipation are reduced.27
Incidence
Talley and colleagues surveyed 690 nonelderly residents of
Olmsted County, Minnesota, at baseline and after 12 to 20
months.28 Constipation, defined as frequent straining at stool
and passing hard stool, a weekly stool frequency of fewer than
3, or both, was present in 17% of respondents on the first
survey and 15% on the second. The rate of new constipation
in this study was 50/1000 person-years, whereas the disap-
pearance rate was 31/1000 person-years. In a similar study,
residents were surveyed at baseline and about 12 years later.
The cumulative incidence of constipation over a 12-year
period was 17.4% and, in subjects younger than age 50, was
higher in women (18.3%) than men (9.2%).29
Chapter 19  Constipation   271
BOX 19-2 Risk Factors for Constipation
Advanced age
Female gender
Low level of education
Low level of physical activity
Low socioeconomic status
Nonwhite ethnicity
Use of certain medications (see Box 19-3)
Public Health Perspective
Constipation results in more than 555,000 emergency depart-
ment visits, 38,000 hospitalizations,30 and several hundred
million dollars of laxative sales in the United States each year.31
Using data from the National Ambulatory Medical Care
Survey and the National Hospital Ambulatory Medical Care
Survey, the number of ambulatory care visits for constipation
in the United States has been estimated to have increased from
4 million in 1993 to 1996 to roughly 8 million in 2001 to 2004.31
Some 85% of physician visits for constipation lead to a pre-
scription for laxatives or cathartics.32 In a health maintenance
organization setting, the mean annual direct health care costs
for constipation have been estimated to be $7522, with annual
out-of-pocket costs of $390.33 Over a 15-year period, consti-
pated women incur direct medical costs ($63,591) more than
double that of nonconstipated women ($24,529).34 In 2004, the
direct costs for constipation were nearly $1.6 billion, with
indirect costs of $140 million, making constipation among the
top 10 digestive disorders in attributable direct costs.35 In an
analysis of physician visits for constipation in the United
States between 2001 and 2004, 33% of patients who required
medical attention were seen by internal medicine and family
practitioners, followed by pediatricians (21%) and gastroen-
terologists (14.1%).36 In a National Canadian Survey, 34% of
people who reported constipation had seen a physician for
their symptoms.9
RISK FACTORS
Risk factors for constipation in the United States include
female gender, advanced age, nonwhite ethnicity, low
levels of income and education, and a low level of physical
activity.4,24,26,37 Other risk factors include use of certain medica-
tions (e.g., acetaminophen [>7 tablets/week], aspirin, other
NSAIDs13) and certain underlying medical disorders (see
later). Diet and lifestyle may also play a role in the develop-
ment of constipation (Box 19-2).
Gender
The prevalence of self-reported constipation is 2 to 3 times
higher in women than in men,11,20,24,27 and infrequent bowel
movements (e.g., once a week) are reported almost exclusively
by women.38 In a meta-analysis of 26 studies, the pooled
prevalence of constipation in women was 17.4% compared
with 9.2% in men.26 In a study of 220 healthy subjects eating
their normal diets, 17% of women but only 1% of men passed
less than 50 g of stool daily.39 The reason for the female pre-
dominance is unknown. Colonic transit time is significantly
longer in women during the luteal phase of the menstrual
cycle compared with the follicular phase, when estrogen
levels are relatively low.40 A reduction in levels of steroid
hormones has been observed in women with severe idiopathic
272   Section III  Symptoms, Signs, and Biopsychosocial Issues
constipation, although the clinical significance of this finding
is dubious.41 Overexpression of progesterone receptors on
colonic smooth muscle cells has been reported to down-
regulate contractile G proteins and up-regulate inhibitory G
proteins.42 Overexpression of progesterone receptors in colon
epithelial cells is also associated with reduced serotonin
transporter, high 5-hydroxytryptamine (5-HT), and normal
tryptophan hydroxylase levels.43 In addition, overexpression
of progesterone receptor B on colonic muscle cells, thereby
making them more sensitive to physiologic concentrations of
progesterone, has been proposed as an explanation for severe
slow-transit constipation in some women.44
Age
The prevalence of self-reported constipation among older
adults ranges from 15% to 30%, with most11,31,37,45 but not
all9,11,13,24 studies showing an increase in prevalence with age.
Constipation is particularly problematic in nursing home resi-
dents, among whom constipation is reported in almost half,
and 50% to 74% use laxatives on a daily basis.46,47 Similarly,
hospitalized older patients appear to be at high risk of devel-
oping constipation. A study of patients on a geriatrics ward in
the United Kingdom showed that up to 42% had a fecal impac-
tion.48 Older adults also tend to seek medical assistance for
constipation more commonly than their younger counterparts.
In an analysis of physician visits for constipation in the United
States between 1958 and 1986, the frequency was about 1% in
persons younger than age 60, 1% to 2% in those 60 to 65, and
3% to 5% in those older than 65.32
Constipation in older adults is most commonly the result
of excessive straining and hard stools49 rather than a decrease
in stool frequency. In a community sample of 209 people aged
65 to 93 years, the main symptom used to describe constipa-
tion was the need to strain at defecation; only 3% of men and
2% of women reported that their average bowel frequencies
were less than 3 per week.44 Possible causes for the increased
frequency of straining in older adults include decreased food
intake, reduced mobility, weakening of abdominal and pelvic
wall muscles, chronic illness, psychological factors, and medi-
cations, particularly pain-relieving drugs.47,50
Constipation is also common in children younger than age
4.51 In Great Britain, the frequency of a consultation for consti-
pation in general practice was 2% to 3% for children aged 0 to
4, about 1% for women aged 15 to 64, 2% to 3% for both
genders aged 65 to 74, and 5% to 6% for patients aged 75 years
or older. Fecal retention with fecal soiling is a common cause
of impaired quality of life and the need for medical attention
in childhood.
Ethnicity
In North America, constipation is reported more commonly
by nonwhites than whites. In a survey of 15,014 persons, the
frequency was 17.3% in nonwhites and 12.2% in whites.4,24,52
Age-specific increases in prevalence were found in both
groups.4 Data regarding constipation in developing countries
are limited. A study comparing the prevalence in South
America and Asia found comparable frequencies of constipa-
tion, with rates of 21.7% in Colombia and 16.7% in South
Korea.45 In Sri Lanka, constipation (as defined by the Rome III
criteria using a self-administered survey) was reported by
15.4% of children between 10 and 16 years of age. The preva-
lence of constipation was significantly higher in children with
a family history of constipation (49% vs. 14.8%), those living
in a war-affected area (18.1% vs. 13.7%), and those attending
an urban school (16.7% vs. 13.3%).53
Socioeconomic Class and Education Level
The prevalence of constipation is influenced by socioeconomic
status. In population-based surveys, persons with lower-
income status have rates of constipation higher than those
who have higher-income status.4,7,22,24 Similarly, persons who
have a lower education level tend to have a prevalence of
constipation higher than those who have a higher education
level.4,9,24,52 A meta-analysis found an increased prevalence of
constipation in persons of lower socioeconomic status com-
pared with those of higher socioeconomic status.26
Diet and Physical Activity
Cross-sectional studies have not linked low intake of fiber
with constipation,44,54 yet data suggest that increased con-
sumption of fiber decreases colonic transit time and increases
stool weight and frequency.55 An analysis from the Nurses
Health Study, which assessed the self-reported bowel habits
of 62,036 women between 36 and 61 years of age, demon-
strated that women who were in the highest quintile of fiber
intake (median intake, 20 g/day) and who exercised daily
were 68% less likely to report constipation, defined as 2 or
fewer bowel movements weekly, than women who were in the
lowest quintile of fiber intake (median intake, 7 g/day) and
exercised less than once a week.37 Although other observa-
tional studies have supported a protective effect of physical
activity on constipation, results from trials designed to test this
hypothesis are conflicting. In 1 trial, symptoms of constipation
did not improve after a 4-week exercise program.56 Likewise,
among Department of Veterans Affairs employees, physical
activity levels did not differ between those with or without
constipation.57
Dehydration has been identified as a potential risk factor
for constipation. Some but not all observational studies
have found an association between a slow intestinal transit
time and dehydration.58,59 Among female Japanese dietetic
students, however, total water intake was not associated
with constipation.54 Although patients with constipation
are routinely advised to increase their intake of fluid, the
benefit of increased fluid intake has not been thoroughly
investigated.
Medication Use
In a review of 7251 patients with chronic constipation (and
nonconstipated controls) from a general practice database,
medications that were significantly associated with constipa-
tion were opioids, diuretics, antidepressants, antihistamines,
antispasmodics, anticonvulsants, and aluminum antacids
(Box 19-3).60 Use of acetaminophen (>7 tablets weekly), aspirin,
and other NSAIDs was also found to be associated with an
increased risk of constipation.13
COLONIC FUNCTION
Luminal Contents
The main contents of the colonic lumen are food residue, water
and electrolytes, bacteria, and gas. Unabsorbed food entering
the cecum contains carbohydrates that are resistant to diges-
tion and absorption by the small intestine, such as starches
and nonstarch polysaccharides. Some of the unabsorbed car-
bohydrate serves as substrate for bacterial proliferation and
fermentation, yielding short-chain fatty acids and gas (see
 Chapter 19  Constipation   273

BOX 19-3 Secondary Causes of Constipation Absorption of Water and Sodium

Mechanical Obstruction The colon avidly absorbs sodium and water (see Chapter 101).
Anal stenosis Increased water absorption can lead to smaller, harder stools.
Colorectal cancer The colon extracts most of the 1000 to 1500 mL of fluid that
Extrinsic compression crosses the ileocecal valve and leaves only 100 to 200 mL of
Rectocele or sigmoidocele fecal water daily. Less reabsorption of electrolytes and nutri-
Stricture ents takes place in the colon than in the small intestine, and
sodium-chloride exchange and short-chain fatty acid trans-
Medications port are the principal mechanisms for stimulating water
Acetaminophen (>7 tablets weekly) absorption. Colonic absorptive mechanisms remain intact in
Antacids (aluminum containing)
patients with constipation. One proposed pathophysiologic
Anticholinergic agents (e.g., antiparkinsonian drugs,
mechanism in slow-transit constipation is that the lack of peri-
antipsychotics, antispasmodics, tricyclic antidepressants)
Anticonvulsants (e.g., carbamazepine, phenobarbital,
staltic movement of contents through the colon allows more
phenytoin) time for bacterial degradation of stool solids and increased
Antineoplastic agents (e.g., vinca derivatives) NaCl and water absorption, thereby decreasing both stool
Calcium channel blockers (e.g., verapamil) weight and frequency.65 The volume of stool water and quan-
Calcium supplements tity of stool solids seem to be reduced proportionally in con-
Diuretics (e.g., furosemide) stipated persons.66
5-Hydroxytryptamine3 antagonists (e.g., alosetron)
Iron supplements
NSAIDs (e.g., ibuprofen)
Diameter and Length
Mu-opioid agonists (e.g., fentanyl, loperamide, morphine) A wide or long colon may lead to a slow colonic transit rate
(see Chapter 98). Although only a small fraction of patients
Metabolic and Endocrinologic Disorders
with constipation have megacolon or megarectum, most
Diabetes mellitus
Heavy metal poisoning (e.g., arsenic, lead, mercury)
patients with dilatation of the colon or rectum report constipa-
Hypercalcemia tion. A colonic width of more than 6.5 cm at the pelvic brim
Hyperthyroidism on a barium enema film is abnormal and has been associated
Hypokalemia with chronic constipation.67
Hypothyroidism
Panhypopituitarism Motor Function
Pheochromocytoma
Porphyria Colonic muscle has 4 main functions (see Chapter 100): (1)
Pregnancy delays passage of the luminal contents to allow time for water
absorption, (2) mixes the contents and allows contact with the
Neurologic and Myopathic Disorders mucosa, (3) allows the colon to store feces between defeca-
Amyloidosis
tions, and (4) propels the contents toward the anus. Muscle
Autonomic neuropathy
Chagas’ disease
activity is affected by sleep and wakefulness, eating, emotion,
Dermatomyositis colon contents, and drugs. Neural control is partly intrinsic
Intestinal pseudo-obstruction and partly extrinsic by the sympathetic nerves and the para-
Multiple sclerosis sympathetic sacral outflow.
Parkinsonism Transit of contents along the colon normally takes hours
PSS or days (longer than transit in other portions of the GI tract).
Shy-Drager syndrome The mean colonic transit time in healthy volunteers is 34 to 35
Spinal cord injury hours, with an upper limit of normal of 72 hours.68,69 Scinti-
Stroke graphic studies in constipated subjects have shown that
overall transit of colonic contents is slow. In some patients, the
rate of movement of contents is about normal in the ascending
colon and hepatic flexure but delayed in the transverse and
Chapter 17). On average, bacteria represent about 50% of stool left colon. Other patients show slow transit in the right and
weight.61 In an analysis of feces from 9 healthy subjects on a left sides of the colon.70
metabolically controlled British diet, bacteria constituted 55% Colonic propulsions are of 2 basic types: low-amplitude
of the total solids, and fiber represented approximately 17% of propagated contractions (LAPCs) and high-amplitude propa-
the stool weight.62 The role of intestinal microbiota in constipa- gated contractions (HAPCs).71 The frequency and duration of
tion is beginning to be explored (see Chapter 3).63 HAPCs are reduced in some patients with constipation. In 1
A meta-analysis suggested that wheat bran increases stool study, 14 chronically constipated patients with proved slow
weight and decreases mean colonic transit time in healthy transit of intestinal contents and 1 or fewer bowel movements
volunteers.62 The effect of bran may primarily be the result of weekly were compared with 18 healthy subjects. Four of the
increased bulk within the colonic lumen; the increased bulk patients had no peristaltic movement, whereas peristaltic
stimulates propulsive motor activity. The particulate nature of movement was normal in all the healthy subjects during a
some fibers may also stimulate the colon. Ingestion of coarse 24-hour period. Peristaltic movements in other subjects with
bran (10 g twice daily) was shown to reduce colonic transit constipation were fewer in number and shorter in duration,
time by about a third, whereas ingestion of the same quantity and thus passed for a shorter distance along the colon, as
of fine bran led to no significant decrease.61 Similarly, ingestion compared with the findings in the healthy controls. All the
of inert plastic particles similar in size to coarse bran increased healthy subjects reported abdominal discomfort or an urge
fecal output by almost 3 times their own weight and decreased to defecate during peristaltic movements, and 2 defecated,
colonic transit time.64 whereas only 4 of the 14 subjects with constipation
274   Section III  Symptoms, Signs, and Biopsychosocial Issues
experienced any sensation during such movements, and none
defecated.72
Innervation and the Interstitial
Cells of Cajal
Proximal colonic motility is under the involuntary control
of the enteric nervous system, whereas defecation is volun-
tary. Slow-transit constipation may be related to autonomic
dysfunction.73,74 Histologic studies have shown abnormal
numbers of myenteric plexus neurons involved in excitatory
or inhibitory control of colonic motility, thereby resulting in
decreased amounts of the excitatory transmitter substance P75
and increased amounts of the inhibitory transmitters vasoac-
tive intestinal polypeptide (VIP) or nitric oxide (NO) (see
Chapter 4).76
The interstitial cells of Cajal (ICCs) are intestinal pace-
maker cells and play an important role in regulating GI motil-
ity (see Chapters 99 and 100). They facilitate conduction of
electric current and mediate neural signaling between enteric
nerves and muscles. ICCs initiate slow waves throughout the
GI tract. Confocal images of ICCs in patients with slow-transit
constipation show not only reduced numbers but also abnor-
mal morphology of ICCs, with irregular surface markings and
a decreased number of dendrites. In patients with slow-transit
constipation, the number of ICCs has been shown to be
decreased in the sigmoid colon77 or the entire colon.78,79 Patho-
logic examination of colectomy specimens of 14 patients
with severe intractable constipation has revealed decreased
numbers of ICCs and myenteric ganglion cells throughout
the colon.80
Defecatory Function
The process of defecation in healthy persons begins with a
predefecatory period during which the frequency and ampli-
tude of propagating sequences (3 or more successive pres-
sure waves) are increased. Stimuli such as waking and meals
(gastroileal reflex, also referred to as gastrocolic reflex) can stim-
ulate this process. In patients with slow-transit constipation,
this predefecatory period is blunted and may be absent.71
The gastroileal reflex is also diminished in persons with
slow-transit constipation. Stool is often present in the rectum
before the urge to defecate arises. The urge to defecate is
usually experienced when stool comes into contact with
receptors in the upper anal canal. When the urge to defecate
is resisted, retrograde movement of stool may occur, and
transit time increases throughout the colon (see Chapter
100).81
Although the sitting or squatting position seems to facili-
tate defecation, the benefit of squatting has not been studied
in patients with constipation. Full flexion of the hips stretches
the anal canal in an anteroposterior direction and straightens
the anorectal angle, thereby promoting emptying of the
rectum.82 Contraction of the diaphragm and abdominal
muscles raises intrapelvic pressure, and the pelvic floor relaxes
simultaneously. Striated muscular activity expels rectal con-
tents, with little contribution from colonic or rectal propulsive
waves. Coordinated relaxation of the puborectalis muscle
(which maintains the anorectal angle) and the external anal
sphincter at a time when pressure is increasing in the rectum
results in expulsion of stool (Fig. 19-1).
The length of the colon emptied during spontaneous def-
ecation most commonly extends from the descending colon to
the rectum.83 When the propulsive action of smooth muscle is
normal, defecation usually requires minimal voluntary effort.
If colonic and rectal waves are infrequent or absent, however,
the normal urge to defecate may not occur.72
During straining
Puborectalis
muscle
Anorectal angle
Descent of the
pelvic floor
FIGURE 19-1. Physiology of defecation. Defecation requires relax-
ation of the puborectalis muscle with descent of the pelvic floor
and straightening of the anorectal angle during straining, as well
as relaxation of the internal anal sphincter. (From Lembo A,
Camilleri M. Chronic constipation. N Engl J Med 2003;
349:1360-8.)
Size and Consistency of Stool
In a study of normal subjects who were asked to expel single
hard spheres of different sizes from the rectal ampulla, the
intrarectal pressure and time needed to pass the objects
varied inversely with their diameters. Small, hard stools are
more difficult to pass than large, soft stools. When larger
stimulated stools were tested, a hard stool took longer to
expel than a soft silicone rubber object of roughly the same
shape and volume. Similarly, more subjects were able to expel
a 50-mL water-filled compressible balloon than a hard 1.8-cm
sphere.84
Human stools may vary in consistency from small hard
lumps to liquid. The water content of stool determines con­
sistency. Rapid colonic transit of fecal residue leads to dimin-
ished water absorption and (perhaps counterintuitively) an
increase in the bacterial content of the stool. The Bristol
Stool Scale38 is used in the assessment of constipation and is
regarded as the best descriptor of stool form and consistency
(Fig. 19-2). Stool consistency appears to be a better predictor
of whole-gut transit time than of defecation frequency or stool
volume.85
CLASSIFICATION
Mechanical small and large bowel obstruction, medications,
and systemic illnesses can cause constipation, and these causes
of secondary constipation must be excluded, especially in
patients presenting with new-onset constipation (see Box
19-3). Most often, constipation is due to disordered function
of the colon or rectum (functional constipation). Functional
constipation can be divided into 3 broad categories—normal-
transit constipation, slow-transit constipation, and defecatory
or rectal evacuation disorders (Table 19-1). In a study of more
than 1000 patients with functional constipation who were
evaluated at the Mayo Clinic, 59% were found to have normal-
transit constipation, 25% had defecatory disorders, 13% had
slow-transit constipation, and 3% had a combination of a def-
ecatory disorder and slow-transit constipation.86
 Chapter 19  Constipation   275

TABLE 19-1 Clinical Classification of Functional Constipation

Category Features Physiologic Test Results

Normal-transit constipation Incomplete evacuation; abdominal pain may be Normal

present but not a predominant feature

Slow-transit constipation Infrequent stools (e.g., ≤1/wk), lack of urge to Delay in colonic transit (e.g., retention in
defecate, poor response to fiber and laxatives, colon of >20% of radiopaque markers
generalized symptoms (e.g., malaise, fatigue); 5 days after ingestion)
more prevalent in young women

Defecatory disorder* Frequent straining, incomplete evacuation, need Abnormal balloon expulsion test and/or
for manual maneuvers to facilitate defecation anorectal manometry

*Pelvic floor dysfunction, anismus, descending perineum syndrome, and rectal prolapse.

Whole-gut Type Pictorial movement/week). Associated symptoms include abdominal

transit time of stool Description representation pain, bloating, and malaise. Symptoms are often intractable,
Long transit and conservative measures like fiber supplements and osmotic
(e.g., 100 hours) laxatives are usually ineffective.90,91 Symptom onset is gradual
and usually occurs around the time of puberty. Slow-transit
Separate hard lumps,
Type 1 constipation arises from disordered colonic motor function.
like nuts, hard to pass
Patients who have mild delays in colonic transit have symp-
Sausage shaped toms similar to those seen in persons with IBS.92 In patients
Type 2
but lumpy with more severe symptoms, the pathophysiology includes
delayed emptying of the proximal colon and fewer HAPCs
Like sausage but with after meals. Colonic inertia is a term used to describe the dis-
Type 3
cracks on its surface order in patients with symptoms at the most severe end of the
Like sausage or snake, spectrum. In this condition, colonic motor activity fails to
Type 4 smooth and soft increase after a meal,93 ingestion of bisacodyl,94 or administra-
tion of a cholinesterase inhibitor such as neostigmine.95
Soft blobs with clear-cut
Type 5 edges (passed easily)
Fluffy pieces with ragged Defecatory Disorders
Type 6 edges, a mushy stool Defecatory disorders arise from failure to empty the rectum
effectively because of an inability to coordinate the abdominal,
Type 7 Watery, no solid pieces Entirely liquid rectoanal, and pelvic floor muscles. Many patients with defe-
catory disorders also have slow-transit constipation.96 Defeca-
Short transit tory disorders are also known as anismus, dyssynergia, pelvic
(e.g., 10 hours)
floor dyssynergia, spastic pelvic floor syndrome, obstructive defeca-
FIGURE 19-2. The Bristol Stool Form Scale. Common stool forms tion, or outlet obstruction. These disorders appear to be acquired
and their consistency in relation to whole-gut transit time are and may start in childhood. They may be a learned behavior
shown. (From Heaton KW, Radvan J, Cripps H, et al. Defecation to avoid some discomfort associated with passage of large,
frequency and timing, and stool form in the general population: hard stools or pain associated with attempted defecation in
A prospective study. Gut 1992; 33:818-24.) the setting of an active anal fissure or inflamed hemorrhoids.
Individuals with defecatory disorders commonly have inap-
propriate contraction of the anal sphincter when they bear
down (Fig. 19-3). This phenomenon can occur in asymptom-
PATHOPHYSIOLOGY atic patients but is more common among those who complain
of difficult defecation.97 Some patients with a defecatory dis-
Normal-Transit Constipation order are unable to raise intrarectal pressure to a level suffi-
cient to expel stool, a disturbance that manifests clinically as
In normal-transit constipation, stool travels along the colon failure of the pelvic floor to descend on straining.98
at a normal rate.87 Patients with normal-transit constipation Defecatory disorders are particularly common in older
may have misperceptions about their bowel frequencies and adults with chronic constipation and excessive straining,
often exhibit psychosocial distress.88 Some patients have many of whom do not respond to standard medical treat-
abnormalities of anorectal sensory and motor function indis- ment.99 Rarely, defecatory disorders are associated with struc-
tinguishable from those in patients with slow-transit constipa- tural abnormalities (e.g., rectal intussusception, obstructing
tion.89 Whether increased rectal compliance and reduced rectal rectocele, megarectum, excessive perineal descent).100
sensation are effects of chronic constipation or contribute to Patients with defecatory disorders may report infrequent
these patients’ failure to experience an urge to defecate is bowel movements, ineffective and excessive straining, and the
unclear, but most patients have normal physiologic testing. need for manual disimpaction, but symptoms—particularly in
the case of pelvic floor dysfunction—do not correlate with
physiologic findings.101 For a diagnosis of a defecatory disor-
Slow-Transit Constipation der, a Rome working group102 has specified the criteria listed
Slow-transit constipation is most common in young women in Box 19-4. In patients with this disorder, constipation is func-
and characterized by infrequent bowel movements (<1 bowel tional and due to dysfunction of the pelvic floor muscles as
276   Section III  Symptoms, Signs, and Biopsychosocial Issues
Cough Strain
200
EMG
Control subject
µV
100
Pressure
cm H2O
50
0 wall above the anorectal junction, and a layer of fascia runs
5 sec
Cough (x 3) Strain
Constipated patient
cm H2O EMG
200
µV
150
Pressure
100
50
0 5 sec
FIGURE 19-3. Electromyography (EMG) and pressure tracings
during defecation in a normal (control) subject and a constipated
patient with a defecatory disorder. In both the control subject and
constipated patient, a cough produces a rise in pressure. When
a normal subject strains (upper tracing), EMG activity of the
external anal sphincter is inhibited, and pressure in the anal canal
falls. In a constipated patient with a defecatory disorder, EMG
activity of the anal sphincter is not inhibited on straining, and
pressure within the anal canal increases (lower tracing). This
paradoxical contraction has been termed anismus, anal dyssyn-
ergia, and spastic perineum. (From Preston DM, Lennard-
Jones JE. Anismus in chronic constipation. Dig Dis Sci 1985;
30:413-18.)
BOX 19-4 Rome III Criteria for Functional Defecation
Disorders102*
The patient must satisfy diagnostic criteria for functional
constipation (see Box 19-1).
During repeated attempts to defecate, the patient must have at
least 2 of the following:
Evidence of impaired evacuation, based on balloon expulsion
test or imaging
Inappropriate contraction of pelvic floor muscles (i.e., anal
sphincter or puborectalis) or <20% relaxation of basal
resting sphincter pressure by manometry, imaging,
or EMG
Inadequate propulsive forces assessed by manometry or
imaging
*Criteria fulfilled for the previous 3 months, with symptom onset at least 6
months prior to diagnosis.
EMG, electromyography.
determined by physiologic tests (see later). Pelvic floor dys-
synergia affects a subset of these patients in whom the anal
sphincter fails to relax more than 20% of its basal resting pres-
sure during attempted defecation, despite the presence of
adequate propulsive forces in the rectum.
Functional fecal retention (FFR) is the most common def-
ecatory disorder in children. It is a learned behavior that
results from withholding defecation, often because of fear of
a painful bowel movement.103 The symptoms are common
and may result in secondary encopresis (fecal incontinence)
due to leakage of liquid stool around a fecal impaction. FFR
is the most common cause of encopresis in childhood (see
Chapter 17).104
CAUSES
Disorders of the Anorectum and Pelvic Floor
Ext. sphincter
Rectocele
A rectocele is the bulging or displacement of the rectum
Anal canal through a defect in the anterior rectal wall. In women, the
perineal body supports the anterior rectal (posterior vaginal)
from the rectovaginal pouch of Douglas to the perineal body
and adheres to the posterior vaginal wall. The anterior rectal
wall is unsupported above the level of the perineal body, and
the rectovaginal septum can bulge anteriorly to form a recto-
Ext. sphincter
cele (Fig. 19-4). Rectoceles can arise from damage to the recto-
vaginal septum or its supporting structures during vaginal
Anal canal childbirth. These injuries are exacerbated by repetitive
increases in intra-abdominal pressure and the long-term
effects of gravity. Prolapse of other pelvic organs may be
present. Urinary incontinence and previous hysterectomy are
more common in patients with a rectocele than in patients
with difficult defecation and no demonstrable rectocele.105
Studies using defecating proctography (see later) have
shown that rectoceles are common in symptomless healthy
women and may protrude as much as 4 cm from the line of
the anterior rectal wall without causing bowel symptoms,
although 2 cm is the generally accepted lower limit of a recto-
cele that may be regarded as clinically significant.106 Symptom-
atic patients report inability to complete fecal evacuation,
perineal pain, sensation of local pressure, and appearance of
a bulge at the vaginal opening on straining. Women may
report the need to use their thumb or fingers to support the
posterior vaginal wall to complete defecation.105 Women may
also report the need to use a finger to digitally evacuate
the rectum.
Defecating proctography can be used to demonstrate a
rectocele, measure its size, and determine whether barium
becomes trapped within the rectocele. In 1 study, trapping of
barium in rectoceles changed with the degree of rectal empty-
ing and was related to the size of the rectocele.107 However,
rectocele size or degree of emptying on defecation have not
been shown to correlate with surgical repair outcomes.108,109
Asymptomatic women with rectoceles do not require sur-
gical treatment. Kegel exercises (designed to strengthen pelvic
floor muscles that support the urethra, bladder, uterus, and
rectum) and instructions to avoid repetitive increases in intra-
abdominal pressure may help prevent progression of the rec-
tocele. Surgery should be considered only for patients in
whom contrast is retained during defecography and patients
in whom constipation is relieved with digital vaginal pressure
to facilitate defecation.110 Surgical repair can be performed by
an endorectal, transvaginal, or transperineal approach. Other
types of genital prolapse may also be present, and collabora-
tion between the surgeon and gynecologist may be appropri-
ate. In carefully selected patients, surgical repair benefits some
75% of patients. In a review of 89 women who underwent a
combined transvaginal and transanal rectocele repair for
symptoms of obstructive defecation, the repair was successful
in 71% of patients, as assessed by the absence of symptoms
after 1 year.111 Reduction in rectocele size, as judged by defe-
cating proctography, does not appear to correlate clearly with
symptom improvement.109
Descending Perineum Syndrome
In descending perineum syndrome, the pelvic floor descends
to a greater extent than normal (1 to 4 cm) when the patient
 Chapter 19  Constipation   277

Levator plate

Rectum Perineal Vagina Rectocele

body
Rectovaginal
A septum B
FIGURE 19-4. Development of a rectocele. A, Normal anatomy of the female pelvis. The levator plate is almost horizontal, supporting
the rectum and vagina. The perineal body provides support for the lower posterior vaginal wall; above it lies the rectovaginal septum.
B, Pelvic floor weakness leads to a more vertical levator plate. The perineal body is attenuated, which favors formation of a rectocele.
Pelvic floor laxity also favors rectal mucosal prolapse. (From Loder PB, Phillips RKS. Rectocele and pelvic floor weakness. In: Kamm
MA, Lennard-Jones JE, editors. Constipation. Peterfield U.K.: Wrightson Biomedical; 1994. p 281.)

strains during defecation, and rectal expulsion is difficult. The

anorectal angle is widened as a result of pelvic floor weakness,
and the rectum is more vertical than normal. The perineal
body is weak (facilitating rectocele formation), and lax mus-
cular support favors intrarectal mucosal intussusception or
rectal prolapse. The pelvic floor may not provide the resistance
necessary for extrusion of solid stool through the anal canal.
A common reason for pelvic floor weakness is trauma or
stretching during parturition. In some cases, repeated and
prolonged defecation appears to be a damaging factor. Symp-
toms include constipation, incomplete rectal evacuation,
excessive straining, and the need for digital rectal evacua-
tion.112 Electrophysiologic studies show partial denervation of
the striated muscle and evidence of pudendal nerve damage.
Histologic examination of operative specimens of the pelvic
floor muscles confirms loss of muscle fibers.
Diminished Rectal Sensation
The urge to defecate depends in part on tension within the
rectal wall (determined by the tone of the circular muscle
of the rectal wall), rate and volume of rectal distention, and
size of the rectum. Some patients with constipation appear
to feel pain normally as the rectum is distended to the maximal
tolerable volume, but with intermediate volumes they fail
to experience an urge to defecate.113 In a study of women
with severe idiopathic constipation, a higher-than-normal
electrical stimulation current applied to the rectal mucosa was
required to elicit pain, suggesting a possible rectal sensory
neuropathy.114
Rectal hyposensitivity (RH) is defined as insensitivity of the
rectum to balloon distention on anorectal physiologic investi-
gation, although the pathophysiology of RH is not entirely
clear. Constipation is the most common presenting symptom
of RH. In an investigation of 261 patients with RH, 38% had a
history of pelvic surgery, 22% had a history of anal surgery,
and 13% had a history of spinal trauma.115
Rectal Prolapse and Solitary Rectal Ulcer Syndrome
Full-thickness rectal prolapse and solitary rectal ulcer syn-
drome are part of a spectrum of defects that arise from pelvic
floor weakening. Some patients complain of many fruitless
visits to the bathroom, with prolonged straining in response
to a constant desire to defecate. The patient has a sense of
incomplete evacuation and may spend an hour or more daily
on the toilet. Infrequent passage of small hard stools is
common, as are other features of a functional bowel disorder,
such as abdominal pain and distention.
Rectal prolapse refers to complete protrusion of the rectum
through the anus (see Chapter 129). Occult (asymptomatic)
rectal prolapse has been found in 33% of patients with clini-
cally recognized rectoceles and defecatory dysfunction116 and
can be easily detected on physical examination by asking the
patient to strain as if to defecate. A laparoscopic rectopexy—in
which the prolapsed rectum is raised and secured with sutures
to the adjacent fascia—is the recommended treatment.117
Solitary rectal ulcer syndrome is a rare disorder characterized
by erythema or ulceration, generally of the anterior rectal
wall, as a result of chronic straining (see Chapter 119). Mucus
and blood may be passed when the patient strains during
defecation.118,119 Endoscopic findings may include erythema,
hyperemia, mucosal ulceration, and polypoid lesions. The
syndrome’s heterogeneous findings and misleading name (an
ulcer need not be present) can lead to misdiagnosis. In a study
of 98 patients with solitary rectal ulcer syndrome, 26% were
initially diagnosed incorrectly. In patients with a rectal ulcer
or mucosal hyperemia, the most common misdiagnoses were
Crohn’s disease and ulcerative colitis. In those with a polypoid
lesion, the most common misdiagnosis was a neoplastic
polyp.120 Histology of full-thickness specimens of the lesion
reveals extension of the muscularis mucosa between crypts
and disorganization of the muscularis propria. Defecography,
transrectal US and anorectal manometry are helpful in the
diagnosis.
278   Section III  Symptoms, Signs, and Biopsychosocial Issues
Varying degrees of rectal prolapse exist in association with
solitary rectal ulcer syndrome. Rectal prolapse and paradoxi-
cal contraction of the puborectalis muscle can lead to rectal
trauma secondary to the high pressures generated within the
rectum. In addition, rectal mucosal blood flow is reduced.121
Medical treatment may be difficult. The patient should be
advised to resist the urge to strain. Bulk laxatives and dietary
fiber may be of some benefit.122 Surgery may be required;
rectopexy is performed most commonly. Following surgery
for solitary rectal ulcer syndrome with rectal prolapse, 55% to
60% of patients report long-term satisfaction, although a colos-
tomy is eventually required in about a third of patients.123
Repair of a rectal prolapse may aggravate constipation. Bio-
feedback appears to be a promising mode of therapy for
patients with solitary rectal ulcer syndrome.124
Systemic Disorders
Hypothyroidism
Constipation is the most common GI complaint in patients
with hypothyroidism. The pathologic effects are due to altera-
tion of intestinal motor function and possible infiltration of the
intestine by myxedematous tissue. The basic electrical rhythm
that generates peristaltic waves in the duodenum decreases in
hypothyroidism, and small bowel transit time is increased.125
Myxedema megacolon is rare but can result from myxedema-
tous infiltration of the muscle layers of the colon. Symptoms
include abdominal pain, flatulence, and constipation (see
Chapter 36).126
Diabetes Mellitus
The mean colonic transit time is longer in diabetics than in
healthy controls. In 1 study, mean total colonic transit time in
28 diabetic patients (34.9 ± 29.6 hours; mean ± SD) was signifi-
cantly longer than that in 28 healthy subjects (20.4 ± 15.6 hours;
P < 0.05).127 Among the 28 diabetic patients, 9 of 28 (32%) met
the Rome II criteria for constipation, and 14 of 28 (50%) had
cardiovascular autonomic neuropathy. Mean colonic transit
times in diabetic patients with and without cardiovascular
autonomic neuropathy were similar. By contrast, a previous
study reported that asymptomatic diabetic patients with car-
diovascular autonomic neuropathy had significantly longer
whole-gut transit times (although still within the range of
normal) than a control group without neuropathy.128 In another
study, diabetic patients with mild constipation demonstrated
delayed colonic myoelectrical and motor responses after
ingestion of a standard meal, whereas diabetics with severe
constipation had no increases in these responses after food.
Neostigmine increased colonic motor activity in all diabetic
patients, suggesting the defect was neural rather than muscu-
lar (see Chapter 36).129
Hypercalcemia
Constipation is a common symptom of hypercalcemia result-
ing from hyperparathyroidism.130 It may also be a manifesta-
tion of hypercalcemia due to other conditions (e.g., sarcoidosis,
malignancy involving bone [see Chapter 36]).
Nervous System Disease
Loss of Conscious Control
Cerebral disability or dementia with a decrease in or complete
loss of bodily perception can lead to defecatory failure, pos-
sibly because of inattention.
Parkinson’s Disease
Constipation frequently occurs in patients with Parkinson’s
disease (PD). In a study of 12 patients with PD compared with
normal controls, slow colonic transit, decreased phasic rectal
contractions, weak abdominal wall muscle contraction, and
paradoxical anal sphincter contraction on defecation were
all features in patients with PD and frequent constipation.131
Loss of dopamine-containing neurons in the central nervous
system (CNS) is the underlying defect in PD; a defect in dopa-
minergic neurons in the enteric nervous system may also
be present. Histopathologic studies of the myenteric plexuses
of the ascending colon in 11 patients with PD and constipation
revealed that in 9 patients the number of dopamine-positive
neurons was one tenth or less the number in control subjects.
Dopamine concentrations in the muscularis externa were
significantly lower in patients with PD than in controls
(P < 0.01).132
Another possible contributor to constipation is the inabil-
ity of some patients with PD to relax the striated muscles
of the pelvic floor on defecation. This finding is a local mani-
festation of the extrapyramidal motor disorder that affects
skeletal muscle. Preliminary observations suggest that injec-
tion of botulinum toxin into the puborectalis muscle is a
potential therapy for this type of outlet dysfunction (see
Chapter 36).133,134
Multiple Sclerosis
Constipation is common among patients with multiple sclero-
sis (MS). In an unselected group of 280 patients with MS, the
frequency of constipation (defined as diminished bowel fre-
quency, digitation to facilitate defecation, or use of laxatives)
was 43%. Almost 25% of the subjects passed fewer than 3
stools/week, and 18% used a laxative more than once a week.
Constipation correlated with the duration of MS but preceded
the diagnosis of MS in 45%. Constipation did not correlate
with immobility or use of medications.135 In another question-
naire study of 221 patients with MS, the frequency of constipa-
tion was as high as 54%.136 Constipation in patients with
MS can be multifactorial and related to a reduction in post-
prandial colonic motor activity, limited physical activity, and
medications.
Patients with advanced MS and constipation have evi-
dence of a visceral neuropathy. In a group of patients with
advanced MS and severe constipation, all had evidence of
disease in the lumbosacral spinal cord and decreased compli-
ance of the colon. The usual increase in colonic motor activity
after meals is absent. Among less severely affected patients,
slow colonic transit and manometric evidence of pelvic
floor muscular and anal sphincter dysfunction have been
demonstrated. Patients may have fecal incontinence.137,138
Therapy with biofeedback has been reported to relieve consti-
pation and fecal incontinence, although in a study of 13
patients with MS with either constipation or incontinence,
only 38% improved with biofeedback (see Chapters 18
and 36).139
Spinal Cord Lesions
Lesions Above the Sacral Segments
Spinal cord lesions or injury above the sacral segments lead to
an upper motor neuron disorder with severe constipation. The
resulting delay in colonic transit primarily affects the rectosig-
moid colon.140,141 In a study of patients with severe thoracic
spinal cord injury, colonic compliance was abnormal, with a
rapid rise in colonic pressure on instillation of relatively small

volumes of fluid. Motor activity after meals did not increase,
but the colonic response to neostigmine was normal, thereby
excluding myopathy.
Studies of anorectal function in patients with severe trau-
matic spinal cord injury have shown that rectal sensation to
distention is abolished, although a dull pelvic sensation is
experienced by some patients at maximum levels of rectal
balloon distention. Anal relaxation on rectal distention is
exaggerated and occurs at a lower balloon volume than in
normal subjects. Distention of the rectum leads to a linear
increase in rectal pressure, without the plateau at intermedi-
ate values seen in normal subjects, and ends in high-pressure
rectal contractions after a relatively small volume (100 mL)
has been instilled. As expected, the rectal pressure generated
by straining is lower in patients than in control subjects and
is less with higher than lower spinal cord lesions. Patients
demonstrate a loss of conscious external anal sphincter
control, and the sphincter does not relax on straining, sug-
gesting that in normal subjects, descending inhibitory path-
ways are present.142 These findings explain why some patients
with spinal cord lesions experience not only constipation but
also sudden uncontrollable rectal expulsion with inconti-
nence. Other patients cannot empty the rectum in response
to laxatives or enemas, possibly because of failure of the
external anal sphincter to relax, and may require manual
evacuation.
Electrical stimulation of anterior sacral nerve roots S2, S3,
and S4 via electrodes implanted for urinary control in paraple-
gic patients leads to a rise in pressure within the sigmoid colon
and rectum and contraction of the external anal sphincter.
Contraction of the rectum and relaxation of the internal anal
sphincter persist for a short time after the stimulus ceases. By
appropriate adjustment of the stimulus, it was possible for 5
of 12 paraplegic patients to evacuate feces completely and for
most of the others to increase the frequency of defecation and
reduce the time spent emptying the rectum.143 In another
series, left-sided colonic transit time decreased with regular
sacral nerve stimulation.144
Lesions of the Sacral Cord, Conus Medullaris, Cauda Equina,
and Nervi Erigentes (S2 to S4)
Neural integration of anal sphincter control and rectosigmoid
propulsion occurs in the sacral segments of the spinal cord.
The motor neurons that supply the striated sphincter muscles
are grouped in Onuf’s nucleus at the level of S2. There is
evidence that efferent parasympathetic nerves that arise in
the sacral segments enter the colon at the region of the recto-
sigmoid junction and extend distally in the intermuscular
plane to reach the level of the internal anal sphincter
and proximally to the midcolon via the ascending colonic
nerves, which retain the structure of peripheral nerves (see
Chapter 100).145
Damage to sacral segments of the spinal cord or to efferent
nerves leads to severe constipation. Fluoroscopic studies show
a loss of progression of contractions in the left colon. When
the colon is filled with fluid, the intraluminal pressure gener-
ated is lower than normal, in contrast to the situation after
higher lesions of the spinal cord. The distal colon and rectum
may dilate, and feces may accumulate in the distal colon.
Spasticity of the anal canal can occur. Loss of sensation of the
perineal skin may extend to the anal canal, and rectal sensa-
tion may be diminished. Rectal wall tone depends on the level
of the spinal lesion. In a study of 25 patients with spinal cord
injury, rectal tone was significantly higher than normal in
patients with acute and chronic supraconal lesions, but signifi-
cantly lower than normal in patients with acute and chronic
conal or cauda equina lesions.146
Chapter 19  Constipation   279
Structural Disorders of the Colon, Rectum,
and Anus
Obstruction
Anal atresia in infancy, anal stenosis later in life, or obstruction
of the colon may manifest as constipation. Obstruction of the
small intestine generally manifests as abdominal pain and
distention, but constipation and inability to pass flatus may
also be features (see Chapters 98 and 123).
Disorders of Smooth Muscle
Myopathy Affecting Colonic Muscle
Congenital or acquired myopathy of the colon usually mani-
fests as pseudo-obstruction. The colon is hypotonic and inert
(see Chapter 124).
Hereditary Internal Anal Sphincter Myopathy
Hereditary internal anal sphincter myopathy is a rare condi-
tion characterized by constipation with difficulty in rectal
expulsion and episodes of severe proctalgia fugax, defined as
the sudden onset of brief episodes of pain in the anorectal
region.147-149 Three affected families have been reported. The
mode of inheritance appears to be autosomal dominant with
incomplete penetrance. In symptomatic persons, the internal
anal sphincter muscle is thickened, and resting anal pressure
is greatly increased. In 2 patients, treatment with a calcium
channel blocker improved pain but had no effect on constipa-
tion. In another family, 2 patients were treated by internal anal
sphincter strip myectomy; 1 showed marked improvement
and 1 had improvement in constipation but only slight
improvement in pain. Examination of the muscle strips
showed myopathic changes with polyglucosan bodies (glucose
polymers) in the smooth muscle fibers and increased endo-
mysial fibrosis.
Progressive Systemic Sclerosis
Progressive systemic sclerosis (scleroderma) may lead to con-
stipation. In patients with progressive systemic sclerosis and
constipation, 9 of 10 had no increase in colonic motor activity
after ingestion of a 1000-kcal meal. Histologic examination of
colonic specimens from these subjects revealed smooth muscle
atrophy of the colonic wall (see Chapter 36).150
Muscular Dystrophies
Muscular dystrophies are usually regarded as disorders of
striated muscle, but visceral smooth muscle may also be
abnormal. In myotonic muscular dystrophy, a condition in
which skeletal muscle fails to relax normally, megacolon may
be found, and abnormal function of the anal sphincter is
demonstrable.151 Cases associated with intestinal pseudo-
obstruction have been reported (see Chapter 124).152
Disorders of Enteric Nerves
Congenital Aganglionosis or Hypoganglionosis
Congenital absence or reduction in the number of ganglia in
the colon leads to functional colonic obstruction with proximal
dilatation, as seen in Hirschsprung’s disease and related con-
ditions (see Chapter 98). In Hirschsprung’s disease, ganglion
cells in the distal colon are absent because of an arrest in
caudal migration of neural crest cells in the intestine during
280   Section III  Symptoms, Signs, and Biopsychosocial Issues
embryonic development. Although most patients present
during early childhood, often with delayed passage of meco-
nium, some patients with a relatively short segment of
involved colon present later in life.153 Typically, the colon
narrows at the area that lacks ganglion cells, and the bowel
proximal to the narrowing is usually dilated. Two genetic
defects have been identified in patients with Hirschsprung’s
disease—a mutation in the RET (rearranged during transfec-
tion) proto-oncogene, which is involved in the development
of neural crest cells, and a mutation in the gene that encodes
the endothelin B receptor, which affects intracellular calcium
levels.154,155
Hypoganglionosis is reported when small, sparse myen-
teric ganglia are seen. Neuronal counts can be made on full-
thickness tissue specimens and compared with published
reference values obtained from autopsy material. Because of
variations in the normal density of neurons, establishing the
diagnosis of hypoganglionosis is not easy.156 Quantitative
declines in the number of neurons in the enteric nervous
system are also seen in patients with severe slow-transit con-
stipation and characterized morphologically as oligoneuronal
hypoganglionosis.157
Congenital Hyperganglionosis (Intestinal Neuronal Dysplasia)
Congenital hyperganglionosis, or intestinal neuronal dyspla-
sia, is a developmental defect characterized by hyperplasia of
the submucosal nerve plexus. Clinical manifestations of the
disease are similar to those seen in Hirschsprung’s disease
and include young age of onset and symptoms of intestinal
obstruction (see Chapter 98). In contrast to functional consti-
pation, affected children do not have symptoms of soiling or
evidence of a fecaloma.158 A multicenter study of interob-
server variation in histologic interpretation of findings in
children with constipation caused by abnormalities of the
enteric nervous system showed complete agreement in the
diagnosis of Hirschsprung’s disease but accord in only 14%
of children with colonic motility disorders other than agangli-
onosis. Some of the clinical features and histologic changes
previously associated with congenital hyperganglionosis
may evolve to normal as children age.156 A diagnosis of
congenital hyperganglionosis can be made on the basis of
hyperganglionosis of the submucous plexus with giant
ganglia and at least 1 of the following features in rectal biopsy
specimens: (1) ectopic ganglia, (2) increased acetylcholinester-
ase (AChE) activity in the lamina propria, and (3) increased
AChE nerve fibers around the submucosal blood vessels.
Most patients with congenital hyperganglionosis respond to
conservative treatment, including laxatives. Internal anal
sphincter myectomy may be performed if conservative man-
agement fails.159
Acquired Neuropathies
Chagas’ disease, which results from infection with Trypano-
soma cruzi, is the only known infectious neuropathy. The
reason for neuronal degeneration in this disorder is unclear
but may have an immune basis.160 Patients with Chagas’
disease present with progressively worsening symptoms of
constipation and abdominal distention resulting from a seg-
mental megacolon that may be complicated by sigmoid vol-
vulus (see Chapter 113).
Paraneoplastic visceral neuropathy may be associated
with malignant tumors outside the GI tract, particularly small
cell carcinoma of the lung and carcinoid tumors. Pathologic
examination of the affected intestine reveals neuronal degen-
eration or myenteric plexus inflammation.161 An antibody
against a component of myenteric neurons has been identified
in some patients with this disorder (see Chapter 124).162 Dis-
ruption of the ICCs has been associated with a case of small
cell lung carcinoma–related paraneoplastic colonic motility
disorder.163
Neuropathies of Unknown Cause
Severe acute neuropathies that present mainly with obstruc-
tive symptoms and not principally with constipation have
been described. As noted earlier, neuropathic features affect-
ing the colon may occur in some patients with severe idio-
pathic constipation.
Medications
Constipation may be a side effect of a drug or preparation
taken long term. Drugs commonly implicated are listed in Box
19-3. Common offenders include opioids used for chronic
pain, anticholinergic agents (including antispasmodics),
calcium supplements, some tricyclic antidepressants, pheno-
thiazines used as long-term neuroleptics, and antimuscarinic
drugs used for parkinsonism.
Psychological Disorders
Constipation may be a symptom of a psychiatric disorder or
a side effect of its treatment (see Chapter 22). Healthy men
who are socially outgoing, energetic, and optimistic—and not
anxious—and who described themselves in more favorable
terms than others have heavier stools than men without these
personality characteristics.164 Psychological factors associated
with a prolonged colonic transit time in constipated patients
include a highly depressed mood state and frequent control of
anger.165 In 1 study, women with constipation had higher
somatization and anxiety scores than healthy controls, and the
psychological scores correlated inversely with rectal mucosal
blood flow (used as an index of innervation of the distal
colon).166 In a study that assessed psychological characteristics
of older persons with constipation, a delayed colonic transit
time was related significantly to symptoms of somatization,
obsessive-compulsiveness, depression, and anxiety.58 In a
study of 28 consecutive female patients undergoing psycho-
logical assessment for intractable constipation, 60% had evi-
dence of a current affective disorder. One third reported
distorted attitudes toward food. Patients with slow-transit
constipation reported more psychosocial distress on rating
scales than those with normal-transit constipation.167
Depression
For some patients, constipation can be a somatic manifesta-
tion of an affective disorder. In a study of patients with
depression, 27% said that constipation developed or became
worse at the onset of the depression.168 Constipation can
occur in the absence of other typical features of severe depres-
sion, such as anorexia or psychomotor retardation with phys-
ical inactivity. Psychological factors are likely to influence
intestinal function via autonomic efferent neural pathways.166
In an analysis of 4 million discharge records of U.S. military
veterans, major depression was associated with constipation,
and schizophrenia was associated with both constipation and
megacolon.169
Eating Disorders
Patients with anorexia nervosa or bulimia often complain of
constipation, and a prolonged whole-gut transit time has been
demonstrated in patients with these disorders.170 Colonic

transit time returns to normal in most patients with anorexia
nervosa once they are consuming a balanced diet and gaining
weight for at least 3 weeks.171 Pelvic floor dysfunction is found
in some patients with an eating disorder and does not improve
with weight gain and a balanced diet.172
Anorexia nervosa should be considered as a possible diag-
nosis in young underweight women who present with consti-
pation. Patients with an eating disorder often resort to regular
use of laxatives as treatment for constipation or to facilitate
weight loss or relieve the presumed consequences of binge
eating. Treatment of such patients is directed at the underlying
eating disorder (see Chapter 9).
Denied Bowel Movements
Patients may deny or fail to report defecation when solid
inert markers have been demonstrated to disappear from
the abdomen by radiologic examination, proving that elimina-
tion has occurred (see later). Such patients need skilled
psychiatric help.
CLINICAL ASSESSMENT
History
It is important to determine exactly what the patient means
when he or she reports constipation. A detailed history that
includes duration of symptoms, frequency of bowel move-
ments, and associated symptoms like abdominal discomfort
and distention should be obtained. The history should include
an assessment of stool consistency, stool size, and degree of
straining during defecation. The presence of warning symp-
toms or signs—unintentional weight loss, rectal bleeding,
change in the caliber of stool, severe abdominal pain, family
history of colon cancer—should be elicited. A long duration of
symptoms that have been refractory to conservative measures
is suggestive of a functional colorectal disorder. By contrast,
the new onset of constipation may indicate a structural
disease.
A dietary history should be obtained. The amount of daily
fiber and fluid consumed should be assessed. Many patients
tend to skip breakfast,173 and this practice may exacerbate
constipation, because the postprandial increase in colonic
motility is greatest after breakfast.174,175 Although caffeinated
coffee (150 mg of caffeine) stimulates colonic motility, inges-
tion of a meal has a greater effect.176
A patient’s past medical history must be reviewed. Obstet-
ric and surgical histories are particularly important. Neuro-
logic disorders may also explain some cases of constipation. A
carefully taken drug history, including use of over-the-counter
laxatives and herbal medications and their frequency of intake,
is important.
A detailed social history may provide useful information
as to why the patient has sought help for constipation at this
time; potentially relevant behavioral background information
may also be obtained. In patients with IBS, the frequency of a
history of sexual abuse is increased as compared with healthy
controls.177 In a survey of 120 patients with dyssynergia, 22%
reported a history of sexual abuse, and 32% reported a history
of physical abuse. Bowel dysfunction adversely affected sexual
life in 56% and social life in 76% of patients.178 The physician
should be alert to manifestations of depression, such as insom-
nia, lack of energy, loss of interest in life, loss of confidence,
and a sense of hopelessness. A history of physical or sexual
abuse may not emerge during the initial visit, but if the physi-
cian evinces no surprise at whatever is revealed, indicates that
distressing events are common in patients with intestinal
Chapter 19  Constipation   281
symptoms, and maintains a sensitive, encouraging attitude,
the full story often gradually emerges during subsequent
visits, provided there is privacy, confidentiality, and adequate
time (see Chapter 22).
Physical Examination
The patient’s general appearance or voice may point to a clini-
cal diagnosis of hypothyroidism, parkinsonism, or depression.
The general physical examination should exclude major CNS
disorders, especially spinal lesions. If spinal disease is sus-
pected, the sacral dermatomes should be examined for loss of
sensation. The abdomen should be examined for distention,
hard feces in a palpable colon, or an inflammatory or neoplas-
tic mass. If the abdomen appears distended, a hand should be
passed under the lumbar spine while the patient is lying
supine to exclude anterior arching of the lumbar spine as a
cause of postural bloating (see Chapter 17).
The rectal examination is paramount in evaluating a
patient with constipation. Placing the patient in the left lateral
position is most convenient for performing a thorough rectal
examination. Painful perianal conditions and rectal mucosal
disease should be excluded, and defecatory function should
be evaluated. The perineum should be observed both at rest
and after the patient strains as if to have a bowel movement.
Normally, the perineum descends between 1 and 4 cm during
straining. With the patient in the left lateral position, descent
of the perineum below the plane of the ischial tuberosities (i.e.,
>4 cm) usually suggests excessive perineal descent. A lack of
descent may indicate the inability to relax the pelvic floor
muscles during defecation, whereas excessive perineal descent
may indicate descending perineum syndrome. Patients with
descending perineum syndrome strain excessively and achieve
only incomplete evacuation because of lack of straightening
of the anorectal angle. Eventually, excessive descent of the
perineum may result in injury to the sacral nerves from
stretching, a reduction in rectal sensation, and ultimately
incontinence due to denervation.112 Rectal prolapse may be
detected when the patient is asked to strain.
The perianal area should be examined for scars, fistulas,
fissures, and external hemorrhoids. A digital rectal examina-
tion should be performed to evaluate the patient for the pres-
ence of a fecal impaction, anal stricture, or rectal mass. A
patulous anal sphincter may suggest prior trauma to the anal
sphincter or a neurologic disorder that impairs sphincter func-
tion. Other important functions that should be assessed during
the digital examination are summarized in Box 19-5. Specifi-
cally, inability to insert the examining finger into the anal canal
may suggest an elevated anal sphincter pressure, and tender-
ness on palpation of the pelvic floor as it traverses the poste-
rior aspect of the rectum may suggest pelvic floor spasm. The
degree of descent of the perineum during attempts to strain
and expel the examining finger provides another way of
assessing the degree of perineal descent. A thorough history
and physical examination can exclude most secondary causes
of constipation (see Box 19-3).
DIAGNOSTIC TESTS
Further diagnostic testing is unnecessary for most patients
who complain of mild symptoms, especially adolescents,
young adults, and those without alarm features. Investiga-
tions may be indicated for 1 of 2 reasons: (1) to exclude a
systemic illness or structural disorder of the GI tract as a cause
of constipation or (2) to elucidate the underlying pathophysi-
ologic process when symptoms are unresponsive to simple
treatment.
282   Section III  Symptoms, Signs, and Biopsychosocial Issues

BOX 19-5 Clinical Clues to an Evacuation Disorder

History
Prolonged straining to expel stool
Assumption of unusual postures on the toilet to facilitate stool
expulsion
Support of the perineum, digitation of rectum, or application of
pressure to the posterior vaginal wall to facilitate rectal
emptying
Inability to expel enema fluid
Constipation after subtotal colectomy for constipation
Rectal Examination (with patient in left lateral position)
Inspection
Anus “pulled” forward during attempts to simulate strain during
defecation
Anal verge descends <1 cm or >4 cm (or beyond ischial
tuberosities) during attempts to simulate straining at
defecation
The perineum balloons down during straining; rectal mucosa
partially prolapses through anal canal
Palpation
High anal sphincter tone at rest precludes easy entry of the
examining finger (in absence of a painful perianal condition
[e.g., anal fissure])
Anal sphincter pressure during voluntary squeeze only minimally
higher than anal pressure at rest
The perineum and examining finger descend <1 cm or >4 cm
during simulated straining at defecation
The puborectalis muscle is tender to palpation through the FIGURE 19-5. Abdominal film from a colonic transit study. This
rectal wall posteriorly, or palpation reproduces pain constipated patient had ingested 20 inert ring markers 120 hours
Palpable mucosal prolapse during straining previously and 20 cube-shaped markers 72 hours previously.
“Defect” in anterior wall of the rectum, suggestive of Most markers are still present, indicating slow whole-gut transit.
rectocele
Anorectal Manometry and Balloon Expulsion
(with patient in left lateral position) only 5.5% had a polyp, and no cancers were found.180 A colo-
Elevated resting anal sphincter pressure
noscopy is recommended only when there has been a recent
Delay in balloon expulsion test (normal values for women < 50
years: 4-75 seconds; normal values for women ≥ 50 years of
change in bowel habits, blood in the stool, or other alarm
age: 3-15 seconds199 symptoms (e.g., weight loss, fever).181 All adults older than age
50 should undergo screening for colorectal cancer, as widely
recommended.182

Tests for Systemic Disease
Determination of the hemoglobin level, erythrocyte sedimen-
tation rate, and biochemical screening test levels (e.g., thyroid
function, serum calcium, glucose, and other appropriate
investigations) are indicated if the clinical picture suggests
that symptoms may be due to an inflammatory, neoplastic,
metabolic, or other systemic disorder.
Tests for Structural Disease
Imaging of the colon by CT, MRI, or barium enema study
reveals the width and length of the colon and may be indi-
cated to exclude an obstructing lesion severe enough to cause
constipation. When fecal impaction is present, a limited enema
study with a water-soluble contrast agent outlines the colon
and fecal mass without aggravating the condition. Imaging of
the small bowel is indicated only if obstruction or pseudo-
obstruction involving the small bowel is suspected (see Chap-
ters 123 and 124). Endoscopy allows direct visualization of the
colonic mucosa. The yield of colonoscopy in the absence of
“alarm” symptoms in patients with chronic constipation is
low and comparable to that for asymptomatic patients who
undergo colonoscopy for colon cancer screening.179 Among
786 patients who underwent colonoscopy for constipation,
Physiologic Measurements
Physiologic testing is reserved for patients with refractory
symptoms. Testing can be performed to measure colonic
transit time, evaluate pelvic floor functioning during defeca-
tion, and exclude anatomic abnormalities that could cause
constipation.
Measurement of Colonic Transit Time
Studies that measure colonic transit time are important for
confirming and quantifying a patient’s complaint of constipa-
tion and identifying slow transit and regional delay. The
American and European Neurogastroenterology and Motility
Societies recommend 3 methods for assessing colonic transit
time: radiopaque markers, wireless motility capsule, and
scintigraphy.183
Radiopaque Markers
Radiopaque marker testing is used to distinguish normal from
slow colonic transit, assess segmental transit times, and evalu-
ate the response to new treatments.183 Colonic transit time is
measured by performing abdominal radiography at predeter-
mined times after the patient ingests plastic beads or rings,
and counting the number of retained markers (Fig. 19-5).
 Chapter 19  Constipation   283

Before the study, patients should be maintained on a high-

fiber diet and should avoid laxatives, enemas, or medications
that may affect bowel function. Because the markers are
eliminated only with defecation, the process of measuring
colonic transit is discontinuous, and the result of a transit
measurement should be regarded with caution, taking recent
defecation into account. If the markers are retained exclusively
in the sigmoid colon and rectum, the patient may have a def-
ecatory disorder. The presence of markers throughout the
colon, however, does not exclude the possibility of a defeca-
tory disorder, because delayed colonic transit can result from
a defecatory disorder. Therefore, anorectal physiological
testing should be considered in appropriate patients prior to
performing radiopaque marker testing (see later).183 Measure-
ments of transit through different segments of the colon are of
doubtful value in planning treatment, except for megarectum,
in which all the markers move rapidly to the rectum and are
retained there.
In nonconstipated subjects, the mean colonic transit
time using radiopaque marker testing is 30 to 40 hours, with
an upper limit of normal of 72 hours (see earlier).184 Women
often have longer maximal colonic transit times than men
(70 to 106 hours vs. 50 hours).
Wireless Motility Capsule
The wireless recording capsule is a single-use capsule that
assesses colonic transit without radiation exposure. It is used
to distinguish normal from slow colonic transit and can also
be used in patients with a suspected motility disorder of the
upper GI tract, because it measures gastric emptying, small
bowel transit, and colonic transit times (Fig. 19-6). The wire-
less motility capsule is ingested following a standardized
meal and 50 mL of water. The capsule continuously sends
temperature, pH, and pressure measurements to a data
receiver as it moves along the GI tract. Patients wear a data
receiver on their waists for 5 days, or until the capsule is
passed, and keep a log of daily activities like meals, sleep, and
bowel movements.
Most studies that have compared the wireless motility
capsule with conventional radiopaque marker testing have
found concordance between the 2 methods (wireless motility
capsule specificity of 0.95 and sensitivity of 0.46 for identifying
an abnormal transit time, compared with radiopaque marker
testing specificity of 0.95 and sensitivity of 0.40).185-187 In 1
retrospective study, however, the wireless motility capsule
showed only 86% positive test agreement and 43% negative

250 Gastric Region SB Colon 10 104

225 9 100.4

205 96.8
8

185
93.2
7
165
89.6
145 6
Pressure mmHg

86

Temperature F
125

pH
5
82.4
105
4
85 78.8

3
65 75.2

45 2
71.6

25
1 68

5
−5 0 64.4
0:12 12:00 24:00 36:00 48:00 60:00 72:00 84:00 93:32
Time (hr:min)

FIGURE 19-6. Tracing from a wireless motility capsule study in a constipated patient. After the wireless motility capsule is swallowed,
temperature (blue line), pressure (red line), and pH (green line) are recorded. Gastric emptying time is determined by a rise in pH,
signifying that the capsule has passed into the duodenum. A drop in pH (at ≈ 24 hours) occurs when the capsule passes into the
colon. The time when the capsule is passed through the rectum and into the toilet is determined by a drop in temperature. In this
patient, colonic transit is prolonged. SB, small bowel.
284   Section III  Symptoms, Signs, and Biopsychosocial Issues
test agreement with radiopaque marker testing.188 The wire-
less motility capsule has also been found to be comparable
to both gastric emptying scintigraphy and whole-gut
scintigraphy.189,190
Normal colonic transit time using the wireless motility
capsule is 10 to 59 hours, with delayed colonic transit consid-
ered greater than 44 hours in men and 59 hours in women.186
The difference in colonic transit times between radiopaque
marker testing and a wireless motility capsule is not unex-
pected, given the different methods of quantifying colonic
transit time and the larger size of the wireless motility capsule
compared with the smaller plastic beads used in radiopaque
marker testing.186,187 Wireless motility capsule testing is par-
ticularly useful in patients being considered for colectomy as
treatment for severe constipation when assessment of upper
GI transit is recommended (see later).191 Although the wireless
motility capsule is well tolerated and permits ambulatory
testing, device failure is reported in some 3% of cases,183 and
its use is not recommended in patients with pacemakers or
defibrillators, swallowing disorders, suspected strictures or
fistulas, or a high risk for strictures.
Colonic Transit Scintigraphy
Colonic transit scintigraphy is used to measure whole-gut
and regional colonic transit in patients with diffuse disorders
involving the stomach or small intestine or with a suspected
colonic motility disorder. Transit time is measured by captur-
ing serial abdominal images using a gamma camera at speci-
fied times after ingestion of a labeled meal (111In-DTPA-labeled
water with standard 99mTc egg sandwich192 or 111In-labeled
activated charcoal particles contained in a capsule193). Anterior
and posterior images of the colon are obtained at specified
times over 2 to 3 days following meal ingestion. Using
111
In-DTPA-labeled water with the standard 99mTc egg sand-
wich allows gastric, small bowel, and colonic transit times to
be measured in the same study.192 The capsule containing
111
In-labeled activated charcoal particles, however, does not
dissolve until it reaches the distal ileum, where it releases the
labeled particles into the colon, permitting measurement of
only colonic transit.193 Results are reported as ascending colon
emptying, indicating the time for 50% emptying, or overall
colonic transit expressed as the geometric center (weighted
average of the radioactivity distribution within the colon
and stool).183
Using scintigraphy, the mean colonic transit, expressed
as the geometric center, is 2.7 ± 1.05 at 24 hours. A 24-hour
colonic transit time less than 1.7 is considered slow transit.193
A low geometric center is considered slow transit because
the majority of the radioactivity is in the proximal colon,
whereas a high geometric center is considered accelerated
transit because the majority of the radioactivity has moved
to the left side of the colon or into the expelled stool. Colonic
transit scintigraphy has been shown to be comparable
with radiopaque marker testing, except in the descending
colon,194 but is available in only a limited number of special-
ized centers.
Tests to Assess the Physiology of Defecation
Clinical tests to assess for a defecatory disorder include defe-
cography, balloon expulsion test, anorectal manometry, and
electromyography (EMG). To diagnose dyssynergic defeca-
tion, the Rome criteria require a combination of 2 of the fol-
lowing 3 abnormal tests of the pelvic floor on attempted
defecation: (1) impaired evacuation on balloon expulsion or
defecography, (2) inappropriate contraction of the pelvic floor
muscles on manometry, imaging, or electromyography, and (3)
inadequate propulsive forces as assessed by manometry
or imaging.102
A meta-analysis of 79 studies in patients with chronic con-
stipation found that dyssynergic defecation is common in
patients with chronic constipation. The pooled frequency of
abnormal findings differed depending on the test: anorectal
manometry 48%, balloon expulsion 43% (by any criteria),
defecography 15% (absent opening of the anorectal angle) and
37% (excessive perineal descent), and EMG 44% (increased
activity of the puborectalis muscles).195
Defecography
Defecography evaluates the rate and completeness of rectal
emptying, anorectal angle, and amount of perineal descent
and identifies structural abnormalities (e.g., large rectocele,
internal mucosal prolapse, intussusception). Thickened
barium is instilled into the rectum, and films or videos are
taken during fluoroscopy with the patient sitting on a radio-
lucent commode while resting, deferring defecation, and
straining to defecate. Importantly, identified anatomic abnor-
malities are not always functionally relevant. For example, a
rectocele is only relevant if it fills preferentially (i.e., instead of
the rectal ampulla) and fails to empty after simulated defeca-
tion. The limitations of defecography include variability
among radiologists in interpreting studies, inhibition of
normal rectal emptying because of patient embarrassment,
and differences in texture between barium paste and stool.
Magnetic resonance defecography may offer advantages over
standard barium defecography, such as lack of radiation expo-
sure and increased detection of abnormalities during the def-
ecation phase,196,197 but is not yet widely available and rarely
can be performed with the patient in a sitting position.
Balloon Expulsion Test
The balloon expulsion test can suggest a defecatory disorder
in a patient with no or delayed evacuation of a 50-mL water-
filled balloon from the rectum while sitting on a commode. In
a study of 359 patients with constipation, the balloon expul-
sion test was abnormal in 21 of 24 patients with pelvic floor
dyssynergia (as determined by manometry and defecogra-
phy). By contrast, an abnormal balloon expulsion test was also
found in 12 of 106 patients who did not have pelvic floor dys-
synergia.198 Therefore, the balloon expulsion test is often used
in conjunction with anorectal manometry. In healthy women,
balloon expulsion time decreases with age; normal values
range from 4 to 75 seconds in those younger than age 50 and
from 3 to 15 seconds in those 50 or older.199
Anorectal Manometry
Anorectal manometry can assess the resting and maximum
squeeze pressures of the anal sphincters, presence or absence
of relaxation of the anal sphincter during balloon distention
of the rectum (rectoanal inhibitory reflex), rectal sensation, and
ability of the anal sphincter to relax during straining.179,200 A
high resting anal pressure suggests the presence of an anal
fissure or anismus (paradoxical contraction of the external
anal sphincter in response to straining or pressure within the
anal canal). Rectal hyposensitivity suggests a neurologic dis-
order, but the volume of rectal content necessary to induce
rectal urgency may also be increased in patients with fecal
retention, so the results of rectal sensitivity testing must be
interpreted with caution. Absence of a rectoanal inhibitory
reflex raises the possibility of Hirschsprung’s disease.
Patients with a defecatory disorder commonly have inap-
propriate contraction of the anal sphincter when they bear

down. A positive rectoanal gradient (i.e., higher rectal than
anal pressure) is generally thought to be necessary for normal
defecation, whereas a negative rectoanal gradient (i.e., lower
rectal than anal pressure) is associated with a defecatory dis-
order; however, asymptomatic persons often have abnormal
anal sphincter contraction during anorectal manometry. In a
study of healthy subjects, 36% had dyssynergia in the left
lateral position, but the presence or absence of dyssynergia did
not predict the ability to expel a balloon.201 In a subsequent
study using high-resolution anorectal manometry, the recto-
anal gradient was negative in a majority of asymptomatic
women.199 Although a negative rectoanal gradient may be sup-
portive of a diagnosis of dyssnergic defecation, it is not con-
clusive by itself and should be used in conjunction with other
physiologic testing.
Electromyographic Testing of Striated Muscle Activity
In general, EMG studies of the external anal sphincter and
puborectalis muscles using concentric needle or surface
electrode recordings are not essential and rarely indicated.
An exception is the use of EMG in patients with a suspected
spinal cord or cauda equina lesion, in whom bilateral or
unilateral dysfunction of the external anal sphincter can be
demonstrated.
Rectal Sensitivity and Sensation Testing
Rectal sensitivity to distention can be measured by introduc-
ing successive volumes of air into a rectal balloon and record-
ing the volume at which the stimulus is first perceived, the
volume that produces an urge to defecate, and the volume
above which further addition of air can no longer be tolerated
owing to discomfort.
TREATMENT
Initial treatment of constipation is based on nonpharmaco-
logic interventions. If these measures fail, pharmacologic
agents may be used. If a defecatory disorder is present, initial
treatment should include biofeedback; up to 75% of patients
with disordered evacuation respond to biofeedback, and
many do not respond well to fiber supplementation or oral
laxatives. Otherwise, initial treatment should include exercise
and increased fluid and fiber intake through changes in diet
or use of commercial fiber supplements. Patients who do not
improve with fiber should be given an osmotic laxative like
milk of magnesia or polyethylene glycol, and the dose should
be adjusted until soft stools are attained. Stimulant agents
(e.g., bisacodyl, senna derivatives) should be reserved for
patients who do not respond to fiber or osmotic laxatives.
Newer pharmacologic agents such as lubiprostone and lina-
clotide should be considered for patients who have not
responded to initial therapy. Figure 19-7 provides an algo-
rithm for evaluation and treatment of patients with severe
constipation.
General Measures
Reassurance
Some people can be helped by being told that an irregular
bowel habit and other mild defecatory symptoms are common
in the healthy general population and that their symptoms are
not harmful. Patients who are concerned that their symptoms
may indicate disease may be helped by appropriate investiga-
tion to relieve their fears.
Chapter 19  Constipation   285
Lifestyle Changes
The need to set aside an unhurried and, if possible, regular
time for defecation and always to respond to a defecatory
urge should be stressed. If patients experience difficulty in
expelling stool, they should be advised to place a support
approximately 6 inches in height under their feet when sitting
on a toilet seat so that the hips are flexed toward a squatting
posture. For persons with an inactive lifestyle, activity
should be encouraged. Use of constipating drugs, includ-
ing over-the-counter medications (see Box 19-3), should be
avoided.
Psychological Support
Constipation may be aggravated by stress or may be a mani-
festation of emotional disturbance (e.g., previous sexual abuse
[see Chapter 22]). For such patients, an assessment of the
person’s circumstances, personality, and background and sup-
portive advice may help more than any physical measures of
treatment. Behavioral treatment (see later) offers a physical
approach with a psychological component and is often accept-
able and beneficial.
Fluid Intake
Dehydration or salt depletion is likely to lead to increased salt
and water absorption by the colon, leading in turn to the
passage of small hard stools. In the absence of clinical dehy-
dration, however, no data support the notion that increasing
fluid intake relieves constipation.202 Increasing water intake to
1.5 to 2 L may enhance the effects of fiber intake in patients
with constipation.203
Dietary Changes and Fiber Supplementation
After studying the dietary and stool patterns of rural
Africans in the early 1970s, Dr. Denis Burkitt speculated that
a deficiency in dietary fiber was contributing to constipation
and other colonic diseases in Western societies.204 Since then,
studies have shown that when nonconstipated persons
increase their intake of dietary fiber, stool weight increases in
proportion to the baseline stool weight and frequency of def-
ecation and correlates with a decrease in colonic transit
time.205 Every gram of wheat fiber ingested yields approxi-
mately 2.7 g of stool expelled. It follows that when an
increased intake of dietary fiber leads to an increase in stool
weight in constipated subjects who pass small stools, the
resulting stool weight may still be lower than normal. For this
reason, the therapeutic results of a high-fiber diet are often
disappointing as a treatment for constipation. In a study of 10
constipated women who took a supplement of wheat bran
(20 g/day), average daily stool weight increased from roughly
30 to 60 g/day, with only half of patients achieving a normal
average stool weight. Bowel frequency increased from a mean
of 2 to 3 bowel movements weekly.206 In a controlled cross-
over trial, 24 patients took 20 g of bran or placebo daily for 4
weeks. Although bran was more effective than placebo in
improving bowel frequency and oroanal transit rate, the
occurrence and severity of constipation experienced by the
patients did not differ between the 2 treatment periods,207
probably because constipated patients complain mainly of
difficulty in defecation rather than decreased frequency of
bowel movements. A systematic review of 6 randomized con-
trolled trials (4 using soluble fiber and 2 using insoluble fiber)
found that soluble fiber improved constipation symptoms
and that evidence in support of insoluble fiber was
conflicting.208
286   Section III  Symptoms, Signs, and Biopsychosocial Issues

Constipation
Treat secondary History and physical
causes examination

Stop or change
Medication history
offending agent

Increase fiber intake to at least 20 g/day

Inadequate response

Pharmacologic treatment (e.g.,

laxatives, lubiprostone, linaclotide)

Inadequate response

Anorectal manometry
Balloon expulsion test

Normal Inconclusive Abnormal

Colonic transit study Barium or MR Defecatory disorder

defecography

Slow Normal
Normal Abnormal

Slow-transit Normal-transit
constipation constipation

Osmotic laxative, Defecation training;

stimulant laxative, Treat as for consider consultation
prokinetic agent; IBS with a psychologist
rarely colectomy and/or dietician;
occasionally repair of
prolapse or rectocele

FIGURE 19-7. Algorithm for the evaluation and treatment of severe constipation.

Dietary fiber appears to be effective in relieving mild to
moderate64 but not severe constipation,90 especially if severe
constipation is associated with slow colonic transit, an evacu-
ation disorder, or medications. Although dietary modification
may not succeed, most constipated subjects should be advised
initially to increase their dietary fiber intake as the simplest,
most physiologic, and cheapest form of treatment. Patients
should be encouraged to consume about 25 g of nonstarch
polysaccharides (NSPs) daily by eating whole-wheat bread,
unrefined cereals, plenty of fruit and vegetables, and if neces-
sary a supplement of raw bran, either in breakfast cereals or
with cooked foods. Specific dietary counseling is often needed.
Side effects of fiber supplementation include abdominal
distention, bloating, flatulence, and poor taste and can lead to
poor patient adherence to therapy, especially for the first
several weeks. Most controlled studies of the effect of fiber
have shown that the minimum amount needed to consistently
and significantly alter bowel function or colonic transit time
is 12 g/day. To improve adherence, patients should be
instructed to increase their dietary fiber intake gradually over
several weeks to about 20 to 25 g/day. If results of therapy are
disappointing, commercially packaged fiber supplements
should be tried (Table 19-2). Fiber and bulking agents are
concentrated forms of NSPs based on wheat, plant seed
mucilage (ispaghula), plant gums (sterculia), or synthetic
methylcellulose derivatives (methylcellulose, carboxymethyl-
cellulose [see later]).
Some patients, particularly women with markedly delayed
colonic transit, find that fiber aggravates abdominal disten-
tion. Bran may also be unhelpful in young people with mega-
colon and in older adults, in whom it may lead to fecal
incontinence. For these patients, a reduction in fiber intake
may relieve symptoms.
Specific Therapeutic Agents
Commercial Fiber Products
Methylcellulose
Methylcellulose is a semisynthetic NSP of varying chain
length and degree of methylation. Methylation reduces bacte-
rial degradation in the colon. One study of constipated patients
with an average daily fecal weight of only 35 g showed an
increase in fecal solids with 1, 2, and 4 g of methylcellulose/
day, but fecal water increased only with the 4-g dose. Bowel
frequency in this group of patients increased from an average
of 2 to 4 stools weekly, but the patients did not report
 Chapter 19  Constipation   287

TABLE 19-2 Commercial Fiber Products Calcium Polycarbophil

Calcium polycarbophil is a hydrophilic polyacrylic resin that
Starting
is resistant to bacterial degradation and thus may be less likely
Daily
to cause gas and bloating. In patients with IBS, calcium poly-
Agent Dose (g) Comments
carbophil appears to improve global symptoms and ease of
Methylcellulose 4-6 Semisynthetic cellulose fiber that stool passage212 but not abdominal pain (see Table 19-2).
is relatively resistant to colonic
bacterial degradation and tends Guar Gum
to cause less bloating and flatus
than psyllium Guar gum is a natural high molecular weight polysaccharide
extracted from the seed of the leguminous shrub Cyamopsis
Psyllium 4-6 Made from ground seed husk of tetragonoloba. It hydrates rapidly to form a highly viscous solu-
the ispaghula plant; forms a gel tion. Guar gum is approved for use in a number of foods and
when mixed with water, so an cosmetics and as a supplement. When used in high doses, guar
ample amount of water should gum has been reported to cause intestinal obstruction.
be taken with psyllium to avoid
intestinal obstruction; undergoes
Flaxseed
bacterial degradation, which may
contribute to side effects of Flaxseed, also known as linseed, has not been well studied in
bloating and flatus; allergic constipation, and conflicting results have been reported in
reactions (e.g., anaphylaxis, small studies of patients with IBS.213,214
asthma) have been reported but
are rare
Other Laxatives
Polycarbophil 4-6 Synthetic fiber made of polymer The main groups of laxatives other than fiber are osmotic
of acrylic acid, which is resistant agents and stimulatory laxatives; stool softeners and emol-
to bacterial degradation lients are additional therapeutic agents (see later) (Tables 19-3
and 19-4).
Guar gum 3-6 Soluble fiber extracted from
seeds of the leguminous shrub
Cyamopsis tetragonoloba Poorly Absorbed Ions
Magnesium, sulfate, and phosphate ions are poorly absorbed
by the intestine and thereby create a hyperosmolar intralumi-
nal environment. Their primary mode of action appears to be
osmotic, but they may have other possible effects with unclear
marked improvement in consistency or ease of passage of consequences, such as increasing prostaglandin concentra-
stools (see Table 19-2).209 tions in the stool.215 Stool weight increases by 7.3 g for each
additional millimole of soluble magnesium excreted.216 Stan-
dard doses of magnesium hydroxide (see Table 19-3) contain
Ispaghula (Psyllium) 40 to 80 mmol of magnesium ion and typically produce a
Ispaghula is derived from the husks of a plant mainly grown bowel movement within 6 hours. Magnesium sulfate is a more
in India, has high water-binding capacity, is fermented in the potent laxative that tends to produce a large volume of liquid
colon to a moderate extent, and increases bacterial cell mass. stool and often leads to abdominal distention and sudden
It is available as effervescent suspensions, granules, and a passage of a foul-smelling liquid stool.
powder. The suspensions, which are popular, have to be drunk Use of magnesium, particularly in older adults, can be
quickly before the husk absorbs water. The granules may be limited by adverse effects like flatulence, abdominal cramps,
stirred briskly in a half-glass of water and swallowed at once; and intravascular volume shifts. A small percentage of mag-
carbonated water may be preferred. Some people prefer to nesium is actively absorbed in the small intestine; the remain-
swallow the solid granules and then drink a glass of water. der draws water into the intestine along an osmotic gradient.217
Ispaghula (3.4 g as Metamucil) has been shown to increase Hypermagnesemia can occur in patients with renal failure and
fecal bulk to the same extent as methylcellulose 1 to 4 g daily in children. Hypermagnesemia-induced paralytic ileus is a
in constipated subjects. Although both stool dry and wet rare complication,218 and hypermagnesemia with coma requir-
weights increased, the total weekly weights remained less ing hemodialysis has occurred in a child given 18 g/day of
than those of a healthy control group without treatment. In an magnesium hydroxide for 7 days.219 Patients with renal insuf-
observational study, 149 patients were treated with psyllium ficiency or cardiac dysfunction can experience electrolyte and
in the form of Plantago ovata seeds (15 to 30 g daily) for a volume overload from the absorption of magnesium. Even
period of at least 6 weeks. The response to treatment was poor patients who are otherwise healthy can experience these com-
among patients with slow colonic transit or a disorder of def- plications, in addition to dehydration, with excessive use.
ecation, whereas 85% of patients without abnormal physio- Because phosphate is absorbed by the small intestine, a
logic testing results improved or became symptom free. substantial dose must be ingested to produce an osmotic laxa-
Nevertheless, the authors recommend that a trial of dietary tive effect, and it is not ideal for daily use. A rare but serious
fiber be undertaken before diagnostic testing is performed.90 form of acute kidney injury has been associated with sodium
Ispaghula can cause an acute allergic immunoglobulin E– phosphate solution used before colonoscopy, even in patients
mediated response, with facial swelling, urticaria, tightness in with normal baseline renal function (see Chapter 41). Risk
the throat, cough, and asthma.210 Workers who inhale the com- factors for kidney injury from phosphate include hyperten-
pound during manufacture or preparation can have a similar sion, advanced age, volume depletion, and use of angiotensin-
reaction211 (see Table 19-2). converting enzyme inhibitors or NSAIDs.220,221
288   Section III  Symptoms, Signs, and Biopsychosocial Issues

TABLE 19-3 Laxatives Commonly Used for Constipation

Type of Laxative Generic Name(s) Dose Comments

Osmotic Laxatives
Poorly Absorbed Ions
Magnesium Magnesium hydroxide 15-30 mL once or Hypermagnesemia can occur in patients with renal
twice daily failure and in children
Magnesium citrate 75-150 mL every day Often used as part of a bowel preparation
Magnesium sulfate 10-15 g every day
Sulfate Sodium sulfate 5-10 g every day Sodium sulfate is generally not used by itself as a
(Glauber’s salt) laxative agent
Phosphate Sodium phosphate 0.5-10 mL with 12 oz Hyperphosphatemia can occur, especially in patients
of water with renal failure

Poorly Absorbed Sugars

Disaccharides Lactulose 15-30 mL once or Gas and bloating are common side effects
twice daily
Sugar alcohols Sorbitol 15-30 mL once or Sorbitol is commonly used as a sweetener in
twice daily sugar-free products. In older adults, sorbitol has
Mannitol 15-30 mL once or an effect similar to lactulose but costs less. Rarely
twice daily used as a laxative
Polyethylene glycol Polyethylene glycol 17-34 g once or twice Tends to cause less bloating and cramps than other
electrolyte daily agents; tasteless and odorless, can be mixed with
noncarbonated beverages. Typically used to
prepare the colon for diagnostic examinations and
surgery; also available as a powder without
electrolytes for regular use

Stimulant Laxatives
Anthraquinones Cascara sagrada 325 mg (or 5 mL) at Cause apoptosis of colonic epithelial cells that are
bedtime phagocytosed by macrophages; result in a
Senna 1-2 7.5-mg tablets lipofuscin-like pigmented condition known as
daily pseudomelanosis coli; no definitive association has
been established between anthraquinones and
colon cancer or myenteric nerve damage (cathartic
colon)
Ricinoleic acid Castor oil 15-30 mL at bedtime Cramping is common
Diphenylmethane Bisacodyl 5-10 mg at bedtime Has effects in the small intestine and colon
derivatives Phenolphthalein 30-200 mg at bedtime Removed from the U.S. market because of
teratogenicity in animals
Sodium picosulfate 5-15 mg at bedtime Likely has effects only on the colon. Although widely
used in Europe, it is only available in the USA as
part of a colonoscopy preparation

Stool Softeners Docusate sodium 100 mg twice daily Efficacy in constipation is not well established

Emollients Mineral oil 5-15 mL at bedtime Long-term use can cause malabsorption of fat-
soluble vitamins, anal seepage, and lipoid
pneumonia in patients predisposed to aspiration
of liquids

Enemas, Suppositories Phosphate enema 120 mL Serious damage to rectal mucosa can result from
Mineral oil retention 100 mL extravasation of the enema solution into the
enema submucosa. Hypertonic phosphate enemas and
Tap water enema 500 mL large-volume water or soapsuds enemas can lead
Soapsuds enema 1500 mL to hyperphosphatemia and other electrolyte
Glycerin suppository 60 g abnormalities if the enema is retained. Soapsuds
Bisacodyl suppository 10 mg enemas can cause colitis. Prescribed on an
as-needed basis

Chloride Channel Lubiprostone 8-24 µg twice daily Increases secretion in the intestine. Its mechanism of
Activator action is presumed to be via the chloride 2
channel

Guanylate Cyclase C Linaclotide 145 µg once daily Increases secretion in the intestine through cyclic
Agonist guanosine monophosphate
 Chapter 19  Constipation   289

In 1 trial, only about half of patients were found to be truly

TABLE 19-4 Grade of Evidence for Laxative Use According constipated; among these patients, lactulose was effective in
to the ACG Task Force on Chronic Constipation 80%, as compared with 33% of those who received placebo
(glucose) (P < 0.01).224 The second trial was conducted in a
Grade of
nursing home over 8 to 12 weeks in 42 older patients with
Laxative Evidence*
constipation.225 The initial dose of lactulose was 30 mL/day,
Bulking agents and the dose was reduced temporarily or permanently to
  Psyllium B 15 mL, depending on bowel frequency. Lactulose showed an
  Calcium polycarbophil B advantage over placebo (a 50% glucose syrup) by increasing
  Bran † the mean number of bowel movements each day and mark-
edly reducing episodes of fecal impaction (P < 0.015) and the
Stool softeners B need for enemas.
Sorbitol.  Sorbitol is widely used in the food industry as
Lubricants C an artificial sweetener but is rarely used in clinical practice.
Ingestion of as little as 5 g causes a rise in breath hydrogen,
Osmotic laxatives and 20 g produces diarrhea in about half of normal subjects.226
  PEG A Sorbitol is as effective as lactulose and less expensive. A
  Lactulose A randomized double-blind crossover trial of lactulose (20 g/
†
  Milk of magnesia day) and sorbitol (21 g/day) in ambulant older men with
chronic constipation showed no difference between the 2 com-
Stimulant laxatives B pounds with regard to frequency or normality of bowel move-
Prokinetic agent ments or patient preference.227 The frequency of side effects
  Tegaserod‡ A was similar except for nausea, which was more common
with lactulose. Mannitol is another sugar alcohol that can be
Chloride channel activator used as a laxative. Like sorbitol it is rarely used clinically for
  Lubiprostone §
constipation.
Guanylate cyclase C agonist
  Linaclotide §
Polyethylene Glycol
*Grade A: Based on 2 or more randomized controlled trials (RCTs) with adequate Polyethylene glycol (PEG) is an isosmotic laxative that is meta-
sample sizes and appropriate methodology. Grade B: Based on evidence from a bolically inert and able to bind water molecules, thereby
single RCT of high quality or conflicting results from high-quality RCTs or 2 or increasing intraluminal water retention.228 PEG is not metabo-
more RCTs of lesser quality. Grade C: Based on noncontrolled trials or case
lized by colonic bacteria. Ingestion of PEG leads to an increase
reports.
†
Insufficient data. in stool volume and softer stools, which may become liquid
‡
Removed from the U.S. market. depending on the volume of PEG consumed. PEG is excreted
§
Not yet graded. mostly unchanged in the feces. Electrolytes are added to PEG
PEG, polyethylene glycol.
Data from Brandt LJ, Prather CM, Quigley EM, et al. Systematic review on the
solutions used for colonic lavage before colonoscopy to avoid
management of chronic constipation in North America. Am J Gastroenterol 2005; the potential adverse effects associated with diarrhea, such as
100(Suppl 1):S5-21. dehydration and electrolyte imbalance. PEG-3350 without
electrolytes is available in the United States as an over-the-
counter (OTC) powder that is mixed in smaller doses with
water for regular use to treat constipation.
Poorly Absorbed Sugars Several studies have demonstrated the efficacy of PEG in
Lactulose.  Lactulose is a nonabsorbable synthetic disaccharide the treatment of chronic constipation. In a trial in which 70
that consists of galactose and fructose linked by a bond resis- ambulatory outpatients were treated for 4 weeks with a PEG-
tant to lactase. Lactulose is not absorbed by the small intestine electrolyte solution containing 14.6 g of PEG, patients who
but undergoes fermentation in the colon to yield short-chain responded to PEG (>3 bowel movements per week) at the end
fatty acids, hydrogen, and carbon dioxide, with consequent of the 4 weeks were then randomized to continue PEG or a
lowering of the fecal pH. When healthy volunteers take lactu- placebo for 20 weeks at a dose of 17 g or 34 g daily. Compared
lose 20 g (30 mL) daily, none of the sugar is detectable in the with placebo, PEG resulted in improvement in bowel fre-
stool. In larger doses, some of the sugar passes though the quency and consistency. At the end of follow-up, complete
colon unchanged. remission of constipation was reported by 77% of patients
The recommended dose of lactulose for adults is 15 to randomized to PEG compared with only 20% of those ran-
30 mL once or twice daily. The time to onset of action is longer domized to placebo. The dropout rate in the placebo group,
than that for other osmotic laxatives, and 2 or 3 days are mostly secondary to treatment failure, was 46%.229
required for lactulose to achieve an effect. Some patients In another randomized multicenter trial that compared
report that lactulose is effective initially but then loses its standard and maximum doses of 2 PEG formulations of dif-
effect, perhaps because the intestinal flora are altered in ferent molecular weights (PEG-3350 and PEG-4000) in 266
response to the medication.222 Adverse effects related to lactu- outpatients, most patients had their first stool within 1 day of
lose include abdominal distention or discomfort, presumably initiating PEG treatment, and stool consistency improved in
as a result of colonic gas production. Cases of lactulose- both treatment groups. The lowest dose of PEG produced
induced megacolon have been reported.222 the most normal stool consistency, whereas higher doses pro-
In a group of young, chronically constipated volunteers duced more liquid stools.230 Low-dose PEG appears to be
who reported fewer than 3 stools a week, lactulose increased more effective than lactulose in the treatment of chronic
bowel frequency and percentage of stool moisture and constipation.231,232 A study of 307 patients with chronic
softened stools when compared with a control syrup that constipation who were randomized to 17 g of PEG or placebo
contained only sucrose. The effectiveness of lactulose was for 6 months showed continued benefit of PEG compared
dose dependent.223 The effect of lactulose in older patients with placebo and no electrolyte abnormalities or intestinal
has been studied in 2 double-blind placebo-controlled trials. malabsorption.232
290   Section III  Symptoms, Signs, and Biopsychosocial Issues
PEG solutions may be useful for short-term treatment of
fecal impaction. In 1 study,233 16 severely ill patients aged 26
to 87 years who, despite treatment with various laxatives, had
not had a bowel movement in the hospital for 5 to 23 days, all
had a fecal impaction on clinical examination and were treated
with a PEG solution, 1 L taken as 2 portions of 500 mL, each
over 4 to 6 hours. The regimen was repeated on a second and
third day if necessary. The full dose was taken by 12 patients
on the first day, and the remainder took at least half the recom-
mended dose; only 8 patients needed treatment on the second
day and 2 patients on the third day. The treatment was highly
effective; after the last dose, most patients were passing mod-
erate or large volumes of soft stool, with resolution of impac-
tion. No adverse side effects apart from abdominal rumbling
occurred, and only 1 patient, who was paraplegic, experienced
fecal incontinence. Successful treatment with PEG has been
described in outpatients with refractory constipation and
older adults (with administration of PEG by mouth or by a
nasogastric tube).234
The most common adverse events of PEG include abdomi-
nal bloating and cramps.228 The most commonly reported
adverse effects of PEG used for colonoscopy preparation
include electrolyte imbalances, allergic reactions, and Mallory-
Weiss tears.235 Cases of fulminant pulmonary edema have
been reported after administration of PEG solution by naso-
gastric tube, with 1 fatality.236,237 In each case, the patient had
emesis, suggesting aspiration of PEG. PEG also may delay
gastric emptying.238
Stimulant Laxatives
Stimulant laxatives increase intestinal motility and secretion.
They begin working within hours and often are associated
with abdominal cramps. Stimulant laxatives include anthra-
quinones (e.g., cascara, aloe, senna) and diphenylmethanes
(e.g., bisacodyl, sodium picosulfate, phenolphthalein). Castor
oil is used less commonly because of its side-effect profile. The
effect of stimulant laxatives is dose dependent. Low doses
prevent absorption of water and sodium, whereas high doses
stimulate secretion of sodium, followed by water, into the
colonic lumen.
Stimulant laxatives are sometimes abused, especially in
patients with an eating disorder (see Chapter 9),239 even
though at high doses they have only a modest effect on calorie
absorption. Although a cathartic colon (i.e., a colon with
reduced motility) has been attributed to prolonged use of
stimulant laxatives, no animal or human data support this
effect. Rather, cathartic colon, as seen on a barium enema
examination, is probably a primary motility disorder.
Stimulant laxatives can produce normal, soft, formed
stools in some patients but are often associated with abdomi-
nal cramps and diarrhea even in standard doses. They act
rapidly and are particularly suitable for use in a single dose
for temporary constipation. Most clinicians are cautious about
recommending indefinite daily dosing of stimulant laxatives
for chronic constipation. Stimulant laxatives vary widely in
clinical effectiveness, and some patients with severe constipa-
tion are not helped by them.
Anthraquinones.  Anthraquinones (e.g., cascara, senna, aloe,
frangula) are produced by a variety of plants. The compounds
are inactive glycosides; when ingested, they pass unabsorbed
and unchanged down the small intestine and are hydrolyzed
by colonic bacterial glycosidases to yield active metabolites
that increase the transport of electrolytes into the colonic
lumen and stimulate myenteric plexuses to increase intestinal
motility. The anthraquinones typically induce defecation 6 to
8 hours after oral dosing.
Anthraquinones cause apoptosis of colonic epithelial cells,
which are then phagocytosed by macrophages and appear as
a lipofuscin-like pigment that darkens the colonic mucosa, a
condition termed pseudomelanosis coli240 (see Chapter 128 [Figs.
128-7 and 128-8]). Anthraquinone laxatives do not appear to
cause significant adverse functional or structural changes in
the intestine. Animal studies have shown neither damage to
the myenteric plexus after long-term administration of sen-
nosides241 nor a functional defect in motility.242 A case-control
study in which multiple colonic mucosal biopsy specimens
were examined by electron microscopy showed no differences
in the submucosal plexuses between patients taking an anthra-
quinone laxative regularly for 1 year and those not taking
one.243 An association between use of anthraquinones and
colon cancer or myenteric nerve damage and the development
of cathartic colon has not been established.244
Senna has been shown in controlled trials to soften stools245
and increase the frequency and wet and dry weights of stool.
The formulations available for clinical use vary from crude
vegetable preparations to purified and standardized extracts
to a synthetic compound.
Castor Oil.  Castor oil comes from the castor bean. After oral
ingestion, it is hydrolyzed by lipase in the small intestine to
ricinoleic acid, which inhibits intestinal water absorption and
stimulates intestinal motor function by damaging mucosal
cells and releasing neurotransmitters.246 Cramping is frequent,
and consequently castor oil is not commonly used in clinical
practice.
Diphenylmethane Derivatives.  Diphenylmethane compounds in-
clude bisacodyl, sodium picosulfate, and phenolphthalein.
After oral ingestion, bisacodyl and sodium picosulfate are
hydrolyzed to the same active metabolite, but the mode of
hydrolysis differs. Bisacodyl is hydrolyzed by intestinal
enzymes and thus can act in the small and large intestines.
Sodium picosulfate is hydrolyzed by colonic bacteria. Like
anthraquinones, the action of sodium picosulfate is confined
to the colon, and its activity can be unpredictable because its
activation depends on the bacterial flora.
The effects of bisacodyl, and presumably sodium picosul-
fate, on the colon are similar to those of the anthraquinone
laxatives. When applied to the colonic mucosa, bisacodyl
induces an almost immediate, powerful, propulsive motor
activity in healthy and constipated subjects, although the
effect is sometimes reduced in the latter.247 These laxatives also
stimulate colonic secretion.
Like the anthraquinone laxatives, bisacodyl leads to apop-
tosis of colonic epithelial cells, the remnants of which accumu-
late in phagocytic macrophages, but these cellular remnants
are not pigmented.248 Aside from these changes, bisacodyl
does not appear to cause adverse effects with long-term use.249
Bisacodyl is a useful and predictable laxative, especially
suitable for single-dose use in patients with temporary consti-
pation. Its possible effect on the small bowel is a disadvantage,
in contrast to anthraquinones and sodium picosulfate. Long-
term use of bisacodyl or related agents is sometimes necessary
for patients with chronic severe constipation. In the doses
used, liquid stools and cramps tend to result, and it is difficult
to adjust the dose to produce soft, formed stools. In a multi-
center randomized double-blind, placebo-controlled study,
247 patients with chronic constipation were randomized to
bisacodyl 5 to 10 mg once daily for 4 weeks. Patients in the
bisacodyl group reported a greater number of complete spon-
taneous bowel movements per week during the treatment
period compared with those in the placebo group (1.1 ± 0.1 at
baseline in both groups increased to 5.2 ± 0.3 in the bisacodyl
group and 1.9 ± 0.3 in the placebo group). In addition, patients
receiving bisacodyl reported improvements in straining,
feeling of anal obstruction, and stool form and had increased

quality-of-life scores compared with placebo. However, 72%
of patients in the bisacodyl group reported at least 1 adverse
event (diarrhea and abdominal pain most commonly), with a
decrease in frequency after the first week of treatment. In addi-
tion, adverse events caused 18% of patients in the bisacodyl
group to withdraw from the study, compared with 5% of
patients in the placebo group.250
Sodium picosulfate is commonly used outside the United
States. It is available in the United States as part of a colonos-
copy preparation. In a randomized double-blind, placebo-
controlled study conducted in Germany, 233 patients with
chronic constipation were randomized to sodium picosulfate
(10-mg drops) once daily for 4 weeks. Patients in the sodium
picosulfate group reported a greater number of complete
spontaneous bowel movements per week during the treat-
ment period, compared with those in the placebo group (0.9
± 0.1 at baseline increased to 3.4 ± 0.2 in the sodium picosulfate
group and 1.1 ± 0.1 at baseline increased to 1.7 ± 0.1 in the
placebo group). Patients who received sodium picosulfate
reported improvement in straining, incomplete evacuation,
feeling of anal obstruction, and stool form and had increased
quality-of-life scores compared with patients who received a
placebo. Diarrhea was reported by 32% of patients who
received the sodium picosulfate.251
Phenolphthalein inhibits water absorption in the small
intestine and colon by effects on eicosanoids and the Na+/
K+-ATPase pump present on the surface of enterocytes (see
Chapter 101). The drug undergoes enterohepatic circulation
(see Chapter 64), which may prolong its effects. Although
effective, a 2-year feeding study in rodents found increased
incidences of ovary, adrenal gland, kidney, and hematopoietic
neoplasms in treated animals,252 and in 1997 the U.S. Food
and Drug Administration (FDA) proposed that phenolphtha-
lein be reclassified as “not generally recognized as safe and
effective.” Subsequently, most phenolphthalein-containing
laxatives were voluntarily withdrawn from the U.S. market.
Subsequent studies have failed to show an association between
phenolphthalein laxatives and cancers.253
Stool Softeners and Emollients
Docusate Sodium
Although the detergent dioctyl sodium sulfosuccinate (docu-
sate sodium) is available as a stool softener, further studies of
its efficacy are needed. The compound stimulates fluid secre-
tion by the small and large intestines but does not increase the
volume of ileostomy output or the weight of stools in normal
subjects.254,255 A double-blind crossover trial has shown benefit
in 5 of 15 older constipated subjects, as judged by patients
and their caregivers, and a significant increase in bowel fre-
quency.256 In a multicenter double-blind randomized trial in
adults, however, docusate sodium was less effective than psyl-
lium for treating chronic idiopathic constipation.257
Mineral Oils
Mineral oils alter the stool by undergoing emulsification into
the stool mass and providing lubrication for stool passage.
Long-term use can cause intestinal malabsorption of fat-
soluble vitamins, anal seepage, and lipoid pneumonia in
patients predisposed to aspiration of liquids.
Enemas and Suppositories
Compounds may be introduced into the rectum to stimulate
contraction by distention or chemical action, soften hard
stools, or both. Serious damage to the rectal mucosa can result
Chapter 19  Constipation   291
from extravasation of the enema solution into the submucosal
plane. The anterior rectal mucosa is the site most vulnerable
to trauma from the tip of a catheter introduced through the
backward-angulated anal canal (see Chapter 129). The enema
nozzle should be directed posteriorly after the anal canal has
been passed.
Phosphate Enemas
Hypertonic sodium phosphate enemas are often effective.
They cause distention and stimulation of the rectum. A histo-
logic study in normal subjects showed that a single hypertonic
phosphate enema caused disruption of the surface epithelium
in 17 of 21 biopsy specimens. Scanning electron microscopy
showed patchy denudation of the surface epithelium, with
exposure of the lamina propria and absence of goblet cells. The
proctoscopic appearance of the mucosa was abnormal in every
case but returned to normal within 1 week.258 Therefore, super-
ficially damaged mucosa appears to heal rapidly. Phosphate
enemas are used widely, although studies documenting their
efficacy are lacking.
A phosphate enema, if given to a patient who cannot evac-
uate it promptly, can lead to dangerous hyperphosphatemia
and hypocalcemic tetany; 1 patient (age 91) died after a single
phosphate enema,259 and coma developed in an adult who
was given 6 phosphate enemas at hourly intervals without
evacuation.260 Severe hyperphosphatemia, hypocalcemia, and
seizure have been reported in a 4-year-old child with normal
renal function after retention of 2 phosphate enemas.261 Phos-
phate enemas are not recommended in children age 3 and
younger.262,263
Saline, Tap Water, and Soapsuds Enemas
Saline, tap water, or soapsuds enemas can be effective mainly
by distending the rectum and softening feces. Stool evacuation
typically occurs 2 to 5 minutes following administration. A
saline enema does no damage to the rectal mucosa and may
be effective.258 Water enemas and soapsuds enemas also may
be used, but with large volumes, dangerous water intoxication
can occur if the enema is retained. Large-volume water or
soapsuds enemas can also lead to hyperphosphatemia and
other electrolyte disturbances if the enema is retained. Soap-
suds enemas can cause rectal mucosal damage and necrosis.
Stimulant Suppositories and Enemas
Glycerin can be administered as a suppository and is often
clinically effective. The rectum is stimulated by an osmotic
effect. The effect of glycerin, if any, on the rectal mucosa is
unknown. Bisacodyl 10 mg is available as a suppository that
appears to act topically by stimulating enteric neurons.220 In
normal subjects, a single bisacodyl suppository or an enema
containing 19 mg of bisacodyl in 100 or 200 mL of water pro-
duced marked changes in 23 of 25 rectal mucosal biopsy speci-
mens. The epithelium of the surface and within the crypt was
altered; with use of the enema, the surface epithelium was
absent.258 Regular use of bisacodyl suppositories therefore
appears unwise. Oxyphenisatin (Veripaque), which is no
longer available in the United States, is a stimulant enema that
was used in the past mainly before diagnostic procedures.
When given by mouth, this compound led to some cases of
chronic hepatitis.
Chloride Channel Activator
Lubiprostone is a bicyclic fatty acid derived from prostaglan-
din E1 that is reported to work predominantly by activating
292   Section III  Symptoms, Signs, and Biopsychosocial Issues
the intestinal chloride 2 channels, thereby increasing intestinal
fluid secretion and transit264 without altering serum electrolyte
levels. Lubiprostone was approved for the treatment of chronic
idiopathic constipation for men and women in the United
States in 2006. In 2 phase III randomized placebo-controlled
trials, lubiprostone (24 µg twice daily) increased the number
of spontaneous bowel movements (i.e., bowel movements
that occur without laxative use in the previous 24 hours) in
patients with chronic constipation as defined by the Rome II
criteria (5.89 at week 1 in lubiprostone-treated patients vs. 3.99
at week 1 in placebo-treated patients).265 Lubiprostone also
significantly decreased straining, improved stool consistency,
and reduced overall severity of symptoms. The frequency of
spontaneous bowel movements increased in men and women,
as well as older patients, who took the drug. A rebound effect
after withdrawal of the drug was not evident.266 Nausea and
abdominal pain were reported in 21% and 7% of patients,
respectively, in the lubiprostone group compared with 4% and
4%, respectively, in the placebo group.265 Lubiprostone, 8 µg
twice daily, is also approved in the United States for the treat-
ment of women with IBS with constipation.
Guanylate Cyclase C Agonists
Linaclotide
Linaclotide is a minimally absorbed 14–amino acid peptide
that activates the guanylate cyclase C receptor on the luminal
surface of the intestinal epithelium, resulting in increased
levels of cyclic guanosine monophosphate (cGMP) and
increased secretion of chloride and bicarbonate into the intes-
tinal lumen. In animal models, cGMP also appears to reduce
firing of afferent nerves in the bowels.267 In 2 phase III studies
involving 1276 patients with chronic constipation, linaclotide
significantly increased the percentage of people who reported
3 or more complete spontaneous bowel movements (i.e., asso-
ciated with the sensation of complete emptying) per week and
an increase of 1 or more from baseline during at least 9 of the
12 weeks (20% of patients who received linaclotide 145 µg or
290 µg, compared with 5% of patients who received placebo).
Linaclotide also increased stool frequency, improved stool
consistency, and reduced straining, abdominal bloating, and
discomfort as compared with placebo. Diarrhea was the most
common adverse event, leading to discontinuation of treat-
ment in about 4% of patients.268 Linaclotide, 145 µg once daily,
was approved by the FDA in 2012 for the treatment of men
and women with chronic constipation, and in a dose of 290 µg
once daily for those with IBS with constipation. Linaclotide is
contraindicated in children younger than age 6 because of
deaths in juvenile mice younger than age 3 weeks. Similar
findings were not found in mice older than 6 weeks of age.
Linaclotide is not recommended in children between 6 and 18
years of age.
Plecanatide
Plecanatide (SP-304) is an investigational guanylate cyclase C
agonist mechanistically similar to linaclotide. In a phase II
dose-escalation and repeated-dose study, 84 patients with
chronic constipation (using modified Rome III criteria) were
randomized to 0.3, 1, 3, or 9 mg of plecanatide or placebo for
14 days. The median change from baseline in complete spon-
taneous bowel movements was 3.0 for patients receiving ple-
canatide 1 mg, compared with 0.5 for patients receiving
placebo. Abdominal discomfort, stool consistency, and strain-
ing were also improved. Plecanatide was well tolerated, and
none of the patients who received the drug reported
diarrhea.269
5-Hydroxytryptamine4 Agonists
Stimulation of the 5-hydroxytryptamine4 (5-HT4) receptor on
afferent nerves in the wall of the GI tract induces peristaltic
contraction of the intestine. Several 5-HT4 agonists have been
tested for treating constipation. Cisapride, a benzodiazepine,
has had variable results in treating constipation.270 Potentially
lethal cardiac dysrhythmias led to its withdrawal from the
commercial U.S. market in July 2000. Newer 5-HT4 agonists
without cardiac effects (e.g., prucalopride, velusetrag [TD-
5108]) appear promising as future treatments for chronic
constipation.
Tegaserod
Tegaserod, a partial 5-HT4 agonist, is an aminoguanidine
indole derivative of serotonin that is structurally different
from cisapride. Because of cardiovascular safety concerns,
tegaserod was withdrawn from the market in April 2007. The
frequency of cardiovascular events in previous clinical trials
was 13 in 13,614 (0.11%) compared with 1 in 7031 (0.01%) in
control subjects. The cardiovascular events reported were
myocardial infarction (n = 3), sudden cardiac death (n = 1),
unstable angina (n = 6), and stroke (n = 3). The FDA’s decision
to withdraw the drug has been the subject of debate.271 In a
12-week randomized double-blind, placebo-controlled trial of
1348 subjects with chronic constipation, response rates were
41.4%, 43.2%, and 25.1% for tegaserod 2 mg twice daily, tega-
serod 6 mg twice daily, and placebo recipients, respectively.272
Diarrhea was more common with tegaserod 2 and 6 mg twice
daily (4.5% and 7.3%, respectively) than with placebo (3.8%).272
Tegaserod had also been used in women with IBS with consti-
pation (see Chapter 122).273
Prucalopride
Prucalopride, a full 5-HT4 agonist, is a benzofuran derivative
that accelerates colonic transit in healthy humans and patients
with chronic constipation.274 Three large 12-week randomized
placebo-controlled phase III trials of similar design that eval-
uated the efficacy and safety of prucalopride 2 mg or 4 mg
once daily versus placebo in patients with chronic constipa-
tion have been published.275-277 In 1 of these studies, the
percentage of patients achieving more than 3 complete spon-
taneous bowel movements per week was 30.9% for those
receiving prucalopride 2 mg and 28.4% for those receiving
prucalopride 4 mg, compared with 12.0% in the placebo
group (P < 0.001 for both comparisons). All other secondary
efficacy endpoints, including patients’ satisfaction with their
bowel function and treatment and their perception of the
severity of their constipation symptoms, were improved sig-
nificantly at week 12 with the use of 2 or 4 mg of prucalo-
pride as compared with placebo. A meta-analysis of 7
randomized controlled trials with 2639 constipated patients
found the number needed to treat to be 6; the percentage of
patients who responded to prucalopride was 28.3%, com-
pared with 13.3% for placebo.278 The most frequent adverse
effects were headaches, nausea, and diarrhea. Although
cardiac side effects were reported in patients receiving tegas-
erod and cisapride, which are partial 5-HT4 agonists, no car-
diovascular side effects have been observed to date with
prucalopride, nor have any electrocardiographic abnormali-
ties been reported. In addition, in a study of elderly consti-
pated patients in nursing homes, no differences in vital signs,
electrocardiograph parameters, or Holter-monitoring results
were found in patients receiving prucalopride and placebo.
Approximately 88% of the patients had a history of cardio-
vascular disease.279 Prucalopride has been approved for use

in the European Union, Canada, and elsewhere in the world,
but not in the United States as of 2014.
Velusetrag
Velusetrag (TD-5108) is another full 5-HT4 agonist. In a 4-week
phase II trial, 401 patients with chronic constipation were ran-
domized to receive velusetrag 15, 30, or 50 mg or placebo once
daily. Spontaneous bowel movements increased by 3.6 (15 mg),
3.3 (30 mg), and 3.5 (50 mg) per week in the patients receiving
velusetrag compared with an increase of 1.4 per week for
placebo.280
Peripheral Mu-Opioid Antagonists
Peripherally acting opioid antagonists have been shown to
reverse opioid-induced bowel dysfunction without reversing
analgesia or precipitating CNS withdrawal signs.
Methylnaltrexone
Methylnaltrexone is a peripherally acting mu-opioid receptor
antagonist approved by the FDA in 2008 for the treatment of
opioid-induced constipation in patients with a late-stage
advanced illness who are receiving an opioid on a continuous
basis to relieve pain. In a phase III trial involving 133 patients
with a life expectancy of less than 6 months and fewer than 3
bowel movements in the week prior to treatment or no bowel
movements within 2 days before the first study dose, patients
were randomized to receive methylnaltrexone 0.15 mg/kg
subcutaneously or placebo every other day for 2 weeks. This
was followed by a 3-month open-label treatment period; 48%
of patients reported having a bowel movement within 4 hours
of starting methylnaltrexone, compared with 15% of those
who received placebo (P < 0.001).281 In a similar phase III trial
involving 154 patients with a life expectancy of less than 6
months and no bowel movements within 2 days prior to the
first study dose, patients were randomized to receive a single
subcutaneous injection of methylnaltrexone 0.15 mg/kg,
0.3 mg/kg, or placebo, followed by a 4-month open-label
treatment period. The percentage of patients who reported
having a bowel movement within 4 hours was 62% for meth-
ylnaltrexone 0.15 mg/kg and 58% for methylnaltrexone
0.3 mg/kg, compared with 14% for placebo. The 0.3-mg/kg
dose of methylnaltrexone was not found to be more efficacious
than the 0.15-mg/kg dose and was associated with more
abdominal pain.282 Methylnaltrexone did not appear to pre-
cipitate opioid withdrawal symptoms or affect central analge-
sia. An oral methylnaltrexone formulation has also shown
efficacy.283 In this study, 804 patients with non–cancer-related
pain and opioid-induced constipation were randomized to
oral methylnaltrexone tablets, 150 mg, 300 mg, or 450 mg
daily for 4 weeks, followed by 8 weeks of as-needed dosing.
A spontaneous bowel movement occurred within 4 hours of
dosing in 21.0% of the methylnaltrexone 150-mg group (P <
0.0001), 24.6% of the 300-mg group (P = 0.0040), and 27.4 % of
the 450-mg group (P = 0.3078), compared with 18.1% of the
placebo group. Oral methylnaltrexone has been approved by
the FDA for the treatment of opioid-induced constipation.
Alvimopan
Alvimopan is another mu-opioid receptor antagonist approved
by the FDA to accelerate bowel recovery following surgery,
but not for opioid-induced constipation. Results in several
phase III trials of alvimopan for opioid-induced constipation
have been mixed. In a study of 485 patients receiving opioids
for non-cancer pain, patients were randomized to alvimopan
Chapter 19  Constipation   293
0.5 mg once daily, 0.5 mg twice daily, or placebo for 12 weeks.
The percentage of patients who reported greater than 3 spon-
taneous bowel movements per week over the treatment period
was 63% in both alvimopan groups, compared with 56% in the
placebo group, a difference that was not statistically signifi-
cant.284 In a similar study, 518 patients receiving opioids for
non-cancer pain were randomized to alvimopan 0.5 mg once
daily, 0.5 mg twice daily, or placebo for 12 weeks. The percent-
age of patients who reported greater than 3 spontaneous
bowel movements per week over the treatment period was
72% in those receiving alvimopan 0.5 mg twice daily, com-
pared with 48% of those receiving placebo.285 The most
common side effects were abdominal pain, nausea, and diar-
rhea.286 Alvimopan is only available for short-term in-hospital
use for postoperative ileus through a restricted access program.
Other Agents
Colchicine, a drug used for gout, and misoprostol, a prosta-
glandin analog, have been used to treat patients with severe
chronic constipation. In a randomized placebo-controlled,
double-blind crossover trial, colchicine increased the fre-
quency of bowel movements as compared with placebo (3/
week at baseline compared with 10/week while on colchicine
0.6 mg 3 times a day); however, abdominal pain was greater
during administration of colchicine than placebo.287 Data for
misoprostol are limited, and side effects of the drug are
common.288
Cholinergic Agents
Cholinergic agents have also been used to treat constipation.
Bethanechol, a cholinergic agonist, appears to benefit patients
in whom constipation results from therapy with tricyclic anti-
depressants; data to support its use in patients with other
causes of constipation are limited. A single intravenous dose
of neostigmine, a cholinesterase inhibitor, has been shown to
be remarkably effective in decompressing the colon in patients
with acute colonic pseudo-obstruction289 (see Chapter 124),
but controlled studies of this class of drugs have not been
completed in patients with normal-transit or slow-transit con-
stipation. Side effects like bradycardia, increased salivation,
vomiting, and abdominal cramping are common.
Botulinum Toxin
Clostridium botulinum toxin type A (Botox), a potent neurotoxin
that inhibits presynaptic release of acetylcholine, has been
injected intramuscularly into the puborectalis muscle to treat
defecatory disorders. Preliminary data suggest that botulinum
toxin may be effective for patients in whom spastic pelvic floor
dysfunction causes outlet delay,290 including those who also
have Parkinson’s disease.133,134 In 1 study, 19 of 24 patients
experienced improvement in symptoms and physiologic mea-
surements of pelvic floor function at 2 months.291 Controlled
trials have not been performed, however, and this approach is
not recommended in lieu of biofeedback, for which clinical
experience is greater (see later).
Newer Agents
Neurotrophin-3.  A newer approach to treating constipation
involves using neurotrophins, a multigene family of proteins
that includes nerve growth factor (NGF), brain-derived neu-
rotrophic factor (BDNF), and neurotrophin-3 (NT-3).292,293 In
healthy persons, R-metHuNT-3 administered subcutaneously
has been shown to accelerate gastric, small bowel, and colonic
transit. Effects on stool frequency are observed within 3 days
294   Section III  Symptoms, Signs, and Biopsychosocial Issues
of the start of treatment and last up to 5 days after cessation
of treatment. R-metHuNT-3 has been well tolerated, although
half of patients treated experienced injection site reactions or
paresthesias, presumably by stimulating noncholinergic exci-
tation and suppressing nitrergic inhibition.
Chenodeoxycholate.  Chenodeoxycholic acid is a bile acid previ-
ously used to treat patients with gallstones; it caused diarrhea
in 40% of patients receiving 750 to 1000 mg/day.294 A double-
blind placebo-controlled study of 36 female patients with IBS
with constipation were randomized to delayed-release sodium
chenodeoxycholate (500 or 1000 mg) or placebo for 4 days.
Colonic transit time, stool consistency, and stool frequency
were improved in the chenodeoxycholate groups, compared
with placebo. The most common side effect was abdominal
cramping or pain.295 Studies in patients with chronic constipa-
tion have not been performed.
Elobixibat.  Elobixibat (A3309) is a novel investigational, mini-
mally absorbed ileal bile acid–transporter inhibitor that
increases the flow of bile into the colon. In a phase II study,
190 patients with chronic constipation (defined using modi-
fied Rome III criteria) were randomized to elobixibat (5, 10, or
15 mg) or placebo once daily for 8 weeks. Elobixibat increased
stool frequency for week 1 by 2.5, 4.0, and 5.4 spontaneous
bowel movements in patients receiving 5, 10, and 15 mg of
elobixibat, respectively, compared with 1.7 for those receiving
placebo; the improvement was maintained over 8 weeks.
Abdominal bloating and straining were also improved
with elobixibat compared with placebo. The most com-
monly reported adverse events were abdominal pain and
diarrhea.296
Other Forms of Therapy
Defecation Training
Defecation training typically involves 3 to 5 treatment ses-
sions, each lasting at least 30 minutes. During these sessions,
the normal defecation process is taught and misconceptions
are dispelled. Patients are encouraged to give a detailed
description of their bowel symptoms, prompted by a sympa-
thetic listener who is familiar with the full range of problems
experienced by those with defecatory dysfunction. This
process is in itself therapeutic because it enables patients to
discuss symptoms that otherwise might be regarded as a
private burden. Recommendations regarding the proper
amount of fiber intake are often given. For patients with infre-
quent defecation, the importance of developing a regular
bowel habit and not ignoring a call to defecate is emphasized.
For those who spend excessive time in the bathroom because
of ineffective straining, a regimen of less frequent visits to the
bathroom and more effective defecation is recommended. The
optimum posture for defecation, including the benefit of
raising the feet above floor level when using a Western-type
toilet, is described. Patients are encouraged to practice what
they are taught; that they may be able to help themselves often
gives patients new self-confidence. At each visit, patients are
encouraged to reduce any dependence on laxatives, enemas,
and suppositories. Progress is praised.
Anorectal Biofeedback
During anorectal biofeedback, which typically follows defeca-
tion training, patients receive visual or auditory feedback, or
both, on the functioning of their anal sphincter and pelvic floor
muscles. Biofeedback can be used to train patients to relax
their pelvic floor muscles during straining and to coordinate
this relaxation with abdominal maneuvers to enhance entry of
stool into the rectum. Biofeedback can be performed with an
EMG or anorectal manometry catheter. Simulated evacuation
with a balloon or silicone-filled artificial stool is commonly
taught to patients to emphasize normal coordination of suc-
cessful defecation.297 Patient education and rapport between
the therapist and patient are integral components of successful
biofeedback.298 Patients typically complete from 6 sessions in
6 weeks to 3 sessions/day for 10 successive days.
A systematic review of biofeedback studies performed up
to 1993 revealed an overall success rate of 67%, although con-
trolled studies were lacking.299 Biofeedback may be less effec-
tive for patients with descending perineum syndrome than for
those with spastic pelvic floor disorders.112 In a review of 38
biofeedback studies, psychological factors were found to influ-
ence the response to biofeedback.300 Successful biofeedback
training, as defined by an improvement in global bowel satis-
faction, was also found to be correlated with harder stool
consistency, greater willingness to participate, higher resting
anal pressure, and prolonged balloon expulsion time, but not
age, duration of symptoms, stool frequency, compliance with
therapy, straining rectal pressure, or relaxation of anal sphinc-
ter on straining.301 More recently, several controlled trials have
found biofeedback to be more effective than sham feedback or
standard therapy,302,303 diazepam,304 or laxatives.305,306 Patients
with pelvic floor dyssynergia who failed fiber (20 g/day) plus
enemas or suppositories were randomized to 5 weekly bio-
feedback sessions (n = 54) or PEG (14.6 to 29.2 g/day) plus 5
weekly counseling sessions (n = 55). At 6 months, major
improvement was reported by 80% of patients who under-
went biofeedback compared with 22% of the laxative-treated
patients (P < 0.001). The benefits of biofeedback were sus-
tained at 12 and 24 months and produced greater reductions
in straining, sensations of incomplete evacuation and anorec-
tal blockage, use of enemas and suppositories, and abdominal
pain (all P < 0.01). Stool frequency increased in both groups.
All biofeedback-treated patients reporting major improve-
ment were able to relax the pelvic floor and defecate a 50-mL
balloon at 6 and 12 months.305 In another controlled trial, 77
patients with dyssynergic defecation were randomized to bio-
feedback, sham therapy, or standard therapy for 3 months.
Patients who received biofeedback were significantly more
likely to correct dyssynergia, improve the defecation index,
decrease balloon expulsion time, increase the number of com-
plete spontaneous bowel movements per week, and decrease
use of digital maneuvers; global bowel satisfaction was also
higher.302 Thirteen patients from each group elected to partici-
pate in a long-term follow-up trial. The number of complete
spontaneous bowel movements per week increased signifi-
cantly in the biofeedback group after 1 year (1.91 at baseline
compared with 4.85 after 1 year) but not in a standard-
treatment control group (1.66 at baseline compared with 1.43
after 1 year). The 3-month improvement in dyssynergia, def-
ecation index, and decreased balloon expulsion time in the
biofeedback group was also maintained after 1 year, and
colonic transit time normalized.303
Originally, biofeedback training was intensive and initi-
ated during admission to the hospital,307 but subsequent expe-
rience has shown that training as an outpatient is satisfactory.
A small comparative trial has shown no difference in outcome
with or without use of an intrarectal balloon or home train-
ing.308 Results are similar when training is conducted with or
without access to a visual display of muscular activity. In the
absence of a visual display, the instructor gives continuous
information and encouragement to the patient and assesses
the effect of instruction by observing how the patient strains
and by sensing the effectiveness of straining through gentle
tension on a rectal balloon.
Most patients who complete defecation training continue
to report improvement in symptoms up to 2 years later.307,308

Symptoms reported to improve include bowel frequency,
straining, abdominal pain, bloating, and need for laxatives.309
Physiologic measurements before and after treatment have
shown that training results in appropriate relaxation of the
puborectalis and external anal sphincter muscles,310-312 increase
in intrarectal pressure,96 a widened rectoanal angle on strain-
ing during defecation, an increased rate of rectal emptying, an
increased rate of colonic transit, and increased rectal mucosal
blood flow.
Most published series have restricted defecation training
and anorectal biofeedback to patients with a defecatory disor-
der (i.e., paradoxical contraction of pelvic floor muscles). At 1
center, however, such training appeared to benefit a high pro-
portion of unselected patients with chronic constipation,
regardless of the results of investigation of colonic transit or
pelvic floor dysfunction, including patients with slow colonic
transit.311,313 In another series, treatment results did not depend
on the presence or absence of a rectocele, intussusception, or
perineal descent.309 Other investigators, however, have shown
that patients who fail to respond to defecation training
and biofeedback have a greater degree of perineal descent
than those who respond.112 Defecation training has benefited
some patients in whom constipation developed after hyster-
ectomy314 and some patients with solitary rectal ulcer
syndrome.315
Complementary and Alternative Medical Therapies
Many complementary and alternative therapies are used by
patients with constipation,316 but clinical studies are limited
and generally of poor quality (see Chapter 131), and no defini-
tive recommendations regarding their use in constipation can
be made. A systematic review of acupuncture for the treatment
of chronic constipation identified in the Chinese Biomedical
Database is in progress.317 The popularity of probiotics contin-
ues to grow, yet few studies have been conducted to date. One
prospective study showed that in women with chronic consti-
pation, Bifidobacter animalis (DN-173 010) and fructoligosaccha-
ride improved bowel frequency and consistency, straining,
and pain with defecation (P < 0.010).318 The role of traditional
Chinese medicine in constipation remains unclear. Yun-chang
capsule (hemp seed pill) has shown some efficacy in a small
placebo-controlled trial.319
Sacral Nerve Stimulation
Data suggest that sacral nerve stimulation may be helpful for
patients with severe constipation.320 Sixty-two patients with
chronic constipation who failed treatment with laxatives,
suppositories, enemas, and biofeedback underwent a 21-day
test period with a temporary stimulation wire connected to
an external pulse generator. Forty-five patients reported an
increase to at least 3 bowel movements per week, reduction
by 50% or more in the number of episodes of straining, or a
decrease of more than 50% in the sensation of incomplete
evacuation met the criteria for permanent neurostimulator
implantation. Successful treatment was defined as improve-
ment in any of the following: (1) increase in bowel frequency
from 2 or less to 3 or more bowel movements per week, (2)
50% or greater reduction in the proportion of defecation epi-
sodes associated with straining, or (3) 50% or greater reduc-
tion in the proportion of defecation episodes associated with
a sense of incomplete evacuation. Of the patients who
received the permanent neurostimulator, 87% met the criteria
for successful treatment. During the follow-up period, which
ranged from 1 to 55 months with a median of 28 months,
the number of bowel movements per week increased from
2.3 to 6.6.321
Chapter 19  Constipation   295
Surgery
The goal of surgical treatment for patients with severe consti-
pation is to increase bowel frequency and ease of defecation;
a possible additional benefit is relief of abdominal pain and
distention. Procedures may be divided into 3 groups: partial
or total colectomy, construction of a stoma, and anorectal
operations undertaken to improve defecatory function.322
Colectomy
Colectomy for constipation produces variable results. A review
of 32 published studies of surgery for chronic constipation
found considerable variability in rates of patient satisfaction
(39% to 100%).323 The most common complications following
surgery are small bowel obstruction, diarrhea, and inconti-
nence, but diarrhea and incontinence tend to improve after the
first year following surgery.
Selection of Patients.  Preoperative psychological assessment is
essential because poor results are common among patients
who are psychologically disturbed.324 Because the aim of
surgery is to increase bowel frequency, slow colonic transit
must be demonstrated by an objective method. Also, defeca-
tory function must be assessed. Finally, a generalized intesti-
nal dysmotility or pseudo-obstruction syndrome should be
excluded (as much as possible) by radiologic study of the
small intestine and, when available, studies of gastric empty-
ing and small bowel transit.
Series in which these steps have been taken to select a
homogeneous group of patients have shown the best results,
although longer follow up is awaited. At 1 center, only 74 of
1009 patients referred for possible surgical treatment of chronic
constipation underwent surgery. Measurement of intestinal
transit and tests of pelvic floor function revealed that 597
patients had no quantifiable abnormality and that 249 patients
had pelvic floor dysfunction without slow colonic transit. Col-
ectomy with an ileorectal anastomosis was performed in 52
patients with demonstrable slow colonic transit and normal
defecatory function. The operation was also performed in 22
patients with slow colonic transit and pelvic floor dysfunction
after the latter had been treated by a training program. Of the
74 patients treated surgically, 97% were satisfied with the
result, and 90% had good or improved quality of life after a
mean follow-up of 56 months. There was no operative mortal-
ity, but 7 patients had a subsequent episode of small bowel
obstruction.61
Type of Operation.  The results of colectomy with cecorectal or
ileosigmoid anastomosis are inferior to those for a subtotal
colectomy with an ileorectal anastomosis.325 Occasional reports
have described proctocolectomy with ileoanal anastomosis
and construction of an ileal pouch, usually following failure
of colectomy and ileorectal anastomosis.326 In 1 patient, ileo-
rectal anastomosis failed because the rectal capacity was larger
than normal.327 Laparoscopic subtotal colectomy appears to be
as effective as an open approach.328,329
Construction of a Stoma
A colostomy is occasionally performed for slow-transit consti-
pation, because it is reversible and the results of colectomy are
uncertain. Most patients report subjective improvement after
a colostomy performed as a primary procedure for slow-
transit constipation or for neurologic disease.110 Many patients,
however, continue to require laxatives or regular colonic
irrigation.
An ileostomy is occasionally performed after failure of
colectomy and ileorectal anastomosis for slow-transit consti-
pation, either because constipation persists or because severe
296   Section III  Symptoms, Signs, and Biopsychosocial Issues
diarrhea and incontinence occur. Patients who do not benefit
from colectomy with ileorectal anastomosis are likely to be
those with a generalized disorder of intestinal motility or
those with a psychological disturbance.
Creation of a continent catheterizable appendicostomy or
cecostomy through which antegrade enemas can be adminis-
tered can sometimes benefit patients with paraplegia or those
unable or unwilling to undergo colectomy. A retrospective
study of 32 patients who underwent this procedure and were
followed for a median of 36 months (range, 13-140 months)
reported satisfactory long-term results in about half of the
patients. Revisions were frequently required.330 Such a proce-
dure can decrease the time and medication needed for bowel
care; most of the experience is in children.331
Operations for Defecatory Disorders
The stapled transanal rectal resection (STARR) procedure has
been used with some success, particularly for patients who
also have a rectocele and intussusception.332-334 Puborectalis or
internal anal sphincter muscle division is unsuccessful in
patients with slow-transit constipation.335 Procedures to correct
a rectocele should be considered only for patients who have
evidence of retained contrast during defecating proctography
or women in whom constipation is relieved with digital
vaginal pressure.110
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Chapter 19  Constipation   296.e9
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