Medical Management of

Intractable Constipation
Hery Djagat Purnomo
Division Of Gastroentero-Hepatology Departement of Internal Medicine
Dr Kariadi Hospital - Diponegoro University Semarang

SEMARANG DISGESTIVE WEEK (SDW), Hotel Grand Candi ,28 November 2014

Epidemiology - General
The prevalence of constipation among the general population
in North America has been quoted as 1.9% to 27.2%

50% to 74% of the institutionalized elderly reporting

daily use of laxatives.
Leung, L, et al. Chronic Constipation: An Evidence-Based Review. J Am Board Fam Med. 2011;24:436451.

11 January 2015

Indonesian Modern Way of Life:

Lack of Fibers & Physical Activity,
More Food Additive

1/11/2015

Sumber: Riskesdas 07

47.6% of FEMALE WORKERS AGED 18-55 YEARS

in Jakarta, INDONESIA had constipation symptoms or
functional bowel disorders
Women aged less than 30 y had a significantly higher prevalence of
constipation as compared to those aged 30 y and over
The frequency of stool was found to be highly varied from 1 to 21
stools per week.

Bardosono, Sunardi: Study on 210 female workers. MKI vol 6,no 3 Maret 2011

Epidemiology - Children
Worldwide prevalence of childhood constipation of 0.7-29.6%
(median 12%).
Prevalence was 10-20% in the United States and UK and 20-30% in
Australia, South Africa, and China.
Auth, M. K. H, et al. Childhood constipation. BMJ 2012;345:e7309. 38-43.

Up to one third of children ages six to 12 years

report constipation during any given year.
Constipation generally first appears between
the ages of two and four years.
Biggs, W. S, et al. Evaluation and Treatment of Constipation in Infants and Children.
Am Fam Physician 2006;73:469-77,479-80,481-2

11 January 2015

Epidemiology - Adults
Women are 2 to 3 times more likely to have constipation than men
in terms of prevalence and physical symptoms.

Possible reasons include higher risk of injury to the pelvic

floor from childbirth and the general willingness of women
to report their symptoms and respond to surveys.
Leung, L, et al. Chronic Constipation: An Evidence-Based Review. J Am Board Fam Med. 2011;24:436451.

It is estimated that constipation affects

between 2% and 27% of the population
(European perspective).
12% of people worldwide reporting self-defined
constipation
Tack, J. Diagnosis and treatment of chronic constipation a European perspective.
Neurogastroenterol Motil. 2011; 23:697710

11 January 2015

Epidemiology - Pregnancy
The prevalence of
constipation in pregnant
women is as high as 1138%.
Tytgat, G. N, et al. Contemporary understanding and management of reflux and
constipation in the general population and pregnancy: a consensus meeting. Aliment
Pharmacol Ther .2003; 18: 291301

11 January 2015

Epidemiology- Geriatric
Advanced age is also a risk factor for chronic constipation,
with the largest increase in prevalence after the age of 70
years.

This can be due to effects of medication, immobility,

and blunted urge to defecate.
Leung, L, et al. Chronic Constipation: An Evidence-Based Review. J Am Board Fam Med. 2011;24:436451.

In studies of self-reported constipation:

Age 65 years or older:
26 % women and 16 % men considered themselves to
be constipated
Subgroup 84 years or older:
34% women and 26 % men
Gallegoz-Orozco, J. F., et al. Chronic Constipation in the Elderly. Am J Gastroenterol
2012; 107:1825

11 January 2015

Chronic Constipation and Quality of Life

11 January 2015

Tuteja, A.K, et al. Chronic Constipation: Overview and Treatment Options. P&T. 2007; 32(2): 91-92,
99-102, 104-105

PHYSIOLOGY OF DEFECATION

10

Pathophysiology
PATHOPHYSIOLOGY OF FUNCTIONAL CONSTIPATION

11 January 2015
World Gastroenterology Organization Global Guidelines. Constipation: a global perspective. 2010

11

Definition of functional constipation

Can J Gastroenterol Vol 25 Suppl B October 2011

3 Types of Constipation

Tack, J. Diagnosis and treatment of chronic constipation a European perspective. Neurogastroenterol Motil. 2011; 23:697710

11 January 2015

13

Normal-transit constipation
Normal-transit constipation (=functional
constipation)
The most common form of constipation seen by
clinicians.
Reported symptoms:

the presence of hard stools

a perceived difficulty with evacuation
on testing, stool transit is not delayed
the stool frequency is often within the
normal range
may experience bloating and abdominal
pain or discomfort, will frequently meet
criteria for irritable bowel syndrome with
constipation (IBS-C)
may exhibit increased psychosocial
distress.

Cn Andrews, M storr. The pathophysiology of chronic constipation. Can J gastroenterol 2011;25(suppl B):16B21B

14

Slow-transit constipation
causes infrequent bowel
movements (typically less than
once per week)
most common in young women
often, patients do not feel the urge
to defecate
may complain of associated
bloating and abdominal discomfort
colonic transit time is prolonged in
these patients
believed to be a neuromuscular
disorder of the colon.

Cn Andrews, M storr. The pathophysiology of chronic constipation. Can J gastroenterol

2011;25(suppl B):16B-21B

15

Defecation disorder
group of functional and
anatomical abnormalities of
the anorectum lead to
symptoms of constipation
Symptoms:
significant straining
spending large amounts of time on the toilet daily
manual rectal evacuation using a finger
position changes or frequent enema use is common
pelvic floor tone may be constantly increased lead
to hemorrhoid formation and anal fissuring

Cn Andrews, M storr. The pathophysiology of chronic constipation. Can J gastroenterol

2011;25(suppl B):16B-21B
16

Dyssynergia
the most common functional Defecation
Disorder (DD), is an acquired behavioural DD
result of poor toileting habits, painful
defecation, obstetric or back injury, or braingut dysfunction
In children, fecal retention may result in
encopresis due to leakage of liquid stool
around impacted stool
Patients with dyssynergia are unable to
coordinate the abdominal, rectoanal and pelvic
floor muscles during defecation, and may also
demonstrate rectal hyposensitivity

Other terms: anismus, pelvic floor dysfunction,

puborectalis spasm and outlet constipation.

Cn Andrews, M storr. The pathophysiology of chronic constipation. Can J gastroenterol

2011;25(suppl B):16B-21B

17

Possible causes and constipation-associated

conditions/ Secondary constipation

11 January 2015
World Gastroenterology Organization Global Guidelines. Constipation: a global perspective. 2010

18

Medication associated with constipation

Antihypertensive drugs (clonidine, calcium
antagonists, and ganglionic blockers) reduce
smooth muscle contractility can cause
constipation
In patients with constipation, these should be preferably replaced by betablockers, angiotensin-converting enzyme inhibitors, or angiotensin II receptor
antagonists

Antidepressants, especially tricyclic

antidepressants.
Oral iron supplementation frequently causes
constipation
patients in whom iron supplementation is necessary, intravenous
supplementation of iron or the addition of a laxative may be options.

Aluminum-containing drugs such as sucralfate

and antacids can cause constipationmay be
replaced by proton pump inhibitors

Cn Andrews, M storr. The pathophysiology of chronic constipation. Can J gastroenterol

2011;25(suppl B):16B-21B

19

Medication associated with constipation

Analgesics, such as opiates and
cannabinoids, are especially notorious for
causing constipation.
Switching to a different class of analgesic drugs or using an opiate in
combination with a peripherally active opiate receptor antagonist, such as
naloxone or methylnaltrexone, may be considered

Anti-Parkinson, antiepileptic and

antipsychotic drugs are associated with
constipation due to their anticholinergic and
dopaminergic actions, and should be
avoided or combined with the regular use of
laxatives.
Antihistamines, antispasmodics and vinca
alkaloids are associated with constipation as
a side effect and should be replaced

Cn Andrews, M storr. The pathophysiology of chronic constipation. Can J gastroenterol

2011;25(suppl B):16B-21B

20

DIAGNOSTIC APPROACH

11 January 2015

PLEASE INSERT Presentation title

21

Symptoms of Chronic Constipation

Tuteja, A.K, et al. Chronic Constipation: Overview and Treatment Options. P&T. 2007; 32(2): 91-92,
99-102, 104-105

22

Rome III Criteria

Tuteja, A.K, et al. Chronic Constipation: Overview and Treatment Options. P&T. 2007; 32(2): 91-92,
99-102, 104-105

23

Rome III Diagnostic Criteria of Irritable Bowel Syndrome

Gastroenterology 2006;130(5):1481

24

Evaluation

Focus on identifying possible causative

conditions and alarm symptoms.

Stool consistency. (Bristol Stool Chart)

Patients description of constipation
symptoms; symptom diary:

Bloating, pain, malaise

Nature of stools
Bowel movements
Prolonged/excessive straining
Unsatisfactory defecation
Laxative use (past and present; frequency
and dosage)
Current conditions, medical history, recent
surgery, psychiatric illness

Constipation: a global perspective. World Gastroenterology Organisation Global

Guidelines. 2010

25

Bristol Stool Chart

Auth, M. K. H, et al. Childhood constipation. BMJ 2012;345:e7309. 38-43.

26

Evaluation (cont.)

Focus on identifying possible causative

conditions and alarm symptoms.

Patients lifestyle, dietary fiber, and fluid intake

Use of suppositories or enemas, other medications
Physical examination:
Gastrointestinal mass
Anorectal inspection:

Fecal impaction
Stricture, rectal prolapse, rectocele
Paradoxical or nonrelaxing puborectalis
activity
Rectal mass
If indicated: blood testsbiochemical profile,
complete blood count, calcium, glucose, and
thyroid function
Constipation: a global perspective. World Gastroenterology Organisation Global
Guidelines. 2010

27

Diagnostic evaluation
Clinical Findings and Possible Associated Causes
in Patients with Constipation

Jamshed, N, et al. Diagnostic Approach to Chronic Constipation in Adults. Am Fam Physician.

2011;84(3):299-306.

28

Alarm Symptoms and Indication for Endoscopy

ALARM SYMPTOMS in CONSTIPATION

Indications for endoscopy in

patients with constipation

ASGE GUIDELINE 2005

Constipation: a global perspective. World Gastroenterology Organisation

Global Guidelines. 2010
Jamshed, N, et al. Diagnostic Approach to Chronic Constipation in Adults. Am
Fam Physician. 2011;84(3):299-306.

29

Primary Care Management of Chronic Constipation in Asia:

The ANMA Chronic Constipation Tool

J Neurogastroenterol Motil, Vol. 19 No. 2 April, 2013

Clinical Evaluation
Categories constipation based on clinical evaluation

11 January 2015
Constipation:
a global perspective. World Gastroenterology Organization Global
Guidelines. 2010

31

Screening tests (DIAGNOSTIC TESTING)

Laboratory studies, imaging or endoscopy, and function tests
indicated in patients with severe chronic constipation or alarm symptoms.
PHYSIOLOGY TESTS FOR CHRONIC CONSTIPATION

11 January 2015
Constipation:
a global perspective. World Gastroenterology Organization Global
Guidelines. 2010

32

Measurement Colon Transit

( Sitzmarks Methode)

11 January 2015

MANOMETRY ANORECTAL

11 January 2015

34

Balloon expulsion test

BE Lee et al, J Neurogastroenterol Motil, Vol. 20 No. 3 July,

Screening tests (DIAGNOSTIC TESTING)

Laboratory studies, imaging or endoscopy, and function tests
indicated in patients with severe chronic constipation or alarm symptoms.
PHYSIOLOGY TESTS FOR CHRONIC CONSTIPATION

NOT ROUTINELY RECOMMENDATE IN THE

INITIAL EVALUATION OF THE PATIENTS WITH
CHRONIC CONSTIPATION WITHOUT ALARM
SYMPTOM

11 January 2015
Constipation:
a global perspective. World Gastroenterology Organization Global
Guidelines. 2010

36

Management
1. Comprehensive therapy :
Physiological defecation function and
etiology of constipation
2. Start empirical therapy:
Alarm sign (-)
Age < 40 yo
Abnormality in rectal toucher (-)
Secondary causes of defecation(-)

Management
3. Empirical therapy
Non-pharmacological and pharmacological

therapy
Non pharmacological therapy:
- Education
- Fiber and enough water consumption
- Probiotic consumption (Bifidobacterium sp) e.g
bifidobacterium animalis lactis DN -173010: Activia
- Physical activity
- Defecation habits, avoid straining during defecation, train
postprandial bowel movement reflex, avoid drugs that can
cause constipation

Management
Pharmacological therapy
A. Laxative
Bulk laxative

Osmotic laxative: saline, disaccharide, sugar alcohol, PEG

Stimulant laxative
Rectal enema/suppositoria
Lubiproston

B. Non-laxative Prokinetic
Empirical therapy in 2-4 weeks

Further evaluation if there is no improvement

Management
4. STC (slow transit constipation) : stimulant
laxative therapy + prokinetic besides non
pharmacological therapy
5. Anorectal dysfunction: biofeedback
therapy/botulinum type A toxin injection into
puborectalis muscle

6. Secondary constipation: therapy for underlying

disease
7. Operative therapy: no response from medical
therapy, anorectal problems (-)

Specific consideration
Elderly
Pregnancy and lactation
Diabetes

Constipation Management Algorithm

in Primary Health Care Center
Constipation
Alarm sign
Age 40 y.o
Suspicion of secondary constipation
Abnormality in rectal toucher

Empirical therap
2-4 weeks

+
Continue the treatment

+
Further
investigation/reffered

Algorithm for Management of Constipation

in Advanced Health Care Center
Constipation
Alarm sign
Age 40 y.o
Suspicion of secondary constipation
Abnormality in rectal toucher (+)

Empirical therapy (2-4 wk)

Faeces examination/lab/colonoscopy

+
Continue the treatment

No organic lesion

Colon transit
test/anorectal
manometry

Organic lesion +
Treatment based on etiology

NTC

STC

ARD

STC Algorithm
NTC Algorithm

ARD Algorithm

Algorithm for Management of Constipation

in Normal Transit Constipation (NTC)
Normal Ttransit Constipation (NTC)
Fiber + Probiotic
Milk of magnesia/bisacodyl/lactulose/PEG
Improvement

No improvement
Fiber+probiotic+bisacodyl+laktulosa/
MOM/PEG

Continue the treatment

Improvement
Continue the treatment

No improvement
Fiber+probiotic+bisacodyl+lactulose+PEG
Improvement

Continue the treatment

No improvement
Therapy adjustment

Algorithm for Management of Constipation in

Slow Transit Constipation(STC)
Slow transit constipation

Fiber +probiotic+ MOM+bisacodyl/prokinetic

Improvement

Continue the treatment

Improvement

Continue the treatment

No improvement

Add lactulose/PEG
No improvement

Considered to operation

Algorithm of Anorectal Dysfunction Management

Anorectal Dysfunction

Fiber + Probiotic, Suppositoria, Enema

Biofeedback + Fiber + Probiotic

Improvement
Follow up

No improvement
Re-investigation

Intractable Constipation
The definition of, and clinical approach to patients with
diffi-cult, refractory or intractable constipation is
still unclear.
Intractable chronic constipation in children as chronic
constipation with duration of symptoms > 2 years, not
responding to maximal laxative therapy, behavioural
therapy or a toilet training program.
Another definition ; a subset of constipated
patients fails to benefit from conventional and
sometimes even intensive treatments.

General consideration
Refractory constipation is suspected when a
patient, fulfilling the standard diagnostic
criteria for functional constipation and lacking
any alarm feature for organic conditions, fails to
improve upon intake of a high-fiber diet and
laxatives, usually polyethylene glycol (PEG) or
other osmotic agents, the former being superior
to lactulose in improving stool frequency, stool
consistency and abdominal pain.

Several issue before judgment RC

Reliability of information and patient compliance
Misunderstandings with the prescribing physician
Misconceptions
Patient expectations
Discontinued drug intake after a very few days of therapy
owing to the lack of effect onset
Poor basal evaluation
should be accurately re-evaluated for secondary forms of
constipation

Further diagnostic step

Intestinal transit time
Anorectal manometry (complemented
by the rectal balloon expulsion test and
defecography
Upper gastrointestinal (which might limit or
preclude surgical procedures) and colonic
manometry (possibly with pharmacological
testing in patients regarded as eligible for
surgery.

Two group of RC
STC (Slow transit constipation)
delayed colonic transit, a condition which can
be documented by a delayed distribution of
radiopaque markers (or radionuclides)
throughout the visceral lumen and is
characterized by a severe impairment of
colonic motor activity that, in some instances,
can be almost absent or progress up to a true
picture of colonic inertia

 OD (Obstructed Defecation)
Main pathophysiological features
are basically related to rectoanal dysfunction,
including the inability to relax or the paradoxical
contraction of the pelvic floor while attempting
to defecate, the lack of rectal motor activity, and
an abnormal rectal sensitivity although
anatomical abnormalities (particularly rectocele
and rectal intussusceptions) can also play a role in
this setting.

Pharmacologic Management
Combination agent :
Osmotic laxative + Stimulant laxative (bisacodyl and
sodium picosulfate)
Tegaserod
Prucalopride 1-2 mg/day (5HT4 full agonist
,enterokinetic properties+) or combination with PEG.
Enteric secretagogues ; Lubiprostone at a dose of 24 g
twice a day
linaclotide, a guanylate cyclase-C agonist (dose 145
ug/day)

Other pharmacological options

Colchicine 0.6 mg three times per day
(selected case)
The inhibitor of ileal bile acid transporter
A3309 (10 mg/day Fase 2 study)
Cholinesterase inhibitor pyridostigmine (60120 mg three times per day) DM patients
with constipation (available market)

OTHER
THERAPEUTIC APPROACHES
Behavioral and retraining techniques
(biofeedback)particularly in OD patients
Electrogalvanic stimulation
Local injections of botulinum toxin
Surgery approach/procedures

Take Home messeges

Reassesment of define/precense of
refractory/intractable constipation before
therapy
Define type of constipation STC or OD
Start with combination therapy with
difference mechanism of drugs (old drugs or
new drug its available)
Used other therapeutic approach its possible
Think for surgery if not improve

Frequency and stool form in Indian

Population
Conclusions
Median stool frequency in the studied population was
14/week (range 2-42) and predominant form was Bristol type
IV. Older age was associated with lesser stool frequency,
particularly among female subjects
Multivariate Analysis
On multivariate analysis, female gender (< 0.001) and age > 35
years (< 0.001) were independent predictors of passing 3
stools per week but vegetarianism and physical activity were
not significant
J Neurogastroenterol Motil. Jul 2013; 19(3): 374380.

Prevalence
median ; 16% (range, 0.7%79%) in adults overall
and 33.5% in adults aged 60 to 101 years.
nonwhite population more than in the white
population.
median female-to-male ratio of 1.5:1
in institutionalized more than community-living
elderly residents
Women seek laxative >>

Forest plot of standardized mean difference in intestinal

transit time across studies with probiotic in constipated
patients

World J Gastroenterol 2013 August 7; 19(29): 4718-4725

Forest plot of standardized mean difference in intestinal

transit time across studies with probiotic in constipated
patients

CONCLUSION:

Overall, short-term probiotic supplementation decreases ITT with

consistently greater treatment effects identified in constipated or
older adults and with certain probiotic strains

Miller et al, World J Gastroenterol 2013 August 7; 19(29): 4718-4725

Flow diagram for management of chronic constipation

Leung et al , J Am Board Fam Med 2011;24:436451

Summary of Various Management Options for Chronic Constipation

According to the Strength of Recommendations Taxonomy (SORT)