Rational use

of medication
in
constipation

dr. Fatima Safira Alatas, PhD, SpA(K)

Gastrohepatology Division, Department of Child Health,
Faculty of Medicine Universitas Indonesia, Cipto Mangunkusumo
Hospital, Jakarta
Disclosure

“No conflict of interest with any company regarding this topic”

Constipation
• In a healthy infants and children, it is a
common problem Hirschsprung,
anorectal Hard Painful
malformation, stools stools
neuromuscular,
endocrine, metabolic

5%
no organic Difficulty Incomplete
SYMPTOMS of
cause passing passing
constipation stool
underlying stool
pathologies
95%

Infrequent Dry,
passing hardened
stool stool

• We should focus on fecal elimination

using reassurance and no/minimal
medical intervention
Epidemiology
Prevalence of constipation using Rome IV criteria
40% 37.90%

35%

30%
25%
25%
21.40%
20% 18.50%

15% 14.10%
12.10%
10%

5%
1% 0.20%
0%
nonretentive fecal
infant dyschezia functional constipation any FGID
incontinence
infant (n=58) 1% 12.10% 37.90%
toddler (1-4yo) 18.50% 21.40%
child/adolescent (> 4yo) (n=959) 14.10% 0.20% 25%

infant (n=58) toddler (1-4yo) child/adolescent (> 4yo) (n=959)

How to approach • Rarely a sign of a more serious
disease (absence of red flags
constipation in general symptoms)
• Included in functional
gastrointestinal disorder (FGID)
→ without any structural or
biochemical findings (Rome IV
criteria)

Should not consider

“functional” unless
physical and biochemical
parameters are normal
 RED FLAGS
Red flags / alarm signs
 “RED FLAGS” potential disorders with constipation as a symptom
SYMPTOM OR FINDING EXAMPLES OF POSSIBLE CAUSES OR ASSOCIATIONS
Passage of meconium >48 h Hirschsprung disease Hirschsprung disease
Constipation in the first month after birth
Family history of Hirschsprung disease
Family history of autoimmune disease such as celiac disease, type 1 diabetes Celiac disease
Family history of cystic fibrosis Pancreatic insufficiency
Meconium ileus equivalent
Chronic pancreatitis
Chromosomal abnormality (ie, Down syndrome) Hirschsprung disease (2.6% of patients with Down syndrome)
Intestinal malformation (atresia)
Intestinal web
Physical asymmetry Intestinal malformation
Ribbon stools Rectal narrowing or atresia with fistula
Blood in the stool in the absence of anal fissures Inflammation (NEC), milk allergy, polyp, intussusception
Weight loss or inadequate weight gain Hirschsprung disease
Numerous medical conditions
Lagging growth Hirschsprung disease
Chronic illness
Bilious vomiting Intestinal obstruction
SYMPTOM OR FINDING EXAMPLES OF POSSIBLE CAUSES ORASSOCIATIONS
Severe abdominal distention Intestinal obstruction; ileus; severe obstipation
Hirschsprung disease
Episodes of inconsolable crampy abdominal Intussusception
pain (especially if followed by sense of Volvulus or torsion
exhaustion)
Urinary tract symptoms Urinary tract disorder including obstruction or infection
Abnormal thyroid gland/function Hypothyroidism
Abnormal position of the anus Imperforate anus with fistula
Anterior displacement with malpositioning of colon
Absent anal or cremasteric reflex Spinal cord lesions (including sacrococcygeal teratoma)
Decreased lower extremity strength/tone/reflex
Sacral dimple
Tuft of hair on spine
Gluteal cleft deviation
Dilated colon þ/– ureters Pseudo-obstruction disorders including neuropathies
Medication consumption Iron intake, diuretics (dehydration),
antispasmodics, calcium-containing
medications, aluminum antacids, opioids,
SSRIs and TCAs, unknown drugs, and herbals
Restricted diet Low fiber
Unbalanced intake
Physical activity Too sedentary, any chronic illness
Other
causes of
functional
and organic
constipation
Constipation: Infant Dyschezia (0-9 months)
Signs and symptoms

• Isolated episodes of distressing straining with crying

• Baby’s face turning red, effort to defecate

Medical approach

• Make sure no red flags

Cause

• baby’s inability to coordinate the voluntary and involuntary movement required for stool expulsion

Treatment

• Parents often perform rectal stimulation or use suppository drugs → should be DISCOURAGED
• EDUCATION → will resolve over time
• COMFORT the baby during episodes, cuddle, abdominal massage → relieves baby and parents stress
 Constipation: Infant Dyschezia (0-9 months)
Rome IV Diagnostic Criteria for Infant Dyschezia
MUST INCLUDE IN AN INFANT <9 MO OF AGE:

1. >10 min of straining and crying before successful or unsuccessful passage

of soft stools
2. No other health problems
Simplified approach to constipation in infants <6mo
constipation

Delayed meconium
passage? (>48hrs) History taking, Functional
physical exam, constipation
YES NO occult blood test
Treatment: Maintenance
Evaluate for Red flags? education, diet therapy if
possible organic modification effective
etiologies YES NO
Not effective
Exclusively breastfed?
Treatment: Maintenance
YES NO medication therapy if
(lactulose,PEG, etc) effective
Most likely Functional
normal constipation Not effective If fail despite good
adherence and
education, refer for
further evaluation
Complete
ESPGHAN
NASPGHAN
algorithm for
evaluation and
treatment of
constipation in
<6mo
Constipation: Functional Constipation (FC) in
infant, Toffler and older child (0-18 years)
Signs and symptoms

• Hard, dry, painful stools that are difficult to pass

Medical approach

• Comprehensive history taking and physical examination to exclude red flags

• Digital rectal examination → if uncertain, and if at least 1 ROME III criteria present + presence of red flags in
intractable constipation (evidence suggests digital rectal exam provides little additional information)
• Abdominal radiography → only if suspect of fecal impaction but physical examination is not reliable or possible
→ very minimal role in diagnosing FC (discordance between symptoms and examination findings)

Cause

• Presumed dietary inadequacy

• Voluntary withholding leading to stool retention

Treatment

• EDUCATION → ensure its functional, will respond to the measures offered

 ROME III vs ROME IV criteria for FC
In the absence of organic pathology, 2 of the following
must occur. Of child with devp age <4 yo symptoms must
occur for at least 1 month. For devp age 4yo symptoms
must occur for at least 1/week for 2 months
1. <2 defecations in the toilet per week in a child with
developmental age of ‡4 y
2. >1 episode of fecal incontinence per week (after toilet
training)
3. History of retentive posturing or excessive volitional
stool retention
4. History of painful or hard bowel movements
5. Presence of a large fecal mass in the rectum
6. History of large-diameter stools that can obstruct the
toilet
Accompanying symptoms may include irritability,
decreased appetite, and/or early satiety, which may
disappear immediately following passage of a
large stool
Include >2 of the following occurring at least once per
week for a minimum of 1 mo with insufficient criteria for a
diagnosis of irritable bowel syndrome:
1. <2 defecations in the toilet per week in a child with
developmental age of ‡4 y
2. >1 episode of fecal incontinence per week (after toilet
training)
3. History of retentive posturing or excessive volitional
stool retention
4. History of painful or hard bowel movements
5. Presence of a large fecal mass in the rectum
6. History of large-diameter stools that can obstruct the
toilet
After appropriate medical evaluation, the symptoms
cannot be explained by another medical condition
Simplified approach to constipation in >6mo
FC without fecal
constipation
History taking, impaction
physical exam,
Red flags?
occult blood test Tx: education,
Refer for YES NO behaviour,
Maintenance
further modification, diet
therapy if
evaluation Functional modification, oral
effective
constipation medications, close
follow-up
FC with fecal
impaction? Not effective

Reassess, reeducate,
Initiate oral/ rectal medication Maintenance
monitor treatment
for disimpaction therapy if
adherence, change
effective
FC without fecal medications
Effective?
impaction
Not effective If fail despite good
adherence and
education, refer for
further evaluation
Complete
ESPGHAN
NASPGHAN
algorithm for
evaluation and
treatment of
constipation in
> 6mo
 • When to start using medication?
Rational use of • What medication to use?
medication in • How long to use?
constipation • When to switch?
• When to stop?
Hard stool
Commonly used oral and rectal laxatives
 Type of medications for constipation

BULK-FORMING LAXATIVES
OSMOTIC AGENTS PROKINETIC AGENTS
Retain fluid in stool → ↑stool LUBRICANTS
Poorly absorbable substance → Act on intrinsic neuron 5-
weight and consistency
draw water into lumen Hydroxytryptamine receptors Mineral oil→ aids tool passage
e.g. psyllium, fiber,
e.g. milk of magnesia, lactulose, → inducing mucosal secretion smoothly
carboxymethylcellulose,
sorbitol, PEG e.g. cisapride,
methylcellulose

STIMULANT LAXATIVES
LINACLOTIDE
Stimulate myenteric plexus → SURFACE ACTIVE AGENTS LUBIPROSTONE
↑intestinal secretion and Induces cGMP → CFTR
Lower surface tension → water Cl channel activator → water
motility, ↓luminal water regulator → water and
and fats penetrating stool → and Cl secretion onto stool
absorption electrolyte secretion into the
soften stool →softer consistency
lumen
e.g. bisacodyl, senna, cascara
Lactulose
• As a laxative and as a treatment for porto-systemic encephalopathy
• Active substance: 1,4 beta gallactoside-fructose

• Mechanism of action:
• Indigestible by human (lacks lactulose) → reaches colon →
digested by colonic bacteria → monosaccharides, volatile fatty
acids, hydrogen methane → ↑gas and osmolality → ↓ intestinal
transit time → laxative effect
Lactulose
• Mechanism of action in reducing ammonia:
• Lactulose (prebiotic) → substrate for bacteria (probiotic) → increased
ammonia uptake (NH3 → NH4+) → unable to penetrate mucosal barrier →
decreases ammonia (treatment for encephalopathy)
• Lactulose → decreases pH → acidic environment decreases urease-producing
bacteria & blocks glutamine uptake → decreased ammonia production
(treatment for hepatic encephalopathy)

• Evidence:
• Lactulose (prebiotic) → significantly alters gut microbiota in rat model of
hepatic encephalopathy
• Increase in Bifidobacteria, and decreases Enterobacterceae colony (colon
colony, and decreases upshift of bacteria count (stomach-jejunum-ileum-
colon) → decreases likelihood of bacteria translocation)
Phases of constipation treatment in children

Phase 1
Phase 2
Target:
Bowel emptying Phase 3
Target:
Restore muscle tone, Target:
Duration: return of gut diameter to
normal size, stool softens Restore regular bowel
1-3 days movements & relapse
avoidance
Duration:
>2-6months Duration:
>4-6 months
Fecal disimpaction
• If fecal impaction present → disimpaction is required before initiation of
maintenance therapy
• Oral medications compared to rectal
• Less invasive, need cooperation, slower to relieve symptoms
• Polyethylene glycol-based solutions (Miralax)
• Effective, easy to administer, nonivasive, well-tolerated
• Rectal therapies VS PED = equally effective

ESPGHAN NASPGHAN recommendations

• PEG with or without electrolytes orally 1 to 1.5 g /kg/day for 3 to 6 days is recommended as the first-
line treatment for children presenting with fecal impaction.
• An enema once per day for 3 to 6 days is recommended for children with fecal impaction, if PEG is
not available.
Medications for disimpaction
Maintenance therapy in constipation
• Goal: soft bowel movements (1x/day) → avoid reacummulation of
stool
• Evidence:
• laxatives not much more effective than placebo (??)
• PEG is more superior than other laxatives (lactulose, milk of magnesia)

• Maintenance duration:
• Several weeks to months after regular bowel habit established
• After toilet training is well established

• Limited data on stimulant laxative use in children

• Use should be reserved for older children, and when osmotic laxative is
ineffective
 Maintenance therapy in constipation
ESPGHAN NASPGHAN recommendations
• PEG with or without electrolytes is recommended as the first-line maintenance
treatment. A starting dose of 0.4 g /kg/day is recommended and the dose should
be adjusted according to the clinical response

• Lactulose is recommended as the first-line maintenance treatment, if PEG is not

available.

• Based on expert opinion, the use of milk of magnesia, mineral oil, and stimulant
laxatives may be considered as an additional or second-line treatment.

• Addition of enemas to the chronic use of PEG is not recommended.

• Maintenance treatment should continue for at least 2 months. All symptoms of

constipation symptoms should be resolved for at least 1 month before
discontinuation of treatment. Treatment should be decreased gradually.
Medications for maintenance
Key recommendations for practice
Conclusion
• Constipation is a common problem in healthy infants and children, be
careful in diagnosing constipation for exclusive breastfed <6 mo babies

• Rarely a sign of a more serious disease in the absence of red flags

symptoms

• We should focus on fecal elimination using reassurance and no/minimal

medical intervention

• If medical interventions needed, Lactulose is recommended as the first-

line maintenance treatment, if PEG is not available.
THANK YOU