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Constipation
S. Mimi Mukherjee, PharmD
Sandhya Ventrapragada, MBBS, MD
image BASICS
Unsatisfactory defecation characterized by infrequent stools, difficult stool passage, or both. Characteristics include <3 bowel movements a week, hard stools, excessive straining, prolonged time spent on the toilet, a sense of incomplete evacuation, and abdominal discomfort/bloating.
DESCRIPTION
  • System(s) affected: gastrointestinal (GI)
  • Synonym(s): obstipation
Geriatric Considerations
Colorectal neoplasms may be associated with constipation; new-onset constipation after age 50 years is a “red flag.” Use warm water enemas for impaction instead of sodium phosphate enema in geriatric patients. Sodium phosphate enemas have been associated with fatalities and severe electrolyte disturbances (1)[B].
Pediatric Considerations
Consider Hirschsprung disease (absence of colonic ganglion cells): 25% of all newborn intestinal obstructions, milder cases diagnosed in older children with chronic constipation, abdominal distension, decreased growth; 5:1 male-to-female ratio; associated with inherited conditions such as Down syndrome
Pregnancy Considerations
Avoid misoprostol. Other agents consider risks versus benefits.
EPIDEMIOLOGY
  • More pronounced in children and elderly
  • Predominant sex: female > male (2:1)
  • Nonwhites > whites
Incidence
  • 5 million office visits annually
  • 100,000 hospitalizations
Prevalence
˜15% of population affected
ETIOLOGY AND PATHOPHYSIOLOGY
  • As food leaves the stomach, the ileocecal valve relaxes (gastroileal reflex) and chyme enters the colon (1 to 2 L/day) from the small intestine. In the colon, sodium is actively absorbed in exchange for potassium and bicarbonate. Water follows the osmotic gradient. Peristaltic contractions move chyme through the colon into the rectum. Chyme is converted into feces (200 to 250 mL).
  • Normal transit time is 4 hours to reach the cecum and 12 hours to reach the distal colon.
  • Defecation reflexively follows once stool reaches the rectal vault. This reflex can be inhibited by voluntarily contracting the external sphincter or facilitated by straining to contract the abdominal muscles while voluntarily relaxing the anal sphincter. Rectal distention initiates the defecation reflex. The urge to defecate occurs as rectal pressures increase. Distention of the stomach by food also initiates rectal contractions and a desire to defecate (gastrocolic reflex).
  • Primary constipation
    • Slow colonic transit time (13%)
    • Pelvic floor/anal sphincter dysfunction (25%)
    • Functional: normal transit time and sphincter function, subjective symptoms (bloating, abdominal discomfort, perceived difficulty defecating, presence of hard stools) (69%)
  • Secondary constipation
    • Irritable bowel syndrome (IBS)
    • Endocrine dysfunction (diabetes mellitus, hypothyroid)
    • Metabolic disorder (increased calcium, decreased potassium)
    • Mechanical (obstruction, rectocele)
    • Pregnancy
    • Neurologic disorders (Hirschsprung, multiple sclerosis, spinal cord injuries)
  • Medication effect
    • Anticholinergic effects (antidepressants, narcotics, antipsychotics)
    • Antacids (calcium, aluminum)
    • Nondihydropyridine calcium channel blockers, especially verapamil
Genetics
Unknown but may be familial
RISK FACTORS
  • Extremes of life (very young and very old)
  • Polypharmacy
  • Sedentary lifestyle or condition
  • Improper diet and inadequate fluid intake
GENERAL PREVENTION
High-fiber diet, adequate fluids, exercise, and training to “obey the urge” to defecate
COMMONLY ASSOCIATED CONDITIONS
  • General debilitation (disease or aging)
  • Dehydration
  • Hypothyroidism
  • Hypokalemia
  • Hypercalcemia
image DIAGNOSIS
  • New onset after age of 50 years
  • Hematochezia/melena
  • Unintentional weight loss
  • Anemia
  • Neurologic defects
PHYSICAL EXAM
  • Vital signs, height, weight
  • Digital rectal exam (masses, pain, stool, fissures, hemorrhoids, anal tone)
  • Abdominal/gynecologic exam (masses, pain)
  • Neurologic exam
DIFFERENTIAL DIAGNOSIS
Congenital
  • Hirschsprung disease/syndrome
  • Hypoganglionosis
  • Congenital dilation of the colon
  • Small left colon syndrome
DIAGNOSTIC TESTS & INTERPRETATION
Primarily a clinical diagnosis
Initial Tests (lab, imaging)
CBC, glucose, TSH, calcium, and creatinine routinely and sigmoid/colonoscopy if red flags are present
Follow-Up Tests & Special Considerations
  • If condition is refractory, pursue further testing:
    • Colonoscopy
    • Barium enema to look for obstruction and/or megarectum, megacolon, or Hirschsprung disease
  • Additional testing
    • Measure colonic transit time by ingesting radiopaque (Sitz-Mark) markers.
    • Plain abdominal film obtained 5 days later (120 hours): Retention of >20% markers indicates slow transit.
    • Markers seen exclusively in distal colon/rectum suggests defecatory disorder.
Diagnostic Procedures/Other
Consider referral in refractory cases:
  • Balloon expulsion
  • Defecography using a barium paste
  • Anorectal manometry with a rectal catheter
Test Interpretation
  • Most cases are functional.
  • Paucity or absence of intramural enteric ganglia in certain cases of congenital or acquired megacolon
  • Neuromuscular abnormalities in certain cases of pseudo-obstruction
image TREATMENT
Address immediate concerns:
  • Bloating/discomfort/straining: osmotic agents
  • Postoperative, after childbirth, hemorrhoids, fissures: stool softener to aid defecation
  • If impacted: manual disimpaction, then treat the chronic underlying condition
GENERAL MEASURES
  • Attempt to eliminate medications that may cause or worsen constipation.
  • Increase fluid intake.
  • Increase fiber in diet.
  • Enemas if other methods fail
P.225

MEDICATION
In patients with no known secondary causes of constipation, conservative nonpharmacologic treatment is recommended.
  • Regular exercise
  • Increased fluid intake
  • Bowel habit training
First Line
Bulking agents (must be accompanied by adequate amounts of liquid to be useful):
  • Hydrophilic colloids (bulk-forming agents)
    • Psyllium (Konsyl, Metamucil, Perdiem Fiber): 1 tbsp in 8-oz liquid PO daily up to TID
    • Methylcellulose (Citrucel): 1 tbsp in 8-oz liquid PO daily up to TID
    • Polycarbophil (Mitrolan, FiberCon): 2 caplets with 8-oz liquid PO up to QID
  • Stool softeners
    • Docusate sodium (Colace): 100 mg PO TID
  • Osmotic laxatives
    • Polyethylene glycol (PEG) (MiraLax) 17 g/day PO dissolved in 4 to 8 oz of beverage (current evidence shows PEG to be superior to lactulose) (3)[B]
    • Lactulose (Chronulac) 15 to 60 mL PO QHS (flatulence, bloating, cramping)
    • Sorbitol: 15 to 60 mL PO QHS (as effective as lactulose)
    • Magnesium salts (milk of magnesia) 15 to 30 mL PO once daily; avoid in renal insufficiency
Second Line
  • Stimulants (irritate bowel, causing muscle contraction; usually combined with a softener; work in 8 to 12 hours)
    • Senna/docusate (Senokot-S, Ex-lax, Peri-Colace): 1 to 2 tablets or 15 to 30 mL PO at bedtime
    • Bisacodyl (Dulcolax, Correctol): 1 to 3 tablets PO daily
  • Lubricants (soften stool and facilitate passage of the feces by its lubricating oily effects)
    • Mineral oil (15 to 45 mL/day)
    • Short-term use only. Can bind fat-soluble vitamins, with the potential for deficiencies; may similarly decrease absorption of some drugs
    • Avoid in those at risk for aspiration (lipoid pneumonia)
  • Suppositories
    • Osmotic: sodium phosphate
    • Lubricant: glycerin
    • Stimulatory: Bisacodyl
    • Enemas: saline (Fleet enema)
  • Lubiprostone (Amitiza): a selective chloride channel activator; 24 &mgr;g PO BID
  • Linaclotide (Linzess): guanylate cyclase-C agonist; dose: 145 &mgr;g PO once daily; adult use only
    • Avoid in children <6 years.
    • Peripherally acting &mgr;-opioid receptor antagonists, indicated for opioid-induced constipation
  • Methylnaltrexone (Relistor): dose: 38 to <62 kg: 8 mg; 62 to 114 kg: 12 mg SC every other day PRN
    • Naloxegol (Movantik): dose: 12.5 to 25.0 mg PO daily, discontinue other laxatives for 3 days when initiating naloxegol, avoid in patients on strong Cyp3A4 inhibitors due to increased naloxegol levels and risk of opioid withdrawal
  • Prokinetic agents (partial 5-HT4 agonists) have been withdrawn due to cardiac side effects; only available via IND protocols: tegaserod (Zelnorm), cisapride (Propulsid)
  • Other agents not approved by the FDA:
    • Misoprostol (Cytotec): a prostaglandin that increases colonic motility
    • Colchicine: neurogenic stimulation to increase colonic motility
ADDITIONAL THERAPIES
Other nonpharmacologic therapies include the following:
  • Biofeedback therapy
  • Behavior therapy
  • Probiotics
  • Electric stimulation
SURGERY/OTHER PROCEDURES
Surgery rarely indicated
INPATIENT CONSIDERATIONS
Toxic megacolon
Nursing
Manual disimpaction occasionally required in chronic refractory cases
image ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
Encourage exercise and physical activity.
Patient Monitoring
If functional constipation persists, consider organic cause.
DIET
Increase fiber (bloating and gas can be problematic):
  • Gradually increase intake to 25 g/day over a 6-week period.
  • Bran (hard outer layer of cereal grains)
  • Vegetables and fruits
  • Whole grain foods
  • Encourage liberal intake of fluids.
PATIENT EDUCATION
  • Occasional mild constipation is normal.
  • Bowel training: the best time to move bowels is in the morning, after eating breakfast, when the normal bowel transit and defecation reflexes are functioning.
PROGNOSIS
  • Occasional constipation responsive to simple measures is harmless.
  • Habitual constipation can be a lifelong nuisance.
  • Patients with neurologic compromise can suffer from ill effects such as obstipation, impaction, and toxic megacolon.
  • No evidence for laxative dependence
  • No evidence for harm from stimulant use; melanosis coli may develop, but it is a benign condition.
REFERENCES
1. Ori Y, Rozen-Zvi B, Chagnac A, et al. Fatalities and severe metabolic disorders associated with the use of sodium phosphate enemas: a single center's experience. Arch Intern Med. 2012;172(3):263-265.
2. Bharucha AE, Pemberton JH, Locke GR III. American Gastroenterological Association technical review on constipation. Gastroenterology. 2013;144(1):218-238.
3. Lee-Robichaud H, Thomas K, Morgan J, et al. Lactulose versus polyethylene glycol for chronic constipation. Cochrane Database Syst Rev. 2010;(7):CD007570.
Additional Reading
&NA;
  • Basilisco G, Coletta M. Chronic constipation: a critical review. Dig Liver Dis. 2013;45(11):886-893.
  • Bove A, Pucciani F, Bellini M, et al. Consensus statement AIGO/SICCR: diagnosis and treatment of chronic constipation and obstructed defecation (part I: diagnosis). World J Gastroenterol. 2012; 18(14):1555-1564.
  • Dimidi E, Christodoulides S, Fragkos KC, et al. The effect of probiotics on functional constipation in adults: a systematic review and meta-analysis of randomized controlled trials. Am J Clin Nutr. 2014;100(4):1075-1084.
  • Ford AC, Moayyedi P, Lacy BE, et al. American College of Gastroenterology monograph on the management of irritable bowel syndrome and chronic idiopathic constipation. Am J Gastroenterol. 2014;109(Suppl1):S2-S26.
  • van Dijk M, Benninga MA, Grootenhuis MA, et al. Chronic childhood constipation: a review of the literature and the introduction of a protocolized behavioral intervention program. Patient Educ Couns. 2007;67(1-2):63-77.
Codes
&NA;
ICD10
  • K59.00 Constipation, unspecified
  • K59.01 Slow transit constipation
  • K59.09 Other constipation
Clinical Pearls
&NA;
  • Constipation is unsatisfactory defecation with infrequent stools, difficult stool passage, or both for 3 months.
  • Functional constipation (normal transit time and sphincter function) is most common.
  • Workup red flags: onset >50 years, hematochezia/melena, unintentional weight loss, anemia, neurologic defects
  • Osmotic agents (PEG) have the most evidence supporting clinical effectiveness.