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A. Criteria (Rome II; Table 1, Ref [1])

  1. Adults
    1. At least 2 of the following for at least 12 weeks (may be nonconsecutive) in past year:
    2. Less than 3 bowel movements per week
    3. Straining during >25% of bowel movements
    4. Lumpy or hard stools for >25% of bowel movements
    5. Sensation of incomplete evaucation for >25% of bowel movements
    6. Manual maneuvers to facilitate >25% of bowel movements (such as digital evacuation)
    7. Loose stools not present, and insufficient criteria for irritable bowel syndrome
  2. Infants and Children
    1. Firm stools <3 times per week for at least 2 weeks
    2. Pebble-like hard stools for majority of bowel movements for at least 2 weeks
    3. No evidence of structural, endocrine, or metabolic disease

B. Etiology

  1. Drugs
    1. Aluminum-containing antacids
    2. Anticholinergics
    3. Calcium-channel blockers (especially verapamil)
    4. Opiates
    5. Iron
  2. Abdominal / Peritoneal Process
    1. Peritonitis
    2. Cholecystitis
    3. Gallstone Ileus
    4. Appendicitis
    5. Diverticulitis
    6. Pancreatitis
  3. Metabolic
    1. Hypercalcemia
    2. Hypothyroidism
    3. Uremia
    4. Hypokalemia
    5. Diabetes with autonomic neuropathy
  4. Obstruction
    1. Rectal adenocarcinoma
    2. Colon adenocarcinoma
    3. Metastatic or Bulk Neoplastic Disease
    4. Rectal Prolapse
    5. Fibrosis / Stricture (post-surgical, post-peritonitis, Crohn's Disease, others)
    6. Anal Fissure - may be related to constipation
    7. Endometriosis
    8. Post-surgical "ileus"
  5. Post-Surgical Ileus
    1. Major abdominal surgery
    2. Pelvic surgery
    3. May be related to release of endogenous opiates
  6. Myopathic
    1. Scleroderma
    2. Amyloidosis
  7. Neuropathic
    1. Cerebral Infarction
    2. Multiple Sclerosis
    3. Hirschprung's Disease
    4. Parkinson's Disease
    5. Chagas' Disease
    6. Ganglioneuromatosis
  8. Food Intolerance
    1. Particularly in young children and infants
    2. Try avoidance of dairy products, substituting soy milk [3]
  9. Functional
    1. Idiopathic chronic constipation
    2. Irritable bowel syndrome, constipation variant (IBS-c)

C. Evaluation

  1. Must rule out obstruction
    1. Barium Enema
    2. Small intestinal follow through (from upper gastrointestinal tract)
    3. Small intestinal transit time
    4. Initial screening abdominal radiograph may be helpful
  2. Age >50 years with new complaint of constipation
    1. Colon Cancer is a major concern
    2. Left sided cancers often present with constipation (obstruction)
  3. Colonic Motor Function tests
  4. Anorectal and pelvic floor tests

D. Treatment

  1. Empiric trials may be acceptable once differential is created and obstruction ruled out
  2. Underlying cause
  3. Discontinue drugs
    1. May be very difficult for pain medications - particularly opiates
    2. Intravenous methylnaltrexone blocks peripheral GI receptors and reverses constipation due to methadone [4]
  4. Surgical (Post-Operative) Ileus [5]
    1. Exacerbated by opiates for treatment of pain
    2. ADL 8-2968 is an opiod antagonist with limited oral absorption
    3. Does not cross blood-brain barrier
    4. Reduced time to first bowel movement and hospital stay after major abdominal surgery
  5. Chronic Constipation [1,2]
    1. Prune juice may be helpful
    2. Bulk Laxatives
    3. Osmotic Laxatives
    4. Poorly Absorbed Sugars
    5. Stimulant Laxatives
    6. Rectal Enema or Suppository
    7. Drugs acting on GI tract
    8. Doses given are for adults
    9. Overall, good evidence supports use of polyethylene glycol (PEG) and tegaserod (Zelnorm®) for chronic constipation; moderate evidence for lactulose, psyllium [7]
  6. Bulk Laxatives
    1. Dietary Fiber (Psyllium) ~20gm/day with ample daily fluid intake
    2. Psyllium (Metamucil®, Perdiem®, Fiberall®)
    3. Methylcellulose (Citrucel®) ~20gm/day
    4. Polycarbophil (Fibercon®, Equalactin®, Konsyl®) ~20gm/day
  7. Osmotic Laxatives
    1. Generally not recommended for chronic use
    2. Magnesium Hydroxide (Milk of Magnesia®) 15-30mL qd - bid
    3. Magnesium citrate (Evac-Q-Mag®) 150-300mL prn
    4. Sodium Phosphate (Fleet Enema®, Fleet Phospho-Soda®, Visicol®) 10-25mL + 360mL water
  8. Poorly Absorbed Sugars
    1. Lactulose (Cephulac®, others) 10-30mL/day (10g/15mL) to maximum of 60mL/day
    2. Mannitol 15-30mL qd or bid
    3. Sorbitol 15-30mL qd or bid
    4. Polyethylene glycol (PEG 3350, MiraLax®) - 17-36gm qd or bid for 2 weeks or less
    5. PEG with electrolytes (Colyte®, GoLYTELY®, NuLYTELY®) - 17-36gm qd or bid
    6. PEG shows good efficacy in chronic constipation [7]
  9. Stimulant Laxatives
    1. Docusate (Colace®) - stool softener, not true laxative; 50-200mg/day
    2. Bisacodyl (Dulcolax®) - stimulant laxative, 5mg tabs (10mg suppositories)
    3. Sodium Picosulfate (Lubrilax®, Sur-lax®) 5-15mg qhs
    4. Senna (Senokot®, Ex-Lax®): anthraquinone 187mg qd
    5. Cascara sagrada (Colamin®, Sagrada-lax®): anthraquinone 325mg/5mL daily
    6. Senna (Senokot®) -1-2 tabs po qd-tid
    7. Mineral Oil (Fleet Mineral Oil) 5-15mL po qhs
    8. Long term (>3 month) use of anthraquinones can cause melanosis coli [6]
  10. Rectal Enema or Suppository
    1. Phosphate enema (Fleet®) 120mL qd
    2. Mineral oil retention enema (Fleet Mineral Oil) 100mL qd
    3. Tap water enema 500mL qd
    4. Soapsuds enema 1500mL qd
    5. Glycerin bisacodyl suppository 10mg daily
  11. Drugs Stimulating GI Tract
    1. Lubiprostone (Amitiza®): chloride channel activator, not absorbed, activates CIC-2 chloride channels; dose is 24 mg po bid with food; mild side effects nausea, headache, diarrhea [8]
    2. Lubiprostone is FDA aprpoved for both chronic constipation and IBS-c
    3. Prostaglandin Analog: Misoprostal (Cytotec®) 100-200µg po bid-qid to effect
    4. Tegaserod (Zelnorm®), a serotonin 5-HT4 agonist, 6mg po bid effective in constipation predominant IBS and idiopathic chronic constipation [7]
    5. Tegaserod use may slightly increase ischemic cardiovascular events (but not QTc) and its use should be restricted to women or others that have no responded to other agents
    6. Prucalopride (Movetis®) - 5-HT4 agonist 2-4mg po qd improved laxation in >30% of patients with severe constipation versus 12% on placebo [9]
    7. Methylnaltrexone (Relistor®) - µ-opioid receptor antagonist, 0.15mg/kg given SC qod for 14 weeks significantly improved laxation in opioid-dependent patients with advanced illness [10]
    8. Strongly consider methylnaltrexone for opioid-induced chronic constipation; has no effect on pain-reducing effects of opioids
    9. Colchicine - 0.6mg po bid-qid to effect; generally
    10. Cholinergic Agent: bethanechol (Urecholine®) 5-10mg po bid-qid (may cause hypotension)
    11. Cisapride (Propulsid®), another 5-HT4 agonist, withdrawn due to QTc prolongation, arrhythmia risk
  12. Botulinum toxin injection into puborectalis muscle may relieve spastic pelvic floor muscles
  13. Biofeedback
  14. Severe, Intractable Constipation
    1. Rectal surgery
    2. Colectomy
    3. Other surgery

E. Associated Conditions

  1. Diverticulosis
  2. Hemorrhoids
  3. Impaction (obstruction)
  4. Anal Fissures
  5. Anorectal Bleeding

References

  1. Lembo A and Camilleri M. 2003. NEJM. 349(14):1360 abstract
  2. Horwitz BJ and Fisher RS. 2001. NEJM. 344(24):1846 abstract
  3. Iacono G, Cavataio F, Montalto G, et al. 1998. NEJM. 339(16):1100 abstract
  4. Yuan CS, Foss JF, O'Connor M, et al. 2000. JAMA. 283(3):367 abstract
  5. Taguchi A, Sharma N, Saleem RM, et al. 2001. NEJM. 345(13):935 abstract
  6. Ahmed S and Gunaratnam NT. 2003. NEJM. 349(14):1349 abstract
  7. Ramkumar D and Rao SS. 2005. Am J Gastroenterol. 100:936 abstract
  8. Lubiprostone. 2006. Med Let. 48(1236):47 abstract
  9. Camilleri M, Kerstens R, Rykx A, Vandeplassche L. 2008. NEJM. 358(22):2344 abstract
  10. Thomas J, Karver S, Cooney GA, et al. 2008. NEJM. 358(22):2332 abstract