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Chronic constipation - an evidenced based approach

Robert A. Baldor, MD, FAAFPProfessor, Family Medicine & Community

HealthUMass Medical School

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Learning Objectives

• by the end of the session, you will have a clear understanding of the basic pathophysiology related to chronic constipation

• …and develop an evidenced based approach for the primary care diagnosis and treatment of these chronic problems.

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Mrs Z.• A 34-year-old white female who complains

of constipation; she hasn’t discussed it in the past as “it’s embarrassing,” but states that she has been constipated her entire life and has tried a variety of OTC products without much relief.

• She further reports that she is very active, runs 4 days a week, that she always has a bottle of water with her and tries to eat salads regularly…..

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History

• Character of the problem– Consistency– Frequency– Straining, bloating– Diarrhea

• Medications

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Mrs. Z• Doesn’t have much discomfort, but has to strain

and has hard stools along with blood occasionally on TP – she tends to go about twice a week

• She will occasionally have diarrhea – but it seems related to something she had eaten

• Takes Tums for her ‘bones’

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Constipation No Clear Definition

A group of syndromes with similar findings

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Am College of Gastroenterology …

Unsatisfactory defecation, characterized by infrequent stools and/or difficult stool passage

Brandt 2005

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Pathophysiology…

• As food leaves stomach, gastroileal reflex relaxes the ileocecal valve and digested food (chyme) enters the colon

• Peristaltic contractions move chyme through the colon

• Na+ actively absorbed - water follows because of the generated osmotic gradient

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Normal Colonic Transit Time

• A meal reaches the ileo-cecal valve in 4 hours…the sigmoid colon 12hours later… then slows to the anus.

• Plastic pellets with a meal → 70% recovered in 3 days; remainder in a week!

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Defecation• Food distends the stomach, initiating the gastro-colic

reflex causing rectal contractions & a desire to go!• ‘Urge to defecate’ occurs as rectal pressures ↑• Defecation reflexes can be inhibited by voluntarily

contracting the external sphincter or facilitated by straining

• Pelvic floor/anal sphincter dysfunction interfere with normal defecation

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Most with primary constipation suffer from which one of the following?

1. Slow colonic transit time2. Pelvic floor/anal sphincter dysfunction3. Functional – normal transit time and

sphincter function

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Most with primary constipation suffer from which one of the following?

1. Slow colonic transit time2. Pelvic floor/anal sphincter dysfunction3. Functional – normal transit time and

sphincter function

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Secondary Constipation

• Endocrine dysfunction (DM, hypothyroid)• Metabolic disorder (↑ Ca,↓ K)• Mechanical (obstruction, rectocele)• Pregnancy• Neurologic disorders (Hirschsprung’s,

multiple sclerosis, spinal cord injuries)

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Medication Effect• Anti-cholinergic effects

– Antidepressants– Narcotics– Antipsychotics

• Calcium channel blockers• Antacids (calcium, aluminum)

Mrs. Z taking Tums (ca carbonate) for osteoporosis - ca phosphate (Posture) and ca citrate (Citracal) less constipating.

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IBS ? Rome III Criteria

• Symptoms at least 3 days/month of recurrent abdominal pain or discomfort associated with hard constipated stools interrupted by brief episodes of diarrhea …

Drossman Gastroenterology. 2006

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IBS Treatment

• Multiple RCTs with inconsistent results – best evidence for treating IBS-C:– Bulking agents– Psychotropic agents

DARE review 2001

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Red flags

1. Onset after age of 502. Hematochezia/melena3. Unintentional weight loss4. Anemia5. Neurological defects

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Physical Exam

• Digital rectal examination – Stool character– Pain, anal tone– Masses, fissures, hemorrhoids,

• Abdominal/gynecological exam– Masses, pain

• Neurological exam

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Treatment – Behavioral

• Toileting program to take advantage of natural reflexes

• Obey the urge – Gastro-colic– Defecation reflex

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Medications - Laxatives

• Bulking agents• Stool softeners• Osmotic agents• Stimulants• Lubricants• Other

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Bulking Agents at the Grocery Store…

• Vegetables• Fruits• Whole grain foods• Bran (hard outer layer of cereal grains)*

• Bloating and gas can be problematic– Gradually increase intake to 25 grams/day– Less fermentable fiber like wheat bran tends to be

better tolerated

* Limited evidence for effectiveness

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Food Serving Fiber (Gm)

All Bran® cereal 1/3 cup 10

Whole wheat bread 2 slices 4

Wheat bran muffin medium 3

Brown rice 1cup 3

Apple/Pear medium 4

Banana medium 3

Dried figs 5 8

Prune juice 1 cup 3

Sunflower seeds ¼ cup 3

Baked potato w/skin medium 4

Canned baked beans ½ cup 5

Chickpeas ½ cup 5

Lentils/ Kidney beans ½ cup 8

Corn ½ cup 2

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Bulking Agents at the Pharmacy…• Moderate evidence

– Psyllium (Metamucil 2.5gms fiber/dose)• Limited evidence

– Bran methycellulose (Citrucel 2gms fiber/dose)– Polycarbophil (Fibercon)

Fiber needs to be accompanied by adequate amounts of liquid to be useful - 8oz/2-3gms of added fiber!

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Stool Softeners – Limited Evidence

• Contain docusate (Colace), an anionic detergent with hydrophilic and hydrophobic ends that improves the ability of water to mix with and soften the stool

• Helpful to soften stools to make defecation easier (post-op, childbirth)

• Helpful for hemorrhoids or anal fissures• ↑ dose if no effect is seen after a week

– 40-400mg daily QD-QID

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Stimulants (Irritants)

• Irritate bowel, causing muscle contractions – often in combination with ducosate – work in 8-12 hrs (try qhs, increase to BID)

• Senna/ducosate (Senokot-S, Ex-lax - max 4/d)• Bisacodyl/ducosate (Dulcolax, Correctol- max

30mg/d)• Casanthranol/ducosate (Peri-colace – max 2/d)

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Stimulant Suppositories …

• Contain bisacodyl/ducosate (Dulcolax)• Glycerin suppositories also believed to

have their effect by irritating the rectum• Insertion of the suppository into the

rectum may itself stimulate a bowel movement

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Osmotic Laxatives• Polyethylene glycol - PEG (good evidence)

– 17 grams daily• Saccharines – lactulose (moderate evidence)

– flatulence, bloating, cramping – 15 - 120 ml qhs

• Sorbitol (effective as lactulose in elderly men*)– less bloating than lactulose– 15 - 120 ml qhs

• Magnesium salts (MOM)– avoid in renal insufficiency, best for acute treatment

* Lederle. ACP Journal Club, 1991.

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A Closer Look at Polyethylene Glycol - good evidence for use

• PEG: Large, chemically inert polymer, with substantial osmotic activity– Bowel flora unable to metabolize– Pulls water into colon to soften and increases

fecal bulk (takes 2-4 days to work)– First used in a balanced electrolyte solution for

colon cleansing (Golytely)– PEG 3350 (Miralax) or with electrolytes

(Movical)

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Lubricant Laxatives

• Contain mineral oil (15-45 ml/day)• Short-term use only

– Binds fat-soluble vitamins– May decrease absorption of some drugs

• Avoid lubricants in those at risk for aspiration (lipid pneumonia)

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Lubiprostone (Amitiza)• Selective Chloride channel activator

↑ secretion of Cl- ions into small bowel; Na+ and water follow, resulting in a softer, bulkier stool

• 24 mcgs BID• Nausea is common (32%) • Avoid use in pregnancy, breast-feeding

Methylnaltrexone (Relistor)

• Methyl group reduces lipidophilic properties of the opioid antagonist naltrexone - ↓ ability to cross blood-brain barrier

• Peripherally Acting Mu-Opioid Receptor (PAM-OR) antagonist

• Indicated for palliative care• For short-term use (< 4months)• Side effects - abdominal pain and flatulence

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Other, Non-FDA Approved Agents, Act to Decrease Transit Time

• Misoprostol (Cytotec 100-200mcg QID) – a prostaglandin increases colonic motility1

• Colchicine (0.6mg qd - tid)– neurogenic stimulation ↑ colonic motility 2

1.Roarty. Alimen pharm & Therapeutics. 19972. Verne. Am J. Gastroenterology. 2003, Frame J ABFP, 1998

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A Practical Approach…

R/O treatable secondary causes..Am Gastroenterological Assn (AGA) guidelines:

• CBC, Glucose, TSH, calcium, creatinine• Sigmoid/colonoscopy if red flags are present.

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Address Immediate Concerns

• Bloating/discomfort/straining – Osmotic agent like PEG

• Post-op, childbirth, hemorrhoids, fissures– Stool softener to make defecation easier

• Stimulants and suppositories acutely• Manual disimpaction as needed

then approach the chronic condition….

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Start with Lifestyle Changes …

• Exercise, increase fluids and fiber to 25 grams/day over a period of 6 weeks.* – Fiber must be accompanied by sufficient fluid– Initial approach – fruits and vegetables– Add commercial bulking agents

• Obey the ‘Urge’!• For children trial of rice vs cow’s milk

* Uncontrolled studies support fiber for normal transient constipation. Am J Gastroenterol. 1999; G Nutr 4/2010

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If No Improvement…

• Add osmotic laxative – adjust dose slowly until stools are soft – take several days to work– caution if CHF or renal insufficiency

• Add stimulant laxatives• Lubiprostone

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Trial of Other Agents…

• Misoprostol (Cytotec)• Colchicine

Refractory to empiric approach .…

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Pursue Diagnostic Evaluation• Colonoscopy if not indicated sooner ….• Barium enema for obstruction/megacolon• Radiopaque Sitz-Markers to measure transit time

– markers ingested, KUB in 5 days – retention >20% markers indicates slow transit– markers seen exclusively in distal colon/rectum

suggests pelvic floor dysfunction

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Referral to evaluate defecation….

• Balloon expulsion• Defecography using a barium paste.• Anorectal manometry with a rectal

catheter• Biofeedback with artificial silicon stool • Surgery rarely indicated

Enck. Dig Dis Sci. 1993

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Summary….• Constipation - unsatisfactory defecation, with

infrequent stools, difficult stool passage or both• Functional constipation (normal transit time and

sphincter function) seen most often• Work-up is necessary in the presence of red flags

– onset >50 yrs; hematochezia/melena; unintentional weight loss; anemia; neurological defects

• Best evidence for effectiveness is for osmotic agents

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Long-term Laxative Concerns…

• No evidence for addiction• No evidence for tolerance• No evidence for dependence• No evidence for harm from stimulant use,

melanosis coli may develop, but it is a benign condition

Muller-Lissner. Am J Gastroenterology. 2005

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The End!

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