Constipation

Question 1

Pearls - Constipation

Answer 1

1. When writing an order for an opioid, order a laxative

2. Check the rectum as part of assessment of patients who are constipated

Question 2

Risk factors for constipation

Answer 2

• Lack of fluid or fibre in diet
• Malnutrition
• Decreased mobility
• Environmental factors
• Medications (diuretics, antacids, opioids, sedatives, antipsychotics, anticholinergics, TCAs, NSAIDs, antihistamines, iron, ondansetron, vincristine)
• Metabolic disorders (dehydration, hypercalcemia, hyponatremia, uremeia, hypothyroidism, DM)
• Advanced age or altered attention to rectal fullness
• Depression
• Chronic illness
• Malignancy affecting bowel, spinal cord
• Neurologic disorders (spinal cord compression, autonomic dysfunction)
• Anatomic abnormalities (masses in the pelvis/abdo, adhesions)
• Bowel factors (diverticular disease, rectocele, anal fissuer or stenosis, colitis, hemorrhoids)

In advanced cancer, most common culprits are opioids and debility.

Question 3

Physiology of Gut Motility

Answer 3

• Coordination of gut motility (coordinated through the myenteric plexus autonomic nervous system
• Acetylcholine (ach) and vasoactive intestinal peptide mediate peristalsis. ACh mediates ascending contraction, vasoactive intestinal peptide mediates descending relaxation. Further modulated by opioid receptors and anticholinergics, which can disrupt peristalsis.
• In the intestines, more mixing than propulsion to facilitate bacterial and enzymatic breakdown.
• Colonic transit: Episodic forward peristalsis about 6 times per day, with a largest one on wakening/breakfast and a smaller one at the midday meal. Frequency reduced by inactivity

Gut contents spend 2-4 hours in small bowel, then 24-48 hrs in colon (but may be up to 12 days!)

Question 4

Pathophysiology of Constipation with Opioids

Answer 4

• Opioids increase fluid reabsorption by prolonging transit time (more reabsorption) and inhibition of secretomotor neurons, resulting in less fluid in the gut.
• Opioids reduce peristaltic propulsion and enhance non-propulsive contractions
• Opioids reduce sensation of gut distention, including rectal distention, which may increase risk of fecal impaction.
• Opioids increase rectal sphincter tone

Typical causes of constipation result in increased fluid reabsorption and prolonged transit time

Question 5

How to approach laxatives with opioids

Answer 5

• Always prescribe a prophylactic bowel regimen
• PRN laxatives have little place in the prophylaxis of opioid-induced constipation - may cause alternation between constipation and diarrhea
• Titrate laxative dosing according to response (not opioid dose - constipating effects of opioids are not dose dependent)
• TD Fentanyl patch has decreased constipation when compared to morphine (based on inconsistent effect)
• Methadone may also reduce constipation and laxative requirements due to action on NMDA receptors
• Tramadol may be less constipating as actions are partly mediating by other receptor types

Question 6

Approach to treating constipation

Answer 6

• Individual symptoms, performance status, and preferences need to be considered
• Attention to laxative dosing can halve use of enemas and suppositories, which patients typically dislike.
• Exclude intestinal obstruction and treat correctable causes (e.g. TSH, hypercalcemia, etc.)

1. PEG and/or stimulant
2. If no improvement, rectal supp/enema, consider methylnaltrexone if on an opioid
3. If no improvement, manual evacuation, consider methylnaltrexone if on an opioid

Continue with regimen and encourage lifestyle changes.

Question 7

Stimulant laxatives (onset, side effects, mechanism of action)

Answer 7

• Bisacodyl, Senna
• Onset within 6-12 hours (dose at bedtime)

Side Effects:

• Cramping (may be reduced by BID dosing)
• Lyte disturbances

Mechanism of action: Stimulates myenteric plexus, increasing motility, decreasing fluid/lyte absorption

Indications: Reasonable choice for combating opiod-induced bowel dysfunction.

Question 8

Components of a constipation history

Answer 8

• Present pattern of BMs
• quantity, consistency of stool
• Difficulty with defacation (pain, hardness, etc.)
• Normal pattern of BMs prior to illness or med change (‘normal’ is q3 days to 3x a day)
• Colour (GI bleeding)
• Associated GI symptoms
• Medication history

Question 9

Physical examination for constipation

Answer 9

• Inspection
• Auscultation (all 4 quadrants), list for low-pitched, infrequent sounds.
• Palpation (including of bladder, which may be distended in severe constipation)
• Inspection of the anal area for fissures, tears, fistula, skin changes (resulting in avoidance of defecation and constipation)
• Volume status assessment (cause or consequence of constipation)
• Rectal examination (unless severe neutropenia or septicemia) - assess for loaded rectum or empty but ballooned rectum (fecal mass obstructing beyond the finger)

Question 10

Assessment of constipation

Answer 10

Visual Analog Scale (1-10)

Victoria Bowel Performance Scale (assess both constipation and diarrhea).

Consider TSH, Corrected calcium if clinical picture is suggestive.

• Ask patient number of episodes of formed stool leading to a sense of reasonably complete rectal evaluation, as compared to previous normal pattern.

May also use Bristol Stool Scale as a way to estimate stool form as an adjunct to measuring frequency.

Question 11

Imaging of the abdomen for constipation

Answer 11

Flatplat and upright AXR to evaluate fecal loading (note that this is contested)

• Scoring system to determine need for intervention. Colon divided into four sections (ascending, transverse, descending, recto-sigmoid) and stool versus air is noted. Points given:
  0 = no stool
  1 = stool < 50% of lumen
  2 = stool > 50% of the lumen
  3 = 100% of the lumen.
  If all four quadrants >7, intervention required.
• Note that AXR may differentiate between constipation and obstruction, but should otherwise not be a standard procedure.

Question 12

Docusate for Constipation?

Answer 12

• No more effective than placebo for increasing stool frequency, and no more effective than placebo in alleviating symptoms associated with constipation (e.g. difficulty passing stool, straining, etc.)

Question 13

Lifestyle Interventions for Constipation

Answer 13

• Adequate fluid intake (at least 1.5 L per day if taking fibre supplements)
• Physical activity
• Defecating when the urge hits, comfort and privacy to do so
• Abdominal massage
• Treating other context (e.g. pain and breathlessness to maximize mobility, nausea to maximize intake)

Question 14

Bulk-forming laxatives (onset, side effects, mechanism of action)

Answer 14

Bran, Psyllium, Methylcellulose

Onset 24-72 hrs

Side effects:
Bloating and flatulence

Mechanism of action:
Increased stool bulk, decreased transit time, increased GI motility. Requires adequate fluid intake, often inappropriate in advanced disease as it may precipitate obstruction.

Question 15

Surfactant Laxatives (onset, side effects, mechanism of action)

Answer 15

Docusate (24-72 hours)
Side effects: can cause cramps, diarrhea, nausea
MOA: Increased water penetration, detergent activity. Avoid mineral oil concurrently. Ineffective if overall hydration is poor, not recommended in recent guidelines. Consider in patients with painful defecation.

Mineral oil (6-8 hours)
Side effects: Malabsorption of fat soluble vitamins, other meds, nutritions. Risk of lipoid pna if aspirated, not recommended PO in palliative patients
MOA: Lubricates, softens stool

Question 16

Saline laxatives (onset, side effects, mechanism of action)

Answer 16

Magnesium, sodium phos

Onset: 1-6 hrs

Side Effects: Lyte disturbance, caution in renal, HTN, or cardiac disease as they can be absorbed systemically.

MOA: Osmotically active particles drawing fluid into colonic lumen, promotes reflex peristalsis by gut distention.

Question 17

Osmotic laxatives (onset, side effects, mechanism of action)

Answer 17

Lactulose, sorbitol
Onset: 24-48hrs
Side Effects: Sweet taste, nausea, cramping, flatulence.

MOA Osmotic gradient drawing fluid into intestinal lumen, increasing stool weight, increased peristalsis by mechanical distention. Increase fluids with this.

Question 18

Suppositories (onset, side effects, mechanism of action)

Answer 18

Glycerine
Onset 15 - 60 mins
Side effects: Rectal irritation
MOA: Softens stool in the rectum

Bisacodyl
Onset 15-60 mins
Side effects: Rectal irritation
MOA: Distends rectum, stimulates water and lyte secretion into colon

Question 19

Enemas (onset, side effects, mechanism of action)

Answer 19

Saline enema
Onset 15 min
Side effect: Rectal irritation
MOA: Increased intestinal water secretion, stimulates peristalsis, useful in cases of impaction

Sodium phos enema (Fleet enema)
Onset 15 mins
Side effect: Rectal irritation, hypocalcemia
MOA: Stimulates colonic peristalsis and provides additional volume.

Question 20

Prokinetic agents (onset, side effects, mechanism of action)

Answer 20

Domperidone
Onset: 30 - 60 mins
Side effects: Rarely, EPS - but does not cross the BBB
MOA: D2 antagonists, stimulates intestinal transit. Blocked by anticholinergics (gravol!)

Metaclopramide
Onset: 30-60 mins
Side effects: Confusion, EPS (dose dependent)
MOA: D2 antagonist, stimulates intestinal transit. Blocked by anticholinergic drugs (gravol!).

Question 21

Opioid antagonists as laxatives (onset, side effects, mechanism of action)

Answer 21

Methylnaltrexone or Naloxegol
Onset: 1-24 hrs, given subcut (Methylnaltrexone/Relistor) or PO (Naloxegol/Movantik).
Side effects: No loss of pain control. Contraindicated in bowel obstruction. Used only if osmotic laxatives fail. If after three doses, no effect, seek other tx. Typically used to remove an accumulation of stool with a ‘fresh start’ on typical laxatives.
MOA: Acts peripherally as opioid antagonist (selective mu-receptor antagonist, does not cross BBB) with no loss of analgesia unless arthritic or traumatic pain.

Naloxone
Onset: 1-3 hrs
Side effects: May precipitate opioid withdrawal and loss of pain control - when taken PO, systemic bioavailability of 3%. Limited use.
MOA: Acts as an opioid antagonist but crosses blood brain barrier and reverses analgesia.

Question 22

Constipation in Cord Compression

Answer 22

Caused by loss of rectal sensation, loss of voluntary control, poor anal tone, immobility, and pain. Ano-colonic reflex preserved in cord lesions.

High spinal cord transection abolishes motility response to food. Low cord lesions produce colonic dilatation and slowing of transit in descending and distal transverse colon.

Approach: Controlled continence
- Daily oral laxatives with suppositories q2-3 days, hopefully avoiding manual disimpaction

Question 23

Constipation in Cauda Equina

Answer 23

Caused by loss of rectal sensation, loss of voluntary control, poor anal tone, immobility, and pain. Abolishes the ano-colonic reflex.

Rectal stimulation by suppositories or by digit will stimulate the ano-colonic reflux, aiding in evacuation

Approach: Controlled continence
- Daily oral laxatives with suppositories q2-3 days

Question 24

Constipation definition

Answer 24

• “Passage of small, hard feces infrequently and with difficulty.”

Rome Criteria - >3 months, 2 or more of:

• Straining during at least 25% of defecation
• Sensation of anorectal obstruction during at least 25% of defecation
• Lumpy or hard stools at least 25% of the time
• Fewer than 3 BMs per week

Note that patient experience/perspective on bowel habits trumps all!

Question 25

Prevalance of constipation

Answer 25

General population: 10%, higher in females and older age, and with physical illness 50% of patients admitted to British hospices

Question 26

Autonomic neuropathy in constipation

Answer 26

May occur as a non-metastatic manifestation of malignancy (particularly with small cell lung ca and carcinoid tumours) (paraneoplastic autonomic neuropathy) Neural damage can cause gastroparesis or severe constipation.

Question 27

Physiology of Intestinal Fluid Handling

Answer 27

- 7L of fluid secreted into the gut each day (mucosal crypt cells), + 1.5L of dietary fluid - Most fluid reabsorbed by small bowel (jejunum, villous cells), about 1L left to enter the colon - Difference between constipation and diarrhea is about 100mL per day - Enteric nervous system activates secretion, blood flow, and smooth muscle contraction in response to mechanical stimulation of mucosal sensory neurons

Question 28

Common Palliative Care Meds implicated in constipation

Answer 28

- Opioids (disrupt forward propulsion, increase transit time) - TCAs, antihistamines, antipsychotics (anticholinergics, diminishing effect on ACh on peristalsis)

Question 29

Macrogols in constipation (Onset, side effects, mechanism of action)

Answer 29

PEG Onset: 24-72 hrs Side Effects: No increase in colonic gas, may cause mild diarrhea. Cochrane review found superior to lactulose in terms of stool frequency, form of stool, relief of abdo pain. MOA: Render water unabsorbable by gut - but require volume of water to dissolve. Also contribute to gut contraction as a reflex response to distention. - Best evidenced groups of laxatives! Have been shown to be an effective oral treatment for fecal impaction (but this could require consumption of up to a litre of solution)

Question 30

"Pitfall" in constipation: Intestinal obstruction by tumour or adhesions

Answer 30

Consider this in cases of known intra-abdominal malignant deposits, previous surgery, alternating constipation/diarrhea, gut colic, nausea and vomiting (though also a picture of severe constipation). Attempts to clear constipation through use of stimulant laxatives can causes severe pain in obstruction. AXR may help.

Question 31

"Pitfall" in Constipation: Nausea

Answer 31

Some patients experience nausea and/or vomiting with constipation - unexplained n/v should prompt enquiry/exam for constipation

Question 32

"Pitfall" in Constipation: Abdominal pain

Answer 32

Colicky abdominal pain is common in constipation due to the propulsion of hard feces, which may be exacerbated by abdominal/pelvic tumours. On palpation, fecal mass may be palpable but difficult to differentiate from tumour (though note feces will usually indent to firm pressure and give a crepitus like sensation due to gas). Rectal exam is helpful - if no stool, colonic inertia. May also find rectal tumour, rectocele, lax anal sphincter (spinal cord damage). Vaginal exam may be helpful if rectocele or compression from pelvic tumours is suspected. Hard pellet like stool - slow transit. Ribbon like stool - stenosis or hemorrhoids Blood or mucous - tumour, hemorrhoids, or coexisting colitis.

Question 33

"Pitfall" in constipation: Urinary incontience

Answer 33

Fecal impaction may precipitate urinary incontenince, especially in elderly. New onset incontinence - consider constipation!

Question 34

Macrogols in constipation (Onset, side effects, mechanism of action)

Answer 34

PEG Onset: 24-72 hrs Side Effects: No increase in colonic gas, may cause mild diarrhea. Cochrane review found superior to lactulose in terms of stool frequency, form of stool, relief of abdo pain. MOA: Render water unabsorbable by gut - but require volume of water to dissolve. Also contribute to gut contraction as a reflex response to distention. - Best evidenced groups of laxatives! Have been shown to be an effective oral treatment for fecal impaction (but this could require consumption of up to a litre of solution)