CONTENTS

• Complications of constipation
• Common causes of constipation
• Evaluation of constipation
• General approach to constipation
  • Stage 0: Consider impaction
  • Stage 1: Front-line therapies (including prophylaxis)
  • Stage 2: Refractory to front-line therapy
  • Stage 3: Persistent refractory constipation
  • Stage 4: Super-refractory constipation
• Commonly used medications:
  • Polyethylene glycol
  • Bisacodyl
  • Senna
  • Magnesium ➡️
  • Enemas
  • Medications to avoid

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defining constipation & bowel movement targets

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defining & diagnosing constipation

• Critically ill patients are all at high risk for constipation, usually due to several factors (e.g., critical illness, immobility, older age, and opioid use). The rate of constipation among ICU patients may be ~70% (with variation depending on case mixture). (19592200) Consequently, there should be a high pre-test probability that any ICU patient is constipated.
• The “normal” frequency of bowel movements is roughly between ~3/day and ~3/week. However, some individuals may have substantially different bowel habits.
• There is no great definition of constipation for hospitalized patients, especially intubated patients who are unable to communicate. Allen-Dicker et al. proposed defining constipation in a hospitalized patient as any of the following:
  • [a] A decrease in the frequency of bowel movements compared with the patient's ambulatory baseline.
  • [b] The absence of sensation of complete evacuation.
  • [c] Reported need for increased straining with defecation.
  • [d] The need for digitalization or per rectum therapy to evacuate.
  • (Unfortunately, this definition largely requires that the patient be able to communicate.)

bowel movement target frequency

• This is unknown and ideally may require personalization (based on the patient's baseline frequency of bowel movements). For example, if a patient generally has a bowel movement every 2-3 days, then going one day without a bowel movement isn't necessarily a cause for alarm. However, baseline slow bowel motility may be a risk factor for constipation, so this still requires close attention.
• If the patient isn't having bowel movements, it's not an emergency (e.g., there is no absolute requirement to have one bowel movement per day). Therefore, a gradual escalation of therapies should be instituted to promote bowel movements. Early and gradual escalation is beneficial in promoting adequate bowel movements without precipitating diarrhea. Many therapies require ~12-24 hours to work, so very rapid escalation of treatments within a 24-hour period is more likely to precipitate diarrhea.

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complications of constipation

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Although causation is difficult to prove, constipation can likely cause a variety of complications:

• Nutritional failure:
  • Inability to tolerate enteral feeding.
  • Emesis.
  • Malnutrition.
• Gastrointestinal pathology:
  • Anal fissure.
  • Hemorrhoids.
  • Rectal prolapse.
  • Fecal impaction requiring disimpaction.
  • Colonic pseudo-obstruction.
  • Bowel perforation.
• Respiratory dysfunction:
  • Aspiration following emesis.
  • Increased intraabdominal compartment pressure compresses the thorax, promoting dyspnea and basilar atelectasis.
• Neurological complications:
  • Pain and discomfort.
  • Delirium.

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common treatable causes of constipation

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[1/5] medications

• Opioids.
• Calcium channel blockers (e.g., diltiazem, verapamil, nifedipine).
• Anticholinergic medications, e.g.:
  • Antispasmodics (e.g., dicyclomine).
  • Antidepressants (e.g., amitriptyline).
  • Antipsychotics (e.g., quetiapine).
  • Antihistamines (e.g., diphenhydramine).
• Antiemetics (especially ondansetron).
• Oral iron preparations (these work poorly in critically ill patients and should arguably be avoided).
• Calcium supplements and antacids (with calcium or aluminum). (Allen-Dicker 2015)

[2/5] electrolyte abnormalities

• Hypercalcemia.
• Hypokalemia.
• Hypomagnesemia.

[3/5] diet

• Insufficient fiber.
• Insufficient fluid.

[4/5] immobility

[5/5] rectal impaction

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evaluation of constipation

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history (if possible)

• Chronic constipation before admission?
• Bowel regimen before admission?
• Difficulty passing stools (e.g., straining)?
• Historically, did the patient respond favorably to any particular bowel regimen?

clinical examination

• Distension? (Consider abdominal radiograph to evaluate for ileus, obstruction, or colonic pseudo-obstruction.)
• Impaction? (Digital rectal examination or review of previously performed CT scan).

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general approach to constipation

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Below is a structured approach for a patient with constipation. For patients at high-risk of constipation (most ICU patients), it may be reasonable to institute front-line interventions (Stage #1) proactively before constipation develops. (Allen-Dicker 2015)

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[Stage #0] Consider/evaluate/remove rectal impaction

Rectal impaction is uncommon, yet essential to consider.

clinical features suggestive of impaction

• Persistent constipation despite laxative therapy.
• External examination may reveal abdominal distension and sometimes a palpable mass in the lower abdomen (especially the left lower quadrant).
• Paradoxical overflow diarrhea or fecal incontinence can occur (liquid stool leaks around the impacted mass).
• Abdominal pain. Occasionally, nausea and/or vomiting may occur.

evaluation

• Review any radiological data (especially CT abdomen/pelvis if this was done).
• Rectal examination (if this is being performed, consider the insertion of a bisacodyl suppository).

management

• Manual disimpaction is required.
• Procedural sedation isn't absolutely required, but this should be considered. Manual disimpaction is painful and potentially traumatizing (especially for confused patients who cannot understand what is happening). MidaKet may be useful (figure below).
• After disimpaction, an aggressive bowel regimen may help prevent recurrence.

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[Stage #1] Front-line interventions 

[1a] mobilization

[1b] minimize opioids

• Further discussion of a multimodal pain strategy is here.

[1c] nutritional adjustments

• Adequate nutrition, for example:
  • Full tube feed support (intubated patients).
  • Regular diet (non-intubated patients).
• Adequate hydration:
  • Intubated patients: Free water flushes, ~1 liter/day.
  • Non-intubated patients: Encourage drinking, including coffee.
• Fiber supplementation with soluble fiber. Start this early, because it takes time to work.
  • A daily intake of 10-20 grams of supplemental soluble fiber is recommended in guidelines. (26773077)
  • Guar gum is a good source that has demonstrated benefits (e.g., NutriSource Fiber packets contain 3 grams of fiber, making BID-TID dosing a reasonable option). (35297467, 24711073, 30496956)

[1d] polyethylene glycol +/- stimulant laxative

• Polyethylene glycol powder (e.g., MiraLax) is generally the preferred front-line agent.
  • Start at a moderate dose (e.g., 17 grams/day) and escalate PRN.
• For patients with a history of constipation before admission, consider adding a low-dose stimulant laxative as well:
  • Able to swallow pills: bisacodyl 5 mg PO daily.
  • Enteral feeding tube: senna 7.5 mg per tube daily.

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[Stage #2] Refractory to front-line therapy

[2a] ensure a reasonable polyethylene glycol dosing

• Consider a dose of ~17 grams/day BID.

[2b] consider adding magnesium hydroxide (Milk of Magnesia™️) 

• Advantages:
  • Relatively fast onset (30 minutes – 6 hours). This may provide rapid relief, thereby avoiding the use of multiple laxatives which eventually provoke diarrhea.
  • Many patients are magnesium deficient.
• Disadvantages:
  • Excessive dosing will cause diarrhea.
  • ⚠️ Contraindicated in renal failure (GFR <20-30 ml/min). (37211380) 
• Dose: 30 ml q12 hours PRN (magnesium hydroxide 400 mg/5 ml suspension).

[2c] add a stimulant laxative

• Typical selection:
  • For patients able to swallow tablets: Bisacodyl 10 mg/day.
  • For patients receiving medications via an enteral tube: Senna 15 mg/day.
• Typically, these act within 6-12 hours. They are often effective, but may cause cramping and diarrhea.

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[Stage #3] Persistent refractory constipation

[3a] reconsider underlying causes

• Perform a rectal exam (to exclude impaction) followed by insertion of a bisacodyl suppository. This maneuver can provide both diagnostic and therapeutic benefits. If an impaction is discovered, manual disimpaction is required (see Stage #0 above).
• Obtain an abdominal radiograph (if not already performed).
• (More on the evaluation of constipation above: ⚡️)

[3b] maximize polyethylene glycol

• Consider polyethylene glycol powder 34 grams BID.

[3c] maximize stimulant laxative

• If able to swallow pills: Bisacodyl 15 mg PO daily.
• If receiving medications via enteral tube: Senna 45 mg PO BID.

[3d] opioid-induced constipation

• Consider enteral naloxone (discussed further here: 📖).

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[Stage #4] Super-refractory constipation

Options include the following:

liquid polyethylene glycol bowel preparation 🏆 (e.g., GoLytely™️)

• Overall, this may generally be preferable. (Allen-Dicker 2015)
• Discussed further below: ⚡️

magnesium citrate in a cathartic dose

• ⚠️ Magnesium citrate is contraindicated in renal failure (GFR <20-30 ml/min).
• Consider using divided doses, so that it can be held once the patient is passing their bowel movements adequately (e.g., 150 ml every 12 hours, for a total of 300 ml).
• This may be a good option for patients who are unable to comply with drinking liters of polyethylene glycol.
• (More on the pharmacology of oral magnesium: 📖)

neostigmine or pyridostigmine

• Consider this selectively for patients with unusually prominent colonic dilation (i.e., colonic pseudo-obstruction).
• Obtain a CT scan before administration of neostigmine to exclude anatomic obstruction.
• (Further discussion of colonic pseudo-obstruction is here).

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polyethylene glycol

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polyethylene glycol powder (MiraLax™️)

• Basics:
  • Generally, this is the front-line laxative.
  • Reasonably rapid onset (~24-48 hours).
  • Fewer side effects (e.g., bloating, cramping) as compared to lactulose or stimulant laxatives.
• Dosing:
  • 17 grams/day is a typical dose.
  • 34 grams BID is often considered as a “maximal dose” (but this is an osmotic cathartic agent, so there is no true maximal dose). High doses may cause dehydration, so follow electrolytes and provide adequate water. If you're using >68 grams/day, switch to polyethylene glycol liquid to avoid dehydration (discussed below).

polyethylene glycol pre-mixed liquid with electrolytes (GoLytely™️, GraviLyte™️)

• Basics:
  • This has the same active ingredient as polyethylene glycol powder. However, the solution contains water and electrolytes (instead of relying on osmosis to remove water from the body). This allows massive volumes of polyethylene glycol pre-mixed solution to be administered without causing dehydration or electrolyte shifts (it simply passes through the body).
  • This is safe in renal failure.
  • The onset is generally faster than polyethylene glycol powder (depending on the volume used).
• Dosing:
  • For context, the typical dose for bowel preparation before a colonoscopy is ~4 liters. However, this dose is typically not necessary for treating constipation.
  • For patients with an enteral feeding tube, a moderate dose of polyethylene glycol liquid may be administered continuously (e.g., 200 ml/hr).  This may be discontinued when the patient is producing adequate bowel movements.

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bisacodyl

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contraindications, drug interactions, side effects 👎

contraindications

• ⚠️ Rectal impaction.
• ⚠️ Mechanical bowel obstruction, toxic megacolon.
• ⚠️ Inability to swallow tablets (bisacodyl cannot be crushed).

drug-drug interactions

• Oral potassium chloride (bisacodyl may decrease the GI absorption of potassium chloride).
• Milk, calcium carbonate, or antacids may disrupt the enteric coating, reducing the efficacy of bisacodyl.
• Bisacodyl may decrease digoxin absorption.

side effects

• Abdominal cramping.
• Diarrhea.

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indications, advantages 👍

• Bisacodyl is often a 2nd-line agent for constipation after initiation of osmotic laxatives.
• Bisacodyl has been shown to be effective in several trials. (33751780)
• The superiority of bisacodyl over sennosides is discussed further below. ⚡️

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dosing

• Oral tablets (usual route):
  • 5-15 mg PO daily (usually 10 mg daily). RCTs have frequently utilized 10 mg/day as a starting dose. (16669963) However, for ambulatory patients with chronic constipation, 5 mg/day may be better tolerated. (33751780)
  • A dose of 30 mg PO once daily may be used if complete evacuation is required (e.g., bowel preparation before colonoscopy).
  • It could be ideal to administer bisacodyl before sleep, resulting in a bowel movement the following morning (when the colonic motor activity is normally highest). (33751780)
• Suppository (10 mg):
  • Potential indications:
    • [1] Patients who are unable to take oral medications.
    • [2] Immediately following rectal examination (for example, if a rectal exam is being performed to exclude fecal impaction).
    • [3] If rapid relief is desired (this is the fastest acting agent).
  • Limitations: This may only work for patients in whom stool has reached the rectal vault or the left side of the colon. (Allen-Dicker 2015)
  • Effects may be seen in 30-60 minutes.

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pharmacology

• Absorption:
  • Oral: Minimal systemic absorption occurs in the upper GI tract due to its enteric coating. Only ~10-15% bioavailability is observed.
  • Per rectum: bioavailability is only ~3%. (33751780)
• Distribution:
  • Vd is ~200 liters.
• Metabolism:
  • Bisacodyl is a prodrug converted by intestinal and colonic brush border enzymes into the active metabolite BHPM (bis-p-hydroxyphenyl-pyridyl-2-methane). This is the same active metabolite that sodium picosulfate (another laxative) is converted into. (33751780)
  • Small amounts of absorbed bisacodyl are almost completely conjugated in the intestinal wall and liver to form the inactive BMPH glucuronide. (33751780)
• Elimination:
  • Absorbed bisacodyl is excreted in the urine as BMPH glucuronide.
• Half-life & duration of action:
  • Efficacy usually occurs in 6-12 hours.
• Mechanism of action:
  • [1] Stimulates colonic mucosal electrolyte secretion. Adenylate cyclase in small intestinal enterocytes is activated, leading to increased cAMP with subsequent secretion of chloride and bicarbonate (with passive efflux of sodium, potassium, and water). cAMP upregulation also upregulates colonic big potassium channels, which may promote potassium loss in the gut. (Lawrensia 2024)
  • [2] Direct prokinetic effect via stimulation of the myenteric neurons and smooth muscle.

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senna

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overview of senna pharmacology

• Dosing:
  • Starting dose: 15 mg PO daily.
  • Maximal dose: 45 mg PO BID (max dose ~100 mg/day).
  • Senna can be administered via a feeding tube (unlike bisacodyl). This is the only real advantage that senna has over bisacodyl.
• Onset of action:
  • 6-12 hours (similar to bisacodyl).
• Mechanism of action:
  • Gut bacteria metabolize sennosides into active metabolites (rhein, rheinanthrone).
  • Stimulation of prostaglandin E2 causes chloride secretion and peristalsis.

reasons that senna is generally not preferred (as compared to bisacodyl)

• [1] Sennosides are not a single chemical compound, but rather a collection of various chemicals extracted from plants. This could lead to variations across different batches or formulations of the drug. For example, one study investigated senalin, a product derived from “combining three substances of the senna leaves, fennel seeds, and rose petals at ratios of 34.2, 45, and 15.1%, respectively.” (30993087) In contrast, bisacodyl is a single chemical compound that is chemically synthesized, like most drugs.
• [2] Sennosides are dependent on the gut microbiome to convert them into an active compound. Among patients with dysbiosis (especially ICU patients), this conversion may not be reliable.
• [3] Bisacodyl appears to produce a higher stool sodium concentration as compared to sennosides. Higher stool sodium levels may allow for bowel movements without causing excessive hypernatremia (dehydration).
• [4] Bisacodyl is supported by several RCTs demonstrating efficacy. In contrast, there is only one RCT evaluating the efficacy of senna. That study demonstrated efficacy using 1 gram/day senna, which is a massive dose (~60 times the typical dose of 15 mg). (32969946) It's mysterious why higher senna doses are used in this Japanese study (and in Japan) seem to be much higher than doses utilized in the United States.

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enemas

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• Enemas are generally not preferred. There is little evidence that enemas are effective. (37834791)
• Contraindications to enemas:
  • [1] Enemas are contraindicated in patients who are unable to evacuate the enema (e.g., patients with altered mental status or neurologic deficits). (Allen-Dicker 2015)
  • [2] Sodium phosphate enemas are contraindicated for patients with renal dysfunction.
  • [3] Patients at risk of colonic perforation (e.g., toxic megacolon).
• There are some niche indications for enemas:
  • [1] For a patient who is on the verge of developing a rectal impaction, with the goal of avoiding digital disimpaction.
  • [2] Spinal cord injury causing a lack of rectal sensation.

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agents to avoid

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lactulose

• Lactulose stimulates gas production, which may over-distend the colon and cause cramping (without promoting bowel movements). Polyethylene glycol is more effective and better tolerated than lactulose.
• Among critically ill patients, lactulose has been demonstrated in a prospective RCT to increase the risk of acute intestinal pseudo-obstruction, likely due to excessive intestinal gas production. (17893628)
• Lactulose could be reasonable in patients with cirrhosis to prevent hepatic encephalopathy. However, there is evidence that polyethylene glycol is more effective for hepatic encephalopathy than lactulose (discussed here: 📖). In short: anything that lactulose can do, polyethylene glycol can do better.

docusate (colace™️)

• Docusate is ineffective as a laxative. (30785419)
• Docusate is reasonably safe, so if a patient specifically requests it, that's OK.
• It would be ideal for hospitals to remove docusate from the formulary. Large hospital centers spend a significant amount of money on docusate prescriptions, despite the lack of an established benefit for this medication. The administration of docusate is not itself harmful, but it may delay the administration of drugs that actually do work.

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questions & discussion

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To keep this page small and fast, questions & discussion about this post can be found on another page here.

Guide to emoji hyperlinks 

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