The Hospice Clinician Blog

The management of constipation in hospice patients is notoriously challenging.

Constipation is the one side effect of opioids to which patients do not develop tolerance – which means it is nearly ubiquitous among patients taking opioids routinely. In addition to opioids, hospice patients take many other medications that cause constipation, including the many different medications with anticholinergic properties. Furthermore, hospice patients often have fluctuating dietary and fluid intake and gradually decreasing levels of physical activity and movement, which contribute to constipation.

There are 4 common pitfalls that we should be aware of in the management of constipation in the hospice population. These are:

1. Docusate alone

For the treatment of constipation, docusate is generally ineffective when used alone. The role for monotherapy with docusate is mainly for patients who are having regular bowel movements, but are producing dry, hard stool that is causing discomfort or straining. In hospice, we normally encounter patients who are NOT producing regular bowel movements, especially in the setting of opioid-induced constipation, where the source of the constipation is slowed gastrointestinal motility. When patients are not producing regular bowel movements (regardless of the consistency of the stool), a stool softener alone is insufficient. The popular phrase is that with a stool softener alone you have “all mush and no push”. Docusate can be used, and should be used if the consistency of the stool is hard and dry, but it should be combined with a stimulant laxative (such as senna or bisacodyl) or an osmotic laxative (such as Miralax or milk of magnesia) in order to help the GI contents move along.

2. Magnesium-based laxatives in renal impairment

Many of our patients have impaired renal function, and for these patients, magnesium-based laxatives (such as milk of magnesia) should be avoided as they can lead to electrolyte imbalances. The problem stems from the fact that up to 20% of the magnesium in magnesium salts may be absorbed systemically. Impaired kidneys do not eliminate all that extra magnesium effectively, and hypermagnesemia can result. As an alternative, use polyethylene glycol (Miralax) in patients with renal impairment, which has the same mechanism of action (osmotic laxative) but does not carry the same risk of electrolyte imbalance.

3. Bulk-forming laxatives in patients taking routine opioids

Bulk-forming laxatives, such as psyllium (Metamucil) and methylcellulose (Citrucel) can actually WORSEN constipation when patients are taking opioids. This is because, in the setting of the impaired GI motility that is induced by opioids, bulk-forming laxatives are not adequately propelled through the GI tract. The colon stretches to accommodate the bulk, but does not respond with adequate propulsive action due to the opioid effects. The result is painful, colicky GI symptoms, and potentially complete GI obstruction. For this reason, bulk-forming laxatives should be avoided in patients taking opioids.

4. Overlapping mechanisms of action

Because constipation is so common, and so difficult to treat, we often end up trying to attack it by adding on one laxative after another, using everything in our armamentarium in an attempt to resolve the issue. This often results in therapeutic duplication, which is not only ineffective, but is also costly and increases the risk of side effects. When managing constipation, it is important to keep in mind the underlying mechanism of action of each laxative, and to choose just one medication from each group when combining multiple therapies. Use this chart to help:

Bulk-Formers (hold water in stool to increase bulk-
stimulating peristalsis)

Psyllium (Metamucil)

Methylcellulose (Citrucel)

Calcium polycarbophil (FiberCon)

Stool softeners (facilitate admixture of fat and water to soften stool)

Docusate (Colace)

Stimulant/irritant laxatives (direct stimulant action on intestinal mucosa or nerve plexus)

Senna

Bisacodyl (Dulcolax)

Cascara sagrada

Osmotic laxatives (attract/retain water in intestinal lumen, increasing intraluminal pressure)

Magnesium hydroxide (milk of magnesia), magnesium citrate)
Sodium phosphate (Fleet)
Polyethylene glycol (Miralax)
Lactulose
Sorbitol

Lubricant/emollient laxatives (impairs colonic absorption of fecal water; softens stool)

Glycerin (Fleet)

Photo Credit

The stool softener docusate is widely used in the management of constipation in hospice patients, despite there being little experimental evidence to support this practice. A study recently published in the Journal of Pain and Symptom Management assessed the efficacy of docusate in hospice patients.

The study was a 10-day, prospective, randomized, double-blind, placebo-controlled trial of docusate and sennosides vs. placebo and sennosides in hospice patients in Edmonton, Alberta. The primary outcome measures were stool frequency, stool volume, and stool consistency. Secondary outcomes included type and frequency of additional bowel care interventions, patient's perception of difficulty and completeness of evacuation, and symptoms possibly related to constipation (pain, tiredness, nausea, drowsiness, anxiety, depression, appetite loss, well-being, and shortness of breath). Patients were randomized to receive either docusate 100 mg or placebo twice daily, along with one to three sennoside tablets (8.6 mg/tablet) taken one to three times daily. Patients were allowed to take additional laxatives and bowel interventions as needed throughout the study. Types of additional bowel care interventions included bisacodyl suppository, sodium phosphate enema, oil retention enema followed by soapsuds cleansing enema, lactulose, polyethylene glycol, magnesium hydroxide, or mineral oil. Overall, patients were deemed to have received at least one type of bowel care intervention if they received any bowel intervention on any one of the study days.

A total of 74 patients were randomized into the study (35 to the docusate group and 39 to the placebo group). There were no statistically significant differences between the groups in terms of basic demographics or clinical status, sennoside use, or opioid use (almost all of the patients enrolled in the study were receiving routine opioids).

Analysis of stool frequency showed no statistically significant difference in the overall mean number of bowel movements per day between the docusate and placebo groups. Responder analysis revealed that 56% (14 of 25) of docusate and 71% (22 of 31) of placebo patients had a bowel movement on 50% or more of the study days, and 70.8% (17 of 24) of docusate and 80.6% (25 of 31) of placebo patients had at least one bowel movement every three consecutive days. There was no significant association between stool volume and study group. No significant differences were observed between the docusate and placebo groups regarding patients' perceptions of the difficulty (need to strain) or completeness (sense of full evacuation) of defecation. There was no difference between groups in symptoms of constipation or need for additional bowel interventions.

In summary, this prospective randomized controlled trial found that docusate plus sennosides was not more efficacious than sennosides alone (placebo plus sennosides) in the management of constipation in hospice patients. These findings are consistent with studies that have assessed docusate in chronically ill patients (references are listed below). The study findings of no statistically significant difference between the docusate and placebo groups have clinical and operational implications in the management of constipation in terminally ill hospice patients. Given that these patients are usually taxed with taking multiple medications, eliminating nonefficacious medications is a significant consideration. Reducing the number of medications taken and removing a large capsule from this physically vulnerable population has the potential to improve quality of life at the end of life, decrease the time required for medication distribution by nursing staff, and lower the overall cost of care.

The authors conclude that general standing orders and policies for the use of docusate in the management of constipation in hospice should be reviewed in light of this study. Docusate use should be considered on an individual basis.

References

This study:

Tarumi Y, Wilson MP, Szafran O, Spooner GR. Randomized, Double-Blind, Placebo-Controlled Trial of Oral Docusate in the Management of Constipation in Hospice Patients. Journal of Pain and Symptom Management. Published online 13 August 2012.

Other studies of docusate:

Fain A, Susat R, Herring M, Dorton K. Treatment of constipation in the geriatric and chronically ill patients: a comparison. South Med J. 1978;71:677–680.
Goodman J, Pang J, Bessman AN. Dioctyl sodium sulfosuccinate—an ineffective prophylactic laxative. J Chronic Dis. 1976;29:59–63.
Harris R. Constipation in geriatrics: management with dioctyl sodium sulfosuccinate. Am J Dig Dis. 1957;2:487–492.
Hawley PH, Byeon JJ. A comparison of sennosides-based bowel protocols with and without docusate in hospitalized patients with cancer. J Palliat Med. 2008;11:575–581.
 

Salix Pharmaceuticals and Progenics Pharmaceuticals announced the successful outcome of a recently completed Phase 3 trial evaluating the efficacy and safety of oral methylnaltrexone for the treatment of opioid-induced constipation.

Constipation commonly occurs in hospice and palliative care patients taking opioids for chronic pain. Methylnaltrexone is indicated for relief of opioid-induced constipation in these patients, when laxative therapy has been insufficient. Methylnaltrexone is a peripherally acting mu-opioid antagonist. It antagonizes the effects of opioids on peripheral tissues, including the gastrointestinal tract, without affecting the opioid’s analgesic effect. Methylnaltrexone is highly effective and well-tolerated, but is currently available only in injectable form for subcutaneous injection (brand name Relistor®).

The Phase 3 trial of oral methylnaltrexone evaluated three once-daily oral dosing regimens (150, 300 and 450 mg) and demonstrated highly statistically significant results in both the 300 and 450 mg treatment arms. Overall, efficacy of oral methylnaltrexone in this study was comparable to that reported in clinical studies of subcutaneous methylnaltrexone in subjects with chronic pain. The overall observed safety profile seen in patients treated with oral methylnaltrexone was comparable to placebo.

Salix and Progenics plan to submit a New Drug Application to the FDA in mid-2012.

Photo Credit

"