Polyethylene Glycol (PEG)

Polyethylene Glycol (PEG)

PEP Topic 
Constipation
Description 

Polyethylene glycol (PEG) is a type of osmotic laxative. In the United States, standard-dose PEG with electrolytes is known as Golytely® (PEG 3350 and electrolytes for oral solution) and Colyte®. Low-dose PEG, referred to as PEG 3350, is available in the United States without electrolytes and is marketed as Miralax®. In the United Kingdom and the Netherlands, PEG is available with or without electrolytes. Nulytely® is a sodium-free mixture for specific patient populations. Regardless of the ingredients, PEG acts by opposing water absorption from stool in the large bowel, increasing the water content and volume of the stools, thus making them softer and easier to pass.

Likely to Be Effective

Systematic Review/Meta-Analysis

Ahmedzai, S.H., & Boland, J. (2010, April). Constipation in people prescribed opioids. Clinical Evidence, 2407.

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Purpose:

To answer the following questions: What are the effects of oral laxatives, rectal preparations, and opioid antagonists for constipation in people prescribed opioids?

Search Strategy:

Databases searched were MEDLINE, Embase, Cochrane Central Register of Controlled Trials and Library, NHS Centre for Reviews and Dissemination (CRD), Database of Abstracts of Reviews of Effects (DARE), Health Technology Assessment, TRIP, and the National Institute for Health and Clinical Excellence (NICE) up to August 2009. Alerts from the U.S. Food and Drug Administration and the U.K. Medicines and Healthcare Products Regulatory Agency were included to identify any adverse effects.

Search keyword were constipation and opioids, Lactulose, macrogols, senna, bisacodyl, co-danthrusate/co-danthramer, docusate, ispaghula husk, liquid paraffin, magnesium salts, methylcellulose, arachis oil enema, glycerol suppository, phosphate enema, sodium citrate enema, and opioid antagonists.

Studies were included in the review if they

  • Were randomized controlled trials (RCTs), observational studies, or systematic reviews
  • Had a study sample of at least 20 participants
  • Had a maximum loss to follow-up of 30% per year in longitudinal studies.

Literature Evaluated:

The GRADE System was used to evaluate study quality. Full information is available online with a subscription.

Sample Characteristics:

The final sample comprised 23 systematic reviews, RCTs, or observational studies. This was an update of a previous review that added 1 systematic review and 5 RCTs, with no change in overall recommendations provided.

Results:

Oral Laxatives

  • Lactulose, polyethylene glycols (PEGs) plus electrolytes, and senna were identified as beneficial in this systematic review. Evidence in this area was graded as low-to-moderate quality. Lactulose appears to be as effective as PEG in reducing the number of hard stools, and as effective as senna in reducing the number of days without defecation.
  • Preparations identified as unknown effectiveness included bisacodyl, co-danthrusate and co-danthramer, docusate, ispaghula husk, liquid paraffin, magnesium salts, and methylcellulose.
  • Some oral laxatives such as bisacodyl often are prescribed in combination with other agents or rectal suppositories, but no evidence supports this use, particularly in people taking opioids.
  • Liquid paraffin may be harmful in patients who have difficulty swallowing.

Rectal Preparations

  • All of the rectal preparations studied were categorized as unknown effectiveness. The preparations included arachis oil enema, glycerol suppository, phosphate enema, and sodium citrate micro-enema.

Opioid Antagonists

  • Opioid antagonists, including alvimopan, methylnaltrexone, and naloxone, were categorized as beneficial.  Categorization was based on studies comparing those agents to no treatment or placebo.  The most common side effects reported were abdominal pain, nausea, and diarrhea, particularly with higher doses. 
  • A concern with these agents is the potential for use to reverse the therapeutic action of opioids.  Alvimopan and methylnaltrexone are considered safer than naloxone in this regard, as neither of those agents can cross the blood-brain barrier and a few small studies of acute pain have shown success in blocking the constipating effect of opioids without compromising pain relief.

Limitations:

  • Although various combinations of oral laxatives and rectal agents may be used clinically, their effectiveness for constipation in people taking opioids has not been evaluated. This area can benefit from continued well-designed study.
  • Opioid antagonists are considered effective for reducing constipation in people prescribed opioids. However, only a few studies with small groups of patients have examined the effect of these agents on pain relief with opioids. Use of opioid antagonists may also have implications for which type of opioid should be used for pain control.  Long-term use with chronic pain managed by opioids is not well researched.

Nursing Implications:

Nurses should be aware of potential implications related to the use of opioid antagonists in controlling constipation for opioid interactions and changes in pain control. In addition, nurses should routinely assess for pain relief, as well as symptoms of constipation, in this patient population.

Candy, D., & Belsey, J. (2009). Macrogol (polyethylene glycol) laxatives in children with functional constipation and faecal impaction: A systematic review. Archives of Disease in Childhood, 94, 156–160.

doi: 10.1136/adc.2007.128769
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Purpose:

To determine whether more precise guidance can be given regarding use of osmotic laxatives, and to assess the evidence for their use in children with constipation.

Search Strategy:

Databases searched were PubMed, Embase, the Cochrane Library, and Google Scholar. Reference lists were also hand searched.

Search keywords were polyethylene glycols, lactulose, senna, bisacodyl, picosulphate, constipation, defecation, cathartics, infant, child, preschool, adolescent, and clinical trial.

Studies were included in the review if they

  • Were a randomized clinical trial of osmotic laxative versus placebo or an active comparison
  • Reported on patients aged younger than 18 years with a diagnosis of constipation of more than three months in absence of structural, endocrine, or metabolic disease
  • Recorded a quantitative effect on constipation
  • Were published in a peer-reviewed journal.

Literature Evaluated:

Initial searching provided 100 clinical trials and 71 review articles. A final group of seven trials was identified for consideration in this review.

Sample Characteristics:

The seven final studies encompassed data on 594 patients.

Results:

  • A consensus appears to exist among studies that PEG is more effective than lactulose.
  • One systematic review in 2006 found no evidence to support use of stimulant laxatives or bulk-forming agents among children.
  • One study compared PEG 3550 with milk of magnesia. No difference existed between groups regarding bowel movements; however, more children refused treatment with milk of magnesia than with PEG (35% versus 5%, p < 0.001).

Conclusions:

The review highlights the necessity of considering what treatment children will accept in managing symptoms.

Nursing Implications:

This review was done in children with functional constipation, so findings may not be clearly applicable in children with constipation related to cancer treatment. PEG may be helpful and more effective than lactulose in the management of constipation in children with cancer, and may be more accepted than milk of magnesia.

Lee-Robichaud, H., Thomas, K., Morgan, J., & Nelson, R.L. (2010). Lactulose versus polyethylene glycol for chronic constipation. Cochrane Database of Systematic Reviews, 7, CD007570.

doi: 10.1002/14651858.CD007570.pub2
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Purpose:

To identify and review all relevant data to determine whether lactulose or polyethylene glycol (PEG) is more effective in treating chronic constipation.

Search Strategy:

Databases searched were Medline, Embase, CINAHL, and the Cochrane Central Register of Controlled Trials. Bibliographies of studies and conference proceedings  were hand searched.

Search keywords were fecal impaction, chronic constipation, delayed bowel movement, obstipation, irregularity, polyethylene glycol, ethylene glycol, PEG, ethylene oxide, PEG 3350, lactulose, and disaccharide.

Studies were included in the review if they

  • Were randomized controlled trials comparing the use of lactulose and PEG
  • Reported on adult patients or children diagnosed with chronic constipation or fecal impaction.

Literature Evaluated:

One hundred three initial references to January 24, 2008, were identified. A final set of 10 trials was included in this review. Studies were evaluated for various sources of bias and overall methodological quality. Trials were conducted in different countries in a variety of settings.

Sample Characteristics:

  • The 10 trials included a total of 868 participants.
  • 322 were adults and 546 were children.

Results:

  • In most studies, assessment of study quality by investigators yielded highly variable results and little agreement of bias issues.
  • In five studies, the overall mean difference in stool frequency per week was 0.65 (95% confidence interval [CI] [0.15, 1.15], p = 0.01) in favor of PEG.
  • Among three studies in children, the mean difference in stool frequency per week was 1.57 (95% CI [0.36, 2.77], p = 0.011) in favor of PEG.
  • In two studies that measured stool form and consistency, the mean difference was 0.89 (95% CI [0.43, 1.45], p = 0.00015) in favor of PEG.
  • In one study of adults and two studies in children, the odds ratio for relief of abdominal pain was 2.09 (95% CI [1.26, 3.44], p = 0.004) in favor of PEG.
  • Across three studies, patients on PEG had much less need for additional products to manage constipation (p = 0.000078).

Limitations:

  • Findings suggest that PEG may be more useful than lactulose in both children and adults for improvement in constipation; however, the evidence is insufficient to draw firm conclusions because of the small number of studies and degree of heterogeneity found.
  • Studies had a number of methodological issues.
  • This review involved studies that did not include an oncology population.

Nursing Implications:

One study included a sample of patients on methadone maintenance, which may have some relevance for constipation associated with opioid use.

Miles, C.L., Fellowes, D., Goodman, M.L., & Wilkinson, S. (2006). Laxatives for the management of constipation in palliative care patients. Cochrane Database of Systematic Reviews, 4, CD003448.

doi: 10.1002/14651858.CD003448.pub2
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Purpose:

To determine the effectiveness of laxative administration for constipation in patients receiving palliative care; to differentiate among laxatives being used regarding efficacy for constipation management.

Search Strategy:

Databases searched were Medline, Embase, CANCERLIT, PubMed, CINAHL, System for Information on Grey Literature in Europe (SIGLE), National Technical Information Service (NTIS), Department of Health and Social Security (DHSS-DATA), Science Citation Index, Cochrane Central Register of Controlled Trials (CENTRAL), Dissertation Abstracts, and the Index to Scientific and Technical Proceedings. Conference proceedings and references of articles reviewed were also hand searched.

Search keywords were palliative care, cathartics (adverse effects; therapeutic use), constipation (drug therapy), and randomized controlled trial as topic. 

Studies were included in the review if they

  • Were a randomized controlled trial (RCT) of the efficacy of laxatives in palliative care patients
  • Reported on a sample of adult patients receiving palliative care interventions who reported constipation
  • Involved the use of any oral or rectal laxatives
  • Included the outcome measures patient-reported relief of constipation in terms of frequency and ease of defecation, relief of related symptoms such as distension, appetite improvement, and improvement of quality of life.

Studies were excluded if they included healthy volunteers, patients with constipation as a result of drug misuse, patients with bowel obstruction, or other interventions such as opioid antagonists.

Literature Evaluated:

Two hundred twelve studies were initially retrieved. After removal of duplicates and studies that did not meet inclusion criteria, three studies were finally included. Study quality was assessed using the Jadad scale and additional criteria identified including issues of accrual, homogeneity, attrition, interventions, quality of outcome measurement, and clarity of results presentation. The review provided extensive detail on quality assessment findings and rationale for study exclusion. Included studies used senna, lactulose, danthron combined with poloxamer, misrakasneham, and magnesium hydroxide combined with liquid paraffin.

Sample Characteristics:

The final sample of three studies involved a total of 162 patients, with study samples ranging from 36 to 75.

Results:

  • One study found no differences between groups taking senna and lactulose.
  • One study found no difference between patients with advanced cancer taking misrakasneham and senna.
  • One study of hospice patients with cancer found that those taking lactulose plus senna had significantly higher stool frequency than those using danthron and poloxamer. This pattern was true in patients at varied levels of opioid use. This study used a crossover design and showed that significantly fewer patients reported constipation when taking lactulose plus senna.
  • One study in hospice patients with cancer found no difference between patients taking lactulose plus senna versus those taking magnesium hydroxide and liquid paraffin. In patients taking different levels of opioids, a trend to less constipation existed in the lactulose plus senna group, but the trend was not statistically significant.
  • No significant differences were found between opioid-level groups in terms of laxative results.
  • Diarrhea was reported as an adverse effect in studies for both senna and lactulose.
  • Where patient preference was reported, no differences were found between most combinations. Patients preferred lactulose plus senna over magnesium hydroxide and liquid paraffin. The basis of preference was usually taste.
  • The authors included a general literature review of constipation treatments.

Conclusions:

The treatment of constipation in palliative care patients is not based on sufficient data from RCTs. Recommendations for laxatives may be based as much on cost as on efficacy. Polyethylene glycols are widely used in palliative care despite lack of evidence. The authors did not note evidence in this area in other patient populations that may be applicable.

This review and included studies did not provide sufficient information to draw conclusions about the laxatives in terms of weighing effectiveness versus adverse side effects.

Limitations:

  • Little research exists in this area, and very few direct comparisons have been done between laxative classes and combinations to compare efficacy.
  • Because of the lack of evidence in this area, determining most effective treatments is difficult.

Nursing Implications:

This area could benefit from research to compare effects and cost effectiveness. Some findings suggested effect and preference for lactulose combinations, whereas lactulose tends to be much more expensive than alternatives.

Research Evidence Summaries

Attar, A., Lemann, M., Ferguson, A., Halphen, M., Boutron, M.C., Flourie, B., . . . Barthet, M. (1999). Comparison of a low dose polyethylene glycol electrolyte solution with lactulose for treatment of chronic constipation. Gut, 44, 226–230.

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Intervention Characteristics/Basic Study Process:

In part A, patients were randomized to receive either PEG plus electrolytes (PEG+E) (n = 60) or lactulose (n = 55) for one month. In part B, 65 patients continued on the treatment for another two months. Patients received PEG+E, irrespective of the laxative they received at the start of part A.

PEG 3350 is an osmotic laxative that opposes the colon’s normal drying action on the feces. The increasing fecal bulk stretches the circular muscle fibers in the bowel wall and triggers myogenic peristalsis. PEG+E provides electrolyte depletion and dehydration that can occur with other laxatives.

Lactulose is metabolized to lactic acid by bacteria in the colon. Those bacteria exert a local osmotic effect, drawing water and electrolytes into the colon from the surrounding tissues to bulk feces.

Sample Characteristics:

  • The study reported on a sample of 115 patients.
  • Patients were included in the study if they were aged 18 to 90 years and had fewer than three stools a week and/or difficult evacuation for at least three months.
  • Patients were excluded if they had secondary constipation; were taking concomitant medication that might modify bowel transit; had severe liver, renal, or cardiac impairment; were not likely to comply with treatment; were not able to give informed consent, or were women of childbearing age not using effective contraception.

Study Design:

This was a single-blind, randomized, multicenter study.

Measurement Instruments/Methods:

The efficacy of PEG+E was evaluated by

  • Number of stools per day
  • Evacuation score
  • Dyschezia index (graded from 0-3)
  • Global satisfaction index (analog scale from 0-10)

Results:

Part A

  • At the end of the one-month period, PEG+E showed consistently and significantly better results in number of stools per day, ease of evacuation, and global satisfaction.
  • Sixty percent of PEG+E recipients did not use all their sachets, compared with 40% in the lactulose group.
  • In the lactulose group, 23% increased their dosage to three or more sachets per day, whereas 64% of lactulose recipients used two to three sachets per day.
  • The use of suppositories and micro-enemas was significantly lower in the PEG+E group than the lactulose group (16% versus 34%).

Part B

  • Daily dosage of PEG+E remained stable, with most patients using one to two sachets per day.
  • Patients in the lactulose group tended to increase to three sachets per day.
  • At the end of three months, the efficacy of PEG+E was significantly better than that produced by lactulose in number of stools per day and ease of evacuation.

Conclusions:

Use of PEG+E instead of lactulose doubled the percentage of patients successfully treated at three months. PEG+E was found to be a superior treatment compared to lactulose to treat idiopathic constipation. The study was well designed.

DiPalma, J.A., Cleveland, M.V., McGowan, J., & Herrera, J.L. (2006). An open-labeled study of chronic polyethylene glycol laxative use in chronic constipation. Alimentary Pharmacology and Therapeutics, 25, 703–708.

doi: 10.1111/j.1365-2036.2006.03228.x
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Study Purpose:

To extend the safety data of polyethylene glycol used for chronic treatment of chronic constipation.

Intervention Characteristics/Basic Study Process:

Polyethylene glycol laxative was administered as a single daily dose of 17 g for 12 months.

Sample Characteristics:

  • The study reported on a sample of 311 patients with chronic constipation.
  • 117 patients were aged 65 years and older.
  • 184 patients completed all 12 months of treatment.
  • Study participants who met defined criteria for chronic constipation were enrolled.

Setting:

  • Multicenter
  • 50 centers in the United States

Study Design:

This was a randomized, open-label, single-treatment study.

Measurement Instruments/Methods:

  • Patients returned to their study centers after 2, 4, 6, 9, and 12 months of treatment; blood and urine samples were collected, and adverse events were reviewed.
  • At each visit, patients were queried for Rome constipation criteria and they rated their overall improvement using a global efficacy scale.

Results:

  • No clinically significant changes were found in hematology or blood chemistry, particularly electrolytes, for the study population as a whole or the older adult group.
  • With respect to the global efficacy assessment, depending on the month of observation, 80% to 88% of enrolled patients and 84% to 94% of older adults were treated successfully. Similar results were obtained from secondary efficacy measures that assessed individual Rome constipation criteria at each visit.
  • The response to treatment was durable over time.
  • Over the one-year course of study representing 218 patient-years at the labeled dose, medication-associated adverse effects were gastrointestinal complaints of diarrhea, loose stool, flatulence, and nausea. The effects were generally mild or moderate in severity.

Conclusions:

Polyethylene glycol laxative is safe and effective for treating constipation in adult and older adult patients for periods up to 12 months, with no evidence of tachyphylaxis.

Limitations:

  • None were identified in the discussion of the results.
  • This study was not related to cancer or to opioid-induced constipation.

DiPalma, J.A., Cleveland, M.B., McGowan, J., & Herrera, J.L. (2007a). A comparison of polyethylene glycol laxative and placebo for relief of constipation from constipating medications. Southern Medical Journal, 100, 1085–1090.

doi: 10.1097/SMJ.0b013e318157ec8f
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Study Purpose:

To compare the safety and efficacy of polyethylene glycol (PEG) 3350 (Miralax®) versus placebo for treatment of constipation in patients with chronic constipation.

Intervention Characteristics/Basic Study Process:

PEG 3350 laxative 17 g or placebo was administered daily for 28 days. Use of nonconstipating medications was allowed, but the use of fiber or other laxatives was not permitted. Patients received a 4 L jug containing Crystal Light® with or without study medication. The mixture was reconstituted by unblinded study personnel; investigators remained blinded. A daily bowel diary was used to share bowel movement (BM) experiences and answer questions related to study efficacy and safety criteria. Laboratory evaluation was repeated at study conclusion.

Sample Characteristics:

  • The study reported on a sample of 100 patients (50 in the treatment group and 50 in the placebo group) enrolled and randomized within each site by computer; 93 completed the study.
  • Mean patient age was 58 years (range 31 to 84).
  • The older subgroup (aged 65 years or older) comprised 28 patients.
  • The sample comprised 74 women (74%).
  • The sample was 84% Caucasian and 16% African American.
  • Mean duration of constipation was 18 years.
  • Constipating medications included analgesics, anticholinergics, antidepressants, chemotherapy agents, anticonvulsants, antihistamines, and resins.
  • Patients were included in the study if they had constipation as defined by Rome II criteria and were taking medication with a 3% or higher incidence of constipation.
  • Patients were excluded if they had an allergy or sensitivity to study medication; had prior gastrointestinal (GI) surgery; had known or suspected GI obstruction, ileus, heart failure, renal failure, ascites, or another known chronic bowel or cardiopulmonary condition; were pregnant or lactating; had loose stool; met criteria for irritable bowel syndrome; and currently were taking or previously had taken PEG.

Setting:

Four centers in the United States

Study Design:

This was a double-blind, placebo-controlled, parallel, randomized controlled trial.

Measurement Instruments/Methods:

  • Relief of Rome II criteria for constipation during the last seven days of treatment period
  • Total number of BMs
  • Number of patient-reported satisfactory BMs
  • Symptoms of gas, cramping, straining at stool, stool consistency, and bloating using a 10-cm visual analog scale

Results:

  • Patient withdrawal was equivalent for each reason category except lack of efficacy. Three patients withdrew in the placebo group; none withdrew in the treatment group.
  • Seventeen patients in the PEG group and 15 patients in the placebo group had analgesics associated with constipating medications. The primary responder for treatment success had a 39% difference in favor of PEG (78% in the PEG group versus 39% in the placebo group, p > 0.001). The older adult subgroup had similar results, but findings were not statistically significant because of the small sample size.
  • Baseline constipation (fewer than three BMs per week) was evident in 58% (n = 29) of patients in the PEG group versus 46% (n = 23) of patients in the placebo group.
  • Of 609 patients screened, 300 did not meet criteria or failed the 14-day observational period.
  • Average BM per week in the final week was 8.1 in the PEG group versus 5.4 in the placebo group (p < 0.001).
  • Two of three BMs were rated complete or satisfactory for both treatments.
  • Treatment difference for straining and stool consistency was statistically significantly in favor of PEG (p < 0.001).
  • No difference existed in gas, bloating, or cramps.

Conclusions:

PEG is safe and effective in treating constipation in patients taking constipating medications.

Limitations:

  • The study lacked an observational period prior to treatment initiation to confirm constipation status.
  • Some patients in the study experienced constipation prior to receiving constipating medication. Medication-induced constipation may respond differently.
  • Although the sample included patients with both opioid-induced constipation and chemotherapy-induced constipation, such patients were not included in sufficient numbers to provide dependable data. Additional study is needed.

DiPalma, J.A., Cleveland, M.B., McGowan, J., & Herrera, J.L. (2007b). A randomized, multi-centered, placebo-controlled trial of polyethylene glycol laxative for chronic treatment of chronic constipation. American Journal of Gastroenterology, 102, 1436–1441.

doi: 10.1111/j.1572-0241.2007.01199.x
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Study Purpose:

To compare the safety and efficacy of polyethylene glycol (PEG) versus placebo over a six-month treatment period in patients with chronic constipation.

Intervention Characteristics/Basic Study Process:

PEG 3350 (Miralax®) laxative 17 g or placebo was administered daily for six months. Patients were randomly assigned in a 2:1 ratio to PEG or placebo. This was a subjects mixed study. Medication was administered in 8 oz of juice or another beverage. Bisacodyl 10 mg (5 mg tablets) was used as rescue medication for severe discomfort related to constipation. Fiber was prohibited. Other nonconstipating medications were allowed.

Sample Characteristics:

  • The study reported on a sample of 204 patients in the treatment group and 100 patients in the placebo group.
  • Mean patient age was 53 years (range 20 to 92).
  • The older adult subgroup comprised patients aged 65 years or older (n = 75).
  • The sample comprised 258 women (85%).
  • The sample was 84% Caucasian, 13% African American, and 3% Hispanic or Latino.
  • Average duration of constipation was 23 years.
  • Patients were included in the study if they had a three-month history of fewer than three bowel movements (BMs) per week when not taking laxatives and one or more remaining Rome symptom criteria. Patients also had an average of three or fewer satisfactory BMs per week during the 14-day observational period after eligibility criteria were met.
  • Patients were excluded if they had loose stools, sufficient criteria for irritable bowel syndrome, and currently were being or previously had been treated with PEG.

Setting:

50 centers in the United States

Study Design:

This was a double-blind, placebo-controlled, parallel, randomized controlled trial.

Measurement Instruments/Methods:

  • During the 14-day observational period and qualification period, baseline constipation status was confirmed.
  • During the treatment period, data were collected through an interactive voice response system daily to record BM experiences. Patients answered daily and weekly questions (e.g., number of BMs, straining, lumpy or hard stools, evacuation complete, satisfaction, cramping) on a Likert-type scale from 0 (none) to 4 (extreme).
  • Amount of gas was rated on a Likert-type scale from 0 (no gas) to 4 (extreme gas).

Results:

  • Of 609 patients screened, 300 did not meet criteria or failed the 14-day observational period. Of the remaining patients, 306 enrolled and were randomized, and 2 were excluded. A total of 175 patients completed the study.
  • Primary analysis was based on intention to treat (ITT).
  • Efficacy of the primary variable, treatment success, was defined as relief of modified Rome criteria for constipation for 50% or more of a patient's treatment weeks. The PEG group achieved significant benefit (p < 0.001) versus placebo in 11 of 12 primary and secondary measures.
  • The total sample had a 41% difference in treatment response (52% in the PEG group versus 11% in the placebo group, p < 0.001).
  • The older adult group had a 46% difference favoring PEG.
  • The treatment group had more total BMs per week.
  • Total compliance with study medication was higher than 86%.
  • Patient withdrawal was equivalent for each reason category, except lack of efficacy; twice as many patients in the placebo group withdrew secondary to lack of efficacy.

Conclusions:

PEG is safe and effective in management of constipation in adults and older adults for up to six months.

Limitations:

The study focused on chronic constipation and lacked focus on cancer or opioid-induced constipation.

Hardikar, W., Cranswick, N., & Heine, R.G. (2007). Macrogol 3350 plus electrolytes for chronic constipation in children: A single-centre, open-label study. Journal of Paediatrics and Child Health, 43, 527–531.

doi: 10.1111/j.1440-1754.2007.01116.x
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Study Purpose:

To evaluate the safety and efficacy of macrogol 3350 plus electrolytes in the treatment of chronic constipation in children.

Intervention Characteristics/Basic Study Process:

All children received macrogol 3350 plus electrolytes for 12 weeks. Children aged 2 to 6 years received one sachet daily on days 1 and 2, one sachet twice daily on days 3 and 4, and one sachet three times daily on day 5. Children aged 7 to 11 years received one sachet twice daily on days 1 and 2, and two sachets twice daily on days 3, 4, and 5. After day 5 and until the end of the study, the dosage was titrated according to fecal form. The dose was increased by one sachet per day in the event of continued hard stools or no bowel movement, and decreased by one to two sachets per day in the event of loose stools or diarrhea.

The mean duration of treatment was 75.5 days, during which time the participants took an average of 1.3 sachets (6.9 g) of macrogol plus electrolytes per day.

Sample Characteristics:

  • The study reported on a sample of 78 children with chronic constipation for greater than three months.
  • Patients were aged 2 to 11 years, with a mean age of 4.9 years (SD = 2.6).
  • The sample comprised 34 boys (44%).
  • Patients were included in the study if they had chronic constipation defined as fewer than three complete bowel movements per week over the previous 14 days, in association with either straining or passage of hard stools in at least 25% of bowel movements. The existing constipation was either untreated or inadequately treated by laxatives.
  • Patients were excluded if they were treated for fecal impaction with bowel washouts within the previous two months or if they had a past history of intestinal perforation or obstruction; Hirschsprung disease; paralytic ileus; toxic megacolon; severe inflammation of the intestinal tract; urinary tract infections; uncontrolled renal, hepatic, or cardiac diseases; endocrine disorders; or any other severe unstable coexisting disease within the previous 30 days.

Setting:

Royal Children’s Hospital, Melbourne, Australia

Study Design:

This was an open-label, nonrandomized study.

Measurement Instruments/Methods:

  • The primary outcome was number of spontaneous defecations per week.
  • The secondary outcomes were fecal form, abdominal pain, rectal bleeding, pain on defecation, straining, soiling, amount of stool, stool withholding, and assessments of efficacy by the investigators and parents.
  • Safety assessments included adverse events, laboratory tests (full blood examination; urea, electrolyte, and liver function tests) and changes in vital signs. Adverse events were monitored throughout the study; venous blood samples for laboratory safety were taken at visits 1, 3, and 5. 
  • Compliance was rated on a four-point scale from very poor (less than 25% of prescribed dose taken) to very good (more than 75% of prescribed dose taken).

Results:

  •  Sixty-five patients (80%) completed the study.
  • The mean number of spontaneous defecations per week increased from 1.4 (SD = 0.55) at baseline to 6.8 (SD = 3.45) after 14 days and 7.1 (SD = 3.45) at 12 weeks (p < 0.001).
  • Stool frequency remained unchanged from visit 2 until the final visit (ANOVA: F = 0.81, p = 0.518).
  • Similar improvements were found in the secondary efficacy variables. A significant reduction in reported abdominal pain from 53 children (68%) at baseline to 3 (4%) at the final visit occurred (p < 0.0001). Similarly, 61 children (78%) had pain on defecation at baseline, compared with 7 (9%) at the final visit (p < 0.0001). Treatment was well tolerated.
  • Of 318 adverse events, 262 (82%) were considered mild, and 241 (76%) were deemed unrelated to treatment.
  • Only 3 children (4%) were withdrawn because of poor compliance. Mean duration of treatment was 75.5 days, during which time the participants took an average of 1.3 sachets (6.9 g) of macrogol plus electrolytes per day. Ratings of excellent compliance (higher than 75% intake of study medication) were reported for 86%, 81%, 76%, and 79% of participants at visits 2, 3, 4 and 5, respectively.

Conclusions:

Longitudinal studies are needed to determine the long-term outcome of successful treatment of chronic constipation during childhood.

Limitations:

  • The study did not mention which electrolytes were added and in what amount.
  • This study design did not allow determination of a true treatment effect from spontaneous improvement.
  • Open-label studies are subject to bias in assessments of efficacy, but the findings in this study are supported by results from several nonrandomized and randomized controlled studies of polyethylene glycol 3350–based preparations in children.
  • Study results are not relevant to oncology.

Loening-Baucke, V., & Pashankar, D.S. (2006). A randomized, prospective, comparison study of polyethylene glycol 3350 without electrolytes and milk of magnesia for children with constipation and fecal incontinence. Pediatrics, 118, 528–535.

doi: 10.1542/peds.2006-0220
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Study Purpose:

To compare and evaluate the efficacy, safety, acceptance, and one-year outcome of two laxatives, polyethylene glycol (PEG) without electrolytes and milk of magnesia (MOM).

Intervention Characteristics/Basic Study Process:

Patients were randomly assigned to intervention with PEG 3350 without electrolytes (Miralax®) or MOM by drawing a sealed envelope. Patients initially received 0.7 g/kg of PEG or 2 ml/kg of MOM daily.

Sample Characteristics:

  • A total of 117 children were asked to participate; 79 were enrolled and randomized.
  • The PEG group comprised 39 patients (31 boys and 8 girls), whereas the MOM group comprised 40 patients (34 boys and 6 girls).
  • Patients were included in the study if they were new referrals (more than one per week), were aged four years or older, and had presence of functional constipation with fecal incontinence.
  • Patients were excluded if they had stool toileting refusal, fecal incontinence without constipation, previously refused one of the study medications, Hirschsprung disease, previous surgery involving the colon, chronic intestinal pseudo-obstruction, or come for a second opinion.

Setting:

Children’s Hospital of Iowa

Study Design:

Randomized controlled trial

Measurement Instruments/Methods:

  • Improvement was defined as three or more bowel movements (BMs) per week and two or fewer episodes of fecal incontinence per month with no abdominal pain, with or without laxative.
  • Recovery was defined as three or more BMs per week and two or fewer episodes of fecal incontinence per month with no abdominal pain, without laxative treament for at least one month.
  • Children who received additional senna were counted as not improved or recovered.

Results:

  • Baseline characteristics were not significant (p > 0.07).
  • Compliance rates were significant at 95% for the PEG group and 65% for the MOM group.
  • After 12 months, 62% of the PEG group and 43% of the MOM group exhibited improvement and 33% of the PEG group and 23% of the MOM group recovered (not significant).

Conclusions:

PEG and MOM are effective and safe in long-term treatment, with PEG having better acceptance.

Limitations:

  • The study had a high drop-out rate (loss to follow-up).
  • The study did not measure biochemical profiles for all children.

Nurko, S., Youssef, N.N., Sabri, M., Langseder, A., McGowan, J., Cleveland, M., & Di Lorenzo, C. (2008). PEG3350 in the treatment of childhood constipation: A multicenter, double-blinded, placebo-controlled trial. Journal of Pediatrics, 153, 254–261.e1.

doi: 10.1016/j.jpeds.2008.01.039
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Study Purpose:

To determine the effect and preferred dose of polyethylene glycol 3350 (PEG3350) in children with functional constipation.

Intervention Characteristics/Basic Study Process:

Patients were randomly assigned to placebo or PEG at different doses that were identical in appearance. Dosage groups were 0.2, 0.4, or 0.8 g/kg per day. Patients took the medication for two weeks. Patients in both PEG and placebo groups also underwent behavior modification. Patients returned for evaluation after seven and 14 days of medication.

Sample Characteristics:

  • The study reported on a sample of 103 healthy patients with functional constipation.
  • Mean patient age was 8.5 years (SD = 3.1).
  • The sample was 34% female.

Setting:

  • Multi-site
  • Outpatient
  • United States

Phase of Care and Clinical Applications:

The study has clinical applicability for pediatrics.

Study Design:

This was a double-blind, placebo-controlled, prospective, randomized study.

Measurement Instruments/Methods:

  • Diary (parents)
  • Physical examination
  • Laboratory (chemistry, serum osmolarity, and liver function tests)
  • Printed calendars (pediatrics with stickers)

Results:

  • More patients taking PEG had bowel movements compared with the placebo group (p = 0.026), but no difference existed among the PEG dose groups in terms of one dose being better than another.
  • Patients in the PEG groups had more stools than those in the placebo group (p = 0.017).
  • Response rates were not significantly different between children aged younger than 8 or older than 8.
  • Patients in the PEG groups had other benefits such as improved stool consistency and less straining.
  • The treatment was well tolerated.

Conclusions:

PEG is a well-tolerated, effective treatment for chronic constipation in healthy children.

Limitations:

  • The study only lasted for two weeks.
  • A behavioral modification given as part of the collection process in which children received positive and negative reinforcement could have influenced the results.
  • The sample was healthy children; application in children with cancer is not clear.

Nursing Implications:

This well-done study demonstrated the usefulness of PEG in the management of constipation for healthy children. PEG may be useful for children with cancer, but this specific application has not been studied.

van der Spoel, J.I., Oudemans-van Straaten, H.M., Kuiper, M.A., van Roon, E.N., Zandstra, D.F., & van der Voort, P.H. (2007). Laxation of critically ill patients with lactulose or polyethylene glycol: A two-center randomized, double-blind, placebo-controlled trial. Critical Care Medicine, 35, 2726–2731.

doi: 10.1097/01.CCM.0000287526.08794.29
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Study Purpose:

To determine whether lactulose or polyethylene glycol (PEG) effectively promotes bowel function in critically ill patients, and to identify whether one is superior to the other.

Intervention Characteristics/Basic Study Process:

On day 3 in critical care, consenting patients who had no bowel movements were randomized to one of three arms: lactulose, PEG 3350, or placebo. The lactulose solution was 13 gm of lactulose in 100 ml of sterile water. The PEG 3350 solution was 13.125 gm of PEG 3350 in 100 ml of sterile water. Finally, the placebo was 100 ml of sterile water. Each patient was medicated with the study liquid every eight hours via a nasogastric tube and was to receive 11 doses of treatment medication.

Sample Characteristics:

  • The study reported on a sample of 308 critically ill intensive care unit (ICU) patients who did not have cancer.
  • Mean patient age was 35.3 years (SD = 16.5) in the PEG group, 65.5 years (SD = 15) in the lactulose group, and 68.8 years (SD = 13.8) in the placebo group.
  • The sample comprised 118 women and 190 men.

Setting:

Two ICUs in the Netherlands

Study Design:

This was a double-blind, placebo-controlled, randomized trial.

Measurement Instruments/Methods:

  • Acute Physiology and Chronic Health Evaluation II (APACHE II) 
  • Sepsis-related organ failure assessment score
  • Daily abdominal x-ray in patients with severe abdominal tenderness, abdominal distention, or suspected ileus
  • Medication assessment
  • Stool record

Results:

  • Lactulose and PEG were more effective than placebo (69% versus 74% versus 31%, p = 0.001).
  • No difference was found in the effectiveness of lactulose versus PEG (p = 0.27).
  • Lactulose reduced length of stay (LOS) in the ICU compared with PEG or placebo. In addition, patients with earlier bowel movements had shorter LOS.
  • Morphine affected defecation, but PEG may be better in this patient group. Neither cisapride nor erythromycin appeared to affect defecation.
  • Adverse drug events were acute intestinal pseudo-obstruction, perforated ulcer, acute abdomen, death, and sinus bradycardia.

Conclusions:

Both lactulose and PEG promoted bowel movements equally. In patients receiving morphine, PEG had a more significant effect.

Limitations:

The study lacked a lead-in period or data on patients’ prior bowel function and history of constipation.

Nursing Implications:

Bowel function is promoted with the use of either lactulose or PEG. Lactulose may reduce LOS, and PEG may be better for patients who also are receiving morphine, but additional study is needed.

Wirz, S., Nadstawek, J., Elsen, C., Junker, U., & Wartenberg, H.C. (2012). Laxative management in ambulatory cancer patients on opioid therapy: A prospective, open-label investigation of polyethylene glycol, sodium picosulphate and lactulose. European Journal of Cancer Care, 21, 131–140.

doi: 10.1111/j.1365-2354.2011.01286.x
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Study Purpose:

To determine whether variable effectiveness exists in the use of polyethylene glycol (PEG), sodium picosulphate (SPS), and lactulose in ambulatory outpatients with cancer on opioid therapy.

Intervention Characteristics/Basic Study Process:

Eligible patients were assigned to three treatment groups. A fourth group comprised patients who had discontinued laxative therapy (NL). Laxative groups were treated for a minimum of 28 days prior to data collection with mu agonist and assigned laxative. Prescribers were free to choose the laxative. The standard doses were PEG 13.1 g per day, SPS 10 mg per day, and lactulose 10 g per day. An increase in dose was allowed if participants were directed to do so by the prescriber.

During the five-day data collection phase, investigators assessed participants daily on mobility and pain assessment. Constipation was assessed by documentation of defecation rates, number of participants with lack of bowel movement for more than 72 hours, subjective intensity of constipation using a numeric scale, and consumption of laxatives.

Average defecation rate of all patients was calculated as defecations per patient per five days. The number of patients reporting nausea or emesis also was documented. The daily doses of the original opioid (oral morphine, hydromorphone, oxycodone, tramadol, or transdermal fentanyl) were transferred into morphine equivalent doses for uniform comparison.

Sample Characteristics:

  • The study reported on a sample of 348 patients.
  • Mean patient age was 62.4 years in the PEG group, 62.2 years in the SPS group, 65.6 years in the lactulose group, and 58.3 years in the NL group.
  • Demographic and medical data were similar in all groups.
  • The sample was 60% male and 40% female.
  • Key disease characteristics were cancer-related pain, opioid therapy with mu agonists (equivalent doses of oral morphine, hydromorphone, oxycodone, tramadol, or transdermal fentanyl), ambulatory treatment, patient cooperation, and Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 3.
  • Patients were excluded from the study if they had used opioid antagonists, been referred for nonambulatory treatment, diarrhea at the beginning of therapy, disease likely to cause diarrhea (e.g., pancreatic cancer), opioid dose variations, conditions linked to opioid dose variations (e.g., breakthrough pain), communication deficits, hepatic or renal impairment, current chemotherapy or radiation therapy, nonambulatory status, terminal stage of disease, infection, prior history of drug or alcohol addiction or abuse, concurrent treatment with laxatives other than study medication, used more than a single laxative, partial agonists, and antagonist/agonist combinations.

Setting:

  • Single site
  • Outpatient
  • Pain Clinic, University Hospital, Bonn, Germany

 

Phase of Care and Clinical Applications:

  • Patients were undergoing chronic pain management for cancer diagnoses.
  • The study has clinical applicability for palliative care.
     

Study Design:

This was a controlled, prospective, open-label study.

Measurement Instruments/Methods:

  • ECOG Performance Status for mobility
  • European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) for pain assessment
  • Constipation Assessment Tool
  • Numerical Rating Scale (NRS) for constipation and pain

 

Results:

  • No patients in the study discontinued opioid therapy.
  • NRS values for pain were comparable in all groups.
  • After 28 days, PEG was the most frequently used laxative (n = 95, 27.3%) compared to SPS (n = 36, 10.3%) and lactulose (n = 32, 9.2%).
  • Fifty-three percent of patients (n = 185) discontinued laxative therapy.

Conclusions:

In this prospective study, PEG was more frequently prescribed than SPS and lactulose. However, the data did not prove the superiority of PEG over SPS and lactulose for the management of constipation in ambulatory patients with cancer on opioid therapy.

Limitations:

  • The study took place at a single site and may be biased in that respect.
  • No data exist to support whether opioid-induced constipation is dose-related or substance-related.
  • Daily opioid doses in study groups differed significantly (p = 0.011).
  • Medications were not blinded.
  • Physician preference of PEG over SPS and lactulose may show bias.
  • Some antiemetics used may have constipating effects.

Nursing Implications:

No recommendation can be made.

Guideline/Expert Opinion

Larkin, P.J., Sykes, N.P., Centeno, C., Ellershaw, J.E., Elsner, F., Eugene, B., . . . European Consensus Group on Constipation in Palliative Care. (2008). The management of constipation in palliative care: Clinical practice recommendations. Palliative Medicine, 22, 796–807.

doi: 10.1177/0269216308096908
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Purpose & Patient Population:

To raise awareness of constipation in palliative care; to provide guidance on the assessment, diagnosis, and management of constipation; and to encourage research in this area.

Type of Resource/Evidence-Based Process:

Databases searched were PubMed and the Cochrane Library (2001-2006).

Search keywords were constipation, laxatives, palliative care, terminal care, terminally ill, hospice, guidelines, recommendations, ​and systematic reviews.

Four publications were found for consideration. They were graded according to the UK National Service Framework for Long Term Conditions and the Oxford Quality Scale. A pan-European work group of healthcare professionals with experience in management of constipation in palliative care was assembled to debate and reach consensus on best practice.

Results Provided in the Reference:

  • Constipation was defined as “passage of small, hard feces infrequently and with difficulty.”
  • Estimates of the prevalence of constipation in palliative care range from 32% to 87%.
  • The costs of constipation are as follows.
    • The cost of laxatives per year in England among older adults is 43 million pounds.
    • An economic study of US nursing homes identified costs of $2,253 per long-term resident annually.
    • A UK study found that 80% of community nurses spend up to half a day per week treating patients with constipation.
    • A study reported that 5.5% of calls to a UK district nursing service were directly related to constipation.
  • Pharmacologic agents, metabolic factors, neurologic disorders, structural physical abnormalities, and function factors such as diet and environment contribute to constipation.

Guidelines & Recommendations:

Key approaches to the prevention of constipation include

  • Ensuring privacy and comfort
  • Increasing fluid and fiber intake
  • Encouraging activity and increasing mobility
  • Anticipating constipating effects of agents such as opioids and providing laxatives prophylactically.

Principles of treatment include

  • Oral laxatives should be used in preference to rectal treatments.
  • Arachis oil is derived from peanut oil, and allergy may prevent its use.
  • A combination of a softener and stimulant is recommended. A comprehensive table with types of laxatives, dosage, mechanism of action, speed of action, possible side effects, contraindications, and starting dose is provided.
  • An algorithm for management is provided for
    • First-line treatment: oral combination of a softener (e.g., polyethylene glycol, lactulose, electrolytes) and stimulant (e.g., senna, sodium picosulfate)
    • Second-line treatment: rectal suppositories, enemas, and consideration of opioid antagonist if patient is taking opioids
    • Third-line treatment: manual evaluation and consideration of opioid antagonists if patient is taking opioids
    • Ongoing monitoring and patient education.

Limitations:

  • Little evidence was found in this area, current research is poor, and additional research is needed on many aspects of assessment, diagnosis, and management in palliative care.
  • Although the authors suggest prophylactic approaches, the algorithm provided begins only at patient complaint of constipation.

Nursing Implications:

This guideline provides a practical algorithm for constipation management based on consensus, rather than actual evidence. Specific choices of oral laxatives are not recommended; however, substantial evidence-based information for comparison of available oral laxatives agents is given.

National Comprehensive Cancer Network. (2011). NCCN Clinical Practice Guidelines in Oncology: Adult cancer pain [v. 2.2011]. Retrieved from http://www.nccn.org/professionals/physician_gls/pdf/pain.pdf

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Guidelines & Recommendations:

The guidelines recommend the following for management of opioid-induced constipation.

Preventive Measures:

  • Take polyethylene glycol or a combination of stool softener and stimulant laxative daily.
  • Maintain adequate fluid intake.
  • Maintain adequate fiber intake. Compounds such as psyllium are not recommended because they are unlikely to control opioid-induced constipation.

If Constipation Occurs:

  • Rule out other causes and begin treating.
  • Titrate stool softeners and laxatives as needed.
  • Consider coanalgesics to enable opioid dose reduction.

Persistent Constipation:

  • Consider the addition of agents such as magnesium hydroxide, bisacodyl, rectal suppository, lactulose, and sorbitol.
  • Use enemas.
  • Consider methylnaltrexone 0.15 mg/kg subcutaneously daily.

Limitations:

Recommendations were identified as having low-level evidence and uniform consensus.

National Comprehensive Cancer Network. (2012). NCCN Clinical Practice Guidelines in Oncology: Palliative Care [v.2.2012]. Retrieved from http://www.nccn.org/professionals/physician_gls/pdf/palliative.pdf

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Purpose & Patient Population:

The objective of the guidelines is to provide palliative care practice guidelines for patients with cancer, facilitating the appropriate integration of palliative care into oncology practice.

Type of Resource/Evidence-Based Process:

These are consensus-based guidelines.

Phase of Care and Clinical Applications:

Included in the guidelines are multiple phases of care with palliative care applications. 

Guidelines & Recommendations:

The NCCN made recommendations on the following symptoms.

Anorexia
Nutritional support, including enteral and parenteral feeding, should be considered. Appetite stimulants such as megestrol acetate and corticosteroids can be used when appetite is an important aspect of quality of life.

Chemotherapy-Induced Nausea and Vomiting (CINV)
Recommendations include prochlorperazine, haloperidol, metoclopramide, or benzodiazepines. Adding 5-HT3 receptor agonists, anticholinergics, antihistamines, corticosteroids, antipsychotics, and cannabinoids also can be considered. Palliative sedation can be considered as a last resort.

Constipation
Increase fluid intake, dietary fiber, and physical activity. Opioid-induced constipation should be anticipated and treated prophylactically with laxatives.

Dyspnea
Pharmacologic interventions include opioids or benzodiazapines. Scopolamine, atropine hyoscyamine, and glycopyrrolate are options to reduce excessive secretions.

Pain
Do not reduce opioid dose for symptoms such as decreased blood pressure or respiratory rate. Palliative sedation can be considered for refractory pain.

Sleep/Wake Disturbances
For refractory insomnia with no underlying physiologic cause, pharmacologic management includes diazepam, zolpidem, and sedating antidepressants. Cognitive behavioral therapy may be effective. If present, restless leg syndrome can be treated with ropinirole.

Limitations:

  • Recommendations are predominantly consensus- rather than evidence-based. 
  • Recommendations are generally based on low-level evidence. 
  • Recommendations regarding CINV seem particularly out of date and are not in concert with current evidence.

Nursing Implications:

Recommendations provide expert opinion/consensus-level suggestions for management of various symptoms. Many recommendations, such as those for CINV, do not agree with current evidence in these areas.


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