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.
Ahmedzai, S.H., & Boland, J. (2010, April). Constipation in people prescribed opioids. Clinical Evidence, 2407.
To answer the following questions: What are the effects of oral laxatives, rectal preparations, and opioid antagonists for constipation in people prescribed opioids?
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
The GRADE System was used to evaluate study quality. Full information is available online with a subscription.
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.
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.
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.
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
Initial searching provided 100 clinical trials and 71 review articles. A final group of seven trials was identified for consideration in this review.
The seven final studies encompassed data on 594 patients.
The review highlights the necessity of considering what treatment children will accept in managing symptoms.
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.
To identify and review all relevant data to determine whether lactulose or polyethylene glycol (PEG) is more effective in treating chronic constipation.
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
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.
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.
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.
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
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.
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.
The final sample of three studies involved a total of 162 patients, with study samples ranging from 36 to 75.
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.
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.
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.
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.
This was a single-blind, randomized, multicenter study.
The efficacy of PEG+E was evaluated by
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.
To extend the safety data of polyethylene glycol used for chronic treatment of chronic constipation.
Polyethylene glycol laxative was administered as a single daily dose of 17 g for 12 months.
This was a randomized, open-label, single-treatment study.
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.
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.
To compare the safety and efficacy of polyethylene glycol (PEG) 3350 (Miralax®) versus placebo for treatment of constipation in patients with chronic constipation.
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.
Four centers in the United States
This was a double-blind, placebo-controlled, parallel, randomized controlled trial.
PEG is safe and effective in treating constipation in patients taking constipating medications.
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.
To compare the safety and efficacy of polyethylene glycol (PEG) versus placebo over a six-month treatment period in patients with chronic constipation.
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.
50 centers in the United States
This was a double-blind, placebo-controlled, parallel, randomized controlled trial.
PEG is safe and effective in management of constipation in adults and older adults for up to six months.
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.
To evaluate the safety and efficacy of macrogol 3350 plus electrolytes in the treatment of chronic constipation in children.
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.
Royal Children’s Hospital, Melbourne, Australia
This was an open-label, nonrandomized study.
Longitudinal studies are needed to determine the long-term outcome of successful treatment of chronic constipation during childhood.
Koopmans-Klein, G., Wagemans, M.F., Wartenberg, H.C., Van Megen, Y.J., & Huygen, F.J. (2015). The efficacy of standard laxative use for the prevention and treatment of opioid induced constipation during oxycodone use: A small Dutch observational pilot study. Expert Review of Gastroenterology and Hepatology, 10, 547–553.
To explore the effectiveness of standard laxative treatment in the prevention of oxycodone-induced constipation
From July 2013 to October 2013, standard laxative treatment consisting of polyethylene glycol (PEG) with electrolytes was started at the same time as opioid intake on day 1. Bisacodyl was prescribed, and patients took this as needed. Patients prescribed oxycodone at least 20 mg slow-release tables were started on the standard laxative treatment and followed for 28 days.
The dose of PEG and electrolytes varied between 0-3 sachets, and the bisacodyl dose varied from 5 mg-20 mg. Based on responder analysis criteria, 43% of patients (9 of 21) who were prescribed a standard laxative therapy regimen did not respond.
A standard laxative therapy regimen may not be effective in all patients given the type of opioid they may be prescribed and what their bowel function is at the start of opioid therapy.
Response to prophylactic PEG plus electrolytes is patients taking oxycodone SR is variable.
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.
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).
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.
Children’s Hospital of Iowa
Randomized controlled trial
PEG and MOM are effective and safe in long-term treatment, with PEG having better acceptance.
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.
To determine the effect and preferred dose of polyethylene glycol 3350 (PEG3350) in children with functional constipation.
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.
The study has clinical applicability for pediatrics.
This was a double-blind, placebo-controlled, prospective, randomized study.
PEG is a well-tolerated, effective treatment for chronic constipation in healthy children.
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.
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.
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.
Two ICUs in the Netherlands
This was a double-blind, placebo-controlled, randomized trial.
Both lactulose and PEG promoted bowel movements equally. In patients receiving morphine, PEG had a more significant effect.
The study lacked a lead-in period or data on patients’ prior bowel function and history of constipation.
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.
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.
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.
This was a controlled, prospective, open-label study.
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.
No recommendation can be made.
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.
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.
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.
Key approaches to the prevention of constipation include
Principles of treatment include
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
The guidelines recommend the following for management of opioid-induced constipation.
If Constipation Occurs:
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
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.
These are consensus-based guidelines.
Included in the guidelines are multiple phases of care with palliative care applications.
The NCCN made recommendations on the following symptoms.
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.
Increase fluid intake, dietary fiber, and physical activity. Opioid-induced constipation should be anticipated and treated prophylactically with laxatives.
Pharmacologic interventions include opioids or benzodiazapines. Scopolamine, atropine hyoscyamine, and glycopyrrolate are options to reduce excessive secretions.
Do not reduce opioid dose for symptoms such as decreased blood pressure or respiratory rate. Palliative sedation can be considered for refractory pain.
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.
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.