Lactulose, an osmotic laxative, contains poorly absorbed ions or molecules that create a local osmotic gradient within the intestinal lumen. Fluid and electrolytes are drawn osmotically from the surrounding tissue into the colon, which creates pressure-stimulating peristalsis. Adverse effects of lactulose include electrolyte abnormalities, diarrhea, abdominal bloating, flatulence, and colic.
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, B., Jones, L., Larkin, P.J., Vickerstaff, V., Tookman, A., & Stone, P. (2015). Laxatives for the management of constipation in people receiving palliative care. Cochrane Database of Systematic Reviews, 5, CD003448.
PHASE OF CARE: End-of-life care
APPLICATIONS: Palliative care
No difference in effectiveness was demonstrated in lactulose compared with senna; senna plus lactulose compared with magnesium hydroxide plus liquid paraffin; misrakasneham compared with senna; and docusate plus senna compared with placebo plus senna.
The best laxatives for this patient population is unclear.
Very few clinical trials effectively evaluated the use of laxatives in this patient population.
More RCTs are needed to help evaluate the effectiveness and improve the quality of care of patients in palliative care.
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.
Agra, Y., Sacristan, A., Gonzalez, M., Ferrari, M., Portugues, A., & Calvo, M.J. (1998). Efficacy of senna versus lactulose in terminal cancer patients treated with opioids. Journal of Pain and Symptom Management, 15, 1–7.
To compare senna versus lactulose in relation to efficacy and adverse events in patients with terminal cancer.
Lactulose, an osmotic laxative, is a synthetic disaccharide. Senna acts mainly in the large intestine, directly stimulating the myenteric plexus and increasing water and electrolyte secretions, thus stimulating peristaltic activity. Their action extends over six to 12 hours. Side effects are abdominal pain, nausea, vomiting, and diarrhea.
Group A received senna BID starting at 0.4 ml (12 mg). Group B received lactulose BID starting at 15 ml. Based on clinical response, doses were increased in increments of 0.4 ml and 15 ml, respectively, every three days. Max doses were 1.6 ml (48 mg) for senna and 60 ml (40 g) for lactulose.
When patients reached the ceiling of their respective laxative and had three days without defecation, they were maintained on that dose and, in the absence of side effects, were started on an initial dose of another laxative, which could then be increased at three-day intervals until reaching the experimental maximum. Enema or mechanical bowel evacuation was prescribed after a three-day period without defecation (for ethical reasons), and was recorded as a failure with increase in laxative dose. If no results occurred from mechanical evacuation after six hours, patients were held on standby outside of the study until defecation.
The randomization schedule was stratified for age and gender (limit of eight per stratum). The study period was seven days to assess laxative efficacy on defecation days and at variable opioid dosage, and 27 days to assess mean morphine dose at which a laxative was necessary. Both laxative and opioid treatments were initiated simultaneously. Prescribers were blinded (single doses of identical volume in closed opaque flasks).
The study took place at a palliative care unit (PCU) in Madrid, Spain. The PCU assists patients who are released from the local hospital and is responsible for home care follow-up protocols.
This was a comparative study with a randomized, open, parallel-group design.
No difference existed between senna and lactulose in efficacy as measured by defecation-free intervals, days with defecation, or adverse effects. Senna use is recommend based on its lower cost. The description of the study design was very precise and detailed.
Harris, A.C., & Jackson, J.M. (1977). Lactulose in vincristine-induced constipation. Medical Journal of Australia, 2, 573–574.
To measure the efficacy of lactulose as a treatment for vincristine-induced intractable constipation or for the prevention of vincristine-associated constipation in patients with cancer.
Patients received lactulose 20 ml BID to 25 ml TID.
This was a descriptive study.
Time-to-first bowel movement after vincristine treatment and initiation of lactulose therapy.
All patients obtained relief of constipation within two days of initiating lactulose.
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.
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.