Lactulose

Lactulose

PEP Topic 
Constipation
Description 

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.

Effectiveness Not Established

Research Evidence Summaries

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.

doi: 10.1016/S0885-3924(97)00276-5
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Study Purpose:

To compare senna versus lactulose in relation to efficacy and adverse events in patients with terminal cancer.

Intervention Characteristics/Basic Study Process:

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).

Sample Characteristics:

  • The study reported on a sample of 91 patients with terminal cancer; 43 patients were assigned to the senna arm and 48 patients were assigned to the lactulose arm. 
  • Patients were aged older than 18 years and were in a palliative care program from July 1, 1993, to July 1, 1995.
  • Mean patient age was 67.8 years (range 41–93). 
  • All patients had clearly documented terminal disease with a life expectancy less than six months, and caregivers in the home.
  • Thirty percent had lung cancer, 11% had breast cancer, and 9% had stomach cancer. 
  • Patients were excluded if they had contraindications to the experimental laxatives, including colectomy, steatorrhea, or aphagia; a Karnofsky performance status lower than 10%; or taken opioids (codeine or morphine) or laxatives within 72 hours prior to initiation of the study.

Setting:

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.

Study Design:

This was a comparative study with a randomized, open, parallel-group design.

Measurement Instruments/Methods:

  • Outcome measures were defecation-free intervals of 72 hours, number of days with defecation events, and general state of health (rated on a five-point Likert-type scale).
  • Defecation days as a function of opioid dose and treatment cost also were examined.
  • Laxative efficacy was analyzed by t-test and ANOVA.

Results:

  • Of 91 patients, 75 completed the study for at least seven days and were evaluated in the analysis.
  • Sixteen patients abandoned the study within four days and were not included in the analysis. Reasons for leaving were diarrhea (n = 1), noncompliance (n = 4), dying within the first 24 hours (n = 4), permanent hospitalization (n = 5), and moving out of the jurisdiction of the home care area (n = 2).
  • Opioid dose did not determine laxative efficacy.
  • By the end of the study, 37.5% of patients required both laxatives.

Conclusions:

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.

Limitations:

  • Patients could differentiate medications by taste and texture.
  • Data were based on self-report, which is not considered reliable.
  • The study was done in Spain, so results may not be transferable to a U.S. population.
  • The sample size was fewer than 100 patients in the final analysis.
  • Baseline effects of diet, age, tumor type, and mobility were not discussed in relation to the results.

Harris, A.C., & Jackson, J.M. (1977). Lactulose in vincristine-induced constipation. Medical Journal of Australia, 2, 573–574.

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Study Purpose:

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.

Intervention Characteristics/Basic Study Process:

Patients received lactulose 20 ml BID to 25 ml TID.

Sample Characteristics:

  • The study reported on a sample of eight patients with lymphoma or leukemia.
  • Patients were aged 22 to 67 years.
  • Six patients (five women and one man) had protracted problems with constipation.
  • Two men received prophylactic treatment with lactulose immediately after vincristine therapy was initiated.

Setting:

  • Inpatient
  • Royal Perth Hospital in Western Australia

Study Design:

This was a descriptive study.

Measurement Instruments/Methods:

Time-to-first bowel movement after vincristine treatment and initiation of lactulose therapy.

Results:

All patients obtained relief of constipation within two days of initiating lactulose.

Limitations:

  • The sample size was small.
  • Patients were not randomized.
  • Side effects and duration of use were not reported.

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.

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.

Guideline/Expert Opinion

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.


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