Senna and Docusate

Senna and Docusate

PEP Topic 
Constipation
Description 

Senna, a stimulant laxative, is available as a liquid, powder, granules, and tablets to take orally.

Docusate calcium, docusate potassium, and docusate sodium are a part of the class of drugs known as stool softeners.

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.

Brick, N. (2013). Laxatives or methylnaltrexone for the management of constipation in palliative care patients. Clinical Journal of Oncology Nursing, 17(1), 91–92. 

doi: 10.1188/13.CJON.91-92
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Purpose:

STUDY PURPOSE: To assess the effectiveness of a laxative versus methylnaltrexone for the management of constipation in palliative care patients
 
TYPE OF STUDY: Meta-analysis and systematic review

Search Strategy:

DATABASES USED: Cochrane Library of Systematic Reviews
 
KEYWORDS: Effectiveness of laxatives, methylnaltrexone 
 
INCLUSION CRITERIA: Randomized clinical trials required to have investigated effectiveness of laxatives or methylnaltrexone; published and unpublished studies; adults; cancer and other chronic diseases
 
EXCLUSION CRITERIA: None noted

Literature Evaluated:

TOTAL REFERENCES RETRIEVED: Seven randomized controlled trials (RCTs)
 
EVALUATION METHOD AND COMMENTS ON LITERATURE USED: Review of RCTs with data extraction; meta-analysis was used to provide a pooled estimate effect where the data were of sufficient quality

Sample Characteristics:

  • FINAL NUMBER STUDIES INCLUDED = 7
  • TOTAL PATIENTS INCLUDED IN REVIEW = 616
  • KEY SAMPLE CHARACTERISTICS: Average age = 61–72 years; patients in advanced stage of diseases in palliative care; four studies examined lactulose, senna, co-danthramer, misrakasneham, and magnesium hydroxide with liquid paraffin; three studies evaluated methylnaltrexone

Phase of Care and Clinical Applications:

PHASE OF CARE: End of life care
 
APPLICATIONS: Palliative care 

Results:

All of the studies investigated variables in laxative types, opioid doses, and frequency of stools. Outcome measures included change in frequency of bowel movements, ease of defection, relief of systemic and abdominal symptoms of constipation, change in quality of life, and the use of rescue laxatives. There were no significant cross-findings, except all participants required rescue laxatives despite the initiation of a constipation prevention regimen. In two studies of (288) participants using methylnaltrexone versus a placebo, a statistically significant difference favored the intervention of rescue-free laxation 4 hours and 24 hours after the first dose of methylnaltrexone. Thirty percent of those participants experienced adverse effects. One study of 33 participants with methylnaltrexone showed a statistical difference favoring higher doses. Adverse effects were similar.

Conclusions:

There were no recommendations for optimal laxative management of constipation in palliative care patients.

Limitations:

There was little concrete evidence and too many variables across the studies. There was no information on how the search was conducted. It was very difficult to follow the evidence summary.

Nursing Implications:

The effectiveness of laxatives and the optimum management of constipation in palliative care patients requires further investigation involving the measurement of standardized, clinically relevant outcomes in a clearly defined population.

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

Hawley, P.H., & Byeon, J.J. (2008). A comparison of sennosides-based bowel protocols with and without docusate in hospitalized patients with cancer. Journal of Palliative Medicine, 11, 575–581.

doi: 10.1089/jpm.2007.0178
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Study Purpose:

To determine the efficacy of sennoside-based regimens on the proportion of total days with at least one bowel movement (BM) per day.

Intervention Characteristics/Basic Study Process:

During phase I, the first 30 consecutive eligible patients admitted to the ward received docusate plus sennosides (DS) for management of constipation. Dosing was as follows.

  • Opioid-naive patients received docusate sodium 200 mg BID.
  • For those on opioids or had no BM in 48 hours, the starting dose or next dose was docusate 200 mg BID plus sennosides 17.2 mg every bedtime.
  • If patients had no BM in the next 48 hours, they received docusate sodium 200 mg TID plus sennosides 17.2 mg BID.
  • If patients had no BM in the next 24 hours, they received docusate sodium 200 mg TID plus sennosides 17.2 mg TID.
  • If patients still had no BM after 24 hours, they received docusate sodium 200 mg TID plus sennosides 25.8 mg TID. 

During phase II, the next 30 eligible patients with constipation received sennosides only. Dosing was as follows.

  • Patients received sennosides 17.2 mg every bedtime.
  • For those on opioids or had no BM in 48 hours, the starting dose or next dose was sennosides 17.2 mg BID.
  • If patients had no BM in the next 24 hours, they received sennosides 17.2 mg TID.
  • Finally, if patients had no BM after 24 hours, they received sennosides 25.8 mg TID.

Rescue laxatives included lactulose, a suppository, or enema as needed. Only 12 days of bowel protocol were abstracted from the medical record.

Sample Characteristics:

  • The study reported on a sample of 60 patients.
  • Mean patient age was 59.1 years (SD = 14.8, range 24–87) in the DS group and 62.9 years (SD =13.9, range 25–85) in the sennosides group.
  • The sample comprised 45 women and 15 men.
  • Fourteen patients in the sennosides group had genitourinary cancer, and seven patients in the DS group had breast cancer. 
  • Eighty percent of patients were on opioids and 72% were admitted for symptom control.

Setting:

  • Single site
  • Inpatient
  • Vancouver Center of British Columbia Cancer Agency in Canada

Phase of Care and Clinical Applications:

  • Patients were undergoing the active treatment phase of care.
  • The study has clinical applicability to end-of-life and palliative care.

Study Design:

This was a nonrandomized, nonblinded, sequential cohort study.

Measurement Instruments/Methods:

Nursing chart review

Results:

  • The mean study observation period was eight days (range 5–12 days).
  • Eighty percent of patients in the sennosides group had a BM on at least 40% of days compared with 60% of the DS group (p = 0.09). However, if patients not taking opioids were excluded, the sennosides group had better results (76% versus 50% of days) than the DS group (not significant).
  • Fifty-seven percent of patients in the DS group required additional interventions (lactulose, suppositories, or enemas) compared to 40% in the sennosides group.
  • Twenty-seven percent of patients in the sennosides group reported diarrhea compared to 13% in the DS group.

Conclusions:

Sennosides only produced more BMs than DS.

Limitations:

  • The study had a small sample size (fewer than 100).
  • The design was not randomized.
  • More patients with genitourinary cancer were recruited in the sennosides group than the DS group, and 90% of patients in the DS group were receiving opioids; therefore, an even comparison in diagnosis was not reflected.
  • The dosage of sennosides was higher overall in the sennosides group than the DS group, which could have influenced the results as well.
  • Conclusions were based on a chart review, which was performed to look at side effects, versus interview. Data may have been lost if patients were not asked or side effects were not recorded.

Nursing Implications:

Adding a stool softener such as docusate does not necessarily produce superior results than those seen with a laxative alone. However, additional randomized, double-blind studies should be conducted before conclusions and evidence into practice are drawn. The usefulness of this study is questionable because of its design and execution issues.

Patel, M., Schimpf, M.O., O'Sullivan, D.M., & LaSala, C.A. (2010). The use of senna with docusate for postoperative constipation after pelvic reconstructive surgery: A randomized, double-blind, placebo-controlled trial. American Journal of Obstetrics and Gynecology, 202, 479.e1–479.e5.

doi: 10.1016/j.ajog.2010.01.003
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Study Purpose:

To compare the time of first bowel movement (BM) following pelvic reconstructive surgery in patients randomized to placebo or senna with docusate.

Intervention Characteristics/Basic Study Process:

Patients were enrolled prior to surgery. After surgery, patients were randomized to either senna with docusate or placebo. Dosing was as follows.

  • Take two tablets on the first night postoperation.
  • If no BM, take two tablets the following morning.
  • If no BM, take three tablets in the evening.
  • If no BM the following morning, take three additional tablets twice daily until BM, or take magnesium citrate.

Sample Characteristics:

  • The study reported on a sample of 93 women.
  • Mean patient age was 59.5 years (SD = 12.6) in the senna with docusate group and 56.2 years (SD = 10) in the placebo group.
  • The sample comprised patients with nonmalignant gynecologic and genitourinary cancer undergoing pelvic reconstructive surgery. Vaginal parity was 2 in the senna with docusate group (range 0–4) and 3 in the placebo group (range 0–7).

Setting:

  • Single site
  • Inpatient
  • Hartford Hospital in Connecticut

Phase of Care and Clinical Applications:

Patients were undergoing the active treatment phase of care.

Study Design:

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

Measurement Instruments/Methods:

  • Seven-day bowel diary (baseline)
  • Bristol Stool Scale
  • Degree of strain and pain (11-point visual analog scale from 0 to 10)
  • Medications taken
  • Daily diary

Results:

  • A significant difference existed in time of first BM in the senna with docusate group compared with the placebo group (3 days, SD = 1.5 versus 4 days, SD = 1.5; p < 0.002).
  • More patients in the placebo group needed to use magnesium citrate to initiate a BM than in the senna with docusate group (43.6% versus 7%, p < 0.001).

Conclusions:

The use of a stool softener with a laxative such as senna with docusate decreases the time to first BM following pelvic reconstructive surgery compared with placebo and lessens the need for use of magnesium citrate.

Limitations:

  • The sample size was small (fewer than 100 patients).
  • The study lacked an intention-to-treat analysis.

Nursing Implications:

Nurses should be proactive in the management of patients' bowels following reconstructive surgery. Management with medications such as senna with docusate may be an option for patients following this form of surgery.

Tarumi, Y., Wilson, M.P., Szafran, O., & Spooner, G.R. (2013). Randomized, double-blind, placebo-controlled trial of oral docusate in the management of constipation in hospice patients. Journal of Pain and Symptom Management, 45(1), 2–13. 

doi: 10.1016/j.jpainsymman.2012.02.008
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Study Purpose:

To determine the efficacy of docusate in patients in hospice

Intervention Characteristics/Basic Study Process:

Patients were randomly assigned via a code generated by a public domain computer. Randomization was assigned by a pharmacist, and the research assistant, patient, proxy, attending physician, and nurses were blinded to study treatment. The intervention group received two 100 mg docusate tablets in the morning and late afternoon plus one to three sennoside tablets (8.6 mg per tablet) one to three times per day. The placebo group received two cornstarch tablets in the morning and afternoon in addition to one to three sennoside tablets (8.6 mg per tablet) one to three times per day. All medications were administered by hospice nursing staff for a period of 10 days. Docusate pills were rolled in cornstarch and placed into nontransparent blue capsules, and the placebo pills were only cornstarch in blue capsules so that both the intervention and placebo pills looked the same. All patients were allowed to take laxatives and receive other bowel interventions as needed throughout the study. Nurses received multiple education sessions on stool consistency and volume to ensure inter-rater reliability. Nurses recorded data daily for 10 days.

Sample Characteristics:

  • N = 74
  • AGE = ≥ 18 years 
  • MALES: 55%, FEMALES: 45%
  • KEY DISEASE CHARACTERISTICS: Cancer and non-cancer 
  • OTHER KEY SAMPLE CHARACTERISTICS: Palliative Performance Scale (PPS) score and Mini-Mental State Examination (MMSE) score of 23

Setting:

  • SITE: Multi-site  
  • SETTING TYPE: Inpatient  
  • LOCATION: Edmonton, Alberta, Canada

Phase of Care and Clinical Applications:

  • PHASE OF CARE: End of life care
  • APPLICATIONS: Elder care, palliative care

Study Design:

Randomized, double-blind, placebo-controlled study

Measurement Instruments/Methods:

  • Assessment and recording of bowel movements, which included stool frequency and volume, stool consistency, constipation symptoms, and ease with which defecation occurred.
  • Type/frequency of other bowel interventions
  • Patient perception of completeness of evacuation
  • Edmonton Symptom Assessment System (ESAS)
  • Bowel movement record

Results:

The results revealed no significant difference in stool frequency, volume, or consistency between the two groups. Data showed no significant differences in patients’ perception of the difficulty or completeness of defecation. ESAS scores showed no difference in symptoms experienced between the two groups. No difference was seen in the number of additional bowel-care interventions provided to patients in this study.

Conclusions:

There were no significant differences between the docusate group and the placebo group, suggesting that the use of docusate should be considered on a patient-by-patient basis.

Limitations:

  • Small sample (< 100)
  • Key sample group differences that could influence results
  • Measurement validity/reliability questionable

Nursing Implications:

Nurses must assess patient needs versus what is actually happening. Frequent abdominal inspections should be made with or without the use of docusate. Other things that should be assessed include bowel sounds and pattern of bowel function as well as the color, consistency, and amount of stool produced without regard to docusate use.

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.

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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