Prophylactic Laxatives for Patients on Opioids

Prophylactic Laxatives for Patients on Opioids

PEP Topic 
Constipation
Description 

Prophylactic laxatives are the provision of laxatives prior to any symptoms of constipation to prevent or avoid constipation. This approach has been suggested for patients with cancer on opioids for pain management.

Likely to Be Effective

Research Evidence Summaries

Ishihara, M., Iihara, H., Okayasu, S., Yasuda, K., Matsuura, K., Suzui, M., & Itoh, Y. (2010). Pharmaceutical interventions facilitate premedication and prevent opioid-induced constipation and emesis in cancer patients. Supportive Care in Cancer, 18, 1531–1538.

doi: 10.1007/s00520-009-0775-3
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Study Purpose:

  • To perform a retrospective review of medical records to determine the use of prophylactic laxatives in patients receiving opioids.
  • To determine the incidence of constipation in patients taking opioid medications.
  • To promote use of preventative medications by educating physicians, checking orders, and educating patients.

Intervention Characteristics/Basic Study Process:

In part 1, patients who were admitted and receiving opioids were surveyed for use of prophylactic laxatives to prevent constipation.

In part 2, prescribers were given drug information, orders were reviewed, and patients were educated about laxatives to manage constipation.

Sample Characteristics:

  • The study reported on a sample of 83 patients with cancer in part 1 and 107 patients with cancer in part 2. 
  • Mean patient age was 66.1 years (range 41-92) in part 1 and  63.7 years (range 14-83) in part 2. 
  • The sample comprised 40 women and 43 men in part 1, and 40 women and 67 men in part 2.

Setting:

  • Single site
  • Inpatient
  • Japan

Phase of Care and Clinical Applications:

Patients were undergoing the active treatment phase of care.

Study Design:

This was a retrospective survey followed by an interventional study.

Measurement Instruments/Methods:

  • National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 3.0
  • Constipation medical records were reviewed.

Results:

  • Of the 83 patients, 57% (47 patients) received laxatives with opioids.
  • Patients who did not receive laxatives had a higher incidence of constipation than those who received laxatives (56% versus 21%, p = 0.0024).
  • Patients who received laxatives had more bowel movements in seven days than patients who did not (5.6 versus 3.9, p = 0.005).
  • Taking more laxatives resulted in less constipation, and the absence of prophylactic laxatives resulted in an increased risk of constipation.
  • The incidence of constipation was lowest in patients who received prophylactic combination treatment with magnesium oxide and pantethine.

Conclusions:

Laxative use prophylactically reduced the incidence of constipation in patients taking opioid therapy but did not completely prevent it.

Limitations:

  • The study lacked an appropriate control group.
  • Part 1 had fewer than 100 patients.
  • The validity and reliability of medical records for determination of laxative use was questionable, and patients did not self-report use.

Nursing Implications:

Laxative prophylaxis is beneficial to reduce the risk of opioid-induced constipation. Proactive interventions to increase laxative use may be beneficial to patients.

Ishihara, M., Ikesue, H., Matsunaga, H., Suemaru, K., Kitaichi, K., Suetsugu, K., . . . Japanese Study Group for the Relief of Opioid-Induced Gastrointestinal Dysfunction. (2012). A multi-institutional study analyzing effect of prophylactic medication for prevention of opioid-induced gastrointestinal dysfunction. Clinical Journal of Pain, 28, 373–381.

doi: 10.1097/AJP.0b013e318237d626
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Study Purpose:

To evaluate the effectiveness of prophylactic laxatives and antiemetics on constipation, nausea, and vomiting in patients with cancer receiving opioids for the first time.

Intervention Characteristics/Basic Study Process:

Medical records were reviewed from 2009 to 2010 for patients experiencing constipation, nausea, or vomiting during the first week of opioid analgesic administration. Number of stools recorded was used in the analysis. Constipation was defined as a stool-free interval of at least 72 hours during the first week. One episode of vomiting was counted as evidence of vomiting. Nausea grading was recorded for seven days.

Sample Characteristics:

  • The study reported on a sample of 619 patients.
  • Mean patient age was 66.8 years (range 53-81).
  • The sample was 63% male and 37% female.
  • Gastrointestinal and lung cancer were most prevalent, but the sample included a variety of disease sites.
  • Most patients were receiving extended-release oxycodone.
  • Patients were excluded if they were using transdermal opioids; undergoing surgery within the first week of receiving opioids; or experiencing continuous symptoms of constipation, nausea, or vomiting prior to opioid administration.

Setting:

  • Multi-site
  • Setting type not specified
  • Japan

Phase of Care and Clinical Applications:

  • Patients were undergoing multiple phases of care.
  • The study has clinical applicability to older adult and palliative care.

Study Design:

This was a descriptive, retrospective study.

Measurement Instruments/Methods:

National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE), version 4.0, for nausea grading

Results:

  • Incidence of constipation was 33.7% in those receiving prophylactic laxatives, compared to 54.6% in others (p < 0.001).
  • The most frequently used laxative was magnesium oxide. Some patients also received senna and other combined laxatives. 
  • No significant differences in efficacy existed among different laxatives.
  • Regression analysis showed that no laxative use, use of morphine formulation, and being aged 70 years or older were predictive of constipation (p < 0.01).
  • Odds ratio in favor of laxatives was 0.469 (95% confidence interval [0.231, 0.955], p = 0.037).
  • No effects were observed for use of prophylactic antiemetics on nausea or vomiting. Antiemetics used were prochlorperazine, domperidone, and metoclopramide.

Conclusions:

Use of prophylactic laxatives in patients receiving opioids for the first time was effective in reducing the risk and prevalence of constipation.

Limitations:

  • A risk of bias existed because of the lack of random assignment.
  • Measurement validity and reliability were questionable.
  • The descriptive study design with dependence on medical record documentation limited the data's reliability.
  • The duration of observation was short at only one week. Longer term efficacy is not known. 
  • Dosages of opioids and other factors that could have contributed to constipation were not described.

Nursing Implications:

Findings suggested use of prophylactic laxatives can reduce opioid-induced constipation during the first week in which patients receive opioids. Findings also suggested older patients may be at greater risk for opioid-induced constipation. Nurses can ensure that prophylactic regimens to prevent constipation are suggested for patients beginning opioid use and older adult patients.

Guideline/Expert Opinion

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

doi: 10.1177/0269216308096908
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Purpose & Patient Population:

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

Type of Resource/Evidence-Based Process:

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

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

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

Results Provided in the Reference:

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

Guidelines & Recommendations:

Key approaches to the prevention of constipation include

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

Principles of treatment include

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

Limitations:

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

Nursing Implications:

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

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

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Guidelines & Recommendations:

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

Preventive Measures:

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

If Constipation Occurs:

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

Persistent Constipation:

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

Limitations:

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

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

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Purpose & Patient Population:

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

Type of Resource/Evidence-Based Process:

These are consensus-based guidelines.

Phase of Care and Clinical Applications:

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

Guidelines & Recommendations:

The NCCN made recommendations on the following symptoms.

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

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

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

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

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

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

Limitations:

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

Nursing Implications:

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


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