Clinical Topic A-Z Clinical Speciality

Palliative cancer care - constipation

Palliative cancer care - constipation
D010166Palliative Care
D003248Constipation
GastrointestinalPalliative care
2013-04-01Last revised in April 2013

Palliative cancer care - constipation - Summary

Constipation is defecation that is unsatisfactory because of infrequent stools, difficult stool passage, or seemingly incomplete defecation. Stools are often dry and hard, and may be abnormally large or abnormally small.

About 80% of people with cancer will require treatment with laxatives at some time.

People receiving palliative care have multiple causes of constipation, such as:

Drugs, for example, opioid analgesics, antimuscarinic drugs, antacids.

Secondary effects of disease, for example, dehydration, inadequate dietary fibre, inactivity, delirium, spinal cord compression, lack of privacy.

Direct effects of malignant tumours, causing bowel obstruction, hypercalcaemia, nerve damage.

When assessing a person with constipation in palliative care:

The history should include information about the frequency and character of stools, discomfort, blood or mucus with the stool, or straining.

Other associated symptoms, such as malaise, flatulence, abdominal pain and distension, anorexia, nausea or vomiting; halitosis, and faecal incontinence (overflow diarrhoea), distress, or worsening confusion should be noted.

Examination for faecal loading and impaction, suggested by faecal masses palpable abdominally or perianally, or on internal rectal examination should be done.

Bowel obstruction, anal fissure, painful haemorrhoids, and local tumours should be excluded or managed.

A person with constipation in palliative care should be offered the following management strategies:

Alleviating contributing factors, where possible, such as dehydration, lack of privacy, haemorrhoids.

Treatment with a combination of a stimulant and a softening laxative, such as senna and lactulose.

Titration of the dose of laxatives every few days to achieve comfortable defecation.

If the response is insufficient, the addition of a macrogol or prokinetic drug such as metoclopramide should be considered. Additional treatments may be necessary for faecal loading and/or impaction, such as a suppository or enema.

A laxative should be prescribed to prevent constipation when starting any potentially constipating drug, such as opioid analgesics. The laxative dose needs to increase with increases in opioid dose.

Have I got the right topic?

192months3060monthsBoth

This CKS topic covers the symptomatic management of constipation in people who are receiving palliative care.

There are separate CKS topics on Constipation, Hypercalcaemia, Palliative cancer care - cough, Palliative cancer care - dyspnoea, Palliative cancer care - general issues, Palliative cancer care - malignant ulcer, Palliative cancer care - nausea & vomiting, Palliative cancer care - oral, Palliative cancer care - pain, and Palliative cancer care - secretions.

The target audience for this CKS topic is healthcare professionals working within the NHS in the UK, and providing first contact or primary health care.

How up-to-date is this topic?

How up-to-date is this topic?

Changes

Last revised in April 2013

June 2013 — minor update. The 2013 QOF options for local implementation have been added to this topic [BMA and NHS Employers, 2013].

April 2013 — reviewed. A literature search was conducted in November 2012 to identify evidence-based guidelines, UK policy, systematic reviews, and key RCTs published since the last revision of this topic. Methylnaltrexone (a peripheral opioid-receptor antagonist) is now a therapeutic option in opioid-induced constipation, however CKS recommends this is used only in a specialist setting. No major changes to clinical recommendations have been made.

Previous changes

November 2012 — minor update. The links to the electronic medicines website (www.medicines.org.uk) have been updated.

October 2012 — minor update. The 2012 QIPP options for local implementation have been added to this topic [NPC, 2012].

March 2012 — minor update. The 2012/2013 QOF indicators have been added to this topic [BMA and NHS Employers, 2012]. Issued in April 2012.

May 2011 — minor update. The 2011/2012 QOF indicators have been added to this topic [BMA and NHS Employers, 2011]. Issued in June 2011.

February 2011 — topic structure revised to ensure consistency across CKS topics — no changes to clinical recommendations have been made.

October 2007 to February 2008 — developed as a new CKS topic and replacing the section on Terminal care in the CKS guidance on Constipation. The evidence-base has been reviewed in detail, and recommendations are more clearly justified and transparently linked to the supporting evidence.

There are no major changes to the recommendations on the management of constipation in palliative care. However, there is clearer advice on treatment strategies.

Update

New evidence

Evidence-based guidelines

No new evidence-based guidelines since 1 November 2012.

HTAs (Health Technology Assessments)

New technology appraisals published since the last revision of this topic:

NICE (2013) Methylnaltrexone for treating opioid-induced bowel dysfunction in people with advanced illness receiving palliative care (terminated appraisal). NICE technology appraisal 277. National Institute for Health and Care Excellence. www.nice.org.uk [Free Full-text]

Economic appraisals

No new economic appraisals relevant to England since 1 November 2012.

Systematic reviews and meta-analyses

Systematic reviews published since the last revision of this topic:

Ford, A.C., Brenner, D.M., and Schoenfeld, P.S. (2013) Efficacy of pharmacological therapies for the treatment of opioid-induced constipation: systematic review and meta-analysis. American Journal of Gastroenterology 108(10), 1566-1574. [Abstract]

Ruston, T., Hunter, K., Cummings, G., and Lazarescu, A. (2013) Efficacy and side-effect profiles of lactulose, docusate sodium, and sennosides compared to PEG in opioid-induced constipation: a systematic review. Canadian Oncology Nursing Journal 23(4), 236-246. [Abstract]

Primary evidence

No new randomized controlled trials published in the major journals since 1 November 2012.

New policies

No new national policies or guidelines since 1 November 2012.

New safety alerts

No new safety alerts since 1 November 2012.

Changes in product availability

No changes in product availability since 1 November 2012.

Goals and outcome measures

Goals

To achieve comfortable defecation

QIPP - Options for local implementation

Laxatives:

Review and, where appropriate, revise prescribing of laxatives for adults to ensure they are only prescribed routinely for the short-term treatment of constipation, where dietary and lifestyle measures have proved unsuccessful or where there is an immediate clinical need.

[NICE, 2013]

QOF indicators

Table 1 . Indicators related to palliative care in the Quality and Outcomes Framework of the General Medical Services contract.
Indicator Points Payment stages
PC001 The contractor establishes and maintains a register of all patients in need of palliative care/support irrespective of age 3
PC002 The contractor has regular (at least 3 monthly) multidisciplinary case review meetings where all patients on the palliative care register are discussed 3
Data from: [BMA and NHS Employers, 2013]

Background information

Definition

What is it?

Constipation is defecation that is unsatisfactory because of infrequent stools, difficult stool passage, or seemingly incomplete defecation. Stools are often dry and hard, and may be abnormally large or abnormally small.

This definition of constipation is necessarily subjective because different people have different views about what is infrequent, difficult, dry, hard, abnormally large, or abnormally small.

Note that it is possible to be constipated and have normal or even soft stools, for example when there is failure of propulsion by the bowel (for example opioid-induced, neuropathic).

Attempts therefore continue to be made to develop and agree more objective criteria for the definition of functional constipation, most notably by the Rome criteria [Hyman et al, 2006; Longstreth et al, 2006; Rasquin et al, 2006]. However, many people feel constipated (and benefit from treatment) although they do not meet the Rome criteria [Sykes, 2010].

Prevalence

How common is it?

Constipation is more common in people with advanced cancer than in those dying of other causes [Cartwright et al, 1973].

About 50% of people admitted to British hospices with cancer report constipation, but this is an underestimate of the prevalence as some people will be using laxatives [Sykes, 2010].

About 80% of people with cancer will require treatment with laxatives at some time [Fallon and O'Neill, 1997].

Causes

What are the common causes?

Opioid analgesics are a common cause of constipation in people receiving palliative care [Fallon and O'Neill, 1998; Sykes, 2010].

However, the presence of contributing factors, use of other drugs which constipate, the direct effects of cancer, and the presence of other concurrent disease are common in this group.

Contributing factors

Factors contributing to constipation

Secondary effects of disease that contribute to constipation include:

Inadequate diet (poor intake, limited fibre).

Dehydration.

Weakness or dyspnoea (breathlessness) — prevents effective straining.

Confusion.

Depression.

Inactivity.

Unfamiliar toilet arrangements, or lack of privacy (both auditory and visual).

Having to use a bedpan.

[Sykes, 2010]

Drugs

Drugs which commonly cause constipation in people receiving palliative care include:

Opioids.

Drugs with antimuscarinic effects (cyclizine, hyoscine, phenothiazines, tricyclic antidepressants, some antiepileptic drugs, antiparkinsonian agents).

Antacids (calcium and aluminium compounds).

Diuretics.

Iron.

Antihypertensive agents.

Cytotoxics (for example, vinca alkaloids).

5HT-3 antagonists (for example, ondansetron).

Platinum based chemotherapy agents (present or past use).

[Sykes, 2010]

Direct effects of cancer

What are the direct effects of cancer on constipation?

Cancer can cause constipation in several ways, for example by:

Bowel obstruction due to either tumour in the bowel wall, or external compression by abdominal or pelvic tumour.

Compression or infiltration of the lumbosacral spinal cord, cauda equina, or pelvic plexus.

Causing hypercalcaemia.

Causing painful defecation.

Autonomic neuropathy, a non-metastatic manifestation of malignancy, particularly associated with small cell carcinoma of the lung and carcinoid tumours.

[Sykes, 2010]

Other concurrent disease

People receiving palliative care often have concurrent conditions that cause constipation, for example:

Diverticular disease .

Inflammatory bowel disease (Crohn's disease and ulcerative colitis).

Irritable bowel syndrome .

Endocrine and metabolic conditions (for example diabetes - type 1, diabetes - type 2, hypercalcaemia, hypothyroidism, hypokalaemia).

Hernia.

Colonic strictures (following diverticulitis, ischaemia, surgery).

Rectocele (suspect if the woman needs to insert a finger into the vagina to help pass stool).

Rectal prolapse.

Rectal ulcer (suspect if the person needs to insert a finger into the rectum to push away a flap prior to defecation).

Anal fissure or stenosis.

Haemorrhoids .

Dyssynergic defecation (incomplete evacuation of faeces from the rectum due to paradoxical contraction or failure to relax pelvic floor muscles when straining to defecate).

Weak levator muscles (suspect if the person needs to apply pressure behind the anus to help pass stool).

Spinal cord damage.

Severe neurological diseases.

Severe intellectual disability.

[Chiarioni et al, 2006; Regnard and Dean, 2010; Sykes, 2010; North of England Cancer Network, 2012]

Complications

What are the complications?

Constipation may lead to:

Increased agitation [Regnard and Dean, 2010].

Bowel obstruction.

Pain and abdominal distension.

Urinary retention and urinary tract infection.

Faecal incontinence (overflow diarrhoea).

Faecal retention, distension of the rectum, and loss of sensory and motor function.

Faecal impaction, particularly in the immobile.

Rectal bleeding.

Rectal prolapse.

An autonomic dysreflexia (severe hypertension and risk of seizures, haemorrhage and cardiac arrest) if left untreated in paraplegic people with lesions above T6 [Karlsson, 1999; Krassioukov et al, 2003; NPSA, 2004].

Diagnosis

Diagnosis of constipation in palliative care

Diagnosis

How do I know my patient has it?

Suspect constipation when:

Stools are hard, uncomfortable, or difficult to pass, and are less frequent than usual; or the person has a sense of incomplete evacuation after defecation.

Infrequent stool passage is common in advanced disease, however if the person has not opened their bowels for more than three days, treatment is recommended.

Associated symptoms are present, including malaise; flatulence, colicky abdominal pain and distension; anorexia, nausea, or vomiting; halitosis; and faecal incontinence (overflow diarrhoea).

The person has urinary frequency or retention.

The person is agitated or confused, particularly if they are elderly or have impaired brain function (for example dementia).

Suspect faecal loading/impaction when:

Stools are hard and lumpy, and either large and infrequent (for example every 7–10 days), or small and relatively frequent (for example every 2–3 days).

Straining is ineffective.

Manual methods are necessary to extract faeces.

Overflow faecal incontinence, or loose stools are present.

Faecal masses are palpable abdominally or peri-anally, or on internal rectal examination (avoid rectal examination in people who are receiving chemotherapy, are thrombocytopenic, or who have rectal or anal disease), or on gentle digital examination of the stoma (if the person has a colostomy).

98% of faecal impactions occur in the rectum.

Careful examination can usually distinguish a faecal mass from a tumour or cyst: firm pressure exerted by a finger will leave a palpable indentation in hard faeces.

Suspect bowel obstruction when any of the following symptoms or signs are present:

Absence of passage of flatus per rectum.

Colicky, abdominal pain and abdominal distension.

Anorexia, nausea, or vomiting (which may be faeculent) .

Abdominal tenderness without guarding or rebound.

Active, tinkling bowel sounds; or quiet or absent bowel sounds (later).

Basis for recommendation

Basis for recommendation

These recommendations are based on regional guidelines [North of England Cancer Network, 2012], expert opinion in palliative care textbooks [Fallon and O'Neill, 1998; Regnard and Dean, 2010; Sykes, 2010], and on the opinion of CKS expert reviewers. Information on the symptoms and signs suggestive of bowel obstruction are based on expert opinion in a textbook [Simon et al, 2010].

Management

Management

Scenario: Assessment : covers the assessment of constipation in order to guide further management.

Scenario: Management : covers the prevention and treatment of constipation and faecal loading/impaction in a palliative care situation.

Scenario: Assessment

Scenario: Assessment of constipation in palliative care

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Assessment

How should I assess a person with constipation in palliative care?

Clarify the cause of constipation — this will include an abdominal and rectal examination (avoid rectal examination in people receiving chemotherapy).

Exclude bowel obstruction. Features which suggest obstruction include:

Known presence of intra-abdominal tumour.

Absence of passage of flatus per rectum.

Nausea and vomiting.

Colicky, abdominal pain.

Abdominal distension.

Abdominal tenderness without guarding or rebound.

Active, tinkling bowel sounds; or quiet or absent bowel sounds (later).

Identify when the constipation first became a problem (if constipation pre-dates the illness requiring palliative care, further enquiry may be indicated).

Assess the role (and potential for modification) of contributing factors and drugs.

Identify any direct effects of malignant tumour or other concurrent disease that could cause constipation.

Assess the severity and impact of the constipation and any faecal incontinence.

Is there nausea, vomiting, loss of appetite, or loss of body weight?

Is there abdominal pain or abdominal distension?

Is there pain or bleeding with passing stools?

Is underwear regularly and involuntarily soiled? If yes, what are the social consequences of this?

Are there urinary symptoms, urinary incontinence, difficulty in passing urine or blockage of a urinary catheter?

Assess the effectiveness of management to date.

What measures (self-care and prescribed, non-drug and drug) have been tried?

What has been the response?

Basis for recommendation

Basis for recommendation

These recommendations are based on expert opinion [American College of Gastroenterology Chronic Constipation Task Force, 2005; Longstreth et al, 2006; Paré et al, 2007; Larkin et al, 2008; NHS Lothian, 2010a; NHS Lothian, 2010b; Regnard and Dean, 2010; Cambridgeshire Palliative Care Guidelines Group, 2012] and information from the Oxford textbook of palliative medicine [Sykes, 2010].

Scenario: Management

Scenario: Management of constipation in palliative care

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Preventing constipation

How should I prevent constipation when prescribing a constipating drug?

When introducing an opioid (or any other constipating drug), advise the person of the risks of constipation, and prescribe a stimulant laxative (such as senna or dantron-containing laxative) at the time of first prescription, rather than waiting until constipation is established. Aim for a regular bowel movement, without straining, every 1–3 days.

Dose of senna:

If not constipated start with 15 mg at bedtime. If there is no bowel movement after 24–48 hours, increase to 15 mg at bedtime and 15 mg each morning.

If already constipated, start with 15 mg at bedtime and 15 mg each morning. If there is no response after 24–48 hours, increase to 22.5 mg at bedtime and 22.5 mg each morning.

If there is still no response after a further 24–48 hours, consider adding a third daytime dose.

If necessary, consider increasing to a maximum dose of 30 mg three times a day.

The dose of dantron-containing laxatives is variable, according to the preparation, individual need, and acceptability. For information on dosages, see Table 2.

In people with renal failure prescribe lactulose plus senna, or co-danthramer. For information on dosages, see Table 1 and Table 2.

Encourage an adequate fluid intake, and fruit juice and fruit specifically.

Basis for recommendation

Basis for recommendation

These recommendations are pragmatic advice based on expert opinion [Twycross and Wilcock, 2011].

Treating constipation

How should I treat constipation?

Where possible, alleviate contributing factors (for example, inadequate diet, dehydration, having to use a bedpan, lack of privacy, anal fissure, painful haemorrhoids, or local tumour).

Treat any faecal loading or impaction.

Start treatment with a stimulant laxative (such as senna).

Titrate the dose of laxative in order to achieve comfortable defecation without colic. For instance, senna may be titrated up to a maximum dosage of 2–4 tablets (15–30 mg) three times a day.

If the person finds it difficult to take the required number of tablets, reduce the dose of senna (for example to 15 mg at night) and add in a softener such as docusate (also a weak stimulant).

Increase the dose of laxative in line with any increase in dose of opioid.

Add an osmotic laxative (such as lactulose or a macrogol) or a surface-wetting laxative (such as docusate, which also softens stools) if colic is a problem.

Adjust the dose of softener to produce a comfortable stool (comfort is more important than the frequency or number of stools).

In a palliative care situation, higher and more frequent doses than specified by the product licence may be needed.

Avoid:

Phosphate enemas (if possible) as they can sometimes cause water and electrolyte disturbances, especially in people aged 65 years or older, and when co-morbidities are present.

Bulk-forming laxatives (e.g. bran, ispaghula), especially in opioid-induced constipation.

Paraffin.

Do not carry out rectal interventions (such as enemas, suppositories, or manual evacuation) in people:

On chemotherapy, who may be neutropenic (white blood cell count < 0.5 x 109/ L) and therefore at risk of serious infection.

With thrombocytopenia (platelet count < 20 x 109/ L), who are at risk of bleeding.

With rectal or anal disease.

If the response to laxatives is insufficient, consider adding in a prokinetic agent such as metoclopramide, domperidone, or erythromycin 250–500 mg four times a day (off-label use). Do not use a pro-kinetic if the person has symptoms of colic.

If the person is terminally ill and has not had an adequate response despite these measures, consider the use of a dantron-containing laxative.

Seek specialist advice if constipation still persists despite these measures.

Basis for recommendation

Basis for recommendation

There is no good evidence from clinical trials to guide choice of laxatives for treating constipation in palliative care.

Choice of laxatives

There is consensus between experts that the combination of a stimulant with a softening laxative is effective for constipation in palliative care, including opioid-induced constipation [West Lancs Southport & Formby Specialist Palliative Care Services, 2009; NHS Lothian, 2010b; Regnard and Dean, 2010; Sykes, 2010; Cambridgeshire Palliative Care Guidelines Group, 2012; North of England Cancer Network, 2012], however there is a growing accumulation of evidence which suggests that it is reasonable to use senna alone as a laxative initially, adding a softening agent if colic becomes a problem [Twycross et al, 2012; Sykes, 2013; Tarumi et al, 2013]

Opioids cause constipation by increasing ring contractions, decreasing propulsive intestinal activity, and by increasing the resorption of fluids and electrolytes. Stimulant laxatives reduce intestinal ring contractions, allowing propulsive activity. Both senna and sodium picosulfate given alone are effective treatments for opioid-induced constipation [Twycross and Wilcock, 2011].

Constipation due to opioid analgesics is an ongoing problem as tolerance does not develop. There is no linear relationship between morphine dose and the level of constipation [Fallon and Hanks, 1999] — some people will require small dose increases and some people will require larger dose increases to counteract constipation with an increase in morphine dose. These recommendations are pragmatically based on a synthesis of published expert opinion [Goodheart and Leavitt, 2006; Regnard and Dean, 2010; Sykes, 2010].

The recommendation to reduce the dose of senna and add in a softener such as docusate, in people who cannot tolerate a large number of tablets, is based on the opinion of CKS expert reviewers.

Titration of laxative dose

There is also consensus between experts that the dose of laxatives should be titrated upwards until constipation is effectively controlled. This means that much higher doses and more frequent dosing than those specified on the product licence are often required to manage constipation (particularly opioid-induced constipation) effectively [Fallon and O'Neill, 1998; Twycross and Wilcock, 2011]. The recommendation to adjust the dose of stimulant to produce defecation without colic is based on expert opinion [Sykes, 2010].

Interventions to avoid

Although increasing fluids and dietary fibre can help constipation, it can be difficult for some people to manage this, particularly if they have a poor appetite. It is more important to offer them food and drink that they like.

Phosphate enemas can sometimes cause water and electrolyte disturbances, especially in the over-65 age group and when co-morbidities are present.

Bulk-forming laxatives are less useful for constipation in palliative care because:

Their consistency is unpalatable and they need to be taken with at least 200–300 mL water, which makes them unacceptable to many ill people.

If inadequate water is taken, they can cause intestinal obstruction. This may happen quickly if there is already partial obstruction due to a tumour.

Paraffin is not recommended because there is a risk of lipoid pneumonia if aspirated.

Rectal interventions

The advice on when to avoid rectal interventions is based on Canadian guidelines [British Columbia Medical Association, 2011] and expert opinion [Regnard and Dean, 2010].

Dantron-containing laxatives

The recommendation to consider the use of a dantron-containing laxative in a terminally ill person who has not responded to, or cannot tolerate stimulant and softening laxatives, or prokinetic agents, is based on the opinion of CKS expert reviewers.

Treating faecal loading/impaction

How should I treat faecal loading/impaction?

The aim of treatment is to achieve complete disimpaction, with the minimum of discomfort. This may require several days during which doses and combinations of laxatives are adjusted.

Start treatment with a combination of a stimulant and softening laxative. This is likely to need to be continued once impaction has been cleared.

Hard impacted stools may need softening before a stimulant can be used.

Titrate the dose of laxatives every few days to achieve comfortable defecation.

High doses (off-label) may be needed to achieve this, particularly for people taking opioid analgesics.

If this is ineffective, and impaction is:

High (stool not present in the rectum), consider:

A bowel washout with an oral macrogol, for example Movicol® eight sachets dissolved in 1 litre of water taken over 6 hours by mouth. In heart failure limit the dose to two sachets (250 mL) per hour.

Low (stool in the rectum), consider:

Using a suppository: bisacodyl for soft stools, glycerol alone or glycerol plus bisacodyl for hard stools.

Using a mini-enema: docusate (softener and weak stimulant) or sodium citrate (osmotic).

If the response is still insufficient, and there is hard, impacted stool in the rectum:

Consider using a sodium phosphate enema (osmotic), or an arachis oil retention enema (softener).

For hard faeces it can be helpful to give the arachis oil enema overnight before giving a sodium phosphate (large volume) or sodium citrate (small volume) enema the next day.

Enemas may need to be repeated several times to clear hard, impacted faeces.

If none of these measures provide relief, seek specialist advice.

For more information on choice of treatment, see Choice of laxative.

Basis for recommendation

Basis for recommendation

There is no evidence from clinical trials to choose between alternative strategies for treating faecal loading/impaction in palliative care.

The recommendations for treatment are therefore pragmatically based on a synthesis of published expert opinion [West Lancs Southport & Formby Specialist Palliative Care Services, 2009; NHS Lothian, 2010b; Regnard and Dean, 2010; Sykes, 2010; Cambridgeshire Palliative Care Guidelines Group, 2012].

Important aspects of prescribing information relevant to primary healthcare are covered in this section specifically for the drugs recommended in this CKS topic. For further information on contraindications, cautions, drug interactions, and adverse effects, see the electronic Medicines Compendium (eMC) (http://medicines.org.uk/emc), or the British National Formulary (BNF) (www.bnf.org).

How laxatives work

How do laxatives work?

Bulk-forming laxatives (ispaghula husk, methylcellulose, and sterculia) act by retaining fluid within the stool and increasing faecal mass, leading to stimulation of peristalsis. They also have stool-softening properties.

Osmotic laxatives (lactulose, macrogols, phosphate enemas, and sodium citrate enemas) act by increasing the amount of fluid in the large bowel, by retaining fluid in the bowel and by drawing fluid from the body into the bowel. Fluid accumulation in the lower bowel produces distension, leading to stimulation of peristalsis. Lactulose and macrogols also have stool-softening properties.

Stimulant laxatives cause peristalsis by stimulating colonic nerves (senna) or colonic and rectal nerves (bisacodyl, sodium picosulfate).

Senna is hydrolyzed to the active metabolite by bacterial enzymes in the large bowel.

Bisacodyl and sodium picosulfate are hydrolyzed to the same active metabolite. However, bisacodyl is hydrolyzed by intestinal enzymes, whilst sodium picosulfate relies on colonic bacteria.

Surface-wetting agents (docusate and poloxamer [an active ingredient of co-danthramer]) reduce the surface tension of the stool, allowing water to penetrate and soften it. Docusate also has a relatively weak stimulant effect.

Glycerol suppositories act as a lubricant, and have a weak stimulant action (probably due to an irritant effect).

Arachis oil enemas lubricate and soften faeces, thereby promoting a bowel movement. Bulk laxatives, osmotic laxatives, and docusate also have softening properties.

Peripheral opioid-receptor antagonists (such as methylnaltrexone) antagonize opioid actions at specific gastrointestinal opioid receptors without impairing central analgesic effects.

Basis for recommendation

This information is derived from the Micromedex database [Micromedex, 2007], the Palliative care formulary [Twycross and Wilcock, 2011], the British National Formulary [BNF 64, 2012], and the Oxford Textbook of Palliative Care Medicine [Sykes, 2010].

Choice of laxative

Which laxative should I prescribe?

The final choice of laxative will often depend on individual preference, and what has previously been tried. Advantages and disadvantages of different laxatives are detailed in Table 1.

Table 1 . Advantages and disadvantages of different laxatives.
Laxative Time to effect Points to note
Bulk forming laxatives
Ispaghula (also known as psyllium) 2–3 days Useful first-line choice in adults when it is difficult to get enough fibre in the diet. Better tolerated than bran. Must not be taken immediately before bed. Adequate fluid intake is important, to prevent intestinal obstruction. This may be difficult for the frail or children. Not recommended for people taking constipating drugs.
Sterculia
Methylcellulose 2–3 days Useful first-line choice in adults when it is difficult to get enough fibre in the diet. Better tolerated than bran. Must not be taken immediately before bed. Adequate fluid intake is important, to prevent intestinal obstruction. This may be difficult for the frail or children. Tablets swell in the mouth on contact with water.
Wheat or oat bran Finely ground bran can be given as bran bread or biscuits, but these are less effective than unprocessed bran. May be unpalatable. Can be added to food or fruit juice. Often poorly tolerated (causes flatulence and bloating) unless increased slowly and can be difficult to take enough to be effective on its own. Adequate fluid intake is important.
Osmotic laxatives
Lactulose 2–3 days Palatable — although some find it sickly sweet. Adequate fluid intake recommended. If used alone in opioid–induced constipation, it often needs to be given in large doses that cause bloating and colic.
Macrogols (polyethylene glycol) 2–3 days Some people find it difficult to drink the prescribed volume of macrogol. Licensed for use in faecal impaction. Idrolax® does not contain electrolytes. Movicol-Half® contains half the dose and electrolytes of Movicol®
Surface-wetting laxatives
Docusate sodium 12–72 hours Probably acts both as a softening agent and a stimulant. May be a useful alternative for people who find it hard to increase their fluid intake.
Stimulant laxatives
Senna 8–12 hours Licensed only for short-term use. Syrup is unpalatable.
Sodium picosulfate 6–12 hours Licensed only for short-term use. Syrup is palatable.
Bisacodyl 6–12 hours No syrup available. Licensed only for short-term use.
Dantron (terminal care only) 6–12 hours Restricted to use in terminal care. Prolonged contact with the skin (e.g. faecal or urinary incontinence) can cause a dantron burn — an erythematous rash with a sharply demarcated border. Available only combined with a softener: Co-danthramer (dantron with poloxamer). Co-danthrusate (dantron with docusate). Concerns about possible carcinogenicity (from high-dose studies in rats). People should be warned that it discolours urine red (occasionally blue or green).
Rectal laxatives
All rectal laxatives Easy to use if administered correctly. Timing of effect may be more predictable than with oral laxatives. Some people find them undignified and unpleasant to use. All unlicensed for the treatment of faecal loading/impaction except Relaxit® micro-enema and Arachis oil retention enema.
Glycerol suppositories (lubricating and weak stimulant) 15–30 minutes Can be used for hard or soft stools Licensed for occasional use only. Suppositories must be placed alongside the bowel wall so that body heat causes them to dissolve and distribute around the rectum. Suppositories should be moistened before use to aid insertion.
Bisacodyl suppositories (stimulant) 15 minutes to 3 hours Avoid if large, hard stools, as no softening effect. Use for soft stools.
Sodium phosphate and sodium bicarbonate suppositories (Carbalax®) (effervescent) 30 minutes People should be advised that these suppositories work by an effervescent action.
Docusate sodium enema (softener and weak stimulant) 15–30 minutes Can be used for hard or soft stools Correct administration important to prevent damage to rectal mucosa.
Sodium citrate enema (osmotic) 5–15 minutes Smaller volume (5 mL) than a phosphate enema (130 mL). Useful to remove hard, impacted stools. Correct administration important to prevent damage to rectal mucosa. Licensed for occasional use only.
Phosphate enema (osmotic) 2–5 minutes Useful to remove hard, impacted stools Correct administration important to prevent damage to rectal mucosa. Licensed for occasional use only. Use of phosphate enemas can cause hypocalcaemia and hyperphosphataemia in ill patients or in renal impairment. They can also produce rectal gangrene in ill patients with a history of haemorrhoids.
Arachis oil enema (softener) Retention enema — used overnight and warmed before use. Useful for hard, impacted stools. Should not be used in people with peanut allergy. Licensed for occasional use only.
Peripheral opioid–receptor antagonists
Methylnaltrexone bromide (subcutaneous injection) 30 minutes – 4 hours Useful for opioid-induced constipation in terminally ill people, when response to other laxatives is inadequate. Contraindicated in known or suspected bowel obstruction. Use with caution in people with conditions which may predispose to perforation (e.g. gastrointestinal cancer, peptic ulcer, colonic pseudo-obstruction, nonsteroidal anti-inflammatory drugs, steroids).
Not recommended
Liquid paraffin (softener) 1–3 days Adverse effects include anal seepage and irritation, malabsorption of fat-soluble vitamins, and (rarely) lipoid pneumonia.
Magnesium salts (osmotic) 1–6 hours Not routinely recommended because their purgative action can be undesirably strong.
Data from the Electronic Medicines Compendium www.medicines.org.uk and from [Kyle, 2007; De Conno et al, 2010; Sykes, 2010; Wyeth Canada, 2010; Micromedex, 2011; Twycross and Wilcock, 2011; BNF 64, 2012 ]

Time to wait for laxative effect

How long is it before different laxative preparations take effect?

For information on times for different laxative preparations to take effect, see Table 1

Table 1 . Time to wait for laxative effect.
Laxative preparation Time to wait for laxative effect
Rectal measures

Docusate

(enema)

5–20 minutes

Bisacodyl

(suppository)

15–60 minutes

Glycerol

(suppository)

15–60 minutes

Arachis oil

(enema)

1 hour

Injectable opioid reversal agent

Methylnaltrexone

(subcutaneous)

20 minutes to 4 hours

Contact stimulants (oral)

Senna

8–12 hours

Bisacodyl

6–12 hours

Softening laxatives (oral)

Lactulose 1–2 days
Docusate 1–3 days
Macrogols 1–3 days
Data from: [Regnard and Dean, 2010]
Basis for recommendation

The approximate times for various laxatives to take effect are based on expert opinion [Regnard and Dean, 2010].

Doses of laxatives

What doses of laxatives may be needed in palliative care?

For information on the licensed doses of laxatives and the doses that may be needed in palliative care, see Table 1

Table 1 . Laxative doses that may be needed to manage constipation in palliative care.
Laxative Licensed dose (adults) Dose that may be needed in palliative care (off–label)
Arachis (peanut) oil (retention enema) 1 enema (130 mL) at bedtime, as required Use maximum licensed dose
Bisacodyl (tablets) 5–10 mg at night, increased if necessary to a maximum dose of 20 mg at night 20 mg three times a day
Bisacodyl (suppositories) 1 suppository (10 mg) in the morning 20 mg daily
Co-danthramer Strong (dantron/poloxamer 37.5/500 mg capsules or 75/1000 mg suspension) 1–2 capsules (or 5 mL only) at night 3 capsules three times a day (or 10 mL twice a day)
Co-danthrusate (dantron/docusate 50/60 mg capsules or suspension) 1–3 capsules (or 5–15 mL) at night 3 capsules twice a day (or 15 mL twice a day)
Docusate (capsules or solution) Up to 500 mg per day in divided doses 200 mg three times a day
Docusate (Norgalax® micro-enema) 1 enema (120 mg in 10 g single-use disposable pack), as required Use maximum licensed dose
Glycerol (suppositories) 1 suppository (4 g) moistened with water before use, as required Use maximum licensed dose
Lactulose (syrup) 15 mL twice a day, adjusted according to response Use maximum licensed dose
Macrogol 3350 + electrolytes (Movicol® sachets) For constipation: 1–3 sachets per day, in divided doses, usually for up to 2 weeks; maintenance dose 1–2 sachets per day For high faecal loading/impaction: 4 sachets on the first day, then increased in steps of 2 sachets daily to a maximum dose of 8 sachets per day Contents of each sachet should be dissolved in 125 mL of water After reconstitution the solution should be kept in a refrigerator and drunk within 6 hours Limit to 2 sachets per hour (250 mL) in heart failure Use maximum licensed dose
Senna (tablets or syrup) 2–4  tablets (15–30 mg) at night or 10–20 mL, usually at bedtime 2–4 tablets (15–30 mg) three times a day
Sodium citrate (Micolette®, Micralax®, Relaxit® micro-enemas) Micolette® 1–2 enemas (5–10 mL), as required Micralax® 1 enema (5 mL), as required Relaxit® 1 enema (5 mL), as required Use maximum licensed dose
Sodium picosulfate (capsules or syrup) 5–10 mg at night 30 mg per day
Sodium phosphate (Fleet® Ready-to-use enema, Phosphate enema BP Formula B) Fleet® Ready-to-use enema 1 enema (118 mL), as required Phosphate enema BP Formula B 1 enema (128 mL), as required Use maximum licensed dose
Data from: [Regnard and Dean, 2010; Twycross and Wilcock, 2011; BNF 64, 2012]
Table 2 . Dose schedule for dantron-containing laxatives*
Co-danthramer strong capsules Co-danthramer strong suspension Co-danthrusate capsules Co-danthrusate suspension
Dantron content 37.5 mg/capsule 75 mg/capsule 50 mg/capsule 50 mg/capsule
Start with (prophylactic): 1 at bedtime 2.5 mL at bedtime 1 at bedtime 5 mL at bedtime
Start with (if constipated): 2 at bedtime 5 mL at bedtime 2 at bedtime 10 mL at bedtime
If necessary, adjust every 2–3 days up to: 3 three times a day 10 mL twice a day or 20 mL at bedtime 3 twice a day 15 mL twice a day
Total daily dose 337.5 mg 300 mg 300 mg 300 mg
* because dantron has been linked with liver and bowel tumours in rodents, dantron-containing laxatives are licensed for use only the the 'terminally ill'. † in people with urinary or faecal incontinence, dantron-containing laxatives are best avoided because of the risk of a contact skin burn in the perineum and surrounding areas.
Data from: [Twycross and Wilcock, 2011]
Basis for recommendation

Recommendations on doses of laxatives are based on expert opinion [Regnard and Dean, 2010; Twycross and Wilcock, 2011; BNF 64, 2012].

There is consensus between experts that the dose of laxatives should be titrated upwards until constipation is effectively controlled [Fallon and O'Neill, 1997; Twycross and Wilcock, 2011].

This means that much higher doses and more frequent dosing than those specified on the product licence are often required to manage constipation (particularly opioid-induced constipation) effectively [Fallon and O'Neill, 1997; Twycross and Wilcock, 2011].

Adverse effects of oral laxatives

What are the adverse effects of oral laxatives?

Most adverse effects can be avoided or reduced by increasing the dose of oral laxatives gradually.

Advise people to start at the lowest dose and, if necessary, increase it every few days until one or two soft, formed stools are produced each day. Common adverse effects include:

Bulk laxatives: flatulence and bloating.

Lactulose: flatulence, cramps, and bloating.

Macrogols: bloating, nausea.

Stimulant laxatives: abdominal cramps, diarrhoea.

Peripheral opioid-receptor antagonists: abdominal pain, nausea, diarrhoea, flatulence; postural hypotension; injection site reactions; hyperhidrosis. Cases of gastrointestinal perforation have been reported but the frequency is unknown.

Advise people taking bulk laxatives that an adequate fluid intake is important (to prevent intestinal obstruction) and that they should not be taken immediately before going to bed.

Advise people taking lactulose or macrogols that an adequate fluid intake is important because the drugs can be dehydrating.

The timing of stimulant laxatives can be particularly important for the frail or elderly, so that they provoke a single stool each day, at a time when the individual has adequate time to reach the toilet. Usually stimulant laxatives are given at bedtime, to produce a bowel movement the next morning. However, it may take a little experimentation to find the best time for an individual, especially if they naturally tend to defecate later in the day.

There have been concerns in the past that prolonged use of stimulant laxatives (off-label use) might reduce colonic function or lead to tolerance. However, there is no convincing evidence that this is the case.

Avoid excessive doses of laxatives. This leads to diarrhoea and, if prolonged, electrolyte disturbances such as hypokalaemia. Excessive doses of bulk-forming laxatives, or inadequate fluid intake with bulk-forming laxatives, cause intestinal obstruction rather than diarrhoea.

If intestinal obstruction is suspected, do not use laxatives.

Basis for recommendation

This information is based on the manufacturers' Summaries of Product Characteristics www.medicines.org.uk, except for the following:

The recommendation regarding timing of stimulant laxatives is based on expert opinion [Clayden et al, 2005].

The recommendation that stimulant laxatives are unlikely to reduce colonic function is based on information from a review article [Wald, 2006].

Preventing adverse effects of rectal laxatives

How should I prevent adverse effects of rectal laxatives?

Suppositories:

Must be placed alongside the bowel wall so that body heat causes them to dissolve and distribute around the rectum.

Should be moistened before use to aid insertion.

Enemas:

Correct administration of enemas is important. Incorrect administration can injure the bowel wall, and occasionally even cause necrosis.

After initial insertion of the enema nozzle, angle it towards the back before advancing further. Do not force insertion or administration.

There have been reports of hyperphosphatemia in people with chronic renal impairment following administration of phosphate enemas.

Basis for recommendation

This information is based on published expert opinion [Bowers, 2006; Kyle, 2007].

Evidence

Evidence

Supporting evidence

Laxatives for constipation in palliative care

Evidence on laxatives for constipation in palliative care

The evidence for the efficacy and safety of laxatives in palliative care is very limited.

A Cochrane systematic review that addressed the use of laxatives for the management of constipation in palliative care found seven studies (n = 616 in total) suitable for inclusion [Candy et al, 2011]:

One study of 75 people in palliative care found no difference between lactulose and senna in terms of the mean number of defecation days, or the number of defecation-free 72–hour periods.

One study of 36 people in a hospice setting found no significant difference between self-reported 'satisfactory' bowel movements with misrakasneham (an Indian herbal remedy) compared with senna.

One crossover study of 51 people with cancer compared dantron plus poloxamer (co-danthramer) with lactulose plus senna. A significantly higher stool frequency was reported with lactulose plus senna compared with co-danthramer, regardless of the order the drugs were given in the crossover.

One unpublished crossover study of 118 people in a hospice setting compared magnesium hydroxide plus liquid paraffin (Milipar®) with lactulose plus senna. There was no difference in stool frequency between treatments, regardless of the order the drugs were given in the crossover.

Two studies, with a total of 287 participants, compared subcutaneous methylnaltrexone with placebo. Methylnaltrexone was found to be more effective than placebo at inducing a laxation response, and this response was rapid (four to 24 hours). However, an undisclosed proportion of participants continued to take conventional laxatives during these trials.

One small study of 33 people comparing the effectiveness of different doses of subcutaneous methylnaltrexone (1 mg, 5 mg, 12.5 mg, and 20 mg), found that methylnaltrexone was more effective at inducing laxation at doses of 5 mg or greater compared to a dose of 1 mg.

A randomized, double-blind, placebo-controlled trial (n = 74) compared the use of docusate plus senna (n = 35) with placebo plus senna (n = 39) in adults in a hospice setting over 10 days [Tarumi et al, 2013]. Between 92% and 94% of the participants in the docusate group, and 100% of the participants in the placebo group were taking opioids. People with both malignant and non-malignant disease were included. The results of this study were difficult to interpret because people in the placebo group had a mean daily morphine dose 66% higher than the docusate group. In addition, potential confounders were that there was no specific measure of abdominal pain, a common side effect of senna, and the dose of senna varied substantially compared with a constant dose of docusate [Sykes, 2013].

There was no significant benefit of docusate plus senna compared with placebo plus senna in the primary outcome measures, which were:

Stool frequency – the number of bowel movements per day in the docusate group was 0.74 (SD = 0.47) compared with 0.69 (SD = 0.37, p = 0.58) in the placebo group. The mean difference in the average number of bowel movements was 0.05, 95% CI –0.09, 0.19.

Stool volume – there was no significant difference in stool volume between study groups (p = 0.06).

Stool consistency – using the Bristol Stool Form Scale, more people in the placebo group tended to have Type 4 (smooth and soft, like a sausage or snake) and Type 5 (soft blobs with clear-cut edges) stool, whereas more people in the docusate group had Type 3 (sausage, cracks in surface) and Type 6 (mushy stool, fluffy pieces with ragged edges) stool (p = 0.01).

A greater proportion of people in the placebo group (38.5%) than in the docusate group (14.3%) received another bowel intervention on day 5 of the study (p = 0.35).

Search strategy

Scope of search

A literature search was conducted for guidelines, systematic reviews and randomized controlled trials on primary care management of constipation in palliative care.

Search dates

October 2007 - November 2012

Key search terms

Various combinations of searches were carried out. The terms listed below are the core search terms that were used for Medline.

exp Palliative Care/, exp Terminal Care/, exp Terminally Ill/, palliat$.tw., (terminal adj care).tw., (palliative or terminal$ or end of life).tw., (advanced adj disease).tw.

exp Constipation/, constipat$.tw., exp Fecal Impaction/, ((fecal or faecal) adj impact$).tw., ((fecal or faecal) adj load$).tw., ((difficult$ or delay$ or irregular$ or infrequent or pain$) adj (defecat$ or stool$ or faec$ or fec$)).tw., (bowel adj movement).tw.

Table 1 . Key to search terms.
Search commands Explanation
/ indicates a MeSh subject heading with all subheadings selected
.tw indicates a search for a term in the title or abstract
exp indicates that the MeSH subject heading was exploded to include the narrower, more specific terms beneath it in the MeSH tree
$ indicates that the search term was truncated (e.g. wart$ searches for wart and warts)
Sources of guidelines

National Institute for Health and Care Excellence (NICE)

Scottish Intercollegiate Guidelines Network (SIGN)

Royal College of Physicians

Royal College of General Practitioners

Royal College of Nursing

NICE Evidence

Health Protection Agency

World Health Organization

National Guidelines Clearinghouse

Guidelines International Network

TRIP database

GAIN

NHS Scotland National Patient Pathways

New Zealand Guidelines Group

Agency for Healthcare Research and Quality

Institute for Clinical Systems Improvement

National Health and Medical Research Council (Australia)

Royal Australian College of General Practitioners

British Columbia Medical Association

Canadian Medical Association

Alberta Medical Association

University of Michigan Medical School

Michigan Quality Improvement Consortium

Singapore Ministry of Health

National Resource for Infection Control

Patient UK Guideline links

UK Ambulance Service Clinical Practice Guidelines

RefHELP NHS Lothian Referral Guidelines

Medline (with guideline filter)

Driver and Vehicle Licensing Agency

NHS Health at Work (occupational health practice)

Sources of systematic reviews and meta-analyses

The Cochrane Library :

Systematic reviews

Protocols

Database of Abstracts of Reviews of Effects

Medline (with systematic review filter)

EMBASE (with systematic review filter)

Sources of health technology assessments and economic appraisals

NIHR Health Technology Assessment programme

The Cochrane Library :

NHS Economic Evaluations

Health Technology Assessments

Canadian Agency for Drugs and Technologies in Health

International Network of Agencies for Health Technology Assessment

Sources of randomized controlled trials

The Cochrane Library :

Central Register of Controlled Trials

Medline (with randomized controlled trial filter)

EMBASE (with randomized controlled trial filter)

Sources of evidence based reviews and evidence summaries

Bandolier

Drug & Therapeutics Bulletin

TRIP database

Central Services Agency COMPASS Therapeutic Notes

Sources of national policy

Department of Health

Health Management Information Consortium (HMIC)

Patient experiences

Healthtalkonline

BMJ - Patient Journeys

Patient.co.uk - Patient Support Groups

Sources of medicines information

The following sources are used by CKS pharmacists and are not necessarily searched by CKS information specialists for all topics. Some of these resources are not freely available and require subscriptions to access content.

British National Formulary (BNF)

electronic Medicines Compendium (eMC)

European Medicines Agency (EMEA)

LactMed

Medicines and Healthcare products Regulatory Agency (MHRA)

REPROTOX

Scottish Medicines Consortium

Stockley's Drug Interactions

TERIS

TOXBASE

Micromedex

UK Medicines Information

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