Management of Constipation in Children and Young People with Cancer

• Summary of Guideline
• Background
• Diagnosis
• History and examination
• Investigation
• Treatment / Management
• Appendix 1: Flow chart and abbreviated prescribing hints
• Appendix 2: Further information and rationale for guideline statements

Summary of Guideline

A stepped approach to managing constipation, including consideration of prophylactic treatment, in children and young people receiving systemic anti-cancer treatment, is discussed in this document.

The key features of therapy are:

• Diagnosing constipation through effective history taking and physical examination
• A combination of dietary manipulation and medication use now recommended
• Avoidance of rectal medications except in exceptional circumstances
• Stepped approach to stool softening and bowel stimulation
• Consideration of maintenance treatment with laxatives

Back to top

Background

Constipation is a very common problem in children and young people with cancer and treatment of this complication is subject to wide variation in practice ^{(1, 2)} with different agents, differing doses and diverse strategies in use. Reviews of solid tumours including osteosarcoma and leukaemia patients estimate 50% and 34% prevalence respectively ^{(2, 3)} while approximately 40% of palliative care patients suffer constipation their treatment ⁽⁴⁾

Constipation causes pain, discomfort, and reduced quality of life. ^{(1, 4, 12)}. Severe constipation may cause life-threatening complications and necessitate reduction in the intensity of anti-cancer treatment delivered. ⁽⁵⁾

The aetiology of constipation during treatment can be either historical (e.g. inherited or genetic causes) or acute influencing factors ⁽⁴⁾. Organic acute factors include structural issues as a result of location of tumour, medications or pain ⁽⁴⁾. Functional acute factors occur as a result of a reduction in mobility, diet, hydration and psychological adjustment ^{(1, 4, 6)}. Particular commonly used medications which cause constipation include opiates, vinca alkaloids, carboplatin and ondansetron ^{(3, 4)}. Recent studies suggest there is no benefit in increasing fibre intake to treat constipation ⁽⁶⁾

The most recent (2008) systematic review ⁽⁷⁾ showed no direct evidence for any laxative agents in the paediatric oncology population. Accordingly, all evidence is extrapolated from trials in idiopathic constipation ^{(see reviews 1, 8, 9, 15, 16)}.

The aetiology of constipation in paediatric and teenage/young-adult (TYA) haemato-oncology patients will differ from that of idiopathic childhood constipation. In cases of idiopathic childhood constipation NICE provide guidance regarding diagnosis and management ⁽¹⁾. It may be useful in the haemato-oncology patient to refer to NICE guidance, whilst bearing in mind the potential differences in aetiology and therefore the need to alter accordingly patient investigation and management in children and young people with cancer.

Back to top

Diagnosis

Practically, constipation can be described as the infrequent passage of stool (<3 per week), or the passage of hard/difficult/painful stools. A common historical clue is the presence of abdominal pain with left iliac fossa fullness or tenderness. ⁽²⁾

Constipation has been most recently defined by the Rome III group (2008) as a period of 2 months with at least two or more of the following symptoms occurring at least once a week; two or fewer defecations in the toilet per week; at least 1 episode of faecal incontinence per week; history of retentive posturing or excessive volitional stool retention; history of painful or hard bowel movements; presence of a large faecal mass in the rectum; history of large diameter stools that may obstruct the toilet. ^{(1, 4)}

Be aware that a significantly unwell individual with ‘constipation’ may have intestinal obstruction.

Back to top

History and examination

• Assess the frequency and nature of defecation
• Evaluate dietary, disease, treatment and environmental components
  • Is the child/young person eating a balanced diet? Dehydration?
  • Always remember your red flags such as: Is the location of an abdominal tumour impacting on bowel function? Is a spinal tumour causing cord compression? Is there any evidence of bowel obstruction or vinca-alkaloid related ileus?
  • Are opioids, 5HT3 antagonists or neurotoxic chemotherapies being used? Can they be decreased?
  • What toilets are being used? Can they be made more pleasant? Can the child’s feet reach the floor?
• Remember to evaluate previous history of constipation, including response to treatments in the past and any family history of significant constipation
• Consider early treatment with laxatives in children/young people with a constellation of risk factors (such as pelvic tumour, previous constipation, on ondansetron and morphine)
• Examine (by observation alone) the anus to assess for position (be aware of ‘missed’ anorectal malformations), tone, tears or fissures.
• Consider use of approved patient related outcome measures (PROM’s) such as the BFI tool ⁽⁴⁾

Back to top

Investigation

Undertake diagnostic investigations only if clinically indicated.

• Consider MRI spine if cord compression is a concern: see LHP guideline   Discuss (urgently) with the Consultant in charge of care.
• Do not undertake abdominal radiography ‘just to check’ if the child is constipated but can be useful if bowel obstruction or ileus suspected

Back to top

Treatment / Management

For a flow diagram of management, see Appendix 1

Recognition of constipation as a significant impairment to quality of life is important.
Acknowledging the individual factors involved in its aetiology can lead to more tailored responses

• Treat any underlying tumour if possible
• Minimise any detrimental medications
• Commence medical therapy when dietary and environmental factors have been optimised
• In discussion with the child/young person and their family, commence first-line therapy using osmotic and stimulant laxatives. Ensure an adequate dose is prescribed. No agent has shown marked superiority over any other, though Macrogols (e.g. Movicol) have some evidence of improved effectiveness and are better tolerated.
• Consider concomitant use of osmotic and stimulant laxatives with high risk drugs particularly opiates and vincristine

Review effectiveness of medications regularly
If ineffective, consider dose escalation or addition of alternative agents
When successful, strongly consider maintenance treatment

• Effectiveness of therapy should be assessed in relation to frequency, consistency and comfort of passing stool.
• Try to elicit the amount of laxative taken, rather than just the amount prescribed, when considering effectiveness of therapies
• In severe cases/intractable constipation, consider referral to paediatric surgery for an opinion and involve the haemato-oncology consultant also. See NICE guidance for management of intractable constipation ⁽¹⁸⁾

Back to top

Appendix 1: Flow chart and abbreviated prescribing hints

Constipation
  
Simple measures - effective history taking including diet & fluids, medication review and previous episodes
      
Review toilet facilities

Examine for fissures - Remember; anal fissures are common, painful, treatable and contribute to constipation
      
Soften   if the stools are dry or hard…

1st line - Movicol or lactulose (choice depending on how both tolerated)

2nd line - Increase doses if no effect

If faecally impacted - start faecal impaction movicol regime as per emeds/bnfc

Stimulate & evacuate

When stools softened but still faecally loaded…

1st line - Add stimulant - Docusate (younger children) or senna (TYA patient)

2nd line - Add in bisacodyl or picolax*

Maintain   when unloaded….

If treated using faecal impaction regime - Continue therapy until running clear then maintain using movicol or lactulose
(Remember to check for frequency, consistency and discomfort)

If constipation now resolved - discontinue treatment with caution and consider maintenance laxatives if recurrent issues
(In the absence of a clear & now removed cause)

*Individuals may find particular benefit from a different treatment schema (for example, those unable to tolerate big tablets may prefer bisocodyl, those who cannot tolerate large volumes of fluid will fail Movicol). Be patient-centred in choices.

Recommendations are Grade B(*) or D (Oxford Centre for Evidence-based Medicine Criteria)
     
Drug notes    per-dose schedules

Bisocodyl
4 to 18 years: 5 to 20mg once daily orally

Docusate 
6 months to 2 yrs: 12.5mg tds
2 to 12 years 12.5mg to 25mg tds
12 to 18 yrs: up to 500mg daily in divided doses.

Lactulose
1 month to 1 year 2.5ml bd adjust according to response
1 to 5 years 2.5ml to 10ml bd adjust according to response
5 to 18 years 5 to 20ml bd

Macrogols
Paediatric Formula: Macrogols 3350 plus electrolytes
< 1 year ½ to 1 sachet daily,
1 to 6 years: 1 sachet on day one and
then adjust dose to produce regular soft stools. Max 4 sachets daily
6 to 12 years: 2 sachets on day one and then adjust dose to produce
regular soft stools. Max 4 sachets daily
See e-meds or bnfc for disimpaction regime

Adult formula: Macrogols 3350 plus electrolytes
12 to 18 years: 1 to 3 sachets daily in divided doses. Adjust according to response

Picolax
1 month to 4 years: 2.5mg to 10mg once a day
4 to 18 years: 2.5mg to 20mg daily

Senna
Senna Syrup (7.5mg/5ml)
Child 1 month to 4 years: 2.5ml to 10ml once daily at night
4 to 18 years: 2.5ml to 20ml once daily at night

Senna tablets (1 tablet is 7.5mg)
Child 2 to 4 years: ½ to 3 tablets once daily (at night)
Child 4 to 6 years: ½ to 4 tablets daily
6 to 18 years: 1 to 4 tablets once daily

Back to top

Appendix 2: Further information and rationale for guideline statements

This section expands the rationale and where possible evidence for the steps outlines in the guideline.

Levels of evidence and grades of recommendation are taken from the Oxford Centre for Evidence-based Medicine [Phillips]

Assess the frequency and nature of defecation

This is required to assess the presence and severity of disease ⁽¹⁾ [Grade B].

• Evaluate dietary, disease, treatment and environmental components
• Is the child/YP eating a balanced diet and drinking enough? [Grade B]
• Is the location of an abdominal tumour impacting on bowel function? Is a spinal tumour causing cord compression? [Grade D]
• Are opioids, 5HT3 antagonists or neurotoxic chemotherapies being used? Can they be decreased? [Grade A]
• What toilets are being used? Can they be made more pleasant? Can the child’s feet reach the floor? [Grade D]

Consider early treatment with laxatives in children/young people with a constellation of risk factors (such as pelvic tumour, previous constipation, on ondansetron and morphine).

Although without any firm evidence-base (10), this practice is widely undertaken and felt to be beneficial ^{(1, 3, 4)} [Grade D]

Examine (by observation alone) the anus to assess for position (be aware of ‘missed’ anorectal malformations), tone, tears or fissures.

Anal fissure is strongly associated with constipation and can worsen a difficult situation ⁽¹¹⁾. Anorectal malformations are occasionally missed, even outside infancy ⁽¹²⁾.

Do not undertake abdominal radiography ‘just to check’ if the child is constipated but can be useful if bowel obstruction or ileus suspected 

Plain abdominal X-rays are of poor diagnostic value in excluding or confirming constipation, as their sensitivity scores were high however specificity scores low with a further systematic review’s conclusion echoing these ^{(13, 17)}.

In discussion with the child/young person and their family, commence first-line laxative therapy.
Ensure an adequate dose is prescribed. No agent has shown marked superiority over any other, though Macrogols (e.g. Movicol) have some evidence of improved effectiveness and are better tolerated.

A systematic review of Macrogols in idiopathic constipation shows some benefits for PEG-based laxatives over Lactulose, in impacted, chronic constipation and maintainance phases (8). The benefits are small, but probably real (statistically significant and consistent across studies). They may also be better tolerated. No good data exist regarding their effectiveness in childhood cancer patients. [Grade B] Even fewer data exist for stimulant laxatives such as senna or bisocodyl ⁽⁹⁾. [Grade B]