Constipation in palliative care

At a glance

• Common and under-treated. About half of people with advanced cancer are constipated, and most patients on regular opioids are, whatever the dose.
• Prevent rather than rescue. Every regular opioid gets a regular laxative from the first dose. Tolerance to opioid constipation doesn't develop.
• Before escalating laxatives, ask two questions: is this bowel obstruction, and is this spinal cord compression?
• First line is a regular stimulant plus a softener or osmotic agent, with rectal measures for a loaded rectum.
• For opioid-induced constipation that fails laxatives, use a PAMORA: subcutaneous methylnaltrexone is on the PBS Palliative Care Schedule.

The general approach to constipation, Rome criteria and colonic pseudo-obstruction are in Altered bowel habit and constipation.

Causes

Group	Examples in palliative care
Drugs	Opioids (the commonest), anticholinergics (hyoscine, tricyclics, cyclizine), 5-HT3 antagonists, antipsychotics, iron, calcium, diuretics, vinca alkaloids (vincristine neuropathy)
Disease related	Malignant bowel obstruction, pelvic or peritoneal tumour, spinal cord or cauda equina compression, autonomic neuropathy
Metabolic	Hypercalcaemia, hypokalaemia, uraemia, hypothyroidism, dehydration
General debility	Immobility, weakness, low food and fluid intake, lack of privacy, a bedpan instead of a toilet
Painful defecation	Anal fissure, haemorrhoids, perianal tumour

Usually several act together. A frail patient on morphine, ondansetron and hyoscine who barely eats has four reasons at once.

Pitfall: blaming the opioid for new constipation without checking calcium. Hypercalcaemia causes constipation, nausea, confusion and polyuria together and is treatable (see Hypo- and hypercalcaemia).

Focused history

• What is normal for this patient, the date of the last bowel action, and stool form (Bristol scale). Patients often mean straining, hardness or incomplete emptying rather than infrequency.
• Laxatives actually taken, not just charted. Many patients stop senna because of cramps or skip macrogol because of the volume.
• Opioid dose changes and new constipating drugs.
• Nausea, vomiting, colic, distension, and whether flatus is passing. Vomiting with absolute constipation is obstruction until shown otherwise.
• Back pain, leg weakness, sensory change, urinary retention or incontinence: new constipation with these is cord or cauda equina compression.
• Liquid stool leaking without formed stool suggests overflow from impaction.
• Thirst, polyuria and confusion (hypercalcaemia).

Focused examination

• Abdomen: distension, palpable faecal masses (indentable, unlike tumour), tenderness, bowel sounds. Tinkling sounds and visible peristalsis point to obstruction.
• Rectal examination, with consent and explanation: an empty capacious rectum (high impaction or a colonic problem), hard faeces, soft faeces the patient can't expel (weakness or rectal dysmotility), tumour, or reduced anal tone.
• Neurology of the lower limbs and saddle sensation if there is any hint of cord compression.
• Hydration, mouth, and signs of hypercalcaemia or uraemia.

Red flags

• Vomiting, colic and distension with no flatus: bowel obstruction. Stop stimulants and PAMORAs and see Approach to vomiting.
• Back pain with neurological symptoms, urinary retention or loss of anal tone: urgent MRI of the whole spine for malignant cord compression (see Spinal cord and nerve root compression).
• Severe abdominal pain, fever or peritonism after a PAMORA or in a patient with bowel tumour: perforation.
• Confusion, polyuria and constipation: hypercalcaemia.

Investigations

Most patients need none beyond history and rectal examination. Test only what would change management.

• Calcium (corrected), electrolytes, renal function and glucose if the cause is unclear or the patient is unwell.
• Abdominal X-ray helps when obstruction is a possibility or the rectum is empty but impaction is suspected higher up. Faecal loading scores on plain film correlate poorly with symptoms, so don't use them to diagnose constipation.
• CT abdomen if obstruction is suspected and the result would change care (surgery, stenting, venting gastrostomy).
• MRI whole spine for suspected cord compression.

Management

Principles

• Set the goal with the patient: comfortable passage of soft stool, usually every 1 to 3 days, not daily.
• Reduce causes where possible: deprescribe anticholinergics, review 5-HT3 antagonists, correct calcium, treat pain on defecation, offer privacy and a commode or toilet over a bedpan.
• Prescribe laxatives regularly, not as needed, and titrate every 1 to 2 days.
• Encourage fluids and mobility within what the patient can manage. Dietary fibre is rarely realistic.

Oral laxatives

Class	Examples	Palliative points
Stimulant	Senna 7.5 to 15 mg (1 to 2 tablets) at night, up to 4 tablets twice daily; bisacodyl 5 to 10 mg	Backbone of opioid constipation treatment. Works in 6 to 12 hours. Cramps at high doses. Avoid if obstruction suspected
Softener	Docusate, often combined with senna	Weak evidence alone; used in combination
Osmotic	Macrogol 3350 1 to 3 sachets daily; lactulose 15 to 30 mL once or twice daily	Macrogol works well but needs about 125 mL water per sachet. Lactulose causes bloating and wind and tastes sweet. Avoid magnesium salts in renal impairment
Bulk-forming	Psyllium, sterculia	Avoid in frail patients with low fluid intake: risk of impaction and obstruction

• ESMO 2018 and MASCC 2020 found no laxative clearly superior. Choose by patient preference, stool form, tablet burden and swallowing.
• A common regimen: senna with docusate, 2 tablets at night, increasing to 2 tablets twice daily, then adding macrogol.
• Hard stool suggests more softener or osmotic. Soft stool the patient can't pass suggests more stimulant or rectal measures.

Rectal measures

• Hard faeces in the rectum: glycerol suppository, or a microenema, or an arachis oil enema overnight (check for peanut allergy) followed by a stimulant.
• Soft faeces the patient can't expel: bisacodyl suppository (placed against the rectal wall, not into the stool).
• High impaction: larger-volume enemas or oral macrogol in high dose (up to 8 sachets in a day for up to 3 days in impaction) once obstruction is excluded.
• Phosphate enemas: avoid in renal impairment, dehydration and frailty (hyperphosphataemia, hypocalcaemia).
• Manual disimpaction with analgesia and sedation (for example SC midazolam) is a last resort.
• Neutropenia or thrombocytopenia: avoid rectal examination and rectal medicines where possible (infection, bleeding).

Opioid-induced constipation that fails laxatives

Option	Points
Methylnaltrexone SC	8 mg (38 to 61 kg) or 12 mg (62 to 114 kg), 0.15 mg/kg outside that range, every second day. Listed on the PBS Palliative Care Schedule as Authority Required (Streamlined) for opioid-induced constipation in a patient receiving palliative care who has failed laxatives, given in combination with oral laxatives (12 mg vials only). About half have a bowel action within 4 hours of the first dose (48% vs 15% placebo, Thomas 2008). Abdominal cramps common
Naloxegol oral	25 mg each morning; 12.5 mg with moderate CYP3A4 inhibitors or renal impairment. Avoid with strong CYP3A4 inhibitors
Oxycodone with naloxone	Prolonged-release tablets, used in place of plain oxycodone. Ceiling of 80/40 mg a day. Naloxone becomes systemic in hepatic impairment
Opioid switch	Transdermal fentanyl or buprenorphine may constipate less than oral morphine or oxycodone

• PAMORAs (peripherally acting mu-opioid receptor antagonists) block gut mu receptors without crossing the blood-brain barrier, so analgesia is preserved.
• Contraindication: known or suspected mechanical bowel obstruction. Rare perforations have occurred, mainly with bowel wall disease (peritoneal metastases, diverticular disease, recent bevacizumab).
• Keep the regular oral laxative going alongside the PAMORA.

Pitfall: giving methylnaltrexone to a patient with distension and vomiting from peritoneal carcinomatosis. That patient needs assessment for malignant bowel obstruction, and a PAMORA can cause perforation.

Malignant bowel obstruction

• Commonest with ovarian and colorectal cancer. Partial obstruction may still respond to softeners (docusate, macrogol); stimulants worsen colic and should stop.
• Complete obstruction is managed with antisecretory drugs (hyoscine butylbromide, octreotide), dexamethasone and antiemetics, with surgery or stenting for selected patients. The nausea management is in Nausea and vomiting in palliative care.

Last days of life

• Stop oral laxatives when the patient can no longer swallow safely.
• Don't chase a bowel action in someone who is comfortable. A loaded rectum causing restlessness or urinary retention is the exception and warrants a suppository or enema.
• Explain to families that eating little means less stool.

Special populations

• Renal impairment: avoid magnesium salts and phosphate enemas; at creatinine clearance under 30 mL/min halve the methylnaltrexone dose, with no change for mild or moderate impairment, and avoid it in end-stage kidney disease on dialysis (Australian PI). The EU/UK SmPC instead gives 8 mg for 62 to 114 kg.
• Spinal cord injury or compression: a planned bowel routine with a daily or alternate-day suppository and digital stimulation, as for neurogenic bowel.
• Parkinson disease and dementia: constipation drives agitation, delirium and urinary retention. Check for impaction before increasing antipsychotics.
• Rural and remote patients: methylnaltrexone and suppositories need planning with community nurses and pharmacies before discharge; include a written bowel plan.

Pitfalls

• Prescribing an opioid without a regular laxative, or charting the laxative "as needed".
• Using bulk-forming laxatives in a frail patient who drinks little.
• Treating overflow diarrhoea with loperamide.
• Escalating stimulants or giving a PAMORA in bowel obstruction.
• Missing cord compression in a patient with back pain, new constipation and urinary retention.
• Forgetting hypercalcaemia, 5-HT3 antagonists and anticholinergics as contributors.
• Continuing oral laxatives into the dying phase when they add burden and no benefit.