Key Facts

Rational antiemetic prescribing in palliative care is based on understanding the neuropharmacology of nausea and matching the antiemetic to the underlying cause.

Epidemiology

• Nausea: 40-70% of advanced cancer patients
• Vomiting: 30% of advanced cancer patients
• Often multifactorial
• Significantly impacts quality of life and oral medication absorption

Aetiology

• Chemical/metabolic (CTZ): drugs (opioids, chemotherapy), renal failure (uraemia), hypercalcaemia, infection
• Gastric stasis: opioids, autonomic neuropathy, hepatomegaly, ascites, gastroparesis
• Bowel obstruction: tumour, adhesions, constipation
• Raised ICP: brain metastases, leptomeningeal disease
• Vestibular: opioids (early), motion, labyrinthine disease
• Psychogenic: anxiety, anticipatory nausea
• Serosal/peritoneal: peritoneal metastases, liver capsule stretch

Pathophysiology

• Vomiting centre (medulla): final common pathway; receives input from CTZ, GI tract, vestibular system, higher cortical centres
• CTZ (area postrema): outside blood-brain barrier; responds to circulating toxins; D2 and 5HT3 receptors
• GI tract: vagal afferents from gut (5HT3, 5HT4 receptors); stretch and chemo receptors
• Vestibular: H1 and mACh receptors
• Higher centres: cortical input (anticipatory, anxiety)

Assessment

• Timing (constant, intermittent, related to food/medication/movement)
• Volume and content of vomitus
• Associated symptoms (pain, constipation, headache, vertigo)
• Medication review (opioids started recently?)
• Abdominal examination (distension, bowel sounds, hepatomegaly)
• Neurological examination if raised ICP suspected

Red Flags

• Faeculent vomiting (bowel obstruction)
• Projectile vomiting with headache (raised ICP)
• Haematemesis (GI bleeding)
• Signs of dehydration
• Complete bowel obstruction (absolute constipation + vomiting + distension)

Bedside

• Abdominal examination (distension, bowel sounds, tenderness)
• Medication chart review
• Constipation assessment (DRE if appropriate)
• Neurological examination (if raised ICP suspected)

Bloods

• U&Es (renal failure, dehydration)
• Calcium (hypercalcaemia — common cause)
• LFTs (hepatic causes)
• FBC (infection)

Imaging

• AXR: if bowel obstruction suspected
• CT abdomen: bowel obstruction assessment, level of obstruction
• CT head: if raised ICP suspected

Special Tests

• Not usually needed beyond clinical assessment and targeted investigations

Non-pharmacological

• Identify and treat reversible causes (constipation, hypercalcaemia, medications)
• Small, frequent meals; avoid strong smells
• Cool, fresh air
• Psychological support (anticipatory nausea: relaxation, CBT)

Pharmacological

• Opioid-induced (CTZ):
  • Haloperidol 0.5-1.5mg PO/SC ON (D2 antagonist at CTZ)
  • Usually settles within 5-7 days (tolerance develops)
  • If persists: consider opioid rotation
• Gastric stasis:
  • Metoclopramide 10mg TDS PO/SC (prokinetic + D2 antagonist)
  • AVOID in complete bowel obstruction
• Bowel obstruction (inoperable):
  • Cyclizine 150mg/24h CSCI (H1 antagonist)
  • Hyoscine butylbromide 60-120mg/24h CSCI (reduces secretions and colic)
  • Octreotide 300-600mcg/24h CSCI (reduces GI secretions)
  • Dexamethasone 6-8mg IV/SC (reduces peri-tumoral oedema; may resolve partial obstruction)
  • Venting gastrostomy: for intractable vomiting
• Raised ICP:
  • Dexamethasone 8-16mg daily (reduces oedema)
  • Cyclizine 50mg TDS
• Vestibular: cyclizine 50mg TDS or prochlorperazine 5mg TDS (NOT in Parkinson's)
• Broad-spectrum (cause unclear/multiple causes):
  • Levomepromazine 6.25-25mg ON PO/SC (blocks D2, 5HT2, H1, mACh)
  • Olanzapine 2.5-5mg ON (emerging evidence as broad-spectrum antiemetic)

Surgical/Interventional

• Venting PEG/gastrostomy: for inoperable bowel obstruction with intractable vomiting
• Stenting: for gastric outlet or duodenal obstruction
• Surgical bypass: palliative, in selected patients with good PS

Referral Criteria

• Refractory nausea/vomiting: specialist palliative care
• Bowel obstruction: surgical review for operability; palliative care if inoperable
• Raised ICP: oncology/neurosurgery

• Opioid-induced nausea usually self-limiting (5-7 days; tolerance develops)
• Most nausea can be controlled with appropriate mechanism-based antiemetics
• Bowel obstruction-related nausea: can usually be managed medically if surgery not appropriate
• Refractory nausea significantly impacts quality of life and oral medication absorption

Antiemetic Selection by Mechanism