Nausea and Vomiting in Palliative Care
Summary
Nausea and vomiting are common, distressing symptoms in palliative care, affecting up to 70% of patients with advanced cancer. Management relies on the principle of Mechanism-Based Prescribing: identifying the likely physiological trigger (e.g., chemical, mechanical, vestibular, or cortical) and selecting an anti-emetic that targets the specific receptors involved. Common causes include opioids, hypercalcaemia, constipation, gastric stasis, and bowel obstruction. The subcutaneous route (Syringe Driver) is often required when oral absorption is compromised. [1,2]
Key Facts
- Mechanism-Based Approach: Don't just guess. Ask "Why are they vomiting?"
- The Vomiting Centre (VC): Located in the medulla. It integrates inputs from the Chemoreceptor Trigger Zone (CTZ), Vestibular apparatus, GI tract, and Cortex.
- Prokinetics in Obstruction: Metoclopramide/Domperidone stimulate gastric emptying. They are CONTRAINDICATED in complete mechanical bowel obstruction (risk of perforation/colic).
- Syringe Drivers: Continuous Subcutaneous Infusion (CSCI) is the gold standard for stable symptom control in the terminal phase.
Clinical Pearls
The "Cyclizine + Metoclopramide" Clash: Avoid combining these. Metoclopramide is prokinetic (pushes gut forward). Cyclizine is anticholinergic (relaxes gut). They antagonise each other pharmacologically.
Levomepromazine: The "Broad Spectrum" heavy hitter. It blocks Dopamine, Histamine, Acetylcholine, and Serotonin receptors. Use it as second-line or rescue when single agents fail, but beware of sedation.
Opioid Nausea: Usually transient (first 3-5 days). Haloperidol is first line. Warn patients they will get used to it (tolerance develops to nausea, unlike constipation).
Steroids for Obstruction: Dexamethasone can reduce peri-tumoural oedema in bowel obstruction, potentially turning a complete obstruction into a partial one.
Prevalence
- Advanced Cancer: 40-70%.
- Opioid Naive: 30-40% experience nausea on initiation.
- End Stage Renal Failure: High prevalence (uraemia).
The Four Main Inputs to the Vomiting Centre
| Input Source | Stimuli | Key Receptors | Drug Choices |
|---|---|---|---|
| 1. CTZ (Chemoreceptor Trigger Zone) | Blood-borne toxins: Opioids, Digoxin, Uraemia, Hypercalcaemia, Chemo. | D2, 5HT3 | Haloperidol, Ondansetron, Levomepromazine |
| 2. GI Tract (Vagus Nerve) | Gastric Stasis, Squashed Stomach syndrome, Constipation, Irritation (NSAIDs). | D2, 5HT4 | Metoclopramide, Domperidone |
| 3. Vestibular System | Motion, Base of skull mets, Opioids (sensitise). | H1, M1 | Cyclizine, Hyoscine |
| 4. Cortex | Anxiety, Pain, Anticipatory nausea, Raised ICP (partial). | GABA, H1 | Lorazepam, Dexamethasone, Cyclizine |
Assessment by History
Signs
- Abdomen: Distension (ascites/obstruction?), Bowel sounds (Tinkling?), Tenderness, Hepatosplenomegaly.
- Rectal (PR): Impacted faeces (Constipation is a major, reversible cause).
- Neurological: Papilloedema, Nystagmus.
- Hydration: Mucous membranes, skin turgor.
"Appropriate" Investigation
In palliative care, only investigate if the result will change management.
- Blood: Calcium (Correctable?), Urea/Creatinine (Renal failure drug accumulation?), LFTs.
- Abdominal X-Ray: If obstruction suspected.
- CT Scan: Only if considering surgical/stenting intervention or uncertain diagnosis.
Management Algorithm (Mechanism-Based)
NAUSEA ASSESSMENT
(Identify Cause)
↓
┌───────────┼───────────┐
CHEMICAL GASTRIC OBSTRUCTED BRAIN METS
(Opioids, STASIS BOWEL or or VESTIB
Metabolic) (Fullness) VISCERAL (Motion)
↓ ↓ ↓ ↓
HALOPERIDOL METOCLOP- CYCLIZINE CYCLIZINE
(or Levo) RAMIDE (or Hyoscine (or Dexameth)
Butylbromide)
1. General Measures
- Treat Constipation (Laxatives).
- Treat Hypercalcaemia (Bisphosphonates if appropriate).
- Treat Thrush (Oral antifungals).
- Small, frequent meals. Reduce strong odours.
2. Pharmacotherapy (First Line)
| Cause | First Line Drug | Dose (Oral/SC) | Mechanism |
|---|---|---|---|
| Chemical (Opioids/Renal) | Haloperidol | 1.5-3mg OD/BD | D2 Antagonist (CTZ) |
| Gastric Stasis | Metoclopramide | 10mg TDS | Prokinetic (Gastric) |
| Bowel Obstruction | Cyclizine | 50mg TDS | Anticholinergic (relaxes gut) |
| Raised ICP | Dexamethasone | 8-16mg AM | Reduces Oedema (plus Cyclizine) |
| Motion | Cyclizine | 50mg TDS | H1 Antagonist |
3. Second Line (Broad Spectrum)
- Levomepromazine:
- Neuroleptic with affinity for D2, H1, M1, 5HT2.
- Very effective but sedating.
- Dose: 6.25mg - 25mg SC OD (start low).
4. Malignant Bowel Obstruction
If inoperable:
- Stop Prokinetics (Metoclopramide) if colic present.
- Analgesia: Opioids for pain.
- Anti-secretory:
- Hyoscine Butylbromide (Buscopan): Reduces smooth muscle spasm and secretions. 60-120mg/24h CSCI.
- Octreotide: Somatostatin analogue. Powerful reduction in GI secretions.
5. Syringe Drivers (CSCI)
- If vomiting prevents oral absorption.
- Combine drugs carefully (compatibility).
- Common Mix: Morphine + Midazolam + Haloperidol/Levomepromazine + Glycopyrronium/Buscopan.
- Dehydration / AKI: Worsens nausea (uraemia).
- Drug Toxicity: Accumulation of opioids requiring dose reduction.
- Oral Route Failure: Loss of pain control.
- Most nausea can be well controlled with correct drug selection.
- Refractory cases may require sedation (Midazolam/Levomepromazine) in terminal phase.
Key Guidelines
| Guideline | Organisation | Key Recommendations |
|---|---|---|
| Palliative Care Formulary | PCF / BNF | Gold standard dosing and compatibility data. |
| MASCC | Cancer Care | Guidelines on chemotherapy-induced nausea (CINV). |
| Bowel Obstruction | NICE | Use of Octreotide and Steroids in malignant obstruction. |
Landmark Knowledge
1. The Levomepromazine Rescue
- Studies consistently show Levomepromazine is effective in >80% of refractory cases, acting as a "chemical lobotomy" for the vomiting centre.
2. Haloperidol for Opioid Nausea
- Hardy et al. confirmed Haloperidol (D2) mimics the mechanism of opioid emesis (CTZ stimulation), supporting its use as first line.
Why am I feeling sick?
There are many reasons. It can be the painkillers (morphine), the cancer releasing chemicals into the blood, constipation, or the stomach not emptying properly.
Will it stop?
Yes. We have very effective medicines. Because different things cause sickness, we might need to try one or two to find the specific one that blocks the right "button" in your brain.
Do I need injections?
If you are vomiting up the tablets, they won't work. We can put a small battery-operated pump (syringe driver) under the skin to trickle the medicine in continuously. This works much better and stops you needing injections every few hours.
Primary Sources
- Twycross R, Wilcock A. Palliative Care Formulary (PCF). 7th/8th Ed.
- NICE Clinical Support Guideline (CSG4). Nausea and vomiting in adults in the last days of life. 2013.
- Glare P, et al. Systematic review of the efficacy of antiemetics in the treatment of nausea in patients with far-advanced cancer. Support Care Cancer. 2004;12:432-440.
Common Exam Questions
- Palliative Care: "Anti-emetic for opioid-induced nausea?"
- Answer: Haloperidol (or Ondansetron/Metoclopramide 2nd line, but Haloperidol standard).
- Pharmacology: "Why avoid Cyclizine and Metoclopramide together?"
- Answer: Pharmacological antagonism (Prokinetic vs Anticholinergic). If mixed in syringe driver, they also crystallise.
- Oncology: "Vomiting with Faeculent nature. Drug?"
- Answer: Bowel Obstruction. Use Cyclizine or Levomepromazine. Stop Metoclopramide.
- Medicine: "Mechanism of Ondansetron?"
- Answer: 5HT3 Antagonist. (Best for Chemo/Post-op, less useful for general palliative causes but used).
Viva Points
- Levomepromazine: Know the receptor profile (broad spectrum).
- Prokinetics: Domperidone doesn't cross BBB (less extrapyramidal side effects than Metoclopramide).
- H1 Receptors: Found in Vestibular nuclei AND Vomiting Centre. Hence Cyclizine works for motion sickness and raised ICP (vestibular component).
Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. Clinical decisions should account for individual patient circumstances. Always consult appropriate specialists.