Nausea and vomiting in Palliative Care

What are the 3 causes of nausea and vomitng?

• Chemical stimuli e.g in response to a drug, toxin or metabolite

• Mechanical stimuli e.g. gastric distension, irritation of the stomach lining

• Sensory stimuli e.g. in response to vision, psychological or odour

What is the chemoreceptor trigger zone?

An area which sits outside of the blood-brain barrier and receives stimuli in order to activate emesis in response to toxins, medications, etc.

What is the emetic centre?

The emetic centre is a region of the brain located in the medulla oblongata and is responsible for emesis as it receives stimuli, and once activated, it will cause vomiting. Once you have reached a certain threshold of stimuli, vomiting will occur and you would have lost voluntary control

What is the autonomic response to vomiting?

• Increased saliva production in the oral mucosa to protect the lining from the acidic contents of the stomach

• Abdominal muscles contract as well as the diaphragm to allow for emesis

• Gastric relaxation and pyloric opening to allow for the stomach contents to be expelled

What are the different neurotransmitters involved in emesis (5) and what is the medication which acts on this receptor?

• Antimuscarinic - Ach antagonists - hyoscine butylbromide (preferred in palliative care), hyoscine hydrobromide

• Antihistamine - H1 antagonists - Promethazine, Cyclizine, Cinerezene

• Dopamine receptor antagonist - D1 antagonist - (1st generation antipsychotic/antiemetic) - Haloperidol, prochlorperizine, levomepromazine

• Serontonin antagonist - 5-HT3 - Ondansterone

• Dopamine/Serotonin antagonist - D1/5-HT3 receptor antagonist - Metoclopramide

levomepromazine a broad-spectrum anti-emetic } true or false?

True → Acts on H1, 5-HT3, D2 and muscarinic receptors

Name 5 chemical causes of N&V

• Medication

• Deranged LFTs

• Deranged U&Es

• Hypercalcaemia

• Infection

What receptors are involved in N&V triggered by a chemical stimuli?

• Dopamine

• Serotonin

What antiemetic is favoured for N&V induced by a chemical stimuli in palliative care?

• Haloperidol - dopamine antagonist

• Cyclizine - antihistamine - H1 antagonist

• Metoclopramide - D2/5HT3 antagonist

Which antiemetic would we want to avoid in chemo-induced N&V?

• Avoid ondansteron - 5-HT3 antagonist as it is very constipating, hence limited use in palliative care

True or false: Haloperidol is a good choice in renal/hepatic impairment

True

Where would we want to caution the use of haloperidol?

Prior history of cardiac problems due to risk of haloperidol (and other 1st generation antipsychotics) causing QT prolongation, which can lead to fatal arrhythmia torrades de pointes

How does impaired gastric emptying cause N&V?

• bloating after food due to ascites, tumour pressure or diabetes can caused nausea and vomiting.

• Commonly patients will appear bloated after food and have large volume of vomits and nausea is often relieved by vomiting.

What receptors are involved in N&V caused by impaired gastric emptying?

• Gastric receptors, which stimulate the vagal nerve, which stimulates the vomiting centre

What is the anti-emetic of choice in N&V caused by impaired gastric emptying?

• Metoclopramide (D2/5-HT3 receptor antagonist)

Why is metoclopramide the antiemetic of choice in N&V caused by impaired gastric emptying?

• Metoclopramide is prokinetic, so it increases lower oesophageal sphincter tone and promotes gastrointestinal motility.

What is raised intracranial pressure as a cause of N&V?

• This is N&V caused by brain/ meningeal tumour or a bleed on the brain

How does raised intracranial N&V present? nature of symptoms?

• Effortless vomiting, often projectile and worse in the morning, frequently with other neurological symptoms such as a headache

What receptors cause N&V induced by raised intracranial pressure?

• Cerebral histamine receptors - H1 which are stimulated by mechanoreceptors in the vomiting centre

What antiemetic is used for N&V associated with raised intracranial pressure?

• H1 receptor antagonist/ antihistamine - cyclizine - reduces excitability in the innerear and acts directly on the vomiting centre

• Levopromazine can also be used - very useful as it antagonists D2, 5-HT3, H1, and Ach

• Steroids - reduce inflammation around the tumour and therefore reduce pressure

What side effects would we be concerned about after initiating cyclizine in a patient with N&V secondary to raised intracranial pressure?

• urinary retention, constipation, headache

What side effects would we be concerned about after initiating levomepromazine in a patient with N&V secondary to raised intracranial pressure?

• Sedation and QT prolongation

  • Remember it is also used as first-generation antipsychotic so carries the same risks

How does bowel obstruction cause N&V?

• Can be caused by a tumour which is either partially or fully occluding the GI tract or by faecal matter occluding the bowel

How does nausea present in patients with bowel obstruction?

• intermittent nausea

• can cause feculent vomiting

• colicky pain

• abdominal distension

What receptors are involved in N&V caused by bowel obstruction?

• Stretching of mechanoreceptors stimulates VC

What antiemetics do we use in N&V caused by a partial obstruction in the bowel?

• Partial obstruction in the bowel means that we would attempt to relieve the blockage

• Metoclopramide - prokinetic - only use if partial blockage!

• Steroids to reduce inflammation around the tumour and reduce pressure on the bowel

• Laxatives/softeners to help movement through the bowel

What antiemetics do we use in N&V caused by complete obstruction in the bowel?

• Centrally acting anti-emetics e.g. cyclizine and levomepromazine

• Hyoscine buylbromide to allow relaxation of the gut by antagonising Ach and reduces volume of vomit

True or false: Hyoscine butylbromide reduces the volume of vomit for patients with bowel obstruction induced N&V

True: Anti-secretory and therefore reduces the volume of vomit by inhibiting receptors in the vomit centre

What is post-operative N&V?

• This is vomiting following surgery. Nausea presents in 50% of cases, and vomiting presents in 30% of cases

What are risk factors associated with N&V induced by surgery?

• female gender

• non-smoking status - chronic nicotine exposure desensitises the emetic centre

• post-operative opioids

• previous history of PONV or motion sickness

How would we avoid post-operative N&V?

• Avoid opioids

• Keep patient well hydrated

• use regional anaesthesia where possible

What anti-emetics are used in post-operative N&V?

Using more than one anti-emetic which act on different receptors is key. Initial doses given just before or shortly after induction of anaesthesia

• Ondansterone - 5-HT3 receptor antagonist

• Cyclizine - H1 antagonist

• Dexamethasone - steroid

What is anxiety-induced N&V?

• Nausea, which is caused by psychological reasons e.g. fear, anger, anxiety or anticipatory

How does nausea present in anxiety-induced N&V?

• Nausea comes in waves and can be triggered by stressful events or anticipation of N&V with certain smells

What treatment/ antiemetic do we use in anxiety-induced N&V?

• Use lorazepam → anxiolytic

• Use levomepromazine → Broad spectrum activity acting on H1, 5-HT3, D2 and muscarinic antagonists

• Consider emotional support and avoidance of triggers

What is pharyngeal stimulation as a cause of nausea and vomiting?

• Oral/oesophageal thrush/tenacious sputum (this is sputum which is too thick to cough up e.g. seen in COPD)

How does N&V present in pharyngeal stimulation?

Retching with minimal vomiting

What medication is used for N&V induced by pharyngeal stimulation?

Anti-fungal, carbocistene (mucolytic) or saline nebs (hydrated airways to loosen mucus)

Why is ondansteron not used for N&V in palliative care?

Ondanestron is not used for N&V in palliative care due to the fact its very constipating (5-HT3 receptor antagonist) and therefore limits its use in palliative care

Can a patient take two weak opioids?

No, if a patient is taking two weak opioids, they should instead be given a strong opioid. For example, if a patient is taking tramadol and codeine, then we would convert them to morphine.

• Patient takes Tramadol 400mg and Codeine 240mg

• Convert both the tramadol and codeine doses to equivalent doses of morphine

• Add them together = 60mg morphine, and this becomes the new dose

• Give as a 12-hourly preparation - MST 30mg BD

When treating N&V we commonly use a regime of two antiemetics. How should we go about prescribing anti-emetics for N&V?

Split into two: When treating nausea and vomiting you should seperate it into 2 categories

1) Firstly we are treating nausea so will need an anti-emetic - Cyclizine for example - anti-histamine

2)To reduce vomiting - We will need to reduce vomiting using buscopan / hyoscine butylbromide - an anticholinergic