Management ofNausea & Vomiting

Dr Iain LawrieSpecialist Registrar

in Palliative Medicine

Vomit

Vomiting Centre

Cortical Structures

Gut Mucosa

Vestibular Apparatus

D2 5-HT3 ACh

H1 5-HT2 ACh

Chemoreceptor Trigger Zone

D2 5-HT3 Ach

H1, ACh

Vomit

Vomiting Centre

Cortical Structures

Gut Mucosa

Vestibular Apparatus

D2 5-HT3 ACh

H1 5-HT2 ACh

H1 AChMotion

Emotions, sights, smells,

raised ICP

GI obstruction, bowel colic, tumour mass,

constipation

Chemoreceptor Trigger Zone

D2 5-HT3 AChDrugs, toxins,

uraemia, hypercalcaemia

Vomit

Vomiting Centre

Cortical Structures

Gut Mucosa

Vestibular Apparatus

D2 5-HT3 ACh

H1 5-HT2 ACh

H1 AChMotion

Emotions, sights, smells,

raised ICP

GI obstruction, bowel colic, tumour mass,

constipation

Chemoreceptor Trigger Zone

D2 5-HT3 AChDrugs, toxins,

uraemia, hypercalcaemia

Metoclopramide, Levomepromazine

Granisetron

Haloperidol Metoclopramide

Levomepromazine Granisetron

Dexamethasone

Cyclizine, Hyoscine HBr

Cyclizine, Levomepromazine, Hyoscine HBr

Factors to consider

Mechanism of action of anti-emetic drugs

Response to anti-emetics already given Combinations of drugs should have

different actions Levomepromazine has multiple

receptor affinities

Factors to consider

Effects of anti-emetics on GI motility (prokinetic / antikinetic)

Adjuvant use of anti-secretory drugs Adjuvant use of corticosteroids Adverse effects of drugs Cost of drugs

Management

Correct reversible causes stop gastric irritant drugs treat gastritis

• PPIs / antacids treat cough

• antitussive treat constipation

• laxatives

Management

Raised ICP- steroids / radiotherapy

Anxiety Hypercalcaemia

- rehydration +/- bisphosphonates

Causes of drug-induced N&V Gastric irritation

Gastric stasis

CTZ stimulation

5HT3-receptor stimulation

Antibiotics, iron, NSAIDs

Antimuscarinics, opioids, TCA

Antibiotics, cytotoxics, digoxin

Antibiotics, cytotoxics, SSRIs

What if it’s not working?

Is it being absorbed? Is the dose optimum? Do you have the correct cause? Most anti-emetics can be given SC Doses usually the same PO, SC and IV

Prescribing an anti-emetic

Choice depends on cause of N&V Give regularly Alternative to oral route if unable to

absorb- subcutaneous stat doses- continuous subcutaneous infusion (driver)- rectal route

Anti-emetics – dopamine antagonists Haloperidol (D2)

Metoclopramide (D2, 5-HT3, 5-HT4 agonist) Prochlorperazine (D2) Domperidone (D2) Levomepromazine (D2, ACh, H1, 5-HT3)

Side effects- EPSE- sedation in higher doses- reduce seizure threshold

Anti-emetics – histamine antagonists Cyclizine (H1, ACh) Levomepromazine (D2, ACh, H1, 5-HT3)

Side effects- drowsiness- anticholinergic effects- postural hypotension

Anti-emetics - anticholinergics Hyoscine butylbromide (ACh) Hyoscine hydrobromide (ACh) Cyclizine (ACh) Levomepromazine (D2, ACh, H1, 5-HT3)

Side effects- sedation- anticholinergic effects

Anti-emetics - prokinetics

Metoclopramide (D2, 5-HT3, 5-HT4 agonist)

Domperidone (D2)

Side effects:- colic- EPSE (not domperidone – doesn’t cross BBB)

Anti-emetics – serotonin antagonists Ondansetron, granisetron, tropisetron

Side effects- constipation

Place in palliative care- obstruction / stretch- resistant N&V

Anti-emetics - steroids

Dexamethasone Reduce permeability of BBB & area postrema

to emetogenic substances Reduce neuronal content of GABA in the

brain stem Reduce leuenkephalin release Reduce oedema around lesion or tumour

Gastric stasis & irritation

Nausea made worse by eating Large volume vomits Early fullness & bloating Belching & reflux Hiccups Epigastric fullness & tenderness

Gastric stasis & irritation

1st line metoclopramide

Adjuncts- antiflatulent- PPI- stop irritant drugs

Bowel obstruction without colic Variable nausea Vomiting dependent on site of

obstruction Abdominal distension Background aching pain Constipation Absent or ‘hyperactive’ bowel sounds

Bowel obstruction without colic 1st line metoclopramide 2nd line cyclizine or haloperidol

(substitute)

Adjuvants- diamorphine- octreotide- docusate- steroids

Bowel obstruction with colic

Symptoms as before, but with colicky pains

1st line cyclizine OR haloperidol PLUS buscopan

2nd line cyclizine AND haloperidol OR levomepromazine

Adjuvants- diamorphine, octreotide, docusate

Chemical induced N&V

Significant nausea Variable vomiting Few other GI symptoms Evidence of presence

i.e. new drug started, biochemistry results

1st line haloperidol / metoclopramide 2nd line ADD cyclizine OR substitute

levomepromazine

Raised intracranial pressure

Known intracerebral tumour Early morning headaches Predominant nausea Intermittent vomiting Papilloedema Neurological deficit Seizures

Raised intracranial pressure

1st line dexamethasone & cyclizine

2nd line ADD haloperidol

3rd line 5-HT3 antagonist (substitute)

Motion / movement related N&V Nausea & vomiting worse on movement Can be associated with cranial nerve

lesions and base of skull metastases

1st line cyclizine

2nd line hyoscine hydrobromide

Indeterminate N&V

1st line haloperidol OR cyclizine

2nd line haloperidol AND cyclizine

3rd line levomepromazine (substitute)

4th line consider metoclopramide, dexamethasone, 5HT3 antagonist

Summary

Try to determine the cause wherever possible

1/3 of patients will need more than one anti-emetic

Eliminate reversible causes

Continue anti-emetic indefinitely if cause is not self-limiting