Management of Nausea & Vomiting Dr Iain Lawrie Specialist Registrar in Palliative Medicine

Chemoreceptor Trigger Zone 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

Chemoreceptor Trigger Zone Vomit Vomiting Centre Cortical Structures Gut Mucosa Vestibular Apparatus D2 5-HT3 ACh H1 5-HT2 ACh H1 ACh Motion Emotions, sights, smells, raised ICP GI obstruction, bowel colic, tumour mass, constipation Chemoreceptor Trigger Zone Drugs, toxins, uraemia, hypercalcaemia

Chemoreceptor Trigger Zone Vomit Vomiting Centre Cortical Structures Gut Mucosa Vestibular Apparatus D2 5-HT3 ACh H1 5-HT2 ACh H1 ACh Motion Emotions, sights, smells, raised ICP GI obstruction, bowel colic, tumour mass, constipation Chemoreceptor Trigger Zone Drugs, 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