Management of Nausea & Vomiting

1. Management ofNausea & Vomiting Dr Iain Lawrie Specialist Registrar in Palliative Medicine

2. Gut Mucosa Vestibular Apparatus D2 5-HT3 ACh Cortical Structures Chemoreceptor Trigger Zone D2 5-HT3 Ach Vomiting Centre H1 5-HT2 ACh Vomit H1, ACh

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

4. Gut Mucosa Vestibular Apparatus D2 5-HT3 ACh H1 ACh GI obstruction, bowel colic, tumour mass, constipation Motion Cyclizine, Hyoscine HBr Metoclopramide, Levomepromazine Granisetron Cortical Structures Chemoreceptor Trigger Zone Emotions, sights, smells, raised ICP Dexamethasone D2 5-HT3 ACh Vomiting Centre Drugs, toxins, uraemia, hypercalcaemia H1 5-HT2 ACh Cyclizine, Levomepromazine, Hyoscine HBr Haloperidol Metoclopramide Levomepromazine Granisetron Vomit

5. 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

6. 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

7. Management • Correct reversible causes ­ stop gastric irritant drugs ­ treat gastritis • PPIs / antacids ­ treat cough • antitussive ­ treat constipation • laxatives

8. Management • Raised ICP - steroids / radiotherapy • Anxiety • Hypercalcaemia - rehydration +/- bisphosphonates

9. Gastric irritation Gastric stasis CTZ stimulation 5HT3-receptor stimulation Antibiotics, iron, NSAIDs Antimuscarinics, opioids, TCA Antibiotics, cytotoxics, digoxin Antibiotics, cytotoxics, SSRIs Causes of drug-induced N&V

10. 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

11. 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

12. 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

13. Anti-emetics – histamine antagonists • Cyclizine (H1, ACh) • Levomepromazine (D2, ACh, H1, 5-HT3) • Side effects - drowsiness - anticholinergic effects - postural hypotension

14. Anti-emetics - anticholinergics • Hyoscine butylbromide (ACh) • Hyoscine hydrobromide (ACh) • Cyclizine (ACh) • Levomepromazine (D2, ACh, H1, 5-HT3) • Side effects - sedation - anticholinergic effects

15. Anti-emetics - prokinetics • Metoclopramide (D2, 5-HT3, 5-HT4 agonist) • Domperidone (D2) • Side effects: - colic - EPSE (not domperidone – doesn’t cross BBB)

16. Anti-emetics – serotonin antagonists • Ondansetron, granisetron, tropisetron • Side effects - constipation • Place in palliative care - obstruction / stretch - resistant N&V

17. 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

18. Gastric stasis & irritation • Nausea made worse by eating • Large volume vomits • Early fullness & bloating • Belching & reflux • Hiccups • Epigastric fullness & tenderness

19. Gastric stasis & irritation • 1st line metoclopramide • Adjuncts - antiflatulent - PPI - stop irritant drugs

20. Bowel obstruction without colic • Variable nausea • Vomiting dependent on site of obstruction • Abdominal distension • Background aching pain • Constipation • Absent or ‘hyperactive’ bowel sounds

21. Bowel obstruction without colic • 1st line metoclopramide • 2nd line cyclizine or haloperidol (substitute) • Adjuvants - diamorphine - octreotide - docusate - steroids

22. 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

23. 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

24. Raised intracranial pressure • Known intracerebral tumour • Early morning headaches • Predominant nausea • Intermittent vomiting • Papilloedema • Neurological deficit • Seizures

25. Raised intracranial pressure • 1st line dexamethasone & cyclizine • 2nd line ADD haloperidol • 3rd line 5-HT3 antagonist (substitute)

26. 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

27. Indeterminate N&V • 1st line haloperidol OR cyclizine • 2nd line haloperidol AND cyclizine • 3rd line levomepromazine (substitute) • 4th line consider metoclopramide, dexamethasone, 5HT3 antagonist

28. 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