and Lynne Ghasemi Liz Newell Michelle Street

Assessment • Features of N &V o Onset, frequency, intensity, relieving and exacerbating factors, quantity, force, colour, timing and pattern of vomit • Other symptoms o Heartburn, dyspepsia, early satiety, , diarrhoea, cough, flatus, headache, confusion • Treatment History – Current medication, CT, RT – Anti-emetics and effectiveness • Medical History – Disease extent and location, ulcers or bowel surgery • Examination – Mouth, abdomen, (rectal), fundi – Associated signs Features indicating cause of N & V • Constant nausea, variable vomiting Chemically induced nausea • Infrequent, large volume vomit, symptoms relieved after vomit, reflux, epigastric fullness, early satiation Gastric stasis

• Intermittent nausea (often relieved by vomiting), worsening nausea +/- fecal vomiting, colicky abdo pain & distention Bowel obstruction

Causes of N&V in palliative care Cause Examples Mechanism

Chemical Drugs, toxins, metabolic CTZ GI stretch/irritation Drugs, obstruction, Gut mechanoreceptors constipation, liver mets vagus →VC

Gastric Stasis Drugs, ascites, Gastric receptors hepatomegaly, gastritis vagus →VC

↑ ICP Tumour, bleeding, Cerebral H1 receptors oedema Meningeal mechanoreceptors→VC Movement-related , gastroparesis As GI stretch; opioids → vestibular nerves Anxiety-related Prior to CT Cerebral cortex →VC Anti-emetic: receptor site affinities

Anti-emetic Dopamine H1 Ach antag 5-HT2 D2 antag antag antag * ++ - - - # ++ - - - Cyclizine - ++ ++ - Hyoscine - - +++ - +++ - - - ++ +++ ++ +++

Key: - none or insignificant; + slight; ++ moderate; +++ marked.

*Metoclopramide > 100mg shows 5-HT3 antagonism #Domperidone does not cross BBB so risk of EPSE (, dystonia is negligible)

Chemically induced (e.g. opioids, metabolic) • Review medicines • Check levels e.g. digoxin • CT – seek specialist advice • Give haloperidol 1.5mg nocte or bd to max. 10mg daily • Prn po/sc dose 0.5-1.5mg • No need to give via CSCI as 16hr half-life • Side effects: extrapyramidal, less sedating than levomepromazine

Intracranial Disease • If ↑ICP consider RT, high dose dexamethasone • For N &V add cyclizine • Dose: 25-50mg tds PO / SC; up to 150mg/24hrs CSCI (NB compatibility) • Side effects: sedation, constipation, confusion

Movement related nausea and vomiting • Treat as per cyclizine above

Gastric stasis-related N & V • D2 antagonist domperidone; 10mg tds pre meals. • Works on the gut and also chemo-receptor trigger zone. • Does not cross the blood brain barrier therefore negligible risks of extra pyramidal side effects. Therefore prokinetic of choice with Parkinson’s disease. • MHRA alert: Caution due to risk of increasing the QT interval – Torsades de Pointes. Weigh up risks v benefits • Risk increased if underlying cardiac disease, electrolyte disturbances or in combination with other drugs known to increase the QT interval.

Gastric stasis related nausea and vomting • Metoclopramide Dose: 10mg qds, pre meals; up to 120mg/24hrs CSCI • Side effects: extrapyramidal (acute dystonia, acute akathisia, tardive dyskinesia), colic • (prokinetic, D2 antagonist but crosses the blood brain barrier) • Do not give pro-kinetics with antimuscarinics e.g. cyclizine or hyoscine • EMA restricted use – unlicensed, monitor for movement disorders with long-term use (Parkinson’s disease)

Hyoscine butylbromide (Buscopan) • Not to be confused with hyosine hydrobromide • Peripheral antimuscarinic (does not cross BBB) • Reduces gut secretions and spasm (useful for inoperable bowel obstruction) • Dose: 20mg SC prn; 40-120mg/24hrs CSCI • Poor oral absorption • Avoid in glaucoma, bladder obstruction, pyrexia, acid reflux, paralytic ileus, caution with conditions predisposing to

What if first line anti-emetic fails?

• Confirm cause • Optimise dose of first line treatment • Consider alternative treatment/route • If N &V persists after 2-3 doses of optimal first line: – Change to anti-emetic with different action or combine • Unknown cause – try haloperidol first then consider levomepromazine if need broader spectrum • Levompromazine - , sedative, anxiolytic – 6-25mg once daily PO/SC; – 6.25-25mg/24hrs CSCI for N&V •

Other …

• 5HT3 antagonists – , (e.g. CT, RT post-surgery) • Steroids • Octreotide (e.g. bowel obstruction) • Benzodiazepines (anxiety related) • NK inhibitors – (e.g. CT) • Atypical antipsychotics eg • Mirtazepine ()

Enter the drug names! Anxiety/raised intracranial pressure

Chemical causes e.g. drugs

Higher Centres

Chemoreceptor Trigger Zone (CTZ)

Vestibular Input

Vomiting Centre

Ach H 2 5HT 2

Gastrointestinal Tract

Perception Of nausea Gastric stasis, intestinal obstruction, gastric irritation & Vomiting (e.g.chemotherapy,radiotherapy, hepatomegaly)

Non pharmacological measures • Calm reassuring environment away from sight and smell of food • Small appetising snacks • Move slowly, avoid strong odours • Discretely located receivers / tissues • Washing facilities, changing linen • Oral hygiene • Cold water • Accupuncture/Accupressure • REVIEW ANTI-EMETIC ADMINISTRATION References • Palliative Care Formulary 5 2015 palliativedrugs.com

• Sheffield Palliative Care Formulary 4th Edition: available on the STH intranet