Nausea and Vomiting
Dr Katie Tham
Palliative Medicine Specialist
Department of Palliative Medicine
Eastern Health
Overview
• Nausea, vomiting & related symptoms
• Antiemetic therapy
• Constipation
• Bowel obstruction
• Quiz in the middle…..are you awake?!
Nausea vs Vomiting
Nausea: An unpleasant sensation of being about to vomit
• Common - experienced by 70% palliative care patients
• Cause is frequently multifactorial
• Distressing for patients & carers
• Often accompanied by autonomic symptoms, e.g. pallor, cold
sweat, salivation, tachycardia and diarrhoea
Vomit / Emesis: the forceful expulsion of gastric contents through
the mouth
• Protective reflex pathway
• Complex cascade of muscular contractions in the upper GIT &
upper airway triggered by a threshold of input into the
vomiting centre
The Nausea Experience (Molassiotis 2008)
• More common and distressing than vomiting
• Traditionally ignored in studies for antiemetic efficacy
• Can you rate accurately on a 0-10 severity scale?
• Nausea ≠ Vomiting, rather it is a symptom cluster (Molassiotis et al
2012)
Loss of appetite Dry mouth
Taste disturbance Diarrhoea
Intolerance to smells Bloating
Vomiting Lethargy
Drowsiness Dysphagia
Anxiety General unease
Causes to Consider
What are some causes?
Often multifactorial in
palliative care setting
Approach to Management
• Identify cause(s):
Treat reversible causes if appropriate (constipation,
sepsis, medication toxicity)
• Address consequences:
Dehydration, unstable oral route for medications
• Antiemetic treatment
Mechanistic vs Empirical approach
Mechanistic = targeting presumed etiology for nausea
with antiemetic’s dominant mechanism of action (T To et
al 2014)
Assessment
• Not just a yes/no answer!
• Temporal factors
• Severity
• Quality
Is it vomiting or is it expectoration
or regurgitation?
What are you bringing up?
• Provocation
• Palliation
Assessment
• Associated symptoms
• Dyspepsia / Dysphagia / GORD / Anorexia / Early satiety / Bowel
function / Dry mouth
• Symptoms of underlying cause
• e.g. Infections / headache / constipation / abdominal pain /
dizziness
• Holistic assessment and psychological factors
• Examination and Investigations
Mechanisms Involved
Vestibular
CTZ
System
5HT, D2, NK1
ACh, H1
GIT Cerebral
Cortex
5HT, NK1, D2, H1, 5HT, GABA, NK1,
ACh Vomiting mechanoreceptors
Centre
ACh, H1, 5HT2,
NK1,
Gastrointestinal Tract
• Triggers:
Gastric irritants – Drugs, Chemotherapy, RadioTx
Distension – constipation, obstruction, delayed gastric emptying
• Sx - worse after meals, vomiting (often large volume) common, early
satiety, feeling of fullness
• Receptors:
D2 (peripheral), 5HT4, NK1
• Stimulates vomiting centre via vagus afferents
• Target antiemetics often prokinetics:
Metoclopramide
Domperidone
Erythromycin
‘-trons’ eg. Granisetron, Ondansetron
Chemoreceptor Trigger Zone
• Area Postrema in floor of 4th Ventricle in Medulla
• Not protected by blood-brain barrier, intended purpose is to detect
toxins circulating in blood
• Direct connection to VC
• Triggers:
drugs / toxins / metabolites
Sx – constant nausea, no or small volume
vomits without relief
• Receptors involved:
D2 (central), 5HT3, NK1
• Target anti-emetics:
Haloperidol
Metoclopramide
-trons
Aprepitant
Vestibular Centre
• Triggers:
Head movement
Motion
Inner ear disorders
• Receptors
H1, ACh
• Target anti-emetics:
Promethazine
Prochlorperazine
Cyclizine
Brain
• Triggers:
Mechanoreceptors sensitive to changes in intracranial
pressure
Higher cerebral centres triggered by emotional/abstract
stimuli (pain, anxiety, anticipatory nausea
• Target anti-emetics:
Dexamethasone
Lorazepam
(Olanzapine)
Vomiting Centre
• Located in the medulla oblongata
• Activation initiates & controls vomiting:
gastric atony, retroperistalsis, muscle contraction
• Receptors: ACh, H1, 5HT2, NK1
• Target anti-emetics: Cyclizine, Levomepromazine, Aprepitant
Antiemetic Side Effects
• EPSE (in D2 antagonists)
Parkinsonism, Dystonias, Tardive Dyskinesia & Akathisia
Domperidone = lower risk as mostly peripherally acting
• Anticholinergic
Dry mouth, Blurred vision, Constipation, Urinary
retention
• Constipation (ondansetron)
• Sedation (Cyclizine, Levomepromazine)
• QT interval prolongation
• Neuroleptic Malignant Syndrome
ANTI-EMETICS & RECEPTOR SITE AFFINITY (source: palliative drugs)
Prescribing Guides (Therapeutic Guidelines 2016)
First line:
GIT Metoclopramide/Domperidone
CTZ Haloperidol
Vestibular Promethazine/Prochlorperazine
Intracranial Dexamethasone/Cyclizine
Chemo/radioTx 5-HT3 antagonist plus dexamethasone
Second line agents:
Antihistamine/Anticholinergic – Cyclizine
Broad receptor coverage - Levomepromazine, Olanzapine
Antisecretories – Hyoscine butylbromide (Buscopan), Octreotide
Serotonin antagonists – Ondansetron (rarely used)
Non-pharmacological
• Dietary/environmental modification
• Avoidance of triggers
• Avoiding spicy/salty/fatty foods
• Eat small and often meals
• Behavioural approaches
• Relaxation and distraction
• Complementary therapy
• Massage
• Acupuncture
• Ginger
Summary Mx Principles
• Identify (& treat) underlying cause of N&V
• Not all antiemetics are the same but limited evidence to
guide mechanistic or empirical approach
• If initial choice not effective then either change or add
• Consider which receptors
• 24hr CSCI often valuable
• Don’t forget non-pharmacological
management aids
Which Antiemetic?
Q1 68y.o man dx metastatic pancreatic cancer, early satiety, nausea post
meals with occasional vomiting.
Q2. 54 y.o lady with ESKD, eGFR 6, Ur 48. Continuous nausea, nil vomiting
Q3. 28y.o lady with metastatic breast cancer. Anticipatory nausea pre-
chemotherapy
SELECT MOST APPROPIRATE FIRST LINE ANTIEMETIC
A. Haloperidol 0.5mg BD and PRN
B. Metoclopramide 10mg oral TDS pre-meals
C. Ondansetron 4mg wafer
D. Lorazepam 0.5mg sublingual
Constipation & Bowel
Obstruction
Why is constipation
important?
• Common! 50% – 90% patients
• 3rd most common sx (after pain and anorexia)
• Increases symptom burden:
• N&V
• Abdominal pain
• Anorexia
• Acute urinary retention
• Delirium
• ‘Overshoot’ diarrhoea +/- incontinence
• May impact upon absorption of drugs
• Decreases QOL – distressing for pts and carers
• Increased healthcare resources
Causes
• Lifestyle: Immobility, decreased fluid intake, poor diet
• Drugs: eg. Opioids, Anticholinergics, Ondansetron
• Metabolic: hypercalcaemia, ureamia, DM
• Local disease: Colorectal/Ovarian ca, Cord compression,
other neurological etc.
• Deconditioning / abdominal muscle weakness
• Most often multifactorial!
Assessment of Constipation
• History
• Physical examination:
Abdominal exam
PR
• Investigations:
Bloods – exclude reversible causes
Plain AXR
• Main use to exclude obstruction
Assessment Scales
• Essential to establish pattern & monitor effect of treatment
• Use not evidence based, however recommended by
consensus guidelines, provide a degree of objectivity
• Common tools include:
Bristol Stool Form Scale
Constipation Assessment Scale
Constipation VAS
Eton Scale Risk Assessment for Constipation
Drugs Available
• Bulk formining – Metamucil, Normafibe
• Softeners - Coloxyl
• Stimulants – Senna, Bisacodyl, Nulax
• Osmotic – Lactulose, Movicol
• Lubricants – Agarol, Glycerol suppositories
• Opioid antagonist – Methylnaltrexone
• 40-70% patients prescribed laxatives continue to experience
symptoms
• >50% palliative inpatients receive more than 2 laxatives
simultaneously (K Clark et al 2010)
General Mx Recommendations
• Prevention:
Anticipate constipation with opioids
Prescribe prophylactically
Do not rely on lifestyle advice in palliative care
• Treatment:
First line = combination softener & stimulant
Second line = Osmotic +/- PR therapy if indicated
Third line = Methylnaltrexone if opioid related / manual
disimpaction
• Always continue to monitor and adjust therapy
Bowel Obstruction
Malignant Bowel Obstruction
• Occurs in 3-15% cancer patients
• Terminal event in up to 50% patients with metastatic ovarian
cancer
• 36% of inoperable obstructions spontaneously resolve
• In these cases, rate of recurrence is 60%
• Mean survival 4-5 weeks in patients with a complete non-
resolving bowel obstruction
Classification
• Partial or sub-acute vs Complete
• By the level of obstruction:
- Gastric Outlet Obstruction
- Small bowel obstruction
- Large bowel obstruction
Single transition zone – may be amenable to surgical
intervention
Multiple transition points – medical management & supportive
care
Approach to management
• Specific and individualised approach based on disease
prognosis and goals of care
• Consider surgical options both for life prolonging and
symptom benefits
• Medical management to reduce symptoms
• Parenteral fluids and nutrition needs careful consideration and
discussion
Surgical Options
Procedures
• Resection/diversion
• Endoscopic stents - duodenal or colonic
• Venting gastrostomy
Medical management
General approach
• Refer to specialist palliative care early
• Complete vs partial obstruction
• Remember may spontaneously resolve
• NGT, NBM, Dex, IV fluids and biochemical management
• Symptom reduction using parenteral medications
• Pain – opioids +/- antispasmodic (buscopan)
• Nausea – Haloperidol (1st line)
• Vomiting/gastric secretions – antisecretories (buscopan, ocreotide)
• Don’t forget mouthcare
• Consider need for parental fluids (and occasionally nutrition)
• Address psychosocial factors (often complex)
Summary
• Nausea, Vomiting, Constipation, are common and distressing
• Causes often multifactorial
- Target reversible causes where possible
- Think about receptors involved
• Different management options
- Many not evidence-based as yet!
• Bowel obstruction is complex – refer early
Thank you! Questions....
