Nausea Vomiting Dr Lucy Harris Sp R Palliative

  • Slides: 27
Download presentation

Nausea & Vomiting Dr. Lucy Harris Sp. R Palliative Medicine September 2014

Nausea & Vomiting Dr. Lucy Harris Sp. R Palliative Medicine September 2014

A Starting Point - Definitions • Nausea: An unpleasant sensation of the need to

A Starting Point - Definitions • Nausea: An unpleasant sensation of the need to vomit, often accompanied by autonomic symptoms – sweating, salivation, tachycardia. • Vomiting: Forceful expulsion of gastric contents through the mouth, caused by forceful and sustained contraction of the abdominal muscles and diaphragm. • Anticipatory vomiting: Vomiting in the absence, but caused by anticipation, of the stimulus e. g. chemotherapy • Retching: Rhythmic, laboured, spasmodic movements of the diaphragm and abdominal muscles against a closed glottis

It’s all in the history…. • Regurgitation – The movement of contents of the

It’s all in the history…. • Regurgitation – The movement of contents of the stomach into the oesophagus and / or from the oesophagus into the mouth. • Rumination – The controlled, voluntary regurgitation of undigested food from the stomach into the mouth (food often then swallowed again). Often associated with psychiatric disorders • Oesophageal secretions - Frothy, stringy white or colourless secretions, associated with oesophageal cancer. May respond to steroids.

Why Is It Important? • About 60 % of patients with advanced cancer will

Why Is It Important? • About 60 % of patients with advanced cancer will experience nausea and / or vomiting at some point • Prevalence of about 40% in the last six weeks of life • More common in: Stomach / Breast Cancers Women Patients under 65 • Least common in: Lung Cancer Arch Intern Med. 1986; 146(10): 2021 -2023.

Pathophysiology • Emetic process not fully understood • Awareness of physiology of vomiting and

Pathophysiology • Emetic process not fully understood • Awareness of physiology of vomiting and main neurotransmitters involved can help in assessment and choice of appropriate antiemetic

Cortex CTZ GI VOMITING REFLEX VOMITING CENTRE (Medulla) Vestibular

Cortex CTZ GI VOMITING REFLEX VOMITING CENTRE (Medulla) Vestibular

Receptor Sites • Cortical Structures (eg. anxiety, sights, smells, raised ICP): GABA • Vomiting

Receptor Sites • Cortical Structures (eg. anxiety, sights, smells, raised ICP): GABA • Vomiting Centre: Muscarinic (Ach) Histamine (H 1) Serotonin (5 HT 2) • Chemoreceptor Trigger Zone: Serotonin (5 HT 3) Dopamine (D 2) • Vestibular Apparatus: Muscarinic (Ach) Histamine (H 1) • Gut Mucosa: Dopamine (D 2) Serotonin (5 HT 3) Serotonin (5 HT 4)

The Vomiting Reflex • Involves multiple structures - the pharynx, larynx, upper GI tract,

The Vomiting Reflex • Involves multiple structures - the pharynx, larynx, upper GI tract, the muscles of the thorax, abdomen and diaphragm and the respiratory and salivatory centres. • It causes ; 1) Nausea, with autonomic symptoms 2) Gastric stasis / atony (relaxation of smooth muscle wall of stomach) 3) Retching with closure of vocal cords 4) Elevation of palate (to close nasopharynx) 5) Reverse peristalsis 6) Contraction of the abdominal wall and chest muscles

Consideration of Causes in the Palliative Setting Case Example 1: 75 man, CA lung

Consideration of Causes in the Palliative Setting Case Example 1: 75 man, CA lung with bone metastases lower back. Started regular oromorph for back pain Complaining predominantly of nausea. Case Example 2: 60 women, CA breast with liver, bone and brain metastases. On morphine for several weeks. Not constipated. Complaining of N&V. Vomiting does not relieve nausea.

Management Approach…. ESTABLISH THE CAUSE Investigations Examination History Urine Dip, U&Es, Calcium, Relevant Drug

Management Approach…. ESTABLISH THE CAUSE Investigations Examination History Urine Dip, U&Es, Calcium, Relevant Drug Levels, ? AXR, Brain imaging Hydration, Temperature, Mouth, Abdomen, Rectum, Fundi, Neurology Onset, Timing, N vs V, Triggers, Associated factors, Content of Vomitus, Drugs

Principles of Treatment • 1: Treat the cause • 2: Non-pharmacological approaches • 3:

Principles of Treatment • 1: Treat the cause • 2: Non-pharmacological approaches • 3: Anti-emetics The most common mistakes in treating nausea & vomiting are: – not considering reversible factors – using oral route for anti-emetics in established nausea & vomiting

Non-Pharmacological Approaches • Control Malodour (eg: fungating tumours) • Consider environment - away from

Non-Pharmacological Approaches • Control Malodour (eg: fungating tumours) • Consider environment - away from sight and smell of food. Ask others to take on role of food preparation • Meal Size - Small snacks regularly • Complementary Therapy eg: acupressure bands / Acupuncture • Distraction

Approach to Anti-emetics: • Anticipate • Regular doses and consider most appropriate route of

Approach to Anti-emetics: • Anticipate • Regular doses and consider most appropriate route of delivery • Target the relevant receptors according to cause • Consider Combination

Antiemetic Choice – Think receptors!

Antiemetic Choice – Think receptors!

Receptors in Vomiting Pathways Stimulus Area Drugs, Metabolic Chemoreceptor trigger zone Motion, Position Vestibular

Receptors in Vomiting Pathways Stimulus Area Drugs, Metabolic Chemoreceptor trigger zone Motion, Position Vestibular Visceral Organs ? Nonspecific ↑ ICP CNS Cerebral cortex Receptors D 2 5 HT 3 Muscarinic (Ach) Histamine D 2 5 HT 3 Cannabinoid Histamine Mike Harlos, Manitoba

Antiemetics – site of action CTZ Haloperidol Metoclopramide Domperidone Levomepromazine Ondansetron Granisetron VOMITING CENTRE

Antiemetics – site of action CTZ Haloperidol Metoclopramide Domperidone Levomepromazine Ondansetron Granisetron VOMITING CENTRE Vestibular Hyoscine hydrobromide Cyclizine Prochlorperazine Levomepromazine GI Hyoscine hydrobromide Cyclizine Prochlorperazine Levomepromazine Metoclopramide Domperidone Ondansetron Granisetron Mike Harlos, Manitoba

Management Pharmacological

Management Pharmacological

Other drugs used to manage nausea and vomiting • Dexamethasone Decreases permeability at CTZ,

Other drugs used to manage nausea and vomiting • Dexamethasone Decreases permeability at CTZ, inhibits central PG synth • Ranitidine Decreases volume of gastric secretions • Octreotide Decreases GI secretions (useful for large volume vomits in malignant bowel obstruction) • PPI Decreases acidity • Antifungals Treat oropharyngeal candida • Benzodiazepines For anxiety, ? ? GABA effect

Antiemetic Ladder • • STEP 2 2 nd line narrow spectrum eg ondansetron OR

Antiemetic Ladder • • STEP 2 2 nd line narrow spectrum eg ondansetron OR combination eg cyclizine+haloperidol OR broad spectrum eg levomepromazine • • • STEP 1 Narrow spectrum Metoclopramide Cyclizine Haloperidol

Route is important Essential to consider antiemetic route if already vomiting / absorption concerns

Route is important Essential to consider antiemetic route if already vomiting / absorption concerns • Transdermal: Scopaderm TTS releases 0. 5 m hyoscine hydrobromide / 72 hrs • Buccal: Buccastem (Prochlorperazine tab absorbed from buccal mucosa) 3 mg/12 hrs • Rectal: Prochlorperazine (25 mg tds) Domperidone (30 -60 mg qds) • S/C: Cyclizine (100 -150 mg/24 hrs) – does not combine well in csci Haloperidol (2. 5 -10 mg/24 hrs) Levomepromazine (6. 25 -100 mg/24 hrs) (2: 1 conversion for po : sc) Metoclopramide (30 -120 mg/24 hrs) Octreotide (100 -1200 mcg/24 hrs)

Additional Hints • If using more than one anti-emetic, use those that act on

Additional Hints • If using more than one anti-emetic, use those that act on different receptors • 30% pts require 2 anti-emetics • If previously on regular antiemetics add to these to a syringe driver if started for other reasons • Avoid dopamine antagonists (esp; metoclopramide, haloperidol) in PD Reassess regularly!

Summary • N+V are common in end-stage disease, and significantly affect QOL. • Determining

Summary • N+V are common in end-stage disease, and significantly affect QOL. • Determining and reversing cause(s) if possible is paramount, often multi-factorial • Usually easily treated, many anti-emetics – choice depends on cause. • Use regular antiemetics, by appropriate route, with PRN provision • Oral medication rarely works if established vomiting or severe nausea.

Cause of Vomiting 1 st Line Antiemetic Dose 2 nd Line Antiemetic Dose Drugs

Cause of Vomiting 1 st Line Antiemetic Dose 2 nd Line Antiemetic Dose Drugs / Toxins Haloperidol 1. 5 -3 mg nocte/bd Levomepromazine 6. 25 -25 mg / 24 hrs Radiotherapy Ondansetron 8 mg stat, then bd for 5/7 Haloperidol 1. 5 -3 mg nocte/bd Chemotherapy Ondansetron 8 mg stat, then bd for 5/7 Metoclopramide 20 mg tds/qds Dexamethasone 4 -8 mg od Metabolic (eg. ↑Ca/Uraemia) Haloperidol 1. 5 mg nocte/bd Levomepromazine Cyclizine 6. 25 -25 mg / 24 hrs 50 mg tds Raised ICP Cyclizine + Dexamethasone 50 mg tds 8 -16 mg / 24 hrs Levomepromazine + Dexamethasone 6. 25 -25 mg / 24 hrs 8 -16 mg / 24 hrs Bowel Obstruction (with colic) Cyclizine +/Buscopan +/Octreotide +/Dexamethasone 150 mg / 24 hrs 40 -100 mg /24 hrs s/c 1. 5 -3 mg od/bd 6. 25 -25 mg / 24 hrs 300 -1000 mcg/24 hrs s/c 8 -16 mg / 24 hrs Haloperidol Levomepromazine +/- Buscopan / Octreotide / Dexamethasone Delayed Gastric Emptying Metoclopramide 10 -20 mg tds/qds Domperidone 10 -20 mg qds Gastric Irritation PPI for gastritis Stop irritants- NSAIDs Cyclizine 50 mg tds Ondansetron Metoclopramide Levomepromazine 8 mg bd 10 -20 mg tds/qds 6. 25 -25 mg / 24 hrs

Pharmacokinetics Of Antiemetics Drug Onset of action Duration of Action Half-life Mechanism Of Action

Pharmacokinetics Of Antiemetics Drug Onset of action Duration of Action Half-life Mechanism Of Action Place Of Action Side Effects Metoclopramide 10 -15 mins 1 -2 hrs 2. 5 -5 hrs Prokinetic (D 2 antagonist, 5 HT 4 agonist, 5 HT 3 antagonist) Intestinal CTZ Extrapyramidal Colic (in intestinal obstruction) Domperidone 30 mins 8 -16 hrs 14 hrs Prokinetic (D 2 antagonist) Intestinal Colic (in intestinal obstruction) Cyclizine <2 hrs 4 -6 hrs 5 hrs Anti-histamine (H 1 receptor) Anticholinergic (ACh receptor) Vomiting Centre Dry Mouth Drowsiness Ondansetron <30 mins PO < 5 mins IV 12 hrs 3 hrs 5 HT 3 antagonist CTZ Constipation Headache Levomepromazine 1 -4 hrs PO 30 -90 mins SC 12 -24 hrs 13 -30 hrs Broad Spectrum (ACh, H 1, 5 HTs, D 2 receptors) Vomiting Centre CTZ Sedative Antimuscarinic Anxiolytic Buscopan 1 -2 hrs PO 3 -5 mins SC 15 mins a/spasmotic 1 -9 hrs a/secretory 5 -6 hrs Anticholinergic (ACh receptor) Vomiting Centre Dry Mouth Drowsiness Confusion Haloperidol 10 -15 mins s/c >1 hr PO Up to 24 hrs 13 -35 hrs CTZ Sedation Extra-pyramidal Neuroleptic (D 2 antagonist)

Questions?

Questions?