Approach to Nausea & Vomi2ng
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1 Approach to Nausea & Vomi2ng Med 3 Seminar 2017 Dr. Robin Grant Division of Pallia2ve Medicine robin.grant@nshealth.ca
2 Why nausea and vomi2ng? Pain % Fa2gue / asthenia 75-90% Cons2pa2on 70% Dyspnea 60+ % Nausea 50-60% Vomi0ng 30% Delirium 30-90% Depression / suffering 40-60% Prevalence of symptoms in pallia2ve popula2on, Daeninck presenta2on, 2014
3 Why nausea and vomi2ng? Almost everyone experiences nausea Pancrea22s Tumour migraines Hypercalcemia Alcohol use Anaesthesia gastroenteri2s ver2go Head injury Medica2ons hepa22s Cons2pa2on Cachexia GERD labyrinthi2s
4 Objec2ves 1. Review the pathophysiology of nausea & vomi2ng 2. Recognize the underlying cause(s) of nausea & vomi2ng 3. Know the nonpharmacologic and pharmacologic management of nausea & vomi2ng Concentra2on on pallia2ve popula2on
5 Nausea Unpleasant sensa2on of the need to vomit Pallor, sweats, tachycardia, retching A symptom, not a disease One of the most unpleasant symptoms!
6 Vomi2ng Cardiac sphincter relaxes Abdominal muscles and diaphragm contract Larynx closes Lower por2on of stomach contracts Stomach contents expelled through the esophagus and mouth
7 Pathophysiology of Nausea and Vomi2ng Higher cor2cal centres (memory, fear, an2cipa2on, sensory input) Cannabinoid receptors GABA receptor Dopamine type 2 receptor Cannabinoid receptors 5HT4 receptors Image credit: Krakauer, 2005
8 Pathophysiology Centre Causes Neurotransmi7er involved GI tract and other viscera Tumour Bowel obstruc2on Bowel distension Radiotherapy Ischaemia Serotonin (5HT3, 5HT4) Dopamine (D2) Mechanoreceptors
9 Pathophysiology Centre Causes Neurotransmi7er involved Chemoreceptor trigger zone Medica2on - opioids, SSRIs, chemotherapy Toxins - uremia, hypercalcemia, infec2on Dopamine (D2) Serotonin (5HT3) Substance P / Neurokinin 1
10 Pathophysiology Centre Causes Neurotransmi7er involved Ves2bular apparatus Mo2on-induced nausea Ves2bular disease Histamine (H1) Acetylcholine (M)
11 Pathophysiology Centre Causes Neurotransmi7er involved Brain cortex Other brain causes An2cipatory nausea prior to chemotherapy Anxiety, fear Increased ICP GABA receptors Cannabinoid receptors
12 Pathophysiology Centre Causes Neurotransmi7er involved Vomi2ng Centre Receive input from other causes Chemotherapy Acetylcholine (M) Histamine (H1) Serotonin (5HT3) Substance P / Neurokinin 1
13 Common Causes of Nausea Cons2pa2on Gastric dysmo2lity Gastroparesis Autonomic neuropathy Gastric outlet obstruc2on Ileus Malignant bowel obstruc2on
14 Common Causes of Nausea Abdominal involvement / visceral trac2on Omental metastases Peritoneal carcinomatosis Masses Extensive liver involvement
15 Common Causes of Nausea Medica2ons Opioids SSRIs NSAIDs Digoxin
16 Common Causes of Nausea Severe pain Intracranial disease Radia2on, chemotherapy Poor mouth care Ves2bular apparatus s2mula2on Oien mul2-factorial
17 Mechanism-based Approach 1. Thorough evalua2on 2. Determine the underlying cause(s) and neuroreceptors involved 3. Target treatment to the underlying cause(s) and neuroreceptors remember to align with the pa2ent s goals
18 The case of Mr. L 58M pancrea2c cancer, diagnosed 15 months ago, neoadjuvant chemotherapy followed by par2al resec2on 8 months ago pallia2ve chemotherapy 6 months ago chemotherapy stopped Daily nausea, has ondansetron lei over from chemotherapy treatments
19 History 1. Thorough Evalua2on
20 Physical exam 1. Thorough Evalua2on
21 Inves2ga2ons 1. Thorough Evalua2on
22 2. Determine the underlying cause The case of Mr. L scenario 1 No recent opioid changes Abdominal pain stable No bowel movement in ~ 7 days Epigastric mass Liver mets
23 2. Determine the underlying cause The case of Mr. L scenario 2 Abdominal pain increased No BM x 7 days No flatus x 2+ days
24 2. Determine the underlying cause The case of Mr. L scenario 3 No recent opioid changes Abdominal pain stable No bowel movement in ~ 7 days Epigastric mass Moments of confusion
25 Management Nonpharmacologic Avoid cons2pa2on Small meals and snacks Foods that are tolerable Good mouth care Ginger, herbal products (mild effect) Hypnotherapy for an2cipatory nausea
26 Management Pharmacologic general principles Opioid-induced usually self-limited Dexamethasone for brain involvement Aim to use one an2-eme2c at a 2me. Combine for refractory cases Avoid prokine2c + an2cholinergic agents (theore2cally cancel each other out)
27 Management an2-dopamine & prokine2c Drug / Class Receptor Centre / Mechanism Metoclopramide 5HT4 agonist (prokine2c) 5HT3 antagonist (at high doses) Dopamine (D2) antagonist GI tract, except obstruc2on Chemoreceptor trigger zone Higher cor2cal centres Domperidone - crosses BBB to lesser degree 5HT4 agonist (prokine2c) D2 antagonist GI tract, except obstruc2on Monitor EPS Use carefully in pa2ents with parkinsonism
28 Management an2-dopamine Drug / Class Receptor Centre / Mechanism Haldol Methotrimeprazine Olanzapine Dopamine (D2) antagonist (more potent than metoclopramide) Mul2ple (D2, 5HT2, H1, Ach antagonism) Monitor EPS Seda2ng Use carefully in pa2ents with parkinsonism GI tract, good choice for obstruc2on Chemoreceptor Trigger Zone Higher cor2cal centres GI tract Chemoreceptor Trigger Zone Higher cor2cal centres Vomi2ng centre Ves2bular system
29 Management an2-5ht3 Drug / Class Receptor Centre / Mechanism Ondansetron 5HT3 antagonist Chemoreceptor trigger zone GI tract Vomi2ng centre Expensive, cons2pa2ng, QT-prolonging
30 Management an2-histamine Drug / Class Receptor Centre / Mechanism Dimenhydrinate H1 antagonist Ves2bular system Chemoreceptor trigger zone Vomi2ng centre Increased risk of falls in the elderly
31 Management an2-cholinergic Drug / Class Receptor Centre / Mechanism Scopolamine (Hyoscine hydrobromide) Ach muscarinic antagonist Ves2bular system Vomi2ng centre GI tract dries secre2ons Buscopan (Hyoscine butylbromide) Ach muscarinic antagonist Ves2bular system GI tract- dries secre2ons Scopolamine: seda2ng, available in patch Buscopan: no central effect, doesn t cross BBB
32 Management cor2costeroid Drug / Class Receptor Centre / Mechanism Dexamethasone Unclear Brain involvement (good choice for brain mets, increased ICP) Reduces secre2ons (good choice for bowel obstruc2on) High side-effect profile with long-term use
33 Management cannabinoid Drug / Class Receptor Centre / Mechanism Cannabinoids Nabilone (THC) Sa2vex (THC & CBD) Herbals Cannabinoid receptors Higher cor2cal centres Chemoreceptor trigger zone Vomi2ng centre High side effect profile For chemotherapy-induced nausea and vomi2ng or refractory cases
34 Management benzodiazepine Drug / Class Receptor Centre / Mechanism Benzodiazepines Lorazepam GABA receptors Higher cor2cal centres Seda2ng
35 Mechanism-based Approach 1. Thorough evalua2on 2. Determine the underlying cause(s) and neuroreceptors involved 3. Target treatment to the underlying cause(s) and neuroreceptors remember to align with the pa2ent s goals
36 3. Targeted treatment The case of Mr. L scenario 1 No recent opioid changes Abdominal pain stable No bowel movement in ~ 7 days Epigastric mass Liver mets
37 3. Targeted treatment The case of Mr. L scenario 2 Abdominal pain increased No BM x 7 days No flatus x 2+ days
38 3. Targeted treatment The case of Mr. L scenario 3 No recent opioid changes Abdominal pain stable No bowel movement in ~ 7 days Epigastric mass Moments of confusion
39 Objec2ves 1. Review the pathophysiology of nausea & vomi2ng 2. Recognize the underlying cause(s) of nausea & vomi2ng 3. Know the nonpharmacologic and pharmacologic management of nausea & vomi2ng Concentra2on on pallia2ve popula2on
40 Medica2on Summary Suspected Cause Opioid-induced nausea Malignant bowel obstruc2on Chemotherapy and radiotherapy-induced nausea An2cipatory nausea or anxiety-related nausea Mo2on sickness / ves2bular GI / visceral cause Increased ICP Best choices Metoclopramide, domperidone, haloperidol Haloperidol, dimenhydrinate, ondansetron, dexamethasone Ondansetron, cannabinoids, cor2costeroids, metoclopramide Benzodiazepine, hypnotherapy Dimenhydrinate, scopolamine Metoclopramide Dexamethasone
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