Nausea & Vomiting. Managing a common symptom without becoming sick to your stomach. Amanda Sommerfeldt, MD Medical Director, Hospice Southland

Transcription

1 Nausea & Vomiting Managing a common symptom without becoming sick to your stomach Amanda Sommerfeldt, MD Medical Director, Hospice Southland

2 Objectives 1. Learn the NAUSEA acronym to guide assessment of patients with nausea 2. Learn the VOMIT acronym to identify common causes of vomiting 3. Understand the importance of matching the treatment of nausea and vomiting to the cause of nausea and vomiting 4. Discuss various medications used to palliate nausea and vomiting

3 Disclosures I have no relevant conflicts of interest to disclose I am from the U.S. and I talk and spell like an American. If I say something that doesn t make sense, please stop me and ask for clarification Evidence for use of antiemetic medications in palliative care is limited some of the drugs discussed are used off label Image courtesy of

4 Terminology Nausea Unpleasant sensation Vaguely referred to epigastrium and abdomen With a tendency to vomit (Dorland s Medical Dictionary) From the Greek word naus ( ship ) Reference to seasickness experienced by sailors Nausia (Greek) or Nausea (Latin) Vomit Eject stomach contents through the mouth (Dorland s Medical Dictionary) From the Latin vomere, meaning spew forth or discharge Medical term for vomitus is emesis, from the Greek emein

5 What s so bad about N&V? Reduced quality of life Uncomfortable or distressing to patient Upsetting to family and friends Takes away enjoyment of meals Can contribute to weight loss and malnutrition May be symptoms of serious underlying problem(s) It s common 70-85% of pregnant women Up to 2% with hyperemesis gravidarum % who receive total body irradiation Most prevalent with abdominal, pelvic, or mantle 40-60% with advanced malignancy Present in up to 55% in last 4 weeks of life 16-68% of palliative care patients

6 KEY POINT Nausea and vomiting are symptoms of a diagnosis. They are not the diagnosis.

7 Why are nausea and vomiting difficult to treat? Symptoms may not be reported Seen as normal or expected by patients with cancer Seen as untreatable or part of life Failure to identify and target the cause Medications Unrecognized pregnancy Constipation Brain tumour Wrong anti-emetic medication Failure to match the treatment to the cause Using multiple medications with similar mechanisms of action Failure to recognize the cause can change over time Patient with cancer who had chemo in the past but now has N&V from constipation

8 Inadequate dose Why are nausea and vomiting difficult to treat? Medication not given often enough Fail to increase dose when appropriate Inappropriate route Oral medication + Vomiting patient = Rectal medication + Frequent Diarrhoea =

9 1. Assess the patient History Physical exam Successful management of N&V 2. If possible, identify the cause of the nausea/vomiting 3. Direct treatment toward the cause Fix the cause (if feasible) Medications Non-pharmacologic measures 4. Reassess

10 Step 1 - Assessment Remember N A U S E - A

11 Assessment of N&V Nausea history and intensity Ordinal scale (like 0-10) Description of symptoms Duration of symptoms Aggravating factors what makes it worse? Food, eating / not eating, drinking, medications, movement, time of day quality of life How upsetting is this? Symptoms associated with N&V Dizziness, fatigue, anxiety, depression, sweating, pain, constipation, diarrhoea, fever, weight loss Episodes of vomiting per 24 hour period Alleviating factors what makes it better? Distraction, food, vomiting, medications

12 Examining the patient with N&V Appearance and vital signs How does the patient look? Pale Jaundiced Acutely ill Fever to suggest infection Tachycardia Hypotensive May be bradycardic and hypotensive while vomiting Skin and mucous membranes Hyper salivation Sweating Skin tenting, dry mouth with dehydration Abdominal exam Tenderness Distension Masses Bowel sounds Rectal exam Depends on patient s prognosis and goals of care Constipation Bleeding Mass

13 Step 2 Identify the cause(s) Remember V O M I - T

14 N&V The Major Players 1. GI tract 2. Vestibular apparatus Part of inner ear responsible for sensing motion and body position 3. Chemoreceptor Trigger Zone (CTZ) Area postrema on the floor of the 4 th ventricle Located in the dorsal medulla (brainstem) Loose blood-brain barrier Chemicals in the bloodstream and CSF can affect the CTZ 4. Cerebral cortex Nausea stimulated or suppressed by taste, sight, smell, emotion, and memory

15 Receptors Involved in N&V GI tract 5-HT3, also M1, H1, NK1 CTZ D2, 5-HT3, also M1, H1, NK1 Vestibular apparatus H1, M1 Emetic Centre M1 Cerebral cortex Emetic Centre in the nucleus tractus solitarius in medulla

16 KEY POINT When the emetic centre is signalled by the GI tract, vestibular apparatus, CTZ, and/or cerebral cortex, vomiting is triggered

17 V - Vestibular Motion sickness Benign paroxysmal positional vertigo Meniere s disease Tumour Inner ear infections or inflammation (labrynthitis) Visual cues spinning, tilting Stimulation of inner ear or direct visual stimulus Release of ACh, histamine Stimulation of vestibular nuclei in the brainstem Activation of the Emetic Centre

18 Constipation Ileus Partial or complete bowel obstruction Think of a clogged water pipe O Obstruction of bowel Blocked intestinal flow Dilation of bowel before the blockage and decompression of bowel past the blockage Bowel lumen pressure rises, bowel wall edema, fluid secretion, peristalsis Release of ACh, histamine, +/- serotonin Activation of the Emetic Centre

19 M Motility disorders in upper GI tract Diabetes mellitus Neurologic disorders Motor neurone disease Parkinson s Stroke Medications TCAs Opioids Lithium Nicotine CCBs Clonidine some chemotherapy drugs Scleroderma Small cell lung cancer Acute gastroenteritis Acid reflux disease Hypo/hyperthyroidism AIDS Psychiatric disorders Rumination syndrome

20 M Motility disorders in upper GI tract Medical condition, medication, or injury to vagus nerve Interruption of electrical and/or mechanical processes that regulate stomach contractions Release of dopamine, serotonin, histamine, ACh, +/- substance P Activation of the CTZ then the Emetic Centre, or direct activation of the Emetic Centre

21 I Infection / Inflammation Bacterial toxins Viral infections Meningitis Encephalitis Brain tumour Concussion Stroke Infection or Inflammation Release of dopamine, serotonin, NE, enkephalins, GABA, +/- substance P Activation of the CTZ Activation of the Emetic Centre

22 T - Toxins Metabolic disorders Diabetic ketoacidosis Uraemia Hypoxemia Hypercalcemia Oestrogen release of pregnancy Nicotine Medications Carbidopa/Levodopa Oestrogens Opioids D2 mediated Chemotherapies Digoxin General anaesthetics Ergot alkaloids Toxin Release of dopamine +/- serotonin Activation of the CTZ Activation of the Emetic Centre

23 Step 3 Direct the treatment toward the cause Fix when possible. Palliate when a fix is impossible or not feasible

24 General management principles Treat the cause when possible Benefits/burdens of laxative regimen Senna stimulates the myenteric plexus in the GI tract Docusate without senna is mush without push Two birds, one stone May need more than one medication Avoid using multiple medications with similar mechanisms of action Limited data to support efficacy of meds used Case reports Small studies usually with cancer patients, and usually receiving chemo

25 Medication Classes Anticholinergics (block acetylcholine) Antidopaminergics (block dopamine) 5-HT3 antagonists (block serotonin) Antihistamines (block histamine) Substance P antagonists (particularly NK-1) Other Corticosteroids Cannabinoids Benzodiazepines

26 Mechanism Anticholinergics Block acetylcholine (ACh) at muscarinic (M1) receptors Drugs Hyoscine HBr SC, IM, IV, TD Meclozine hydrochloride - PO (NS) Also acts as an antihistamine Uses Vestibular N&V (room spinning, inner ear problems) Patients who also have secretions Renal or biliary colic Side effects / Risks Blind as a bat, mad as a hatter, dry as a bone, red as a beet Tachycardia, urinary retention, dizziness

27 Mechanism Block dopamine at D2 receptors Drugs 3 classes Uses Antidopaminergics N&V due to opioids, electrolyte imbalances, migraine, CTZ activation, or unknown cause Patients who also have agitation, delirium, or psychosis Metoclopramide specifically if upper GI motility disorders

28 1. Phenothiazines Classes of dopamine blockers Levomepromazine (Nozinan) PO, injection, infusion Trifluoperazine HCl (Stelazine) PO Chlorpromazine PO, IM, IV Prochlorperazine PO and buccal tabs, PR, IM 2. Butyrophenones Haloperidol (Haldol) PO tabs or drops, injection, slow infusion Droperidol (Droleptan) injectable (NS) Domperidone (Motilium (NS), Prokinex (S)) - PO

29 3. Substituted benzamide Metoclopramide PO, IM, IV 4. Atypical antipsychotics Classes of dopamine blockers Also block 5-HT2A receptors (sleep, mood, fewer extrapyramidal symptoms, weight gain) Block H1 receptors (sleep, weight gain, appetite) Block α1 and α2 adrenergic receptors (salivation, improved urine flow) May block other dopaminergic and 5-HT1A receptors as well Drugs Olanzapine PO, ODT, IM Quetiapine - PO Risperidone PO, ODT

30 Common side effects Risks and side effects antidopaminergics Sedation, dizziness, dry mouth Haloperidol is less sedating Rare and more serious side effects Extrapyramidal symptoms tremor, disordered movement, rigidity Tardive dyskinesia repetitive, involuntary movements like lip smacking QT prolongation / torsades de pointes Blood dyscrasias Weight gain, hyperglycemia (especially atypicals) DVT/PE Elevated prolactin (atypicals)

31 Contraindications to using dopamine blockers Parkinson s disease and related conditions Increased risk of dopamine depletion leading to tardive dyskinesia or EPS Low dose quetiapine may be a consideration if necessary Movement disorders Caution if prolonged QT, heart disease, history of arrhythmia or seizure, dementia, elderly

32 5-HT3 antagonists Mechanism Block serotonin at 5-HT3 receptors Drugs Ondansetron PO, ODT, injection Tropisetron injection Granisetron - PO Uses Most data for acute or delayed chemotherapy induced N&V Prevent post-operative emesis Emesis related to radiation therapy Side effects / Risks Headache, flushing, dizziness, itching, urinary retention, constipation, diarrhoea Elevated LFTs Rare EPS Rare QT prolongation

33 Mechanism Antihistamines Block histamine at H1 receptors Many also block acetylcholine (anticholinergic) Drugs Promethazine (Phenergan) PO, IM, caution if IV, PR Diphenhydramine PO, (injection) Why not use a newer antihistamine like loratadine, fexofenadine, or cetirizine? Uses Vestibular N&V Patients who also have nasal allergies, congestion, respiratory infections, or insomnia Side effects / Risks Sedation, blurred vision, dizziness, dry mouth, urinary retention, confusion (especially elderly) Extravasation (IV > IM)

34 Mechanism Block Substance P at NK-1 receptors Emerging therapy Drugs Aprepitant (Emend) PO ($100 for 3 tabs) Uses Substance P antagonists Used with serotonin blockers and dexamethasone to prevent delayed N&V from chemotherapy Prevent post-operative N&V Side effects / Risks Headache, GI upset, elevated LFTs, dizziness, hiccup, asthenia

35 Mechanism Other anti-emetics - Corticosteroids Not well understood. May prevent release of arachidonic acid Drugs Dexamethasone PO, injection, infusion Methylprednisolone PO, injection Uses Nausea due to inflammation, chemotherapy, or unknown cause Patients with concomitant anorexia, fatigue, lethargy Side Effects / Risks Oedema, insomnia, agitation, psychosis, adrenal insufficiency, GI upset, headache, elevated blood sugar, infections, muscle weakness, osteoporosis, avascular necrosis, hypokalaemia, possible bleeding

36 Mechanism Other anti-emetics - Cannabinoids Affect cannabinoid receptors near the Emetic Centre Drugs Natural cannabis and synthetic cannabinoids - illegal Dronabinol (Marinol) in U.S. expensive, limited benefit Nabiximols (Sativex) used only for spasticity due to MS Uses Limited utility Better tolerated and seems more efficacious in younger patients, those who previously benefited from marijuana Side effects / Risks Sedation, dizziness, agitation, hallucinations, seizures

37 Mechanism Other anti-emetics - Benzodiazepines Enhance effects of GABA by binding to benzodiazepine receptors in the brain Drugs Lorazepam PO Alprazolam PO Diazepam PO, injection, PR Midazolam PO, injection, infusion, PR, intranasal, SL Uses Limited Anticipatory or vestibular N&V Associated anxiety, insomnia, seizures, or spasm Side effects / Risks Sedation, dry mouth, dizziness, paradoxical agitation Dependence, abuse

38 What if I have no idea what is causing the nausea or vomiting? Safety Efficacy Simplicity - Cost effectiveness

39 Non-pharmacologic measures Mainly anecdotal evidence Ask and educate What do you think this means? What are your expectations? It is not normal to stop moving bowels when oral intake is poor Diet Small, more frequent meals Low-fat and low residue diets if early satiety or delayed gastric emptying Avoid strong or noxious odours Keep mouth moist and clean Progressive relaxation and guided imagery may help prevent CINV Hypnosis Patient needs to be able to concentrate May reduce nausea, vomiting, anxiety, and early satiety Music Systematic desensitization Distraction

40 Conclusions 1. Nausea and vomiting are common symptoms associated with a variety of medical conditions 2. N&V can adversely affect quality of life in a number of ways 3. The NAUSEA acronym is a tool that can aid in assessment of nausea/vomiting 4. The VOMIT acronym can be used to quickly recall common causes of N&V 5. Management is most likely to succeed when the treatment is matched to the cause

41 References / Resources 1. Aamir T. New Zealand doctors should be allowed to prescribe cannabis for pain No. Journal of Primary Health Care, 7(2): June Abrahm JL and Fowler B. Chapter 169: Nausea, vomiting, and early satiety. Palliative Medicine. Declan Walsh, Ed. P Saunders Bruera E, Belzile M, Neumann C, Harsanyi Z, Babul N, Darke A. A double-blind, crossover study of controlled release metoclopramide and placebo for the chronic nausea and dyspepsia of advanced cancer. J of Pain and Symptom Management, 19(6): June, Camilleri M. Pathogenesis of delayed gastric emptying. UpToDate. Most recent update 7/18/ Critchley P, Plach N, Grantham M, Marshall D, Taniguchi A, Latimer E, Jadad AR. Efficacy of Haloperidol in the treatment of nausea and vomiting in the palliative patient: a systematic review. J of Pain and Symptom Management, 22(2): Aug, Davis MP and Hallerberg G. A systematic review of the treatment of nausea and/or vomiting in cancer unrelated to chemotherapy or radiation. J of Pain and Symptom Management, 39(4): April, Drug Foundation Evidence Review on Medicinal Cannabis. New Zealand Drug Foundation. DF Feb Accessed 14/03/16. dicinal%20cannabis,%20february% pdf 8. Fisch MJ and Kim HF. Use of atypical antipsychotic agents for symptom control in patients with advanced cancer. Supportive Oncology, 2(5): Sept/Oct Hain TC. Emesis. Most recent update 10/21/ Hallenbeck J. Fast Fact #5: The causes of nausea and vomiting (VOMIT), 2 nd Ed. Re-edited 3/ Hallenbeck JL. Chapter 5: Non-pain symptom management: Nausea and vomiting: Overview. Palliative Care Perspectives. Oxford University Press, Inc Hardy JR, O Shea A, White C, Gilshenan K, Welch L, Douglas C. The efficacy of Haloperidol in the management of nausea and vomiting in patients with cancer. J of Pain and Symptom Management, 40(1): July, 2010.

42 References / Resources 13. LeGrand SB and Walsh D. Scopolamine for cancer-related nausea and vomiting. J of Pain and Symptom Management, 40(1): July, Longstreth GF and Hesketh PJ. Characteristics of anti-emetic drugs. UpToDate. Most recent update 4/18/ Kuver R, Sheffield JV, McDonald GB. Nausea and vomiting in adolescents and adults. University of WA School of Medicine CME. Accessed 8/12/ MacKintosh D. Olanzapine in the management of difficult to control nausea and vomiting in a palliative care population: a case series. Journal of Palliative Medicine, 19(1): Jan MacLeod R, Vella-Brincat J, Macleod S. The Palliative Care Handbook: guidelines for clinical management and symptom control. 6 th edition MIMS New Ethicals. Issue 23. Jul-Dec 15. Copyright 2015 MIMS New Zealand. 19. Pan CX, Morrison S, Ness J, Fugh-Berman A, Leipzig RM. Complementary and alternative medicine in the management of pain, dyspnea, and nausea and vomiting near the end of life: a systematic review. J of Pain and Symptom Management, 20(5): Nov Weissman DE. Fast Fact #25: Opioids and nausea, 2 nd Ed. Re-edited 3/ Idiopathic gastroparesis. Johns Hopkins Medicine Gastroenterology and Hepatology website. Accessed 8/15/ A3900F1D&GDL_Disease_ID=DBFA1F C3-A6E0-8A0BEDD710AD 22. Word etymology courtesy of the Online Medical Dictionary. Accessed 8/15/ Medical definitions courtesy of Dorland s Online Medical Dictionary via TheFreeDictionary by Farlex. Accessed 8/15/11.

43 THANK YOU! Questions? Comments? Concerns? Amanda Sommerfeldt