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+Nausea and Vomiting Dr Alistair McKeown Consultant in Palliative Medicine Prince and Princess of Wales Hospice and South Glasgow Acute + Overview Aims and Objectives Background Definitions Pathways Patterns, interventions and medications Case Study Summary + Aims and objectives AIM To increase your knowledge and confidence in the causes and treatment of nausea and vomiting in Palliative Care patients OBJECTIVES By the end of the session you will be able to Describe the various patterns of N+V Describe the biochemical and physical pathways involved Consider appropriate investigations/interventions Be aware of antiemetics and their specific receptor activity Select the appropriate first (and second) line antiemetic regime + Why is it important? A common and debilitating symptom Affects up to 70% patients with advanced cancer Many mechanisms, patterns and treatments Usually a single cause Ranked a highly distressing symptom, often more so than pain or breathlessness A good understanding is important to guide best effective treatment + What is nausea? + What is vomiting? + Definitions Nausea: Unpleasant feeling of need to vomit accompanied by autonomic symptoms (pallor, cold sweat, salivation, tachycardia, diarrhoea) Retching: Rhythmic laboured spasmodic movements of the diaphragm & abdo muscles (usually occurs with nausea and results in vomiting – but not always) Vomiting: The forceful propulsion of gastric contents through the mouth Regurgitation: Effortless expulsion of foodstuffs – e.g. oesophageal obstruction + What is it? Primitive defense mechanism against ingested toxins Mediated via Higher centres - sight, smell, taste (learned response) Receptors in upper gut Chemoreceptor trigger zone (floor of 4th ventricle) Vestibular system + What is it (2) Controlled by integrated vomiting centre in medulla Stimulated by input from various pathways Specific neurotransmitters are involved Specific drugs act on specific receptors (More of which later) + Mechanics Autonomic Lack of interest in surroundings, excess salivation, sweating, hyperventilation, tachycardia Somatic Retching Diaphragm contracts against closed glottis sucking gastric contents into lower oesophagus Vomiting Glottis opens, retrograde peristalsis in oesophagus, abdominal muscles contract and contents of stomach expelled + What are the causes on N+V? + Causes Drugs opioids, chemotherapy, digoxin, etc etc etc Especially gut area Biochemical Hypercalcaemia, uraemia Liver failure Gastric stasis Bowel obstruction Upper/lower Constipation Raised intracranial pressure Cerebellar metastases Anxiety, fear, conditioned Radiotherapy + Pathways + + Treating Relies on: Being able to recognise patterns of N&V Identifying likely cause in individual patients Understanding mode of action of commonly used anti-emetics Prescribing most appropriate antiemetic Choosing most appropriate route Negotiating with patient to ensure compliance + Assessment Distinguish between vomiting, expectoration and regurgitation Note contents and volume Assess relationship between nausea and vomiting Record severity Review drug regime (opioids, digoxin etc) Examine mouth, pharynx and abdomen Check plasma urea, creatinine, calcium, albumin, digoxin as appropriate Examine fundi if raised intracranial pressure possible + Asking the right questions Nausea? Retching? Vomiting? When: did it start? Time(s) of day? Constant/not? What: does vomit look like? Amount? Blood? How: did it start? How has it been treated so far? Why: Exacerbating (& relieving) factors + Drugs Drug Receptor Site of action Route Cyclizine H1 VC PO,PR,IM,CSCI Domperidone D CTZ/Stomach PO/PR Metoclopramide D, 5HT4 CTZ, Stomach, Gut PO, PR, IM,CSCI Haloperidol D2 CTZ PO, IM,CSCI Procloperazine D2, Ach/H1 CTZ/VC PO, Buccal, PR, IM Levomepromazine 5HT2, D, Ach/H1 VC/CTZ PO/CSCI Hyoscine Hydrobromide Ach/H1 VC/Gut PO, patch, IM, CSCI Hyoscine Butyl Ach/H1 Gut PO, IM,CSCI Ondansetron 5HT3 Gut, CTZ PO, IM, CSCI Aprepitant NK1 CTZ PO + Other helpful options: Dexamethasone Octreotide Erythromycin Other options Antacids Laxatives Relaxation Sedation Acupuncture + Extra-Pyramidal Side Effects Akathisia Dystonia Tardive Dyskinesia Parkinsonism Tremor Rigidity Bradykinesia Haloperidol, metoclopramide (especially high dose) and levomepromazine can all cause these. + Cautions IV Metoclopramide + IV Ondansetron: Metoclopramide/Domperidone + Cyclizine may cause serious cardiac arrhythmias Metoclopramide/Domperidone are motility agents while Cyclizine slows down GI transit – makes no sense! Metoclopramide (and others) Oculogyric crisis Especially in young women SC route + MHRA warnings + MHRA warnings + MHRA Cont… + MHRA cont + Management Correct the reversible Non-drug treatment Pain, infection, cough, hypercalcaemia, raised ICP, constipation, address fears/anxieties Control malodour e.g from colostomy or fungating wound Fresh air. Good oropharyngeal hygiene. Suitable distractions. Nurse in the upright position. Avoidance of emetogenic smells and foods. Avoidance of situations in which N&V is a conditioned response. Drug treatment – depends on pattern and cause….. + Patterns of N+V Gastric Stasis Chemical or Metabolic Motion Sickness Raised Intra-Cranial Pressure Bowel Obstruction Unknown or Multiple causes + Gastric Stasis Characteristics Epigastric fullness Early satiety Large volume vomits (?projectile) Hiccups Regurgitation (?Minimal) Nausea quickly relieved by vomiting + Gastric Stasis 2 Contributing factors: Stomach emptying problems Compression of gastric outflow (eg Autonomic: eg Diabetes, Gastritis, Peptic Ulcer) (eg Tumour, Hepatomegaly, Ascites) Drug Side-Effects (eg Anti-Cholinergics, Opioids) + Treating Gastric Stasis Reduce volume of oral intake: Little & often Reduce Gastric secretions: PPI (eg Omeprazole, H2 blockers) Can try octreotide – often minimal effect with high obstruction Pro-kinetic agents: Dopamine D2-Antagonists Metoclopramide 10mg QDS Can use higher doses – up to 120mg via CSCI Domperidone (doesn’t cross blood:brain barrier) + Other options NG Tube Venting Gastrostomy + Chemical or metabolic N+V Characteristics: Constant nausea Less or variable vomiting Worsened by sights/smells + Chemical N+V cont Stimulation of CTZ: D2 and 5HT3 receptors Contributing factors: Chemical: Drugs (many: esp Opioids, Antibiotics, Digoxin, NSAIDs, SSRIs, Chemotherapy) Metabolic (eg Renal / Liver failure, Hypercalcaemia of Malignancy, Hyponatraemia, sepsis) + Treating chemical N+V Reverse the reversible Treat hypercalcaemia (if approrpiate) Treat renal failure (if appropriate) Correct biochemical abnormalities (if appropriate) Stop chemotherapy? Dopamine D2-Antagonist: Haloperidol Metoclopramide 5HT3-Antagonist Ondansetron Granisetron + Motion sickness Characteristics: Vomiting on movement Dizziness ?Nystagmus + Motion sickness cont Stimulation of Vestibular System: H1 & ACh receptors Contributing factors: Stimulation of vestibular system Opioids can increase vestibular sensitivity ?Intracerebral cause Brain mets CVA + Motion sickness cont Anti-Histamine and Anti-Cholinergic Agents: Cyclizine Steroids + Raised ICP Characteristics: Symptoms worse in the morning Headache Nausea Vomiting (?projectile) + Raised ICP Cont Anti-Histamine and Anti-Cholinergic Agents: Cyclizine Depends on cause: eg ?SOL: Steroids Radiotherapy Neurosurgery + Bowel Obstruction Symptoms may depend of level of obstruction Partial or complete? Stomach Small bowel similar to gastric stasis partially/undigested foodstuffs Large volume, feels well inbetween Large bowel faeculent vomiting Less frequent? + Bowel obstruction cont Reverse the reversible Constipation Surgery Medications Steroids – reduce oedema, may allow passage If partial – prokinetics (metoclopramide) If complete – levomepromazine or cyclizine/haloperidol Somatostatin analogues – octreotide Hyoscine butylbromide – reduce spasms and secretions May not stop vomiting completely + Bowel obstruction cont NG Venting gastrostomy + Unknown or multiple Levomepromazine – useful and broad spectrum Non-Drug Measures: Address anxiety as a trigger Minimise smells (eg perfume, cooking, fungating tumour) Try cool fizzy drinks (more palatable than hot still drinks) Acupuncture / Acupressure Ginger Hypnotherapy + Other causes Hiatus hernia Gastritis Gastroenteritis Vestibular disturbance Cough Pharyngeal irritation Conditioning/association + Syringe Drivers NOT JUST FOR TERMINAL CARE CSCI of SC meds over 24hrs If vomiting - very useful Home/ NH/ Hospital/ Hospice + Case Study (1) 46 year old woman Localised ovarian malignancy Previously fit and well Some abdominal pain, seeing oncologists, not yet on CTX Complains of nausea and comes to see you Questions? Investigations? Plan? + Case study (2) Your treatment works! Several weeks later, nausea returns Worse Still constant Comes to see you Questions? Investigations? Plan? + Case study (3) Hospital admission reveals bilateral hydronephrosis Extensive intra abdominal disease Ureteric stents and U+Es normal Ongoing CTX Several weeks pass Nausea returns and back to you again: Questions? Investigations? Plan? + Case study (4) Responds to metoclopramide and steroids Deteriorating condition Call from husband Progressive worsening, nausea and vomiting main symptom Colic House call Questions? Investigations? Plan? + Case study (5) Rotation to levomepromazine (or cyclizine/haloperidol) Buscopan/octreotide Declined NG Symptoms improved – still vomiting every 3/7 Ongoing deterioration accepted, nil reversible Died at home + Summary There is a single cause in 66% cases. Optimise non-pharmacological measures. Reverse the reversible. Diagnose a cause before initiating drug treatment. Give the most suitable drug by the most suitable route. When multiple drugs are required, they should have different modes of action. Review at least every 24 hours. + Any Questions?