1. Nausea and Vomiting in Palliative Care Elizabeth Whiteman M.D.

2. Goals and Objectives Understand the physiologic causes of nausea and vomiting Competence in assessment of multiple causes of nausea and vomiting Treatment non pharmacologic and pharmacologic Determining the cause and then relating this back to the “emetic pathway” to help prescribing drugs

3. Nausea and Vomiting Nausea is the unpleasant subjective sensation as a result from stimulation in the GI tract the chemoreceptor trigger zone in the brain, the vestibular apparatus and the cerebral cortex. Vomiting is the reflex that comes after stimulation of one or more of these regions Associated with many advanced diseases Can also be a result of therapeutic interventions Thorough assessment of nausea and vomiting is important to understand the cause and treatment options

4. Nausea and Vomiting in Palliative Care  When attempts are made to determine a cause in palliative care patients, either none can be found or else multiple causes are identifiable.  Even if a single cause is identifiable, the neuropharmacology of the pathway is largely redundant, because many antiemetics have a broad spectrum of neurotransmitter-blocking activity and work at multiple sites.  Advances in interventional gastroenterology and radiology are increasing the options for nonpharmacological management

5. Mechanisms CNS comprise the Chemoreceptor trigger zone and the vomiting center The CTZ is near the blood brain barrier The vomiting center receives input from other cranial nerves, higher cortical centers, and GI tract GI tract mirrors the CNS and is dependent on similar neurotransmitters Most disorders will activate both CNS and GI tract.

7. Vomiting Vomiting is caused by noxious stimulation of the vomiting center directly or indirectly via 1 or more of 4 additional sites: gastrointestinal (GI) tract the vestibular system the chemoreceptor trigger zone higher centers in the cortex and thalamus

8. Once receptors are activated, neural pathways lead to the vomiting center, where emesis is initiated. Neural traffic originating in the GI tract travels along afferent fibers of cranial nerves IX (glossopharyngeal) and X (vagal).

9. Mechanisms

10. Emetic Receptors Chemoreceptor trigger zone ▫Antihistamine ▫ D2:prochlorperazine, metochlopramide, haldol, promethazine ▫ 5-HT3:ondanseteron, graniseteron, olanzapine Cerebral Cortex ▫Benzodiazepines, Cannabinoids, Corticosteroids Vestibular ▫Acetylcholinesterase: Scopalamine, Hyoscine ▫ H1: diphenhydramine, meclizine, hydroxizine

11. Vomiting Center ▫Acetecholinesterase, histamine GI ▫5HT3

12. Differential Diagnosis arrange the differential into the four categories which are used for classifying the etiology ▫due to the primary disease ▫due to a side effect of therapy ▫secondary to debilitation, dehydration ▫caused by an unrelated co morbid condition

13. Causes Gastric Stasis ▫Cancer related: carcinomatosis, ascities, paraneoplastic, obstruction, external pressure ▫Treatment related :Drug induced (opioids, etc.) ▫Co morbidities: GERD, Gastritis, gastroparesis Metabolic ▫Electrolytes, metastasis, renal failure, toxins ▫Treatment: chemotherapy ▫Comorbidities: organ failure, infection, drugs CNS: increased ICP, Brain mets, vestibular

14. Assessment History ▫Quality, Duration, persistent or intermittent, intensity, pain, aggravating factors ▫Drug history Physical Exam ▫Bowel sounds, distention, organomegaly, masses, rectal exam ▫Other signs illness: Renal failure, sepsis, neurologic changes Studies ▫Labs: electrolytes, renal function, hepatic failure, sepsis ▫Radiology: abdominal series, CT, MRI etc

15. Case 1 Mrs. R is a 60 year old female with ovarian cancer and peritoneal carcinomatosis. She has been treated with chemotherapy. Her last dose was 2 weeks ago. She is on a duragesic patch 75mcg q72 hr and prn dilaudid 2-4 mg q4hr prn. She has regular BM every 3 days. She is now complaining of new achy abdominal pain and nausea.

16. What is the problem? Multiple Assess for constipation ▫ narcotics, dehydration Recent Chemotherapy ▫Side effect chemo, dehydration Hx Peritoneal Carcinomatosis ▫Possible obstruction, mets local or distant Likely a combination of problems contributing to her symptoms

17. Treatments Non Pharmacologic ▫Treat other symptoms (pain, short of breath, constipation, anxiety) ▫Avoid foods that are not pleasing to patient ▫Relaxation and breathing, swallowing techniques ▫Loose, unrestrictive clothing ▫Avoid lying flat 2 hours after eating ▫Encourage more frequent, small meals ▫Acupuncture or acupressure

18. Treatment Pharmacologic ▫Gastrointestinal stimulation Diphenhydramine, antispasmotics, prokinetic agents ▫Vestibular Metoclopramide, scopalamine, meclizine ▫Cerebral cortex (increased pressure) Steroids, neuroleptics ▫Chemoreceptor trigger zone (drug toxins, disease) Evaluate causative agents (chemo, opioids) Dopamine agonists, serotonin antagonists, anticholinergic drugs.

19. Dopamenergic · haloperidol · prochlorperazine · droperidol · promethazine · trimethobenzamide · metoclopramide

20. Histamine Antagonists ▫ diphenhydramine ▫meclizine ▫hydroxyzine Anticholinergics ▫Scopolamine  1–3 transdermal patches q 72 h or  IV or SC infusion

21. Serotonin Antagonist ▫ ondansetron ▫ granisetron Prokinetic agents ▫metoclopramide ▫Cisapride (available for compassionate use only)

22. Antacids and cytoprotective antacids H2 receptor antagonists (cimetidine, famotidine, ranitidine) proton pump inhibitors (omeprazole, lansoprazole Misoprostol carafate

23. Other agents dexamethasone tetrahydrocannabinol lorazepam atypical antipsychotics: olanzapine

24. Case 2 JR is a 43 year old male with metastatic renal ca. He is admitted with persistent vomiting for 4 days and dehydration. A NG tube was placed and there is copious amounts of bile colored fluid. On Exam he is distended, tender to palpation and has high pitched bowel sounds. An Abdominal series shows dilated loops of small bowel

25. NG helps but when clamped he gets more nausea and vomiting. He is unable to tolerate anything by mouth. He is on ATC iv antiemetics. He is started on TPN and his chemo is on HOLD, pending control of his Vomiting and ability to take food. What is the next step?

26. What next? CT abdomen ▫Shows partial small bowel obstruction with thickening of bowel and distended loops. ▫Large L kidney mass impinging on ureter with hydronephrosis and multiple mets in liver and abdomen.

27. Bowel Obstruction octreotide 100 mcg SQ q 8hr, for 48 hr trial Glucocorticoids: decrease inflammation, tumor bulk Stents, Venting ostomies Prokinetics (partial obstruction) Anticholinergics (help colicy pain) Palliative surgery: Bypass, debulking Remember to treat pain! Opioids Continue to treat nausea- antiemetics

28. Nausea and vomiting Can cause significant physical and psychological distress in patients Evaluate for drug -drug interactions Avoid use of aniemetics that antagonize the same receptor, increased side effect risk Try and assess cause of symptoms and use combination of treatments focused on each patient

29. References Glare P, Miller J, Nikova T, Tickoo R, Treating nausea and vomiting in palliative care: a review, Clin Interv Aging. 2011; 6: 243–259. Published online 2011 September 12. Emanuel LL, von Gunten CF, Ferris FD. Common Physical Symptoms, The Education or Physicians on End-of-life Care (EPEC) curriculum, Module 10, 1999. Rousseau P, Management of Malignant Bowel Obstruction in Advanced Cancer: A Brief Review, Journal of Palliative Medicine, Vol 1, Nov 1, 1998.