1. Palliative Care: Anorexia & Cachexia Hong-Phuc Tran, M.D.g013

2. Learning Objectives Identify reversible causes of anorexia Learn management of anorexia Explain features of cachexia Understand that cachexia is often caused by same factors that cause anorexia Understand that increased calories, and enteral / parenteral nutrition cannot reverse cachexia

3. Definitions Anorexia: loss of appetite and reduced caloric intake Cachexia: involuntary loss of more than 10% of premorbid weight and loss of muscle, visceral protein and lipolysis Starvation: loss of weight and loss of needed calories

4. Anorexia: Introduction Anorexia is a decrease or loss of appetite Can be a symptom of a terminal disease process, such as cancer & end-stage CHF Prevalence of anorexia is 66% in patients with advanced cancer. Anorexia may occur in isolation or as part of anorexia- cachexia syndrome Management involves evaluating for reversible causes

5. Causes of Anorexia Medication side effects:GI causes ▫Constipation, fecal Impaction ▫Nausea, vomiting ▫GERD, gastritis, gastro paresis ▫Malabsorbtion: Pancreatic ca, diarrhea Dysphagia Depression, anxiety Oral problems: dry mouth, candidiasis, stomatitis, dental pain, ulcers, poorly fitting dentures

6. Metabolic disorders ▫Thyroid problems ▫Diabetes ▫Adrenal insufficiency Altered taste and smell Odors (e.g. certain smells of food) Generalized weakness, lethargy

7. Cachexia: Introduction A wasting syndrome characterized by disproportionate loss of skeletal muscle over fat Primary cause of death in about 20% of all patients with cancer Often occurs concomitantly with anorexia, as it caused by same factors that cause anorexia Multi-factorial etiology not clearly understood, but chronic inflammation is core mechanism Tends to be very distressing for patients & families

8. Some Examples of Causes of Cachexia Cancer AIDS Chronic obstructive pulmonary disease Chronic renal insufficiency Congestive heart failure Cirrhosis Dementia Chronic infections Autoimmune disease

9. Cachexia: Biochemical markers Biochemical markers may be helpful in assessing cachexia – Primary cachexia/anorexia is associated with high CRP, low albumin – Increasing levels of CRP provide a measure of chronic inflammation – Anemia & decreased lymphocyte count often present – In patients with weight loss, normal albumin & normal/slightly elevated CRP raise concerns for other causes of weight loss

10. Dietary habits in dying people Prospective study 151 advanced cancer patients dietary records aprox 7 mo before death ▫Even patients with highest intakes had weight loss ▫Frequency of eating was important in total energy intake ▫Patients preferred typical foods over supplements

11. Anorexia-Cachexia from Cancer Distinct from other secondary causes of anorexia-cachexia – Includes correctable problems, including pain, infection, emotional disorder, obstruction, constipation Not reversible with aggressive feeding / increased calories – Enteral and parenteral nutrition offer no significant benefits & do not improve survival or comfort – Weight loss correlates with cytotoxic effects of & poor tumor response to chemotherapy Often present at diagnosis of certain cancers – Non-small cell lung, upper GI, pancreatic Concomitant presence of anxorexia carries a poorer prognosis

12. Management of Anorexia Identify and treat reversible causes Educate families, caregivers on natural progression of disease Evaluate whether anorexia is bothersome to patient ▫Anorexia may be more bothersome to families & caregivers than to patient Offer favorite foods Smaller, frequent meals and snacks

13. Supplements and Medications Nutritional supplements – Oral protein shakes, protein powders  Take in ADDITION to food not instead of meals – Calorie dense supplement (Benecalorie)  Add to pureed foods, adds calories, no nutrition Appetite stimulants – Megesterol acetate – Marinol – Dexamethasone

14. Megesterol acetate (Megace) Improves appetite and weight gain – Most of weight gain is from fat not lean muscle – Best absorbed when taken with high-fat meal Start with 400mg/day. If appetite not better in 2 weeks, then increase to 600-800mg/day. Takes a few weeks to take effect but longer duration of benefit than steroids Side effects: Increase risk of venous thromboembolism, fluid retention Contradictions: history of DVT, thrombophlebitis Do not discontinue abruptly if used more than 3 weeks (adrenal suppression); taper off slowly

15. Cannabinoids Marinol (tetrahydrocannabinol, THC) improves weight gain and appetite in patients with AIDs & cancer Start with small dose and up titrate to effect and tolerability 7.5mg to 15mg /day Example dosing: Marinol 2.5mg po TID one hour after meals Adverse side effects: anxiety, somnolence, neurotoxicity

16. Corticosteroids Stimulates appetite short-term Dexamethasone preferred over other corticosteroids for appetite stimulation due to its relative lack of mineralocorticoid effect Rapid effect, long half life but effect limited 2-6 weeks Doses of 2-16 mg/day dexamethasone Side effects: fluid retention, increased infection risk, gastritis, insomnia, proximal muscle wasting with prolonged treatment, steroid psychosis Consider 1 week trial – If no improvement, then discontinue – If helps, then reduce to lowest effective dose. – Reassess need frequently; discontinue when no longer effective

17. Other agents Psychotropics- Mirtazapine, atypical antipsychotics – Mirtazapine can increase appetite, but also may cause drowsiness, constipation – Atypical antipsychotics cause weight gain side effect, caution diabetes, blood sugars Fish oil –small study in pancreatic ca patients showed increase in lean body mass Thalidomide 200-400mg/day increased weight in HIV/AIDS cachexia

18. Anorexia/Cachexia from Cancer: Examples of Correctable Causes & Management (1) Emotional disorders – Anxiolytics, antidepressants, counseling for patients & families Eating issues – Dietitian referral, multivitamin, zinc / flavoring food with spices (for disturbed sense of smell or taste) Oral problems – Oral moisturizers, antifungal meds to treat thrush (if present), change meds that may cause dry mouth Swallowing difficulties – Esophageal dilation, antifungal med for thrush (if present)

19. Anorexia/Cachexia from Cancer: Examples of Correctable Causes & Management (2) Stomach issues – GERD- proton pump inhibitors – Gastric stimulants (for early satiety), treat n/v Bowel issues – Treat constipation / obstruction Malabsorption – Pancreatic enzymes Fatigue – anxiolytics, exercise protocol, sleep protocol Motivation issues – methylphenidate, exercise Pain – appropriate analgesics, nerve blocks, counseling

20. Artificial nutrition and Hydration? (ANH) ANH is a medical treatment ▫Some states make it more difficult to withdraw than other life sustaining treatments Patients should have goals discussion of risk benefit regarding long term ANH ▫Insertion of Gtube, NG tube ▫Risk aspiration with decline in condition Unclear benefits for dying patients

21. Summary Don’t focus on appetite and weight – Let patient guide new eating habits – Liberalize dietary restrictions – Maintain muscle function Intervene early in disease – Nutritional supplements – Exercise – Consider medical therapies Address patient and families fears – Identify alternative non food methods of expressing love, caring

22. References & Suggested Readings AMA EPEC (Education for Physicians on End-of-Life Care) at http://www.cancer.gov/cancertopics/cancerlibrary/epeco/selfstudy/module-3/module- 3b-pdf Holms S. A difficult clinical problem: diagnosis, impact and clinical management of cachexia in palliative care. Int J Palliat Nurs. 2009 Jul; 15(7):320, 322-6. Lasheen W, Walsh D. The cancer anorexia-cachexia syndrome: myth or reality? Support Care Cancer. 2010. Feb; 18(2):265-72. doi: 10.1007/s00520-009-0772-6. Loprinzi CL, Laurie JA, Wieand HS, et al. Prospective evaluation of prognostic variables from patient-completed questionnaires. J Clin Oncol. 1994;12:601­607. McGeer AJ, Detsky AS, O'Rourke K. Parenteral nutrition in cancer patients undergoing chemotherapy: A meta-analysis. Nutrition. 1990;6:233. Morrison RS, Meier DE. Clinical Practice: Palliative Care. N Engl J Med. 2004 Jun 17;350(25):2582-90 Nelson K, Walsh D, Deeter P, et al. A phase II study of delta-9-tetrahydrocannabinol for appetite stimulation in cancer-associated anorexia. J Palliat Care. 1994 Spring;10(1):14-8. Ruiz GV, Lopez-Briz E, Carbonell SR et al. Megesterol acetate for treatment of anorexia- cachexia syndrome. Cochrane Database Syst Rev. 2013 Mar 28;3:CD004310. doi: 10.1002/14651858.CD004310.pub3. Shoemaker LK, Estfan B, Induru R, et al. Symptom management: an important part of cancer care. Cleve Clin J Med. 2011 Jan; 78(1):25-34. doi: 10.3949/ccjm.78a.10053.

23. Effective response to caregivers’ fears that loved ones are “starving” to death a.Listen and assess for feelings of guilt b.Ask about cultural and religious values c.Explain physiologic differences between starvation and anorexia-cachexia d.Explain artificial nutrition nor increased oral intake will not likely improve survival or weight gain in end stage disease e.All of the above

24. Answer E

25. Primary anorexia –cachexia differs from starvation in that a.Less protein synthesis occurs in anorexia cachexia due to decreased production of acute phase b.Decreased cortisol levels suggest a chronically altered neuroendocrine state c.Proinflamatory cytokines are commonly involved, causing immune dysfunction

26. Answer C ▫Anorexia cachexia MORE protein synthesis ▫Cortisol levels do not reflect change

27. Mr. K is a 67 year old male with metastatic colon ca, referred to hospice. Family is concerned he had no appetite and continues to lose weight. a.Insert NG tube and start tube feedings b.Reassure the family his weight loss is normal c.Complete a history and physical d.Order nystatin suspension swish and swallow tid

28. Answer C Complete a H and P first to assess any reversible causes for anorexia cachexia Then consider possible treatments