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The patients who isn’t eating: Cachexia or Starvation

The patients who isn’t eating: Cachexia or Starvation . Nathan I Cherny Director, Cancer Pain and Palliative Care Service Dept of Cancer Medicine Shaare Zedek Medical Center. Anorexia-cachexia syndrome and starvation: The Problem.

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The patients who isn’t eating: Cachexia or Starvation

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  1. The patients who isn’t eating: Cachexia or Starvation Nathan I ChernyDirector, Cancer Pain and Palliative Care ServiceDept of Cancer MedicineShaare Zedek Medical Center

  2. Anorexia-cachexia syndrome and starvation: The Problem • Both cancer related anorexia-cachexia syndrome and starvation are common problems in the management of advanced cancer.

  3. Definitions

  4. Primary Cachexia-anorexia syndrome • Defining qualities imprecise • Caused by a cascade of cytokines and/or tumor products • generated as products of tumor-host interaction. • Control requires reversal of the aberrant metabolic pattern.

  5. Secondary Anorexia Cachexia • Drug induced • Chronic Nausea • Constipation • Infection • Depression

  6. Starvation Syndromes • Obstruction • Mouth and pharynx • Esophagus • Gastric outlet • Small bowel • Malabsorption

  7. Commonalities • They have a common terminal path • Both lead to profound malnutrition and with all of its physiological social and prognostic implications.

  8. Common Final Pathway Body composition (BMI*, fat, muscle, nutrients) Function (mobility, self care, domestic life) Quality of life (fatigue, dyspnea, ...; wounds, ...) Psycho-social-existential distress(pat., family) # Anorexia/Cachexia (Loprinzi C et al.) * Malnutrition Kondrup J et al. Clin Nutr 2003;22:415-21 Weight loss#* (involuntary, 2% 2 mths or 5% 6 mts) Loss of appetite#(VAS >=3/10 or „a problem“) Nutritional intake#*(<20 kcal/kg or <75% normal)

  9. Differences • The physiology and pathophysiology of these 2 syndromes is very different. •  need for different therapeutic strategies

  10. Physiology

  11. Ed7 Pg P-ACS PIF urine, experimental Cancer „activity“ C-reactive protein >10mg/ml (or IL-6) Brain Anorexia food intake  Muscle Gastric emptying  Gut Cytokine-receptors  Protein degradation  Amino-acid uptake  PIF Acute phase proteins  Metabolism Muscle – Liver Axis (Hypermetabolism) Gut – Brain Axis (Vagus, Hormones) Brain – Muscle Axis (Anabolic hormon.) Resting energy expenditure  Whole body protein & Glucose turnover  Insulin resistance Albumin REE (Calorimetry) Autonomic fct Ghrelin, Leptin Testosterone Liver Understanding Primary Anoexia Cachexia Proteolytic factors Lipolytic factors Proinflammatory Cytokines (IL-6, TNF-a, IFN-y, ..) Metabolic, Neuroendocrine, and Anabolic Abnormalities Dahele M, Fearon KC. Palliat Med 2004;18:409-17 MacDonald N. J Support Oncol. 2003;1:279-86 Strasser F. Oxford Textbook of Palliative Medicine, 3rd Ed. 2003:520-33

  12. Medications Chronic Nausea Stomatitis / Autonomic Failure Primary ACS Xer ostomia / Dysphagia Nausea / Vomiting Symptoms - Dyspnea - Pain - Depression - Delirium Constipation / bowel obstruction Malabsorption Protein loss: fluids, skin Infection / Catabolism Deconditioning/ Sarcopenia Secondary Starvation Strasser F, Bruera E Hemat Onc Clin Nor Am 2002;16:589

  13. Starvation Vs Cachexia Cachexia1. Increased lipolysis2. Increased proteolysis3. Variable resting energy4. Increased liver size5. Increased protein synthesis (acute phase) 6. Increased glucose turnover Starvation 1. Increased lipolysis2. Decreased proteolysis3. Reduced resting energy4. Liver atrophy5. Reduced liver metabolism6. Reduced glucose

  14. Anorexia-Cachexia care

  15. Anorexia care: Behavioral approaches • Increasing frequency of meals/snacks • Diverting attention with social activity, e.g. T.V. • Plan ahead for low energy days and take advantage of ‘best’ mealtimes, e.g. morning • Avoiding cooking smells • Dietetics consultation • Liquid nutritional supplements • Recipe guides

  16. Anorexia: Medication: Glucocorticoids • Dexamethasone 3-6 mg/day or Prednisolone 5 mg 3x/day • effective in 60-80% of patients for 2-3 weeks of treatment • Side effects are common • Indication • A short course • Usually used later in the course of illness when efforts to maintain muscle are no longer paramount

  17. Anorexia: Medication: Progestational agents • Megestrol acetate • 320-480 mg/day x 24 days to establish efficacy. • If appetite increases, then the dose can be reduced • Side effects • mild edema, impotence • rarely, deep vein thrombosis. • Physiological effects • increase body mass (fat, not muscle) • can be catabolic with prolonged use. • Indication • should be reserved for the time when appetite is paramount and muscle function is not.

  18. Anorexia: Medication: Other agents • Dronabinol (Marinol) • is a synthetic cannabinoid • Dose is 2.5 mg 2x/day. • Side effects include dizziness and sedation. • Metoclopramide • can be useful for patients with early satiety due in part to the increase in G.I. transit time. • Dose is 10 mg every 6-8 hours.

  19. Anorexia-cachexia therapy: maintenance of muscle and function (1/2) • Amino acids. • Some trials suggest a net gain of lean body mass. • May have promise in combination therapy. • Omega-3 fatty acids • can help maintain lean body mass • probably secondary to their anti-inflammatory effect. • NSAIDS • modify unhelpful tumour associated inflammation.

  20. Anorexia-cachexia therapy: maintenance of muscle and function (2/2) • Anabolic agents. • can facilitate muscle growth. • Testosterone levels are often reduced • reasonable to identify and treat hypogonadism with physiologic testosterone doses. • Use of higher doses remains a subject for research. • Exercise • Within safe limits patients should be encouraged to engage in mixed aerobic – resistance exercise programmes. • Nutrition Counselling • as part of a team approach including pharmacologic stimuli and exercise guidance.

  21. Starvation sydrome care

  22. Starvation Syndromes • Obstruction • Mouth and pharynx • Esophagus • Gastric outlet • Small bowel • Malabsorption

  23. Options for obstructive starvation syndromes • Overcome obstruction • Local treatments • Stents: esophageal, gastric outlet • Bypass obstruction • Enteral feeding: NGT, Gastrostomy, jejunostomy • Non enteral nutrition • TPN

  24. Considering starvation therapies • Define goals of care • Comfort, survival, function • Review anatomy and options • Site and length of obstruction • Tumor distribution • Ascites • Review potential risks • Aspiration, perforation, sepsis

  25. Minimisng aspiration risk with enteral feeding • Elevating the head of the bed to around 30 degrees • Consider using iso-osmotic feeds • high osmolality feeds delay gastric emptying • Postpyloric feeding tubes • Promotility drugs may reduce the possibility of aspiration in patients most at risk. • Continuous pump feeding during day

  26. TPN • Traditionally “Controversial” • Increasing world wide use for selected patients • Patient selection • good PS patients • irreversible obstruction not amenable to enteral feeding • Prolongation of survival remains a goal of care • Expensive • But provided by Kupot

  27. Home TPN for starvation Mayo Retrospective review of Home-TPN 52 Patients with incurable, advanced cancer, 1979-99 Indication: Bowel obstruction (n=20) Shortbowel-Syndr., Malabsorption (n=16) Fistula (n=11) Dysmotility (n=3) Nausea/vomiting, mucositis (n=2, n=1) Anorexia (n=2) Overall survival: 5 months (1-154) Complications: 18 Infections, 4 Thrombosis, .. Hoda D et al. (Mayo-Group), Cancer 2005;103:863

  28. TPN for patients with starvation TPN indicated: no oral intake (starvation) ► GI- dysfunction or treatment toxicity ► Duration expected: >= (5-) 7 (-10) days ► Prognosis > 40-60 days* TPN pre-operative: ► Pts. with Cachexia ► Pts. with GI-tract malignancies (and others?) *Nitrogen loss critical to survival 33-37%, 8-10 wks Bozzetti F Nutrition 2001;17:67 Am Soc PE Nutr. JPEN 2002;26:SA1-138 Klein S et al. Cancer 1986;58:1378

  29. Complications of TPN • Catheter placement and maintenance • - Pneumothorax (0.1-0.5%) • - Thromboembolism (1-2%) • Infections (3-10%) • Intravenous nutrition (wide range) • Fluid imbalance • Glucose  • Electrolyte imbalance (K, Phosp, Mg) • Hepatic toxicity • Bleeding Cumulative frequency of TPN Complications: 6-15%

  30. Monitor TPN Safety Glucose: First 2 days several times, then daily, weekly Phosphat: First week several times, then weekly Triglycerids, AP, GPT, INR, Hb, WBC, Tc: weekly Catheter: weekly Efficacy Prealbumine (transferrin) weekly, (Nitrogenbalance) Agreed-on goals of TPN at pre-specified time points Burden Multidimensional assessment (no specific-TPN tools)

  31. Conclusions and challenges • Recognize differences in ACS and starvation • Treat causes of secondary ACS • Evaluate treatment options for patients with starvation • Defining goals of care, minimizing risks and determining end points • Thoughtful individualized care of patients with starvation syndromes • Avoiding dogmas

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