The patients who isn

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The patients who isnt eating Cachexia or
Starvation
Nathan I ChernyDirector, Cancer Pain and
Palliative Care ServiceDept of Cancer
MedicineShaare Zedek Medical Center
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Anorexia-cachexia syndrome and starvation The
Problem

• Both cancer related anorexia-cachexia syndrome
  and starvation are common problems in the
  management of advanced cancer.

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Definitions
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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.

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Secondary Anorexia Cachexia

• Drug induced
• Chronic Nausea
• Constipation
• Infection
• Depression

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Starvation Syndromes

• Obstruction
• Mouth and pharynx
• Esophagus
• Gastric outlet
• Small bowel
• Malabsorption

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Commonalities

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

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Common Final Pathway
Weight loss (involuntary, 2 2 mths or 5 6
mts) Loss of appetite (VAS gt3/10 or a
problem) Nutritional intake? (lt20 kcal/kg or
lt75 normal)
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Differences

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

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Physiology
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Ed7 Pg P-ACS
Understanding Primary Anoexia Cachexia
Proinflammatory Cytokines (IL-6, TNF-a, IFN-y, ..)
Proteolytic factors Lipolytic factors
Metabolic, Neuroendocrine, and Anabolic
Abnormalities
Dahele M, Fearon KC. Palliat Med
200418409-17 MacDonald N. J Support Oncol.
20031279-86 Strasser F. Oxford Textbook of
Palliative Medicine, 3rd Ed. 2003520-33
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Secondary
Starvation
Strasser F, Bruera E Hemat Onc Clin Nor Am
200216589
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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

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Anorexia-Cachexia care
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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

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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

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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.

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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.

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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.

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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.

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Starvation sydrome care
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Starvation Syndromes

• Obstruction
• Mouth and pharynx
• Esophagus
• Gastric outlet
• Small bowel
• Malabsorption

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Options for obstructive starvation syndromes

• Overcome obstruction
• Local treatments
• Stents esophageal, gastric outlet
• Bypass obstruction
• Enteral feeding NGT, Gastrostomy, jejunostomy
• Non enteral nutrition
• TPN

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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

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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

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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

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Home TPN for starvation
Mayo Retrospective review of Home-TPN 52
Patients with incurable, advanced cancer, 1979-99
Indication Bowel obstruction (n20) Shortbowel-S
yndr., Malabsorption (n16) Fistula
(n11) Dysmotility (n3) Nausea/vomiting,
mucositis (n2, n1) Anorexia (n2)
Overall survival 5 months (1-154) Complications
18 Infections, 4 Thrombosis, ..
Hoda D et al. (Mayo-Group), Cancer 2005103863
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TPN for patients with starvation
TPN indicated no oral intake (starvation) ? GI-
dysfunction or treatment toxicity ? Duration
expected gt (5-) 7 (-10) days ? Prognosis gt
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 20011767
Am Soc PE Nutr. JPEN 200226SA1-138 Klein S et
al. Cancer 1986581378
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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
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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)
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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