Question 2

College Answer

College answer

Define Cachexia 
Weight loss and skeletal muscle wasting due to illness where the body does not reduce catabolism 
(unlike the adaptive reduction in protein metabolism that occurs in starvation)

Predisposing factors 
Mechanisms not clearly understood 
Pre-existing malnutrition / malabsorption. 
Cytokine-induced up-regulation of muscle protein degradation 
Neuro-endocrine – stimulation of hypothalamic-pituitary-adrenal axis 
Reduced circulating anabolic hormones
Immobility and prolonged length of stay 
Corticosteroid therapy 
Malignancy

Consequences
Increased risk of death
Prolonged time on ventilator
Increased ICU and hospital length of stay 
Increased risk of nosocomial infections
Poor wound healing 
Malnutrition and nutritional deficiency syndromes

Discussion

This question asks one to produce a handful of causes for cachexia.

A more recent definition of cachexia is "A syndrome characterised by a loss of body weight and muscle tissue, which occurs in absence of starvation and is not associated with an adaptive decrease in catabolism." This syndrome is briefly discussed in the chapter on cachexia. Moreover, the consequences of malnutrition in the critically ill patient are discussed in detail in yet another chapter.

Oh’s Manual mentions cachexia only once, in the causes of ionized hypocalcemia (pp. 658).

This was disappointing.

There is no widely agreed-upon definition of cachexia (this article told me so). There was a Cachexia Consensus Conference in 2008 during which a new definition was proposed. This definition included only “cachexia proper”, excluding causes such as malnutrition (starvation), malabsorption, and hyperthyroidism. The experts were keen to make the distinction between this weird metabolic syndrome which occurs often in the presence of optimal nutrition, and all other forms of weight loss.

I would go further to separate the college answer into causes and exacerbating factors:

Exacerbating factors:

• Catecholamine excess
• Corticosteroid use
• Immobility
• Hyperthyroidism
• Malabsorption
• Malnutrition

Causes and mechanisms:

• Unclear mechanism; possible combination of the following:
  • Decreased  circulating anabolic hormones (eg. androgens)
  • Increased circulating catabolic cytokines and hormones (eg. cortisol and catecholamines)
  • Pathologically increased nutrient demand by tissues:
    • Aggressively multiplying malignant tissue
    • Increased workload in pathological states, eg. respiratory effort in COPD
  • Pathologically decreased nutrient supply to tissues:
    • Chronically decreased cardiac output in cardiac cachexia
    • Chronic hypoxia in respiratory failure

Consequences of cachexia in ICU patients

These are very similar to the consequences of malnutrition in the critically ill patient, which are discussed in greater detail in a dedicated chapter.

• Poor wound healing
• Impaired immune function and increased risk of sepsis
• Muscle wasting due to protein catabolism:
  • Decreased ventilatory drive
  • Weakness complicating separation from the ventilator
    • Increased duration of ventilation, with associated complications (eg. increased risk of VAP)
  • Weakness complicating physiotherapy and mobilisation
    • Exposure to the complications of immobility, eg. DVT
• Cardiomyopathy as a consequence of atrophy
• Mucosal atropthy and diminished barrier function of the gut
• Apathy and depression
• Increased duration of ICU stay
• Increased in-hospital mortality

Anker SD, Coats AJ. Cardiac cachexia: a syndrome with impaired survival and immune and neuroendocrine activation. Chest. 1999 Mar;115(3):836-47.

Steinborn W, Anker S.D., Cardiac Cachexia: Pathophysiology and Clinical Implications. Basic Appl Myol 13 (4): 191-201, 2003

The experts report that at least in cardiac failure cachexia is a strong independent risk factor for mortality.