Critically ill patients are in a catabolic state, characterized by three major metabolic
changes. First, there is an increased protein turnover with enhanced hepatic protein
synthesis and muscle protein breakdown. Second, during critical illness there is
increased lipolysis, or the breakdown of triglycerides to free fatty acids (FFA) and glycerol.
And third, insulin resistance causes hyperglycemia due to ongoing endogenous
glucose production (glycogenolysis and gluconeogenesis) and blunted peripheral
uptake. These metabolic derangements are caused by various endogenous and exogenous
triggers, including increased inflammatory cytokines (Tumor Necrosis Factor
α, interleukin-1, interleukin-6, and interleukin-8), catecholamines and glucocorticoids,
all in which insulin resistance plays a central role.This response to injury is universal
and has been beneficial all through evolution at the acute onset of severe disease or
trauma. However, modern medicine has improved survival rate and critical illness has
bec

Verbruggen, S.C.A.T. (Sascha)

Verbruggen, S.C.A.T.

EUR Research Repository

English

Protein, energy and their interaction in critically ill children

Critically ill patients are in a catabolic state, characterized by three major metabolic
changes. First, there is an increased protein turnover with enhanced hepatic protein
synthesis and muscle protein breakdown. Second, during critical illness there is
increased lipolysis, or the breakdown of triglycerides to free fatty acids (FFA) and glycerol.
And third, insulin resistance causes hyperglycemia due to ongoing endogenous
glucose production (glycogenolysis and gluconeogenesis) and blunted peripheral
uptake. These metabolic derangements are caused by various endogenous and exogenous
triggers, including increased inflammatory cytokines (Tumor Necrosis Factor
α, interleukin-1, interleukin-6, and interleukin-8), catecholamines and glucocorticoids,
all in which insulin resistance plays a central role.This response to injury is universal
and has been beneficial all through evolution at the acute onset of severe disease or
trauma. However, modern medicine has improved survival rate and critical illness has
become a process which lasts not just mere hours but can last for days or even weeks.
Early last century Sir David P. Cuthbertson described the short initial hypometabolic
“ebb” phase, followed by the prolonged hypermetabolic “flow” phase during adult
critical illness. Persistent glucose overload and breakdown of skeletal muscle and
adipose tissue releasing large amounts of amino acids and FFA are the result. Unfortunately,
although plasma substrate levels may be increased, their availability to
peripheral tissues may be blunted (because of factors such as insulin resistance and
inhibition of lipoprotein lipase), while plasma levels of other substrates (e.g. specific
amino acids, cholesterol) may be insufficient to meet metabolic demands. As a
result, these metabolic changes, beneficial in the initial phase from a teleological viewpoint,
become detrimental during prolonged critical illness

Erasmus University Digital Repository

Stellingen behorend bij het proefschrift‘Protein, Energy and Their Interaction in Critically lll Children’1. Hyperglycemic critically ill newborn infants can effectively be treated according to a ‘tight glucose control protocol’, but require additional safety approaches. (dit proefschrift)2. Acute stress’ induced hyperglycemia in post-surgical infants can safely be prevented by a reduced glucose intake. (dit proefschrift)3. The splanchnic uptake and utilization of the essential amino acid methionine differs with age in critically ill children. (dit proefschrift)4. Both the quantity and quality of parenteral amino acid intakes currently provided to critically ill children of all age groups are inadequate. (dit proefschrift)5. Insulin should not be used to induce anabolism in insulin resistant critically ill adolescents. (dit proefschrift)6. From an evolutionary point of view, the ‘non-essential’ amino acids are in fact those which are truly essential.7. The introduction of the ‘journal of negative results’ emphasizes the underestima-tion of the importance of ‘lack of effect’ by other journals, which leads to an unrepresentative image of the truth.8. The argument ‘planet earth is incapable to feed its growing population’ should not be used to explain the unacceptable high incidence of malnutrition (http://www.fao.org), while at the same time the incidence of overweight and obesity are even higher (http://www.who.int/dietphysicalactivity/publications/facts/obesity).9. Efficient glucose and energy metabolism allow for nature’s most impressive migrations. (PLoS Biology 2010;8(5);e10000362, J Experimental Biology 2010;213(17);3062-3073)10. Stimulating Sinterklaas’ popularity instead of Santa Claus’ popularity in the Netherlands might be a valuable strategy to help prevent pediatric obesity. (BMJ 2009;339:1424-26, J Pediatr Health Care 1996;10:243-44)11. Het nut van stellingen als proeve van bekwaamheid bij een proefschrift stammen uit de tijd waarin de mens nog maar vier smaken dacht te proeven.‘A life without travel is like reading a book without turning a page.’(Augustinus, 354 – 430 AD)I wish you all a nice journeySascha Verbruggen, 22 December 2010

Protein, Energy and Their Interaction in Critically Ill Children

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