Anaplerotic Principles of Nutritional Support for Critically Ill Patients
The article presents the modern anaplerotic concepts of nutritional therapy for modulation of metabolic response in critically ill patients. Metabolic stress — a universal hypermetabolic-hypercatabolic response to the disease, injury with activation of the hypothalamic-pituitary-adrenal system; the release of stress hormones; catecholamines; neuropeptide S; hypoxia-inducible factor α; expression of genes controlling mechanisms of adaptation to hypoxia, including glycolysis and the tricarboxylic acid cycle. The article presents a model we have developed to evaluate metabolic stress and mitochondrial dysfunction. Anaplerotic therapy is based on the concept of using alternative substrates both for tricarboxylic acid cycle and for electron transport in the respiratory chain to enhance adenosine triphosphate production. Many pathological conditions require anaplerotic therapy either by replenishing the pool of anaplerotic substrates (pyruvate, aspartate, asparaginate and other sources, adding to oxaloacetate, glutamine and other acids) or removal from tissues the products of kataplerotic reactions — the citric acid cycle intermediates. Cataplerosis balances anaplerosis by moving excessive intermediators of Krebs cycle from the mitochondrial matrix to the cytoplasm, in extramitochondrial space. Modern anaplerotic concepts for modulating metabolic response in critical conditions include the following: I. The early administration of glucose solutions and intensive insulin therapy: minimum amount of carbohydrates of about 2 g/kg glucose/day; insulin introduction, if two consecutive analyses showed glucose level > 10 mmol/l; to avoid mandatory full caloric intake in the first week, starting with 500 kcal/day. II. Prevention of hyperglycemic metabolic stress — metabolic preconditioning: drinking clear fluids to be stopped 2 hours before the induction of anesthesia, the consumption of solid food — 6 hours before. Preoperative administration of carbohydrates is used in all patients without diabetes mellitus 2 hours prior to induction; if there are contraindications — i/v infusion of glucose 2 hours before surgery. III. Using energy substrates that do not require insulin stimulation for their entry into cells: it was found that people, who received < 60 g of fructose daily, had better health indicators than those, who consumed 100 g/day. IV. Amino acids compounds: if parenteral nutrition is indicated, it is advisable to prescribe balanced amino acid mixtures, at a rate of 1.3–1.5 g/kg/day of the protein; L-glutamine 0.2–0.4 g/kg/day. In case of severe burns, injection mode of protein in amino acid mixtures increases to 1.5–2 g/kg/day. V. Replenishing the pool of anaplerotic fatty acids: fatty emulsions (LCT, MCT) should be administered in an amount of 0.7–1.5 g/kg/day; a mixture of soybean and olive oil should be administered enterally, as well as fish oil containing omega-3, -6, -9 fatty acids; dietary anaplerotic therapy with triheptanoin improves the survival rate of critically ill patients. VI. The use of Krebs cycle intermediates: preventive or therapeutic use of succinate-containing drugs can be effective for activation of urgent adaptive mechanisms. Thiamine is an essential vitamin for maintaining aerobic metabolism and the activity of key enzymes of the Krebs cycle, as well as the shuttle mechanism of pentose phosphate cycle.
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