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.
Full Text:PDF (Русский)
Sjövall F., Morota S., Hansson M.J., Friberg H. et al. Temporal increase of platelet mitochondrial respiration is negatively associated with clinical outcome in patients with sepsis // Crit. Care. — 2010. — № 14. — P. 214.
Brunengraber H., Roe C.R. Anaplerotic molecules: current and future // J. Inherit Metab. Dis. — 2006. — № 29(2–3). — P. 327-331.
Gu L., Zhang G.F., Kombu R.S., Allen F. et al. Parenteral and enteral metabolism of anaplerotic triheptanoin in normal rats. II. Effects on lipolysis, glucose production, and liver acyl-CoA profile // American Journal of Physiology-Endocrinology and Metabolism. — 2010. — Vol. 298. — P. 362-371.
Frye R.E., Buehler B. Genetics of Pyruvate Carboxylase Deficiency Treatment and Management // Medscape. — 2012.
Ariza A.C., Deen P.M., Robben J.H. The succinate receptor as a novel therapeutic target for oxidative and metabolic stress-related conditions // Frontiers in Endocrinology. — 2012. — Vol. 3. — P. 22.
Siekmeyer M., Petzold-Quinque S., Terpe F., Beblo S. et al. Citric acid as the last therapeutic approach in an acute life-threatening metabolic decompensation of propionic acidaemia // Journal of Pediatric Endocrinology and Metabolism. — 2013. — Vol. 26, issue 5–6. — P. 569-574.
Dellinger R.P., Levy M.M., Rhodes A., Annane D. et al. Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock: 2012 // Intensive Care Med. — 2012. — Vol. 41, № 1. — P. 580-637.
Nygren J., Thacker J., Carli F., Fearon K.C. et al. Guidelines for perioperative care in elective rectal/pelvic surgery: Enhanced Recovery After Surgery (ERAS) Society recommendations // Clinical Nutrition. — 2012. — Vol. 31. — P. 801-816.
Sievenpiper J.L., Chiavaroli L., de Souza R.J., Mirrahimi A. et al. «Catalytic» doses of fructose may benefit glycaemic control without harming cardiometabolic risk factors: a small meta-analysis of randomised controlled feeding trials // Br. J. Nutr. — 2012. — № 108(3). — P. 418-423.
Cozma A.I., Sievenpiper J.L., de Souza R.J., Chiavaroli L. et al. Effect of fructose on glycemic control in diabetes: a systematic review and meta-analysis of controlled feeding trials // Diabetes Care. — 2012. — № 35. — P. 1611-1620.
Ha V., Jayalath V.H., Cozma A.I., Mirrahimi A. et al. Fructose-containing sugars, blood pressure, and cardiometabolic risk: a critical review // Curr. Hypertens Rep. — 2013. — № 15. — P. 281-297.
Khitan Z., Kim D.H. Fructose: A Key Factor in the Development of Metabolic Syndrome and Hypertension // J. Nutrition and Metabolism. — 2013. — Article ID682673, 12 pages.
Мосенцев М.М. Варіанти гемодинамічної підтримки для модуляції метаболічної відповіді у хворих з тяжким сепсисом та септичним шоком: Автореф. дис… канд. мед. наук. — Дніпропетровськ, 2008. — 24 с.
Wang J.B., Erickson J.W., Fuji R., Ramachandran S. et al. Targeting mitochondrial glutaminase activity inhibits oncogenic transformation // Cancer Cell. — 2010. — Vol. 18, issue 3. — P. 207-219.
Ogihara T., Chuang J.C., Vestermark G.L., Garmey J.C. et al. Liver X-receptor agonists augment human islet function through activation of anaplerotic pathways and glycerolipid/free fatty acid cycling // Journal of Biological Chemistry. — 2010. — Vol. 285. — P. 5392-5404.
Hecker M., Sommer N., Voigtmann H., Pak O. et al. Impact of short- and medium-chain fatty acids on mitochondrial function in severe inflammation // JPEN J. Parenter. Enteral Nutr. — 2013. — Vol. 37. — P. 568-569.
Roe C.R., Mochel F. Anaplerotic diet therapy in inherited metabolic disease: therapeutic potential // J. Inherit Metab Dis. — 2006. — № 29(2–3). — P. 332-340.
Mochel F., Duteil S., Marelli C., Jauffret C. et al. Dietary anaplerotic therapy improves peripheral tissue energy metabolism in patients with Huntington's disease // European Journal of Human Genetics. — 2010. — № 18. — P. 1057-1060.
Donnino M.W., Andersen L.W., Chase M. Randomized, Double-Blind, Placebo-Controlled Trial of Thiamine as a Metabolic Resuscitator in Septic Shock: A Pilot Study // Critical Care Medicine. — 2016. — Vol. 44, issue 2. — P. 360-367.
Copyright (c) 2016 EMERGENCY MEDICINE
This work is licensed under a Creative Commons Attribution 4.0 International License.
© Publishing House Zaslavsky, 1997-2018