Nutritional support in the acute phase of critical illness—how to break the dilemma

Overfeeding caused by the inaccurate estimation of energy might be one of the most important reasons leading to unsatisfactory outcomes of nutritional support, especially for Parental Nutrition (PN). The current method of determining calorie needs by energy expenditure (EE), either measured by indirect calorimetry (IC) or equations, might not accurately represent the actual energy requirements of critically ill patients, especially in the acute phase. Nutrition protocols based on the measurement of time might not be effective. Research on the real-time metabolic status and the actual energy requirements of the patients, as well as more individualized nutrition therapy, is required. Central regulation, especially those involving hypothalamic pathways, is an effective solution for the current dilemma.

Nutrition; Critical illness; Energy requirement; Hypothalamic, Central regulation

[1] Dhaliwal R, Cahill N, Lemieux M, Heyland DK. The Canadian Critical Care Nutrition Guidelines in 2013: an update on current recommendations and implementation strategies. Nutrition in Clinical Practice. 2014; 29: 29–43.

[2] McClave SA, Taylor BE, Martindale RG, Warren MM, Johnson DR, Braunschweig C, et al. Guidelines for the Provision and Assessment of Nutrition Support Therapy in the Adult Critically Ill Patient: Society of Critical Care Medicine (SCCM) and American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.). Journal of Parenteral and Enteral Nutrition. 2016; 40: 159–211.

[3] Reintam Blaser A, Starkopf J, Alhazzani W, Berger MM, Casaer MP, Deane AM, et al. Early enteral nutrition in critically ill patients: ESICM clinical practice guidelines. Intensive Care Medicine. 2017; 43: 380–398.

[4] McClave SA, Sexton LK, Spain DA, Adams JL, Owens NA, Sullins MB, et al. Enteral tube feeding in the intensive care unit: factors impeding adequate delivery. Critical Care Medicine. 1999; 27: 1252–1256.

[5] De Jonghe B, Appere-De-Vechi C, Fournier M, Tran B, Merrer J, Melchior JC, et al. A prospective survey of nutritional support practices in intensive care unit patients: what is prescribed? what is delivered?Critical Care Medicine. 2001; 29: 8–12.

[6] Ziegler TR. Parenteral Nutrition in the Critically Ill Patient. The New England Journal of Medicine. 2009; 361: 1088–1097.

[7] Villet S, Chiolero RL, Bollmann MD, Revelly J, Cayeux RNM, Delarue J, et al. Negative impact of hypocaloric feeding and energy balance on clinical outcome in ICU patients. Clinical Nutrition. 2005; 24: 502–509.

[8] Zaloga GP. Parenteral nutrition in adult inpatients with functioning gastrointestinal tracts: assessment of outcomes. Lancet. 2006; 367: 1101–1111.

[9] Rice TW, Mogan S, Hays MA, Bernard GR, Jensen GL, Wheeler AP. Randomized trial of initial trophic versus full-energy enteral nutrition in mechanically ventilated patients with acute respiratory failure. Critical Care Medicine. 2011; 39: 967–974.

[10] National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network, Rice TW, Wheeler AP, Thompson BT, Steingrub J, Hite RD, et al. Initial trophic vs full enteral feeding in patients with acute lung injury: the EDEN randomized trial. Journal of the American Medical Association. 2012; 307: 795–803.

[11] Arabi YM, Aldawood AS, Haddad SH, Al-Dorzi HM, Tamim HM, Jones G, et al. Permissive underfeeding or standard enteral feeding in critically Ill adults. The New England Journal of Medicine. 2015; 372: 2398–2408.

[12] Wischmeyer PE. Are we creating survivors…or victims in critical care?Delivering targeted nutrition to improve outcomes. Current Opinion in Critical Care. 2016; 22: 279–284.

[13] Zusman O, Theilla M, Cohen J, Kagan I, Bendavid I, Singer P. Resting energy expenditure, calorie and protein consumption in critically ill patients: a retrospective cohort study. Critical Care. 2016; 20: 367.

[14] Hermans G, Casaer MP, Clerckx B, Güiza F, Vanhullebusch T, Derde S, et al. Effect of tolerating macronutrient deficit on the development of intensive-care unit acquired weakness: a subanalysis of the EPaNIC trial. The Lancet Respiratory Medicine. 2013; 1: 621–629.

[15] Reintam Blaser A, Starkopf J, Alhazzani W, Berger MM, Casaer MP, Deane AM, et al. Early enteral nutrition in critically ill patients: ESICM clinical practice guidelines: ESICM clinical practice guidelines. Intensive Care Medicine. 2017; 43: 380–398.

[16] Hoffer LJ. Protein and energy provision in critical illness. The American Journal of Clinical Nutrition. 2003; 78: 906–911.

[17] Monk DN, Plank LD, Franch-Arcas G, Finn PJ, Streat SJ, Hill GL. Sequential changes in the metabolic response in critically injured patients during the first 25 days after blunt trauma. Annals of Surgery. 1996; 223: 395–405.

[18] Uehara M, Plank LD, Hill GL. Components of energy expenditure in patients with severe sepsis and major trauma. Critical Care Medicine. 1999; 27: 1295–1302.

[19] Boulanger BR, Nayman R, McLean RF, Phillips E, Rizoli SB. What are the clinical determinants of early energy expenditure in critically injured adults? The Journal of Trauma. 1994; 37: 969–974.

[20] Zauner A, Schneeweiss B, Kneidinger N, Lindner G, Zauner C. Weight-adjusted resting energy expenditure is not constant in critically ill patients. Intensive Care Medicine. 2006; 32: 428–434.

[21] Magnuson B, Peppard A, Auer Flomenhoft D. Hypocaloric considera-tions in patients with potentially hypometabolic disease States. Nutrition in Clinical Practice. 2011; 26: 253–260.

[22] Stahel PF, Flierl MA, Moore EE. “Metabolic staging” after major trauma-a guide for clinical decision making? Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine. 2010; 18: 34.

[23] Singer P, Blaser AR, Berger MM, Alhazzani W, Calder PC, Casaer MP, et al. ESPEN guideline on clinical nutrition in the intensive care unit. Clinical Nutrition. 2019; 38: 48–79.

[24] Reid C. Frequency of under-and overfeeding in mechanically ventilated ICU patients: causes and possible consequences. Journal of Human Nutrition and Dietetics. 2006; 19: 13–22.

[25] Biolo G, Toigo G, Ciocchi B, Situlin R, Iscra F, Gullo A, et al. Metabolic response to injury and sepsis: changes in protein metabolism. Nutrition. 1997; 13: 52S–57S.

[26] Rennie MJ. Anabolic resistance in critically ill patients. Critical Care Medicine. 2009; 37: S398–S399.

[27] Van de Wiele B, Askanazi J. Energy metabolism in injury and sepsis. IEEE Engineering in Medicine and Biology Magazine. 1986; 5: 25–29.

[28] Fraipont V, Preiser J. Energy estimation and measurement in critically ill patients. Journal of Parenteral and Enteral Nutrition. 2013; 37: 705–713.

[29] Tappy L, Schwarz JM, Schneiter P, Cayeux C, Revelly JP, Fagerquist CK, et al. Effects of isoenergetic glucose-based or lipid-based parenteral nutrition on glucose metabolism, de novo lipogenesis, and respiratory gas exchanges in critically ill patients. Critical Care Medicine. 1998; 26: 860–867.

[30] Casaer MP, Mesotten D, Hermans G, Wouters PJ, Schetz M, Meyfroidt G, et al. Early versus late parenteral nutrition in critically ill adults. The New England Journal of Medicine. 2011; 365: 506–517.

[31] Rabinowitz JD, White E. Autophagy and metabolism. Science. 2010; 330: 1344–1348.

[32] Wischmeyer PE. Tailoring nutrition therapy to illness and recovery. Critical Care. 2017; 21: 316.

[33] Wischmeyer PE, Puthucheary Z, San Millán I, Butz D, Grocott MPW. Muscle mass and physical recovery in ICU: innovations for targeting of nutrition and exercise. Current Opinion in Critical Care. 2017; 23: 269–278.

[34] Bear DE, Wandrag L, Merriweather JL, Connolly B, Hart N, Grocott MPW, et al. The role of nutritional support in the physical and functional recovery of critically ill patients: a narrative review. Critical Care. 2017; 21: 226.

[35] McClave SA, Heyland DK. The physiologic response and associated clinical benefits from provision of early enteral nutrition. Nutrition in Clinical Practice. 2009; 24: 305–315.

[36] Casaer MP, Van den Berghe G. Nutrition in the acute phase of critical illness. The New England Journal of Medicine. 2014; 370: 2450–2451.

[37] Harvey SE, Parrott F, Harrison DA, Bear DE, Segaran E, Beale R, et al. Trial of the route of early nutritional support in critically ill adults. The New England Journal of Medicine. 2014; 371: 1673–1684.

[38] Doig GS, Simpson F, Sweetman EA, Finfer SR, Cooper DJ, Heighes PT, et al. Early parenteral nutrition in critically ill patients with short-term relative contraindications to early enteral nutrition: a randomized controlled trial. Journal of the American Medical Association. 2013; 309: 2130–2138.

[39] Lewis SR, Schofield-Robinson OJ, Alderson P, Smith AF. Enteral versus parenteral nutrition and enteral versus a combination of enteral and parenteral nutrition for adults in the intensive care unit. The Cochrane Database of Systematic Reviews. 2018; 6: CD012276.

[40] Elke G, van Zanten ARH, Lemieux M, McCall M, Jeejeebhoy KN, Kott M, et al. Enteral versus parenteral nutrition in critically ill patients: an updated systematic review and meta-analysis of randomized controlled trials. Critical Care. 2016; 20: 117.

[41] Berger MM, Pichard C. Development and current use of parenteral nutrition in critical care-an opinion paper. Critical Care. 2014; 18: 478.

[42] Vanhorebeek I, Verbruggen S, Casaer MP, Gunst J, Wouters PJ, Hanot J, et al. Effect of early supplemental parenteral nutrition in the paediatric ICU: a preplanned observational study of post-randomisation treatments in the PEPaNIC trial. The Lancet Respiratory Medicine. 2017; 5: 475–483.

[43] Reintam Blaser A, Berger MM. Early or Late Feeding after ICU Admission? Nutrients. 2017; 9: 1278.

[44] Hartman C, Shamir R, Simchowitz V, Lohner S, Cai W, Decsi T, et al. ESPGHAN/ESPEN/ESPR/CSPEN guidelines on pediatric parenteral nutrition: complications. Clinical Nutrition. 2018; 37: 2418–2429.

[45] Preiser J, van Zanten ARH, Berger MM, Biolo G, Casaer MP, Doig GS, et al. Metabolic and nutritional support of critically ill patients: consensus and controversies. Critical Care. 2015; 19: 35.

[46] Singer P, Berger MM, Van den Berghe G, Biolo G, Calder P, Forbes A, et al. ESPEN Guidelines on Parenteral Nutrition: intensive care. Clinical Nutrition. 2009; 28: 387–400.

[47] Singer P, Hiesmayr M, Biolo G, Felbinger TW, Berger MM, Goeters C, et al. Pragmatic approach to nutrition in the ICU: expert opinion regarding which calorie protein target. Clinical Nutrition. 2014; 33: 246–251.

[48] Waterson MJ, Horvath TL. Neuronal regulation of energy homeostasis: beyond the hypothalamus and feeding. Cell Metabolism. 2015; 22: 962–970.

[49] Betley JN, Cao ZF, Ritola KD, Sternson SM. Parallel, redundant circuit organization for homeostatic control of feeding behavior. Cell. 2013; 155: 1337–1350.

[50] Del Prete A, Iadevaia M, Loguercio C. The role of gut hormones in controlling the food intake: what is their role in emerging diseases?Endocrinologia y Nutricion. 2012; 59: 197–206.

[51] Heijboer AC, Pijl H, Van den Hoek AM, Havekes LM, Romijn JA, Corssmit EPM. Gut-Brain axis: regulation of glucose metabolism. Journal of Neuroendocrinology. 2006; 18: 883–894.

[52] Abbott CR, Small CJ, Kennedy AR, Neary NM, Sajedi A, Ghatei MA, et al. Blockade of the neuropeptide Y Y2 receptor with the specific antagonist BIIE0246 attenuates the effect of endogenous and exogenous peptide YY(3–36) on food intake. Brain Research. 2005; 1043: 139–144.

[53] Korner J, Leibel RL. To eat or not to eat-how the gut talks to the brain. The New England Journal of Medicine. 2003; 349: 926–928.

[54] Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR. Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Critical Care Medicine. 2001; 29: 1303–1310.

[55] Bear DE, Puthucheary ZA, Hart N. Early feeding during critical illness. The Lancet Respiratory Medicine. 2014; 2: 15–17.

[56] NICE-SUGAR Study Investigators, Finfer S, Chittock DR, Su SY, Blair D, Foster D, et al. Intensive versus conventional glucose control in critically ill patients. The New England journal of medicine. 2009; 360: 1283–1297.

[57] Zheng Y, Hu FB, Ruiz-Canela M, Clish CB, Dennis C, Salas-Salvado J, et al. Metabolites of glutamate metabolism are associated with incident cardiovascular events in the PREDIMED PREvención con DIeta MEDiterránea (PREDIMED) trial. Journal of the American Heart Association. 2016; 5: e003755.

[58] Duan K, Yu W, Lin Z, Tan S, Bai X, Gao T, et al. Endotoxemia-induced muscle wasting is associated with the change of hypothalamic neuropeptides in rats. Neuropeptides. 2014; 48: 379–386.

[59] Arora S, Anubhuti. Role of neuropeptides in appetite regulation and obesity—a review. Neuropeptides. 2006; 40: 375–401.

[60] Oyama LM, do Nascimento CMO, Carnier J, de Piano A, Tock L, Sanches PDL, et al. The role of anorexigenic and orexigenic neuropeptides and peripheral signals on quartiles of weight loss in obese adolescents. Neuropeptides. 2010; 44: 467–474.

[61] Duan K, Yu W, Lin Z, Tan S, Bai X, Gao T, et al. Insulin ameliorating endotoxaemia-induced muscle wasting is associated with the alteration of hypothalamic neuropeptides and inflammation in rats. Clinical Endocrinology. 2015; 82: 695–703.

[62] Duan K, Chen Q, Cheng M, Zhao C, Lin Z, Tan S, et al. Hypothalamic activation is essential for endotoxemia-induced acute muscle wasting. Scientific Reports. 2016; 6: 38544.

[63] Cao C, Gao T, Cheng Y, Cheng M, Su T, Xi F, et al. Hypothalamic AMPK-induced autophagy ameliorates hypercatabolism in septic rats by regulating POMC expression. Biochemical and Biophysical Research Communications. 2018; 497: 1089–1096.

[64] Cheng M, Gao T, Xi F, Cao C, Chen Y, Zhao C, et al. Dexmedetomidine ameliorates muscle wasting and attenuates the alteration of hypothalamic neuropeptides and inflammation in endotoxemic rats. PLoS ONE. 2017; 12: e0174894.

[65] Cao C, Gao T, Cheng M, Xi F, Zhao C, Yu W. Mild hypothermia ameliorates muscle wasting in septic rats associated with hypothalamic AMPK-induced autophagy and neuropeptides. Biochemical and Biophys-ical Research Communications. 2017; 490: 882–888.

[66] Oshima T, Berger MM, De Waele E, Guttormsen AB, Heidegger C, Hiesmayr M, et al. Indirect calorimetry in nutritional therapy. A position paper by the ICALIC study group. Clinical Nutrition. 2017; 36: 651–662.

[67] Kreymann G, Grosser S, Buggisch P, Gottschall C, Matthaei S, Greten H. Oxygen consumption and resting metabolic rate in sepsis, sepsis syndrome, and septic shock. Critical Care Medicine. 1993; 21: 1012–1019.