Successive Phases of the Metabolic Response to Stress

  • Jean-Charles PreiserEmail author
  • Carole Ichai
  • A. B. Johan Groeneveld


The metabolic response to stress have been selected as an adaptive response to survive critical illness. Several mechanisms well preserved over the evolution, including the stimulation of the sympathetic nervous system, the release of pituitary hormones, a peripheral resistance to the effects of these and other anabolic factors are triggered to increase the provision of energy substrates to the vital tissues. After an acute insult, alternative substrates are used as a result of the loss of control of energy substrate utilization. The clinical consequences of the metabolic response to stress include sequential changes in energy expenditure, stress hyperglycemia, changes in body composition, psychological and behavioral problems. The loss of muscle proteins and function is a major long-term consequence of stress metabolism. Specific therapeutic interventions, including hormone supplementation, enhanced protein intake and early mobilization are investigated.


Critical Illness Lean Body Mass Metabolic Response Protein Breakdown Preganglionic Neuron 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Preiser JC, Ichai C, Orban JC, Groeneveld ABJ (2014) Metabolic response to the stress of critical illness. Br J Anaesth 113:945–954CrossRefPubMedGoogle Scholar
  2. 2.
    Van den Berghe G, de Zegher F, Bouillon R (1998) Clinical review 95: acute and prolonged critical illness as different neuroendocrine paradigms. J Clin Endocrinol Metab 83:1827–1834PubMedGoogle Scholar
  3. 3.
    Hamill RW, Woolf PD, McDonald JV, Lee LA, Kelly M (1987) Catecholamines predict outcome in traumatic brain injury. Ann Neurol 21:438–443CrossRefPubMedGoogle Scholar
  4. 4.
    Boonen E, Vervenne H, Meersseman P, Andrew R, Mortier L, Declercq PE, Vanwijngaerden YM, Spriet I, Wouters PJ, Vander Perre S, Langouche L, Vanhorebeek I, Walker BR, Van den Berghe G (2013) Reduced cortisol metabolism during critical illness. N Engl J Med 368:1477–1488CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Koch A, Gressner OA, Sanson E, Tacke F, Trautwein C (2009) Serum resistin levels in critically ill patients are associated with inflammation, organ dysfunction and metabolism and may predict survival of non-septic patients. Crit Care 13:R95CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Marques MB, Langouche L (2013) Endocrine, metabolic, and morphologic alterations of adipose tissue during critical illness. Crit Care Med 41:317–325CrossRefPubMedGoogle Scholar
  7. 7.
    Hillenbrand A, Weiss M, Knippschild U, Wolf AM, Huber-Lang M (2012) Sepsis-induced adipokine change with regard to insulin resistance. Int J Inflam 2012:972368CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Fantuzzi G (2009) Adiponectin and inflammation. Am J Physiol Endocrinol Metab 296(2), E397CrossRefPubMedGoogle Scholar
  9. 9.
    Deane A, Chapman MJ, Fraser RJL, Horowitz M (2010) Bench-to-bedside review: the gut as an endocrine organ in the critically ill. Crit Care 14:228CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Nematy M, O’Flynn JE, Wandrag L, Brynes AE, Brett SJ, Patterson M, Ghatei MA, Bloom SR, Frost GS (2006) Changes in appetite related gut hormones in intensive care unit patients: a pilot cohort study. Crit Care 10:R10CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Nematy M, Brynes AE, Hornick PI, Patterson M, Ghatei MA, Bloom SR, Brett SJ, Frost GS (2007) Postprandial ghrelin suppression is exaggerated following major surgery; implications for nutritional recovery. Nutr Metab (Lond) 4:20CrossRefGoogle Scholar
  12. 12.
    Losser MR, Damoisel C, Payen D (2010) Bench-to-bedside review: glucose and stress conditions in the intensive care unit. Crit Care 14:231CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Plank LD, Hill GL (2000) Sequential metabolic changes following induction of systemic inflammatory response in patients with severe sepsis or major blunt trauma. World J Surg 24:630–638CrossRefPubMedGoogle Scholar
  14. 14.
    Lena D, Kalfon P, Preiser JC, Ichai C (2011) Glycemic control in the intensive care unit and during the postoperative period. Anesthesiology 114:438–444CrossRefPubMedGoogle Scholar
  15. 15.
    Biolo G, Grimble G, Preiser JC, Leverve X, Jolliet P, Planas M, Roth E, Wernerman J, Pichard C, European Society of Intensive Care Medicine Working Group on Nutrition and Metabolism (2002) Position paper of the ESICM Working Group on Nutrition and Metabolism. Metabolic basis of nutrition in intensive care unit patients: ten critical questions. Intensive Care Med 28:1512–1520CrossRefPubMedGoogle Scholar
  16. 16.
    Soeters MR, Soeters PB (2012) The evolutionary benefit of insulin resistance. Clin Nutr 31:1002–1007CrossRefPubMedGoogle Scholar
  17. 17.
    Marik PE, Bellomo R (2013) Stress hyperglycemia: an essential survival response! Crit Care 17:305CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Dungan KM, Braithwaite SS, Preiser JC (2009) Stress hyperglycaemia. Lancet 373:1798–1807CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Singer M, De Santis V, Vitale D, Jeffcoate W (2004) Multiorgan failure is an adaptive, endocrine-mediated metabolic response to overwhelming systemic inflammation. Lancet 364:545–548CrossRefPubMedGoogle Scholar
  20. 20.
    Desborough JP (2000) The stress response to trauma and surgery. Br J Anaesth 85:109–117CrossRefPubMedGoogle Scholar
  21. 21.
    Siegel JH, Cerra FB, Coleman B, Giovannini I, Shetye M, Border JR, McMenamy RH (1979) Physiological and metabolic correlations in human sepsis. Surgery 86:163–193PubMedGoogle Scholar
  22. 22.
    Wilmore DW (2000) Metabolic response to severe surgical stress: overview. World J Surg 24:705–711CrossRefPubMedGoogle Scholar
  23. 23.
    Kyle UG, Jolliet P, Genton L, Meier CA, Mensi N, Graf JD, Chevrolet JC, Pichard C (2005) Clinical evaluation of hormonal stress state in medical ICU patients: a prospective blinded observational study. Intensive Care Med 31:1669–1675CrossRefPubMedGoogle Scholar
  24. 24.
    Donatelli F, Corbella D, Di Nicola M, Carli F, Lorini L, Fumagalli R, Biolo G (2011) Preoperative insulin resistance and the impact of feeding on postoperative protein balance: a stable isotope study. J Clin Endocrinol Metab 896:E1789–E1797CrossRefGoogle Scholar
  25. 25.
    Hoffer LJ, Bistrian BR (2013) Why critically ill patients are protein depleted. J Parenter Enteral Nutr 37(3):300–309CrossRefGoogle Scholar
  26. 26.
    Magnuson B, Peppard A, Auer Flomenhoft D (2011) Hypocaloric considerations in patients with potentially hypometabolic disease States. Nutr Clin Pract 26:253–260CrossRefPubMedGoogle Scholar
  27. 27.
    McClave SA, Martindale RG, Kiraly L (2013) The use of indirect calorimetry in the intensive care unit. Curr Opin Clin Nutr Metab Care 16:202–208CrossRefPubMedGoogle Scholar
  28. 28.
    Siirala W, Olkkola KT, Noponen T, Vuori A, Aantaa R (2010) Predictive equations over-estimate the resting energy expenditure in amyotrophic lateral sclerosis patients who are dependent on invasive ventilation support. Nutr Metab (Lond) 7:70CrossRefGoogle Scholar
  29. 29.
    Kreymann G, Grosser S, Buggisch P, Gottschall C, Matthaei S, Greten H (1993) Oxygen consumption and resting metabolic rate in sepsis, sepsis syndrome, and septic shock. Crit Care Med 21:1012–1019CrossRefPubMedGoogle Scholar
  30. 30.
    Uehara M, Plank LD, Hill GL (1999) Components of energy expenditure in patients with severe sepsis and major trauma: a basis for clinical care. Crit Care Med 27:1295–1302CrossRefPubMedGoogle Scholar
  31. 31.
    Vincent JL, Preiser JC (2013) When should we add parenteral to enteral nutrition? Lancet 381:354–355CrossRefPubMedGoogle Scholar
  32. 32.
    Heidegger CP, Berger MM, Graf S, Zingg W, Darmon P, Costanza MC, Thibault R, Pichard C (2013) Optimisation of energy provision with supplemental parenteral nutrition in critically ill patients: a randomised controlled clinical trial. Lancet 381:385–393CrossRefPubMedGoogle Scholar
  33. 33.
    Casaer MP, Mesotten D, Hermans G, Wouters PJ, Schetz M, Meyfroidt G, Van Cromphaut S, Ingels C, Meersseman P, Muller J, Vlasselaers D, Debaveye Y, Desmet L, Dubois J, Van Assche A, Vanderheyden S, Wilmer A, Van den Berghe G (2011) Early versus late parenteral nutrition in critically ill adults. N Engl J Med 365:506–517CrossRefPubMedGoogle Scholar
  34. 34.
    Schetz M, Casaer MP, Van den Berghe G (2013) Does artificial nutrition improve outcome of critical illness? Crit Care 17:302CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Tappy L, Schwarz JM, Schneiter P, Cayeux C, Revelly JP, Fagerquist CK, Jéquier E, Chioléro R (1998) Effects of isoenergetic glucose-based or lipid-based parenteral nutrition on glucose metabolism, de novo lipogenesis, and respiratory gas exchanges in critically ill patients. Crit Care Med 26:860–867CrossRefPubMedGoogle Scholar
  36. 36.
    Watford M (2005) Is the small intestine a gluconeogenic organ. Nutr Rev 63:356–360CrossRefPubMedGoogle Scholar
  37. 37.
    Battezzati A, Caumo A, Martino F et al (2004) Nonhepatic glucose production in humans. Am J Physiol Endocrinol Metab 286:E129–E135CrossRefPubMedGoogle Scholar
  38. 38.
    Shangraw RE, Jahoor F, Wolfe RR, Lang CH (1996) Pyruvate dehydrogenase inactivity is not responsible for sepsis-induced insulin resistance. Crit Care Med 24:566–574CrossRefPubMedGoogle Scholar
  39. 39.
    Burgstad CM, Besanko LK, Deane AM, Nguyen NQ, Saadat-Gilani K, Davidson G, Burt E, Thomas A, Holloway RH, Chapman MJ, Fraser RJ (2013) Sucrose malabsorption and impaired mucosal integrity in enterally fed critically ill patients: a prospective cohort observational study. Crit Care Med 41:1221–1228CrossRefPubMedGoogle Scholar
  40. 40.
    Orban JC, Leverve X, Ichai C (2011) Lactate: métabolisme et physiopathologie. In: Ichai C, Quintard H, Orban JC (eds) Désordres métaboliques et réanimation : de la,physiopathologie au traitement. Springer, Paris, pp 181–198CrossRefGoogle Scholar
  41. 41.
    Van Hall G, Stromstadt M, Rasmussen P et al (2004) Blood lactate is an important source of energy for the human brain. J Cereb Blood Flow Metab 29:1121–1129CrossRefGoogle Scholar
  42. 42.
    Leverve XM (1999) Energy metabolism in critically ill patients: lactate is a major oxidizable substrate. Curr Opin Clin Nutr Metab Care 2:165–169CrossRefPubMedGoogle Scholar
  43. 43.
    Ichai C, Armando G, Orban JC, Berthier F, Rami L, Samat-Long C, Grimaud D, Leverve X (2009) Sodium lactate versus mannitol in the treatment of intracranial hypertensive episodes in severe traumatic brain-injured patients. Intensive Care Med 35(3):471–479CrossRefPubMedGoogle Scholar
  44. 44.
    Stanley WC, Recchia FA, Lopasschuk GD (2005) Myocardial substrate metabolism in the normal and failing heart. Physiol Rev 85:1093–1129CrossRefPubMedGoogle Scholar
  45. 45.
    Levy B, Gibot S, Franck P, Cravoisy A, Bollaert PE (2005) Relation between muscle Na + K+ ATPase activity and raised lactate concentrations in septic shock: a prospective study. Lancet 365:871–875CrossRefPubMedGoogle Scholar
  46. 46.
    Krinsley JS, Egi M, Kiss A, Devendra AN, Schuetz P, Maurer PM, Schultz MJ, van Hooijdonk RT, Kiyoshi M, Mackenzie IM, Annane D, Stow P, Nasraway SA, Holewinski S, Holzinger U, Preiser JC, Vincent JL, Bellomo R (2013) Diabetic status and the relation of the three domains of glycemic control to mortality in critically ill patients: an international multicenter cohort study. Crit Care 17:R37CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Falciglia M, Freyberg RW, Almenoff PL, D’Alessio DA, Render ML (2009) Hyperglycemia-related mortality in critically ill patients varies with admission diagnosis. Crit Care Med 37:3001–3009CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Herridge MS, Tansey CM, Matte A et al (2011) Functional disability 5 years after acute respiratory distress syndrome. N Engl J Med 364:1293–1304CrossRefPubMedGoogle Scholar
  49. 49.
    Hill GL (1992) Jonathan E. Rhoads Lecture. Body composition research: implications for the practice of clinical nutrition. JPEN J Parenter Enteral Nutr 16:197–218CrossRefPubMedGoogle Scholar
  50. 50.
    Lecker SH (2006) Protein degradation by the ubiquitin-proteasome pathway in normal and disease states. J Am Soc Nephrol 17:1807–1819CrossRefPubMedGoogle Scholar
  51. 51.
    Mitch WE, Goldberg AL (1996) Mechanisms of muscle wasting. The role of the ubiquitin-proteasome pathway. N Engl J Med 335:1897–1905CrossRefPubMedGoogle Scholar
  52. 52.
    Hill NE, Murphy KG, Singer M (2012) Ghrelin, appetite and critical illness. Curr Opin Crit Care 18:199–205CrossRefPubMedGoogle Scholar
  53. 53.
    Langouche L, Perre SV, Thiessen S, Gunst J, Hermans G, D’Hoore A, Kola B, Korbonits M, Van den Berghe G (2010) Alterations in adipose tissue during critical illness: an adaptive and protective response? Am J Respir Crit Care Med 2010(182):507–516CrossRefGoogle Scholar
  54. 54.
    Broomhead LR, Brett SJ (2002) Clinical review: intensive care follow-up – what has it told us? Crit Care 6:411–417CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Ligtenberg JJ, Girbes AR, Beentjes JA, Tulleken JE, Van der Werf TS, Zijlstra JG (2001) Hormones in the critically ill patients: to intervene or not to intervene ? Intensive Care Med 27:1567–1577CrossRefPubMedGoogle Scholar
  56. 56.
    Takala J, Ruokonen E, Webster NR et al (1999) Increased mortality associated with growth hormone treatment in critically ill adults. N Engl J Med 341:785–792CrossRefPubMedGoogle Scholar
  57. 57.
    Ruokonen E, Takala J (2002) Dangers of growth hormone therapy in critically ill patients. Curr Opin Clin Nutr Metab Care 5:199–209CrossRefPubMedGoogle Scholar
  58. 58.
    Voerman HJ, Strack van Schijndel RJM, Groeneveld ABJ, de Boer H, Nauta JJP, van der Veen EA, Thijs LG (1992) Effects of recombinant human growth hormone in patients with severe sepsis. Ann Surg 216:648–655CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Schulman RC, Mechanick JI (2012) Metabolic and nutrition support in the chronic critical illness syndrome. Respir Care 57:958–978CrossRefPubMedGoogle Scholar
  60. 60.
    Ichai C, Preiser JC, Société Française d’Anesthésie-Réanimation; Société de Réanimation de langue Française; Experts group (2010) International recommendations for glucose control in adult non diabetic critically ill patients. Crit Care 14:R166PubMedPubMedCentralGoogle Scholar
  61. 61.
    Groeneveld ABJ, Beishuizen A, Visser FC (2002) Insulin: a wonder drug in the critically ill? Crit Care 6:102–105CrossRefGoogle Scholar
  62. 62.
    Whyte MB, Jackson NC, Shojaee-Moradie F, Treacher DF, Beale RJ, Jones RH, Umpleby AM (2010) Metabolic effects of intensive insulin therapy in critically ill patients. Am J Physiol Endocrinol Metab 298:E697–E705CrossRefPubMedGoogle Scholar
  63. 63.
    Maggio M, Nicolini F, Cattabiani C, Beghi C, Gherli T, Schwartz RS, Valenti G, Ceda GP (2012) Effects of testosterone supplementation on clinical and rehabilitative outcomes in older men undergoing on-pump CABG. Contemp Clin Trials 33:730–738CrossRefPubMedGoogle Scholar
  64. 64.
    Heyland D, Muscedere J, Wischmeyer PE, Cook D, Jones G, Albert M, Elke G, Berger MM, Day AG, for the Canadian Critical Care Trials Group (2013) A randomized trial of glutamine and antioxidants in critically ill patients. N Engl J Med 368:489–497Google Scholar
  65. 65.
    Kelemen JJ, Cioffie WG, Mason AD, Mozingo DW, McManus WF, Pruitt BA (1996) Effects of ambient temperature on metabolic rate after thermal injury. Ann Surg 223:406–412CrossRefPubMedPubMedCentralGoogle Scholar
  66. 66.
    De Montmolin E, Aboab J, Mansart A, Annane D (2009) Bench-to-bedside review: ß-adrenergic modulation in sepsis. Crit Care 13:230CrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  • Jean-Charles Preiser
    • 1
    Email author
  • Carole Ichai
    • 2
  • A. B. Johan Groeneveld
    • 3
  1. 1.Department of Intensive CareErasme University Hospital, Free University of BrusselsBrusselsBelgium
  2. 2.Department of Anesthesiology and Intensive CareHôpital Saint-Roch, University of NiceNiceFrance
  3. 3.Department of Intensive CareErasmus Medical CenterRotterdamThe Netherlands

Personalised recommendations