Considerations in Organ Failure

  • Carlos Ortiz-LeybaEmail author


Recent advances about multiple-organ failure have highlighted several aspects of its diagnosis and management. However, broad areas remain undiscovered. The classic differentiation into two hits has been challenged with the discovery of mixed gene responses and prolonged clinical outcomes, leading to a new proposed concept, the persistent inflammation-immunosuppression catabolism syndrome (PICS). The incidence ranges between 15 and 40 % and associated mortality is six- to eightfold higher than patients without organ dysfunction. Current scoring systems are valid but are not useful for prognosis, as all of them lack specificity and sensibility for selected populations. Single organ dysfunction criteria has been revisited and revised: Berlin ARDS criteria, AKIN classification, and gastrointestinal failure. Physiopathology research has specially focused on gene involvement, neural regulation, and mitochondrial damage as future targets for innovative therapies. A search for early biomarkers is underway with limited results, and traditional nutritional support guidelines have been challenged.


Acute Lung Injury Acute Respiratory Distress Syndrome Migration Inhibitory Factor Sequential Organ Failure Assessment Disseminate Intravascular Coagulation 
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.
    Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal S, et al. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock, 2012. Intensive Care Med. 2013;39(2):165–228.PubMedGoogle Scholar
  2. 2.
    Eiseman B, Beart R, Norton L. Multiple organ failure. Surg Gynecol Obstet. 1977;144:323–6.PubMedGoogle Scholar
  3. 3.
    Singer M, De Santis V, Vitale D, Jeffcoate W. Multiorgan failure is an adaptive, endocrine-mediated, metabolic response to overwhelming systemic inflammation. Lancet. 2004;364(9433): 545–8.PubMedGoogle Scholar
  4. 4.
    Moore FA, Sauaia A, Moore EE, Haenel JB, Burch JM, Lezotte DC. Postinjury multiple organ failure: a bimodal phenomenon. J Trauma. 1996;40:501–10.PubMedGoogle Scholar
  5. 5.
    Marshall JC, Christou NV, Meakins JL. The gastrointestinal tract. The “undrained abscess” of multiple organ failure. Ann Surg. 1993;218(2):111–9.PubMedCentralPubMedGoogle Scholar
  6. 6.
    Minei JP, Cuschieri J, Sperry J, Moore EE, West MA, Harbrecht BG, et al. The changing pattern and implications of multiple organ failure after blunt injury with hemorrhagic shock. Crit Care Med. 2012;40(4):1129–35.PubMedCentralPubMedGoogle Scholar
  7. 7.
    Brattstrom O, Granath F, Rossi P, Oldner A. Early predictors of morbidity and mortality in trauma patients treated in the intensive care unit. Acta Anaesthesiol Scand. 2010;54:1007–17.PubMedGoogle Scholar
  8. 8.
    Sauaia A, Moore FA, Moore EE, Moser KS, Brennan R, Read RA, et al. Epidemiology of trauma deaths: a reassessment. J Trauma. 1995;38(2):185–93.PubMedGoogle Scholar
  9. 9.
    Dewar DC, Tarrant SM, King KL, Balogh ZJ. Changes in the epidemiology and prediction of multiple-organ failure after injury. J Trauma Acute Care Surg. 2013;74(3):774–9.PubMedGoogle Scholar
  10. 10.
    Ciesla DJ, Moore EE, Johnson JL, Burch JM, Cothren CC, Sauaia A. A 12-year prospective study of postinjury multiple organ failure: has anything changed? Arch Surg. 2005;140(5):432–8.PubMedGoogle Scholar
  11. 11.
    Kallinen O, Maisniemi K, Böhling T, Tukiainen E, Koljonen V. Multiple organ failure as a cause of death in patients with severe burns. J Burn Care Res. 2012;33(2):206–11.PubMedGoogle Scholar
  12. 12.
    Cabré L, Mancebo J, Solsona JF, Saura P, Gich I, Blanch L, et al. Multicenter study of the multiple organ dysfunction syndrome in intensive care units: the usefulness of Sequential Organ Failure Assessment scores in decision making. Intensive Care Med. 2005;31:927–33.PubMedGoogle Scholar
  13. 13.
    Ulvik A, Kvale R, Wentzel-Larsen T, Flaatten H. Multiple organ failure after trauma affects even long-term survival and functional status. Crit Care. 2007;11(5):1–8.Google Scholar
  14. 14.
    Knaus WA, Draper EA, Wagner DP, Zimmerman JE. Prognosis in acute organ-system failure. Ann Surg. 1985;202(6):685–93.PubMedCentralPubMedGoogle Scholar
  15. 15.
    Zimmerman JE, Knaus WA, Sun X, Wagner DP. Severity stratification and outcome prediction for multisystem organ failure and dysfunction. World J Surg. 1996;20(4):401–5.PubMedGoogle Scholar
  16. 16.
    Hortigüela-Martín VA, Sanchez-Casado M, Rodríguez-Villar S, Quintana-Díaz M, Marco-Schulke C, Gómez-Tello V, et al. Post-Intensive Care Unit mortality and related prognostic factors in a cohort of critically ill patients with multi-organ dysfunction. Med Clin. 2013;140(11):479–86.Google Scholar
  17. 17.
    Lone NI, Walsh TS. Impact of intensive care unit organ failures on mortality during the five years after a critical illness. Am J Respir Crit Care Med. 2012;186(7):640–7.PubMedGoogle Scholar
  18. 18.
    Le Gall JR, Klar J, Lemeshow S, Saulnier F, Alberti C, Artigas A, Teres D. ICU Scoring Group. The logistic organ dysfunction system: a new way to assess organ dysfunction in the intensive care unit. JAMA. 1996;276:802–10.PubMedGoogle Scholar
  19. 19.
    Vincent JL, Moreno R, Takala J, Willatts S, de Mendonça A, Bruining H, et al. The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. Intensive Care Med. 1996;22:707–10.PubMedGoogle Scholar
  20. 20.
    Cook R, Cook D, Tilley J, Lee KA, Marshall J. Multiple organ dysfunction: baseline and serial component scores. Crit Care Med. 2001;29(11): 2046–50.PubMedGoogle Scholar
  21. 21.
    Giannoni C, Chelazzi C, Villa G, Raffaele De Gaudio A. Organ dysfunction scores in ICU. Trends Anaesth Crit Care. 2013;3(3):89–96.Google Scholar
  22. 22.
    Lorente JA, Vallejo A, Galeiras R, Tómicic V, Zamora J, Cerdá E, et al. Organ dysfunction as estimated by the sequential organ failure assessment score is related to outcome in critically ill burn patients. Shock. 2009;31(2):125–31.PubMedGoogle Scholar
  23. 23.
    Vincent JL, De Mendonça A, Cantraine F, Moreno R, Takala J, Suter PM, et al. Use of the SOFA score to assess the incidence of organ dysfunction/failure in intensive care units: results of a multicenter, prospective study. Crit Care Med. 1998;26(11): 1793–800.PubMedGoogle Scholar
  24. 24.
    Sauaia A, Moore EE, Johnson JL, Ciesla DJ, Biffl WL, Banerjee A. Validation of postinjury multiple organ failure scores. Shock. 2009;31(5):438–47.PubMedGoogle Scholar
  25. 25.
    Peres-Bota D, Melot C, Ferreira FL, Ba VN, Vincent JL. The multiple organ dysfunction score (MODS) versus the sequential organ failure assessment (SOFA) score in outcome prediction. Intensive Care Med. 2002;28(11):1619–24.PubMedGoogle Scholar
  26. 26.
    Zygun D, Berthiaume L, Laupland K, Kortbeek J, Doig C. SOFA is superior to MOD score for the determination of non-neurologic organ dysfunction in patients with severe traumatic brain injury: a cohort study. Crit Care. 2006;10(4):R115.PubMedCentralPubMedGoogle Scholar
  27. 27.
    Vincent JL, Moreno R. Scoring systems in the critically ill. Crit Care. 2010;14:207–15.PubMedCentralPubMedGoogle Scholar
  28. 28.
    Hoste EAJ, Clermont G, Kersten A, Venkataraman R, Angus DC, De Bacquer D, et al. RIFLE criteria for acute kidney injury are associated with hospital mortality in critically ill patients: a cohort analysis. Crit Care. 2006;10(3):1–10.Google Scholar
  29. 29.
    Molitoris BA, Levin A, Warnock DG, Joannidis M, Mehta RL, Kellum JA, et al. Improving outcomes of acute kidney injury: report of an initiative. Nat Clin Pract Nephrol. 2007;3(8):439–42.PubMedGoogle Scholar
  30. 30.
    Child CG. Surgery and portal hypertension. In: Child CG, editor. The liver and portal hypertension. Philadelphia, PA: WB Saunders; 1964. p. 50–72.Google Scholar
  31. 31.
    Pugh RN, Murray-Lyon IM, Dawson JL, Pietroni MC, Williams R. Transection of the oesophagus for bleeding oesophageal varices. Br J Surg. 1973;60:646–9.PubMedGoogle Scholar
  32. 32.
    ARDS Definition Task Force. Acute respiratory distress syndrome. JAMA. 2012;307(23):2526–33.Google Scholar
  33. 33.
    Chen GY, Nuñez G. Sterile inflammation: sensing and reacting to damage. Nat Rev Immunol. 2010;10(12):826–37.PubMedCentralPubMedGoogle Scholar
  34. 34.
    Andersson U, Tracey KJ. HMGB1 is a therapeutic target for sterile inflammation and infection. Annu Rev Immunol. 2011;29:139–62.PubMedGoogle Scholar
  35. 35.
    Calandra T, Roger T. Macrophage migration inhibitory factor: a regulator of innate immunity. Nat Rev Immunol. 2003;3(10):791–800.PubMedGoogle Scholar
  36. 36.
    Gao L, Flores C, Fan-Ma S, Miller EJ, Moitra J, Moreno L, et al. Macrophage migration inhibitory factor in acute lung injury: expression, biomarker, and associations. Transl Res. 2007;150(1):18–29.PubMedCentralPubMedGoogle Scholar
  37. 37.
    Donnelly SC, Bucala R, Metz CN, Grant IS, Robertson CR, Haslett C. Macrophage migration inhibitory factor and acute lung injury. Chest. 1999;116 Suppl 1:111S.PubMedGoogle Scholar
  38. 38.
    Rittirsch D, Redl H, Huber-Lang M. Role of complement in multiorgan failure. Clin Dev Immunol. 2012;2012:962927.PubMedCentralPubMedGoogle Scholar
  39. 39.
    Rittirsch D, Flierl MA, Nadeau BA, Day DE, Huber-Lang M, Mackay CR, et al. Functional roles for C5a receptors in sepsis. Nat Med. 2008;14(5):551–7.PubMedCentralPubMedGoogle Scholar
  40. 40.
    Silasi-Mansat R, Zhu H, Popescu NI, Peer G, Sfyroera G, Magotti P, et al. Complement inhibition decreases the procoagulant response and confers organ protection in a baboon model of Escherichia coli sepsis. Blood. 2010;116(6):1002–10.PubMedCentralPubMedGoogle Scholar
  41. 41.
    Rosas-Ballina M, Tracey KJ. The neurology of the immune system: neural reflexes regulate immunity. Neuron. 2009;64(1):28–32.PubMedGoogle Scholar
  42. 42.
    Tracey KJ. Reflex control of immunity. Nature. 2002;420:853–9.PubMedGoogle Scholar
  43. 43.
    Doerschug KC, Delsing AS, Schmidt GA, Haynes WG. Impairments in microvascular reactivity are related to organ failure in human sepsis. Am J Physiol Heart Circ Physiol. 2007;293(2):H1065–71.PubMedGoogle Scholar
  44. 44.
    Shapiro NI, Yano K, Okada H, Fischer C, Howell M, Spokes KC, et al. A prospective, observational study of soluble FLT-1 and vascular endothelial growth factor in sepsis. Shock. 2008;29(4):452–7.PubMedGoogle Scholar
  45. 45.
    Shapiro NI, Schuetz P, Yano K, Sorasaki M, Parikh SM, Jones AE, et al. The association of endothelial cell signaling, severity of illness, and organ dysfunction in sepsis. Crit Care. 2010;14(5):R182.PubMedCentralPubMedGoogle Scholar
  46. 46.
    David S, Mukherjee A, Ghosh CC, Yano M, Khankin EV, Wenger JB, et al. Angiopoietin-2 may contribute to multiple organ dysfunction and death in sepsis. Crit Care Med. 2012;40(11):3034–41.PubMedCentralPubMedGoogle Scholar
  47. 47.
    Sakr Y, Dubois MJ, De Backer D, Creteur J, Vincent JL. Persistent microcirculatory alterations are associated with organ failure and death in patients with septic shock. Crit Care Med. 2001;32(9):1825–31.Google Scholar
  48. 48.
    Trzeciak S, McCoy JV, Dellinger RP, Arnold RC, Rizzuto M, Abate NL, et al. Early increases in microcirculatory perfusion during protocol-directed resuscitation are associated with reduced multi-organ failure at 24 h in patients with sepsis. Intensive Care Med. 2008;34(12):2210–7.PubMedCentralPubMedGoogle Scholar
  49. 49.
    Trzeciak S, Cinel I, Dellinger RP, Shapiro NI, Arnold RC, Parrillo JE, et al. Resuscitating the microcirculation in sepsis: the central role of nitric oxide, emerging concepts for novel therapies, and challenges for clinical trials. Acad Emerg Med. 2008;15(5):399–413.PubMedCentralPubMedGoogle Scholar
  50. 50.
    Singer M. Mitochondrial function in sepsis: acute phase versus multiple organ failure. Crit Care Med. 2007;35(9):S441–8.PubMedGoogle Scholar
  51. 51.
    Singer M. Mechanisms of sepsis-induced organ dysfunction and recovery update in intensive care and emergency medicine. Crit Care Emerg Med. 2007;44:299–310.Google Scholar
  52. 52.
    Harrois A, Huet O, Duranteau J. Alterations of mitochondrial function in sepsis and critical illness. Curr Opin Anaesthesiol. 2009;22(2):143–9.PubMedGoogle Scholar
  53. 53.
    Haden DW, Suliman HB, Carraway MS, Welty-Wolf KE, Al AS, Shitara H, et al. Mitochondrial biogenesis restores oxidative metabolism during Staphylococcus aureus sepsis. Am J Respir Crit Care Med. 2007;176:768–77.PubMedCentralPubMedGoogle Scholar
  54. 54.
    Brealey D, Brand M, Hargreaves I, Heales S, Land J, Smolenski R, et al. Association between mitochondrial dysfunction and severity and outcome of septic shock. Lancet. 2002;360:219–23.PubMedGoogle Scholar
  55. 55.
    Carré JE, Orban JC, Re L, Felsmann K, Iffert W, Bauer M, et al. Survival in critical illness is associated with early activation of mitochondrial biogenesis. Am J Resp Crit Care Med. 2010;182(6):745–51.PubMedCentralPubMedGoogle Scholar
  56. 56.
    Jeger V, Djafarzadeh S, Jakob SM, Takala J. Mitochondrial function in sepsis. Eur J Clin Invest. 2013;43(5):532–42.PubMedGoogle Scholar
  57. 57.
    Xiao W, Mindrinos MN, Seok J, Cuschieri J, Cuenca AG, Gao H, et al. A genomic storm in critically injured humans. J Exp Med. 2011;208(13):2581–90.PubMedCentralPubMedGoogle Scholar
  58. 58.
    Leavy O. Inflammation: trauma kicks up a storm. Nat Rev Immunol. 2011;12(1):3.PubMedGoogle Scholar
  59. 59.
    Gentile LF, Cuenca AG, Efron PA, Ang D, Bihorac A, McKinley BA, et al. Persistent inflammation and immunosuppression: a common syndrome and new horizon for surgical intensive care. J Trauma Acute Care Surg. 2012;72(6):1491–501.PubMedCentralPubMedGoogle Scholar
  60. 60.
    Ashbaugh D, Boyd BD, Petty T, Levine B. Acute respiratory distress in adults. Lancet. 1967; 290(7511):319–23.Google Scholar
  61. 61.
    Rubenfeld GD, Caldwell E, Peabody E, Weaver J, Martin DP, Nef M, et al. Incidence and outcomes of acute lung injury. N Engl J Med. 2005;353:1685–93.PubMedGoogle Scholar
  62. 62.
    Abraham E, Matthay MA, Dinarello CA, Vincent JL, Cohen J, Opal SM, et al. Consensus conference definitions for sepsis, septic shock, acute lung injury, and acute respiratory distress syndrome: time for a reevaluation. Crit Care Med. 2000;28(1):232–5.PubMedGoogle Scholar
  63. 63.
    Ferguson ND, Fan E, Camporota L, Antonelli M, Anzueto A, Beale R, et al. The Berlin definition of ARDS: an expanded rationale, justification, and supplementary material. Intensive Care Med. 2012;38(10):1573–82.PubMedGoogle Scholar
  64. 64.
    Ware LB, Matthay MA. The acute respiratory distress syndrome. N Engl J Med. 2000;342:1334–49.PubMedGoogle Scholar
  65. 65.
    Tsushima K, King LS, Aggarwal NR, De Gorordo A, D’Alessio FR, Kubo K. Acute lung injury review. Intern Med. 2009;48:621–30.PubMedGoogle Scholar
  66. 66.
    Bagshaw SM, Lapinsky S, Dial S, Arabi Y, Dodek P, Wood G, et al. Acute kidney injury in septic shock: clinical outcomes and impact of duration of hypotension prior to initiation of antimicrobial therapy. Intensive Care Med. 2009;35:871–81.PubMedGoogle Scholar
  67. 67.
    Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P, The Acute Dialysis Quality Initiative Workgroup. Acute renal failure definition, outcome measures, animal models, fluid therapy and information technology needs: the second international consensus conference of the Acute Dialysis Quality Initiative Group. Crit Care. 2004;8:R204–12.PubMedCentralPubMedGoogle Scholar
  68. 68.
    Mehta RL, Kellum JA, Shah SV, The Acute Kidney Injury Network. Acute kidney injury network: report of an initiative to improve outcomes in acute kidney injury. Crit Care. 2007;11:R31.PubMedCentralPubMedGoogle Scholar
  69. 69.
    The Kidney Disease Improving Global Outcomes (KDIGO) Working Group. Definition and classification of acute kidney injury. Kidney Int. 2012; Suppl 2:19–36.Google Scholar
  70. 70.
    Bellomo R, Kellum JA, Ronco C. Acute kidney injury. Lancet. 2012;380:756–66.PubMedGoogle Scholar
  71. 71.
    Haase M, Bellomo R, Devarajan P, Schlattmann P, Haase-Fielitz A. Accuracy of neutrophil gelatinase-associated lipocalin (NGAL) in diagnosis and prognosis in acute kidney injury: a systematic review and meta-analysis. Am J Kidney Dis. 2009;54:1012–24.PubMedGoogle Scholar
  72. 72.
    Srisawat N, Wen X, Lee M, Kong L, Elder M, Carter M, et al. Urinary biomarkers and renal recovery in critically ill patients with renal support. Clin J Am Soc Nephrol. 2011;6(8):1815–23.PubMedCentralPubMedGoogle Scholar
  73. 73.
    Obermüller N, Geiger H, Weipert C, Urbschat A. Current developments in early diagnosis of acute kidney injury. Int Urol Nephrol. 2014;46(1):1–7. doi: 10.1007/s11255-013-0448-5 [Epub ahead of print].PubMedGoogle Scholar
  74. 74.
    Werdan K, Schmidt H, Ebelt H, Zorn-Pauly K, Koidl B, Hoke RS, et al. Impaired regulation of cardiac function in sepsis, SIRS, and MODS. Can J Physiol Pharmacol. 2009;87(4):266–74.PubMedGoogle Scholar
  75. 75.
    Hunter JD, Doddi M. Sepsis and the heart. Br J Anaesth. 2010;104(1):3–11.PubMedGoogle Scholar
  76. 76.
    Matsuda N, Hattori Y. Vascular biology in sepsis: pathophysiological and therapeutic significance of vascular dysfunction. J Smooth Muscle Res. 2007; 43(4):117–37.PubMedGoogle Scholar
  77. 77.
    Levy B, Collin S, Sennoun N, Ducrocq N, Kimmoun A, Asfar P, et al. Vascular hyporesponsiveness to vasopressors in septic shock: from bench to bedside. In: Pinsky MR, Brochard L, Mancebo J, Antonelli M, editors. Applied physiology in intensive care medicine 2. Berlin: Springer; 2012. p. 251–61.Google Scholar
  78. 78.
    Lamar CD, Hurley RA, Taber KH. Sepsis-associated encephalopathy: review of the neuropsychiatric manifestations and cognitive outcome. J Neuropsychiatry Clin Neurosci. 2011;23:237–41.PubMedGoogle Scholar
  79. 79.
    Chelazzi C, Consales G, De Gaudio AR. Sepsis associated encephalopathy. Curr Anaesth Crit Care. 2008;19(1):15–21.Google Scholar
  80. 80.
    Garnacho-Montero J, Madrazo-Osuna J, García-Garmendia JL, Ortiz-Leyba C, Jiménez-Jiménez FJ, Barrero-Almodóvar A, et al. Critical illness polyneuropathy: risk factors and clinical consequences. A cohort study in septic patients. Intensive Care Med. 2001;27(8):1288–96.PubMedGoogle Scholar
  81. 81.
    Garnacho-Montero J, Amaya-Villar R, García-Garmendía JL, Madrazo-Osuna J, Ortiz-Leyba C. Effect of critical illness polyneuropathy on the withdrawal from mechanical ventilation and the length of stay in septic patients. Crit Care Med. 2005;33(2):349–54.PubMedGoogle Scholar
  82. 82.
    Ortiz-Leyba C, Ortiz-Moyano C, Jiménez-Jiménez FJ, Garnacho-Montero J, García-Garmendia JL. Nutritional support in severe sepsis. Clin Pulm Med. 2003;10(1):26–33.Google Scholar
  83. 83.
    Gardiner K, Barbull A. Intestinal amino acid absorption during sepsis. JPEN. 1993;17:277–83.Google Scholar
  84. 84.
    Salloun RM, Copeland EM, Souba WW. Brush border transport of glutamine and other substrates during sepsis and endotoxemia. Ann Surg. 1991; 213:401–10.Google Scholar
  85. 85.
    Groeneveld ABJ. Gastrointestinal exocrine failure in critical illness. In: Rombeau JL, Takala J, editors. Gut dysfunction in critical illness, Update in intensive care and emergency medicine, vol. 26. Berlin: Springer; 1996. p. 297–306.Google Scholar
  86. 86.
    Heidegger CP, Berge MM, Graf S, Zingg W, Darmon P, Costanza MC, et al. Optimisation of energy provision with supplemental parenteral nutrition in critically ill patients: a randomised controlled clinical trial. Lancet. 2013;381(9864):385–93.PubMedGoogle Scholar
  87. 87.
    Casaer MP, Mesotten D, Hermans G, Wouters PJ, Schetz M, Meyfroidt G, et al. Early versus late parenteral nutrition in critically ill adults. N Engl J Med. 2011;365(6):506–17.PubMedGoogle Scholar
  88. 88.
    Louis K, Netea MG, Carrer DP, Kotsaki A, Mylona V, Pistiki A, et al. Bacterial translocation in an experimental model of multiple organ dysfunctions. J Surg Res. 2013;183(2):686–94.PubMedGoogle Scholar
  89. 89.
    Reintam A, Poeze M, Malbrain ML, Björck M, Oudemans-van Straaten HM, Starkopf J, Gastro-Intestinal Failure Trial Group. Gastrointestinal symptoms during the first week of intensive care are associated with poor outcome: a prospective multicentre study. Intensive Care Med. 2013;39(5):899–909.Google Scholar
  90. 90.
    Piton G, Manzon C, Cypriani B, Carbonnel F, Capellier G. Acute intestinal failure in critically ill patients: is plasma citrulline the right marker? Intensive Care Med. 2011;37(6):911–7.PubMedGoogle Scholar
  91. 91.
    Malbrain ML, Cheatham ML, Kirkpatrick A, Sugrue M, Parr M, De Waele J, et al. Results from the international conference of experts on intra-abdominal hypertension and abdominal compartment syndrome. I. Definitions. Intensive Care Med. 2006; 32(11): 1722–32.PubMedGoogle Scholar
  92. 92.
    Malbrain ML, De Laet I. AIDS is coming to your ICU: be prepared for acute bowel injury and acute intestinal distress syndrome. Intensive Care Med. 2008;34(9):1565–9.PubMedGoogle Scholar
  93. 93.
    Reintam A, Parm P, Kitus R, Starkopf J, Kern H. Gastrointestinal failure score in critically ill patients: a prospective observational study. Crit Care. 2008;12:R90.PubMedCentralPubMedGoogle Scholar
  94. 94.
    Reintam A, Malbrain ML, Starkopf J, Fruhwald S, Jakob SM, De Waele J, et al. Gastrointestinal function in intensive care patients: terminology, definitions and management. Recommendations of the ESICM Working Group on Abdominal Problems. Intensive Care Med. 2012;38(3):384–94.Google Scholar
  95. 95.
    Dhainaut JF, Marin N, Mignon A, Vinsonneau C. Hepatic response to sepsis: interaction between coagulation and inflammatory processes. Crit Care Med. 2001;29:S42–7.PubMedGoogle Scholar
  96. 96.
    Spapen H. Liver perfusion in sepsis, septic shock, and multiorgan failure. Anat Rec. 2008;291:714–20.Google Scholar
  97. 97.
    Olanders K, Sun Z, Borjesson A, Dib M, Andersson E, Lasson Å, et al. The effect of intestinal ischemia and reperfusion injury on ICAM-1 expression, endothelial barrier function, neutrophil tissue influx, and protease inhibitor levels in rats. Shock. 2002;18(1):86–92.PubMedGoogle Scholar
  98. 98.
    Poeze M, Ramsay G, Buurman WA, Greve JWM, Dentener M, Takala J. Increased hepatosplanchnic inflammation precedes the development of organ dysfunction after elective high-risk surgery. Shock. 2002;17:451–8.PubMedGoogle Scholar
  99. 99.
    Soeters PB, Luyer MS, Willem J, Greve M, Buurman WA. The significance of bowel permeability. Curr Opin Clin Nutr Metab Care. 2007;10:632–8.PubMedGoogle Scholar
  100. 100.
    Kobayashi N, Maekawa T, Takada M, Tanaka H, Gonmori H. Criteria for diagnosis of DIC based on the analysis of clinical and laboratory findings in 345 DIC patients collected by the Research Committee on DIC in Japan. Bibl Haematol. 1987;49:848–52.Google Scholar
  101. 101.
    Taylor Jr FB, Toh CH, Hoots WK, Wada H, Levi M. Towards definition, clinical and laboratory criteria, and a scoring system for disseminated intravascular coagulation: on behalf of the Scientific Subcommittee on Disseminated Intravascular Coagulation (DIC) of the International Society on Thrombosis and Haemostasis (ISTH). Thromb Haemost. 2001;86: 1327–30.PubMedGoogle Scholar
  102. 102.
    Gando S, Iba T, Eguchi Y, Ohtomo Y, Okamoto K, Koseki K, et al. A multicenter, prospective validation of disseminated intravascular coagulation diagnostic criteria for critically ill patients: comparing current criteria. Crit Care Med. 2006;34:625–31.PubMedGoogle Scholar
  103. 103.
    Takemitsu T, Wada H, Hatada T, Ohmori Y, Ishikura K, Takeda T, et al. Prospective evaluation of three different diagnostic criteria for disseminated intravascular coagulation. Thromb Haemost. 2011;105: 40–4.PubMedGoogle Scholar
  104. 104.
    Iskander KN, Osuchowski MF, Stearns-Kurosawa DJ, Kurosawa S, Stepien D, Valentine C, et al. Sepsis: multiple abnormalities, heterogeneous responses, and evolving understanding. Physiol Rev. 2013;93(3):1247–88.PubMedCentralPubMedGoogle Scholar
  105. 105.
    Cuthbertson DP. Post-shock metabolic response. Lancet. 1942;239(6189):433–7.Google Scholar
  106. 106.
    Cerra FB. Hypermetabolism, organ failure, and metabolic support. Surgery. 1987;101:1–14.PubMedGoogle Scholar
  107. 107.
    Van Den Berghe G, Wouters P, Weekers F, Verwaest C, Bruyninckx F, Schetz M, et al. Intensive insulin therapy in critically ill patients. N Engl J Med. 2001;345(19):1359–67.PubMedGoogle Scholar
  108. 108.
    Frankenfield DC, Oniert LA, Badellino MM, Wiles CE, Bagley SM, Goodarzi S, et al. Correlation between measured energy expenditure and clinically obtained variables in trauma and sepsis patients. JPEN. 1994;18(5):398–403.Google Scholar
  109. 109.
    Dickerson RN. Optimal caloric intake for critically ill patients: first, do no harm. Nutr Clin Pract. 2011;26(1):48–54.PubMedGoogle Scholar
  110. 110.
    Silvestri L, van Saene HK, Zandstra DF, Marshall JC, Gregori D, Gullo A. Impact of selective decontamination of the digestive tract on multiple organ dysfunction syndrome: systematic review of randomized controlled trials. Crit Care Med. 2010; 38(5):1370–6.PubMedGoogle Scholar
  111. 111.
    Leal-Noval SR, Muñoz M, Asuero M, Contreras E, García-Erce JA, Llau JV, et al. Spanish Consensus Statement on alternatives to allogeneic blood transfusion: the 2013 update of the “Seville Document”. Blood Transfus. 2013;11(4):1–25.Google Scholar
  112. 112.
    Leal-Noval SR, Muñoz-Gómez M, Jiménez-Sánchez M, Cayuela A, Leal-Romero M, Puppo-Moreno A, et al. Red blood cell transfusion in non-bleeding critically ill patients with moderate anemia: is there a benefit? Intensive Care Med. 2013;39(3):445–53.PubMedGoogle Scholar
  113. 113.
    Gunst J, Derese I, Aertgeerts A, Ververs EJ, Wauters A, Van den Berghe G, et al. Insufficient autophagy contributes to mitochondrial dysfunction, organ failure, and adverse outcome in an animal model of critical illness. Crit Care Med. 2013;41(1):182–94.PubMedGoogle Scholar
  114. 114.
    Levitt JE, Calfee CS, Goldstein BA, Vojnik R, Matthay MA. Early acute lung injury: criteria for identifying lung injury prior to the need for positive pressure ventilation. Crit Care Med. 2013;41(8): 1929–37.PubMedGoogle Scholar
  115. 115.
    Marik PE, Cavallazzi R. Does the central venous pressure predict fluid responsiveness? An updated meta-analysis and a plea for some common sense. Crit Care Med. 2013;41(7):1774–81.PubMedGoogle Scholar
  116. 116.
    European Medicines Agency. Recommendation to suspend marketing authorisations for hydroxyethyl-starch solutions to be re-examined. 12 July 2013. EMA/349341/2013.Google Scholar
  117. 117.
    De Backer D, Aldecoa C, Hassane H, Vincent JL. Dopamine versus norepinephrine in the treatment of septic shock: a meta-analysis. Crit Care Med. 2012;40(3):725–30.PubMedGoogle Scholar
  118. 118.
    Home AJRCCM, Home AJRCMB, By Subject CME. Randomized, placebo-controlled clinical trial of an aerosolized β 2-agonist for treatment of acute lung injury. Am J Resp Crit Care Med. 2011;184(5): 561–8.Google Scholar
  119. 119.
    Jones NE, Heyland DK. Pharmaconutrition: a new emerging paradigm. Curr Opin Gastroenterol. 2008;24(2):215–22.PubMedGoogle Scholar
  120. 120.
    Ortiz-Leyba C, Montejo-González JC, Vaquerizo-Alonso C, Metabolism and Nutrition Working Group of the Spanish Society of Intensive Care Medicine and Coronary Units. Guidelines for specialized nutritional and metabolic support in the critically-ill patient: update. Consensus SEMICYUC-SENPE: septic patient. Nutr Hosp. 2011;26 Suppl 2:67–71.PubMedGoogle Scholar
  121. 121.
    Heyland DK, Novak F, Drover JW, Jain M, Suchner U. Should immunonutrition become routine in critically ill patients? A systematic review of the evidence. JAMA. 2001;286:944–53.PubMedGoogle Scholar
  122. 122.
    Davis J, Anstey N. Is plasma arginine concentration decreased in patients with sepsis? A systematic review and meta-analysis. Crit Care Med. 2011; 39(2):380–5.PubMedGoogle Scholar
  123. 123.
    Wernerman J, Kirketeig T, Andersson B, et al. Scandinavian glutamine trial: a pragmatic multi-centre randomised clinical trial of intensive care unit patients. Acta Anaesthesiol Scand. 2011;55:812–8.PubMedGoogle Scholar
  124. 124.
    Andrews PJ, Avenell A, Noble DW, Campbell MK, Croal BL, Simpson WG, et al. Randomised trial of glutamine, selenium, or both, to supplement parenteral nutrition for critically ill patients. BMJ. 2011;342:d1542.PubMedGoogle Scholar
  125. 125.
    Grau T, Bonet A, Miñambres E, Piñeiro L, Irles JA, Robles A, et al.; for the Metabolism, Nutrition Working Group, SEMICYUC, Spain. The effect of l-alanyl-l-glutamine dipeptide supplemented total parenteral nutrition on infectious morbidity and insulin sensitivity in critically ill patients. Crit Care Med. 2011;39(6):1263–8.Google Scholar
  126. 126.
    Heyland D, Muscedere J, Wischmeyer PE, Cook D, Jones G, Albert M, et al. A randomized trial of glutamine and antioxidants in critically ill patients. N Engl J Med. 2013;368:1489–97.PubMedGoogle Scholar
  127. 127.
    Bruegel M, Ludwig U, Kleinhempel A. Sepsis-associated changes of the arachidonic acid metabolism and their diagnostic potential in septic patients. Crit Care Med. 2012;40(5):1478–86.PubMedGoogle Scholar
  128. 128.
    Umpierrez GE, Spiegelman R, Zhao V, Smiley DD, Pinzon I, Griffith DP, et al. A double-blind, randomized clinical trial comparing soybean oil–based versus olive oil–based lipid emulsions in adult medical–surgical intensive care unit patients requiring parenteral nutrition. Crit Care Med. 2012; 40:1792.PubMedCentralPubMedGoogle Scholar
  129. 129.
    Mateu-de Antonio J, Grau S, Luque S, Marín-Casino M, Albert I, Ribes E. Comparative effects of olive oil-based and soyabean oil-based emulsions on infection rate and leucocyte count in critically ill patients receiving parenteral nutrition. Br J Nutr. 2008;99(4):846–54.PubMedGoogle Scholar
  130. 130.
    Rice TW, Wheeler AP, Thompson BT, de Boisblanc BP, Steingrub J, Rock P, NIH NHLBI Acute Respiratory Distress Syndrome Network of Investigators. Enteral omega-3 fatty acid, γ-linolenic acid, and antioxidant supplementation in acute lung injury. JAMA. 2011;306(14):1574–81.PubMedCentralPubMedGoogle Scholar
  131. 131.
    Grau-Carmona T, Morán-García V, García-de-Lorenzo A, Heras-de-la-Calle G, Quesada-Bellver B, López-Martínez J, et al. Effect of an enteral diet enriched with eicosapentaenoic acid, gamma-linolenic acid and anti-oxidants on the outcome of mechanically ventilated, critically ill, septic patients. Clin Nutr. 2011;30(5):578–84.PubMedGoogle Scholar
  132. 132.
    Wagner E, Frank MM. Therapeutic potential of complement modulation. Nat Rev Drug Discov. 2010;9:43–56.PubMedGoogle Scholar
  133. 133.
    Ghannam S, Bouffi C, Djouad F, Jorgensen C, Noël D. Immunosuppression by mesenchymal stem cells: mechanisms and clinical applications. Stem Cell Res Ther. 2010;1:2.PubMedCentralPubMedGoogle Scholar
  134. 134.
    Groeneveld KM, Leenen LP, Koenderman L, Kesecioglu J. Immunotherapy after trauma: timing is essential. Curr Opin Anaesthesiol. 2011;24(2): 219–23.PubMedGoogle Scholar
  135. 135.
    Gotts JE, Matthay MA. Mesenchymal stem cells and acute lung injury. Crit Care Clin. 2011;27(3):719–33.PubMedCentralPubMedGoogle Scholar
  136. 136.
    Schmidt H, Hoyer D, Rauchhaus M, Prondzinsky R, Hennen R, Schlitt A, et al. ACE-inhibitor therapy and survival among patients with multiorgan dysfunction syndrome (MODS) of cardiac and non-cardiac origin. Int J Cardiol. 2010;140(3):296–303.PubMedGoogle Scholar
  137. 137.
    Dare AJ, Phillips AR, Hickey AJ, Mittal A, Loveday B, Thompson N, Windsor JA. A systematic review of experimental treatments for mitochondrial dysfunction in sepsis and multiple organ dysfunction syndrome. Free Radic Biol Med. 2009;47(11):1517–25.PubMedGoogle Scholar
  138. 138.
    Teoh H, Quan A, Creighton AK, Bang KA, Singh KK, Shukla PC, et al. BRCA1 gene therapy reduces systemic inflammatory response and multiple organ failure and improves survival in experimental sepsis. Gene Ther. 2012;20(1):51–61.PubMedGoogle Scholar
  139. 139.
    Cobb JP. MORE for multiple organ dysfunction syndrome: Multiple Organ REanimation, REgeneration, and Reprogramming. Crit Care Med. 2010;38(11): 2242–6.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Head of the Department of Internal Medicine and Critical Care UnitHospital Quirón Sagrado CorazónSevillaSpain

Personalised recommendations