Microcirculatory and Mitochondrial Distress Syndrome (MMDS): A New Look at Sepsis

  • P. E. Spronk
  • V. S. Kanoore-Edul
  • C. Ince
Part of the Update in Intensive Care and Emergency Medicine book series (volume 42)


Septic Shock Mean Arterial Pressure Septic Shock Patient Ethyl Pyruvate Microcirculatory Dysfunction 
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.


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  1. 1.
    Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Cardcillo J, Pinsky MR (2001) Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med 29:1303–1310CrossRefPubMedGoogle Scholar
  2. 2.
    Guyton AC, Hall JE (1997) Human Physiology and Mechanisms of Disease, 6th edition. WB Saunders, PhiladelphiaGoogle Scholar
  3. 3.
    Robin ED (1980) Of men and mitochondria: coping with hypoxic dysoxia. The 1980 J. Burns Amberson Lecture. Am Rev Respir Dis 122:517–531PubMedGoogle Scholar
  4. 4.
    Ince C, Sinaasappe lM (1999) Microcirculatory oxygenation and shunting in sepsis and shock Crit Care Med 27:1369–1377CrossRefGoogle Scholar
  5. 5.
    Shoemaker WC, Appel PL, Kram HB, Waxman K, Lee TS (1988) Prospective trial of supranormal values of survivors as therapeutic goals in high-risk surgical patients. Chest 94:1176–1186PubMedGoogle Scholar
  6. 6.
    Gattinoni L, Brazzi L, Pelosi P, et al (1995) A trial of goal-oriented hemodynamic therapy in critically ill patients. SvO2 Collaborative Group. N Engl J Med 333:1025–1032CrossRefPubMedGoogle Scholar
  7. 7.
    Hayes MA, Timmins AC, Yau EH, Palazzo M, Hinds CJ, Watson D(1994) Elevation of systemic oxygen delivery in the treatment of critically ill patients. N Engl J Med 330:1717–1722CrossRefPubMedGoogle Scholar
  8. 8.
    Cain SM, Curtis SE (1991) Experimental models of pathologic oxygen supply dependency. Crit Care Med 19:603–6012PubMedGoogle Scholar
  9. 9.
    Nelson DP, Samsel RW, Wood LDH, Schumacker PT (1988) Experimental models of pathologic oxygen supply dependency. J Appl Physiol 64:2410–2419PubMedGoogle Scholar
  10. 10.
    Vallet B, Lund N, Curtis SE, Kelly D, Cain SM (1994) Gut and muscle tissuepO2in endotoxemic dogs during shock and resuscitation. J Appl Physiol 76:793–800PubMedGoogle Scholar
  11. 11.
    Fink M (1997) Cytopathic hypoxia in sepsis. Acta Anaesthesiol Scand Suppl 110:87–95Google Scholar
  12. 12.
    Ellsworth ML, Pittman RN (1990) Arterioles supply oxygen to capillaries by diffusion as well as by convection. Am J Physiol 258(4 Pt 2):H1240–H1243PubMedGoogle Scholar
  13. 13.
    Shonat RD, Johnson PC (1997) Oxygen tension gradients and heterogeneity in venous microcirculation: a phosphorescence quenching study. Am J Physiol 272(5 Pt 2):H2233–H2240PubMedGoogle Scholar
  14. 14.
    Bone RC (1991) The pathogenesis of sepsis. Ann Intern Med 115:457–469PubMedGoogle Scholar
  15. 15.
    Spronk PE, Ince C, Gardien MJ, Mathura KR, Oudemans-van Straaten HM, Zandstra DF (2002) Nitroglycerin in septic shock after intravascular volume resuscitation. Lancet 360:1395–1396CrossRefPubMedGoogle Scholar
  16. 16.
    De Backer D, Creteur J, Dubois MJ, Sakr Y, Vincent JL (2004) Microvascular alterations in patients with acute severe heart failure and cardiogenic shock. Am Heart J 147:91–99CrossRefPubMedGoogle Scholar
  17. 17.
    Lush CW, Kvietys PR (2000) Microvascular dysfunction in sepsis. Microcirculation 7:83–101CrossRefPubMedGoogle Scholar
  18. 18.
    Albuszies G, Bruckner UB (2003) Antioxidant therapy in sepsis. Intensive Care Med 29:1632–1636CrossRefPubMedGoogle Scholar
  19. 19.
    Rank N, Michel C, Haertel C, et al (2000) N-acetylcysteine increases liver blood flow and improves liver function in septic shock patients: results of a prospective, randomized, double-blind study. Crit Care Med 28:3799–3807CrossRefPubMedGoogle Scholar
  20. 20.
    Paterson RL, Galley HF, Webster NR (2003) The effect of N-acetylcysteine on nuclear factor-kappa B activation, interleukin-6, interleukin-8, and intercellular adhesionmolecule-1 expression in patients with sepsis. Crit Care Med 31:2574–2578CrossRefPubMedGoogle Scholar
  21. 21.
    Di Giantomasso D, May CN, Bellomo R (2003) Norepinephrine and vital organ blood flow during experimental hyperdynamic sepsis. Intensive Care Med 29:1774–1781CrossRefPubMedGoogle Scholar
  22. 22.
    Baskurt OK, Temiz A, Meiselman HJ (1997) Red blood cell aggregation in experimental sepsis. J Lab Clin Med 130:183–190CrossRefPubMedGoogle Scholar
  23. 23.
    Piagnerelli M, Boudjeltia KZ, Vanhaeverbeek M, Vincent JL (2003) Red blood cell rheology in sepsis. Intensive Care Med 29:1052–1061CrossRefPubMedGoogle Scholar
  24. 24.
    Boekstegers P, Weidenhofer S, Kapsner T, Werdan K (1994) Skeletal muscle partial pressure of oxygen in patients with sepsis. Crit Care Med 22:640–650PubMedGoogle Scholar
  25. 25.
    Sair M, Etherington PJ, Peter WC, Evans TW (2001) Tissue oxygenation and perfusion in patients with systemic sepsis. Crit Care Med 29:1343–1349CrossRefPubMedGoogle Scholar
  26. 26.
    Sinaasappel M, van Iterson M, Ince C (1999) Microvascular oxygen pressure in the pig intestine during haemorrhagic shock and resuscitation. J Physiol 514:245–253CrossRefPubMedGoogle Scholar
  27. 27.
    Bateman RM, Sharpe MD, Ellis CG (2003) Bench-to-bedside review: microvascular dysfunction in sepsis-hemodynamics, oxygen transport, and nitric oxide. Crit Care 7:359–373CrossRefPubMedGoogle Scholar
  28. 28.
    van Iterson M, Sinaasappel M, Burhop K, Trouwborst A, Ince C (1998) Low-volume resuscitation with a hemoglobin-based oxygen carrier after hemorrhage improves gut microvascular oxygenation in swine. J Lab Clin Med 132:421–431CrossRefPubMedGoogle Scholar
  29. 29.
    Siegemund M, racovitza I, Ince C (2002) The rationale for vasodilator therapy in sepsis. In: Vincent JL (ed) Yearbook of Intensive Care and Emergency Medicine. Springer, Heidelberg, pp 221–231Google Scholar
  30. 30.
    Ince C, Ashruf JF, Avontuur JA, Wieringa PA, Spaan JA, Bruining HA (1993) Heterogeneity of the hypoxic state in rat heart is determined at capillary level. Am J Physiol 264:H294–H301PubMedGoogle Scholar
  31. 31.
    Revelly JP, Ayuse T, Brienza N, Fessler HE, Robotham JL (1996) Endotoxic shock alters distribution of blood flow within the intestinal wall. Crit Care Med 24:1345–1351CrossRefPubMedGoogle Scholar
  32. 32.
    Hollenberg SM (2004) iNOS deficient mice in the study of sepsis. In: Ince C (ed) The Physiological Genomics of the Critically Ill Mouse, Kluwer Academic, New York, pp 159–179Google Scholar
  33. 33.
    Vincent JL, Zhang H, Szabo C, Preiser JC (2000) Effects of nitric oxide in septic shock. Am J Respir Crit Care Med 161:1781–1785PubMedGoogle Scholar
  34. 34.
    Zhang H, Rogiers P, Friedman G, et al (1996) Effects of nitric oxide donor SIN-1 on oxygen availability and regional blood flow during endotoxic shock. Arch Surg 131:767–774PubMedGoogle Scholar
  35. 35.
    Siegemund M, van Bommel J, Ince C (2000) Influence of NO donor SIN-1 on the gut oxygenation in a normodynamic, porcine model of low-dose endotoxaemia. Intensive Care Med 26:S362Google Scholar
  36. 36.
    Buwalda M, Ince C (2002) Opening the microcirculation: can vasodilators be useful in sepsis? Intensive Care Med 28:1208–1217CrossRefPubMedGoogle Scholar
  37. 37.
    Avontuur JA, Bruining HA, Ince C (1997) Nitric oxide causes dysfunction of coronary autoregulation in endotoxemic rats. Cardiovasc Res 35:368–376CrossRefPubMedGoogle Scholar
  38. 38.
    Bakker J, Coffernils M, Leon M, Gris P, Vincent JL (1991) Blood lactate levels are superior to oxygen-derived variables in predicting outcome in human septic shock. Chest 99:956–962PubMedGoogle Scholar
  39. 39.
    De Backer D (2003) Lactic acidosis. Intensive Care Med 29:699–702PubMedGoogle Scholar
  40. 40.
    Vincent JL (2001) Hemodynamic support in septic shock. Intensive Care Med 27(Suppl 1):S80–S92CrossRefPubMedGoogle Scholar
  41. 41.
    Kaplan LJ, McPartland K, Santora TA, Trooskin SZ (2001) Start with a subjective assessment of skin temperature to identify hypoperfusion in intensive care unit patients. J Trauma 50:620–627PubMedGoogle Scholar
  42. 42.
    Rivers E, Nguyen B, Havstad S, et al (2001) Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 345:1368–1377CrossRefPubMedGoogle Scholar
  43. 43.
    Clark CH, Gutierrez G (1992) Gastric intramucosal pH: a noninvasive method for the indirect measurement of tissue oxygenation. Am J Crit Care 1:53–60PubMedGoogle Scholar
  44. 44.
    Dubin A, Murias G, Estenssoro E, et al (2002) Intramucosal-arterial PCO2 gap fails to reflect intestinal dysoxia in hypoxic hypoxia. Crit Care 6:514–520CrossRefPubMedGoogle Scholar
  45. 45.
    Gomersall CD, Joynt GM, Freebairn RC, Hung V, Buckley T, Oh TE (2000) Resuscitation of critically ill patients based on the results of gastric tonometry: A prospective, randomized, controlled trial. Crit Care Med 28:607–614CrossRefPubMedGoogle Scholar
  46. 46.
    Vallet B, Ince C (1999) Noninvasive assessment of tissue oxygenation. Semin Respir Crit Care Med 20:3–10Google Scholar
  47. 47.
    Creteur J, De Backer D, Vincent JL (1999) Does gastric tonometry monitor splanchnic perfusion? Crit Care Med 27:2480–2484CrossRefPubMedGoogle Scholar
  48. 48.
    Marik PE (2001) Sublingual capnography: a clinical validation study. Chest 120:923–927CrossRefPubMedGoogle Scholar
  49. 49.
    Marik PE, Bankov A (2003) Sublingual capnometry versus traditional markers of tissue oxygenation in critically ill patients. Crit Care Med 31:818–822CrossRefPubMedGoogle Scholar
  50. 50.
    Groner W, Winkelman JW, Harris AG, et al (1999) Orthogonal polarization spectral imaging: a new method for study of the microcirculation. Nat Med 5:1209–1212CrossRefPubMedGoogle Scholar
  51. 51.
    Mathura KR, Alic L, Ince C (2001) Initial clinical experience with OPS imaging for observation of the human microcirculation. In: Vincent JL (ed) Yearbook of Intensive Care and Emergency Medicine. Springer Verlag, Heidelberg, pp 233–245Google Scholar
  52. 52.
    Mathura KR, Vollebregt KC, Boer K, De Graaff JC, Ubbink DT, Ince C (2001) Comparison of OPS imaging and conventional capillary microscopy to study the human microcirculation. J Appl Physiol 91:74–78PubMedGoogle Scholar
  53. 53.
    Mathura KR, Bouma GJ, Ince C (2001) Abnormal microcirculation in brain tumours during surgery. Lancet 358:1698–1699CrossRefPubMedGoogle Scholar
  54. 54.
    Pennings F, Bouma GJ, Ince C (2004) Direct observation of the human cerebral microcirculation during aneurysm surgery reveals increased arteriolar contractility. Stroke 35:1284–1288CrossRefPubMedGoogle Scholar
  55. 55.
    Slaaf DW, Tangelder GJ, Reneman RS, Jager K, Bollinger A (1987) A versatile incident illuminator for intravital microscopy. Int J Microcirc Clin Exp 6:391–397PubMedGoogle Scholar
  56. 56.
    De Backer D, Creteur J, Preiser JC, Dubois MJ, Vincent JL (2002) Microvascular blood flow is altered in patients with sepsis. Am J Respir Crit Care Med 166:98–104CrossRefPubMedGoogle Scholar
  57. 57.
    Radermacher P, Buhl R, Santak B, et al (1995) The effects of prostacyclin on gastric intramucosal pH in patients with septic shock. Intensive Care Med 21:414–421CrossRefPubMedGoogle Scholar
  58. 58.
    Bihari D, Smithies M, Gimson A, Tinker J (1987) The effects of vasodilation with prostacyclin on oxygen delivery and uptake in critically ill patients. N Engl J Med 317:397–403PubMedGoogle Scholar
  59. 59.
    Siostrzonek P, Koreny M, Delle-Karth G, Haumer M, Koller-Strametz J, Heinz G (2000) Milrinone therapy in catecholamine-dependent critically ill patients with heart failure. Acta Anaesthesiol Scand 44:403–409CrossRefPubMedGoogle Scholar
  60. 60.
    Cerra FB, Hassett J, Siegel JH (1978) Vasodilator therapy in clinical sepsis with low output syndrome. J Surg Res 25:180–183CrossRefPubMedGoogle Scholar
  61. 61.
    Anzueto A, Beale R, Holzapfel L, et al (1997) Multicenter, placebo controlled, double-blind study of the nitric oxide synthase inhibitor 546C88 in patients with septic shock: effect on resolution of shock and survival. Intensive Care Med 23(Suppl 1):S57 (abst)Google Scholar
  62. 62.
    Grover R, Lopez A, Lorente JA, et al (1999) Multicenter, randomized, placebo controlled, double-blind study of the nitric oxide synthase inhibitor 546C88: effect on survival in patients with septic shock. Crit Care Med 27(Suppl):A33 (abst)CrossRefGoogle Scholar
  63. 63.
    Pittner A, Nalos M, Asfar P, et al (2003) Mechanisms of inducible nitric oxide synthase (iNOS) inhibition-related improvement of gut mucosal acidosis during hyperdynamic porcine endotoxemia. Intensive Care Med 29:312–316PubMedGoogle Scholar
  64. 64.
    Zhao KS, Junker D, Delano FA, Zweifach BW (1985) Microvascular adjustments during irreversible hemorrhagic shock in rat skeletal muscle. Microvasc Res 30:143–153CrossRefPubMedGoogle Scholar
  65. 65.
    Dubois MJ, De Backer D, Creteur J, Anane S, Vincent JL (2003) Effect of vasopressin on sublingual microcirculation in a patient with distributive shock. Intensive Care Med 29:1020–1023PubMedGoogle Scholar
  66. 66.
    Li H, Förstermann U (2000) Nitric oxide in the pathogenesis of vascular disease. J Pathol 190:244–254CrossRefPubMedGoogle Scholar
  67. 67.
    Brealey D, Brand M, Hargreaves I, et al (2002) Association between mitochondrial dysfunction and severity and outcome of septic shock. Lancet 360:219–223CrossRefPubMedGoogle Scholar
  68. 68.
    Kellum JA, Johnson JP, Kramer D, Palevsky P, Brady JJ, Pinsky MR (1998) Diffusive vs. convective therapy: effects on mediators of inflammation in patient with severe systemic inflammatory response syndrome. Crit Care Med 26:1995–2000CrossRefPubMedGoogle Scholar
  69. 69.
    Buist MD, Moore GE, Bernard SA, Waxman BP, Anderson JN, Nguyen TV (2002) Effects of a medical emergency team on reduction of incidence of and mortality from unexpected cardiac arrests in hospital: preliminary study. BMJ 324:387–390CrossRefPubMedGoogle Scholar
  70. 70.
    Uchiyama T, Delude RL, Fink MP (2003) Dose-dependent effects of ethyl pyruvate in mice subjected to mesenteric ischemia and reperfusion. Intensive Care Med 29:2050–2058CrossRefPubMedGoogle Scholar

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© Springer-Verlag Berlin Heidelberg 2005

Authors and Affiliations

  • P. E. Spronk
  • V. S. Kanoore-Edul
  • C. Ince

There are no affiliations available

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