Pharmacological Manipulation in ICU

  • D. De Backer
  • K. Donadello
  • S. Scolletta
Conference paper


Multiple organ failure is a common feature in critically ill patients, and the severity of organ dysfunction is associated with outcome. Multiple mechanisms can be implicated in the development of multiple organ failure, including global and regional haemodynamic alterations and microcirculatory and cellular alterations. Microcirculation may play a crucial role in the pathophysiology of multiple organ failure. Indeed, it is the primary site for gas and nutrient exchange with tissues. In addition, the microcirculatory bed represents the largest endothelial surface of the body and takes an important place in the initiation and amplification of inflammatory processes and of the coagulation cascade. It is also implicated in permeability alterations. Accordingly, even though the importance of global and regional vascular alterations should not be minimised, many events implicated in impairment in tissue oxygenation and inflammatory processes occur at the microcirculatory level.


Septic Shock Multiple Organ Failure Microvascular Perfusion Microvascular Blood Flow Microcirculatory Blood Flow 
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.
    Zhao KS, Junker D, Delano FA et al (1985) Microvascular adjustments during irreversible hemorrhagic shock in rat skeletal muscle. Microvasc Res 30:143–153PubMedCrossRefGoogle Scholar
  2. 2.
    Dammers R, Wehrens XH, oude Egbrink MG et al (2001) Microcirculatory effects of experimental acute limb ischaemia-reperfusion. Br J Surg 88:816–824PubMedCrossRefGoogle Scholar
  3. 3.
    Cryer HM, Garrison RN, Kaebnick HW et al (1987) Skeletal microcirculatory responses to hyperdynamic Escherichia coli sepsis in unanesthetized rats. Arch Surg 122:86–92PubMedCrossRefGoogle Scholar
  4. 4.
    Baker CH, Wilmoth FR (1984) Microvascular responses to E. coli endotoxin with altered adrenergic activity. Circ Shock 12:165–176PubMedGoogle Scholar
  5. 5.
    Lam CJ, Tyml K, Martin CM et al (1994) Microvascular perfusion is impaired in a rat model of normotensive sepsis. J Clin Invest 94:2077–2083PubMedCrossRefGoogle Scholar
  6. 6.
    Farquhar I, Martin CM, Lam C et al (1996) Decreased capillary density in vivo in bowel mucosa of rats with normotensive sepsis. J Surg Res 61:190–196PubMedCrossRefGoogle Scholar
  7. 7.
    McCuskey RS, Urbaschek R, Urbaschek B (1996) The microcirculation during endotoxemia. Cardiovasc Res 32:752–763PubMedGoogle Scholar
  8. 8.
    De Backer D, Creteur J, Preiser J C et al (2002) Microvascular blood flow is altered in patients with sepsis. Am J Respir Crit Care Med 166:98–104PubMedCrossRefGoogle Scholar
  9. 9.
    De Backer D, Creteur J, Dubois MJ et al (2004) Microvascular alterations in patients with acute severe heart failure and cardiogenic shock. Am Heart J 147:91–99PubMedCrossRefGoogle Scholar
  10. 10.
    Jhanji S, Lee C, Watson D et al (2009) Microvascular flow and tissue oxygenation after major abdominal surgery: association with post-operative complications. Intensive -Care Med 35:671–677PubMedCrossRefGoogle Scholar
  11. 11.
    De Backer D, Dubois MJ, Schmartz D et al (2009) Microcirculatory alterations in cardiac surgery: effects of cardiopulmonary bypass and anesthesia. Ann Thorac Surg 88:1396–1403PubMedCrossRefGoogle Scholar
  12. 12.
    Sakr Y, Dubois M J, De Backer D et al (2004) Persistant microvasculatory alterations are associated with organ failure and death in patients with septic shock. Crit Care Med 32:1825–1831PubMedCrossRefGoogle Scholar
  13. 13.
    Singh S, Anning PB, Winlove CP et al (2001) Regional transcapillary albumin exchange in rodent endotoxaemia: effects of fluid resuscitation and inhibition of nitric oxide synthase. Clin Sci 100:81–89PubMedCrossRefGoogle Scholar
  14. 14.
    Hoffmann JN, Vollmar B, Laschke MW et al (2002) Hydroxyethyl starch (130 kD), but not crystalloid volume support, improves microcirculation during normotensive endotoxemia. Anesthesiology 97:460–470PubMedCrossRefGoogle Scholar
  15. 15.
    de Carvalho H, Dorigo D, Bouskela E (2001) Effects of Ringer-acetate and Ringerdextran solutions on the microcirculation after LPS challenge: observations in the hamster cheek pouch. Shock 15:157–162PubMedCrossRefGoogle Scholar
  16. 16.
    Ospina-Tascon G, Neves AP, Occhipinti G et al (2010) Effects of fluids on microvascular perfusion in patients with severe sepsis. Intensive Care Med 36:949–955PubMedCrossRefGoogle Scholar
  17. 17.
    Pottecher J, Deruddre S, Teboul JL et al (2010) Both passive leg raising and intravascular volume expansion improve sublingual microcirculatory perfusion in severe sepsis and septic shock. Intensive Care Med [Epub ahead of print]Google Scholar
  18. 18.
    Genzel-Boroviczeny O, Christ F, Glas V (2004) Blood transfusion increases functional capillary density in the skin of anemic preterm infants. Pediatr Res 56:751–755PubMedCrossRefGoogle Scholar
  19. 19.
    Tsai A G, Cabrales P, Intaglietta M (2004) Microvascular perfusion upon exchange transfusion with stored red blood cells in normovolemic anemic conditions. Transfusion 44:1626–1634PubMedCrossRefGoogle Scholar
  20. 20.
    Schwarte LA, Fournell A, van Bommel J et al (2005) Redistribution of intestinal microcirculatory oxygenation during acute hemodilution in pigs. J Appl Physiol 98:1070–1075PubMedCrossRefGoogle Scholar
  21. 21.
    Sakr Y, Chierego M, Piagnerelli M et al (2007) Microvascular response to red blood cell transfusion in patients with severe sepsis. Crit Care Med 35:1639–1644PubMedCrossRefGoogle Scholar
  22. 22.
    Secchi A, Wellmann R, Martin E et al (1997) Dobutamine maintains intestinal villus blood flow during normotensive endotoxemia: an intravital microscopic study in the rat. J Crit Care 12:137–141PubMedCrossRefGoogle Scholar
  23. 23.
    Secchi A, Ortanderl JM, Schmidt W et al (2001) Effects of dobutamine and dopexamine on hepatic micro- and macrocirculation during experimental endotoxemia: an intravital microscopic study in the rat. Crit Care Med 29:597–600PubMedCrossRefGoogle Scholar
  24. 24.
    De Backer D, Creteur J, Dubois MJ et al (2006) The effects of dobutamine on microcirculatory alterations in patients with septic shock are independent of its systemic effects. Crit Care Med 34:403–408PubMedCrossRefGoogle Scholar
  25. 25.
    Schmidt W, Tinelli M, Secchi A et al (2000) Influence of amrinone on intestinal villus blood flow during endotoxemia. J Crit Care 15:97–102PubMedCrossRefGoogle Scholar
  26. 26.
    Fries M, Ince C, Rossaint R et al (2008) Levosimendan but not norepinephrine improves microvascular oxygenation during experimental septic shock. Crit Care Med 36:1886–1891PubMedCrossRefGoogle Scholar
  27. 27.
    De Backer D, Biston P, Devriendt J et al (2010) Comparison of dopamine and norepinephrine in the treatment of shock. N Engl J Med 362:779–789PubMedCrossRefGoogle Scholar
  28. 28.
    Le Noble LM, Tangelder GJ, Slaaf DW et al (1987) Adrenergic stimulation of the rat mesenteric vascular bed: a combined micro- and macrocirculatory study. Pflugers Arch 410:250–256PubMedCrossRefGoogle Scholar
  29. 29.
    Friesenecker BE, Tsai AG, Martini J et al (2006) Arteriolar vasoconstrictive response: comparing the effects of arginine vasopressin and norepinephrine. Crit Care 10:R75PubMedCrossRefGoogle Scholar
  30. 30.
    Nakajima Y, Baudry N, Duranteau J et al (2006) Effects of vasopressin, norepinephrine and L-arginine on intestinal microcirculation in endotoxemia. Crit Care Med 1752–1757Google Scholar
  31. 31.
    LeDoux D, Astiz ME, Carpati CM et al (2000) Effects of perfusion pressure on tissue perfusion in septic shock. Crit Care Med 28:2729–2732PubMedCrossRefGoogle Scholar
  32. 32.
    Jhanji S, Stirling S, Patel N et al (2009) The effect of increasing doses of norepinephrine on tissue oxygenation and microvascular flow in patients with septic shock. Crit Care Med 7:1961–1966CrossRefGoogle Scholar
  33. 33.
    Dubin A, Pozo MO, Casabella CA et al (2009) Increasing arterial blood pressure with norepinephrine does not improve microcirculatory blood flow: a prospective study. Crit Care 13:R92PubMedCrossRefGoogle Scholar
  34. 34.
    Albert M, Losser MR, Hayon D et al (2004) Systemic and renal macro- and microcirculatory responses to arginine vasopressin in endotoxic rabbits. Crit Care Med 32:1891–1898PubMedCrossRefGoogle Scholar
  35. 35.
    Westphal M, Freise H, Kehrel BE et al (2004) Arginine vasopressin compromises gut mucosal microcirculation in septic rats. Crit Care Med 32:194–200PubMedCrossRefGoogle Scholar
  36. 36.
    Dubois MJ, De Backer D, Creteur J et al (2003) Effect of vasopressin on sublingual microcirculation in a patient with distributive shock. Intensive Care Med 29:1020–1023PubMedGoogle Scholar
  37. 37.
    Buwalda M, Ince C (2002) Opening the microcirculation: can vasodilators be useful in sepsis? Intensive Care Med 28:1208–1217PubMedCrossRefGoogle Scholar
  38. 38.
    Hollenberg SM, Broussard M, Osman J et al (2000) Increased microvascular reactivity and improved mortality in septic mice lacking inducible nitric oxide synthase. Circ Res 86:774–778PubMedGoogle Scholar
  39. 39.
    Spronk PE, Ince C, Gardien MJ et al (2002) Nitroglycerin in septic shock after intravascular volume resuscitation. Lancet 360:1395–1396PubMedCrossRefGoogle Scholar
  40. 40.
    den Uil CA, Caliskan K, Lagrand WK et al (2009) Dose-dependent beneflt of nitroglycerin on microcirculation of patients with severe heart failure. Intensive Care Med 35:1893–1899CrossRefGoogle Scholar
  41. 41.
    Boerma EC, Koopmans M, Konijn A et al (2010) Effects of nitroglycerin on sublingual microcirculatory blood flow in patients with severe sepsis/septic shock after a strict resuscitation protocol: A double-blind randomized placebo controlled trial. Crit Care Med 38:93–100PubMedCrossRefGoogle Scholar
  42. 42.
    Hoffmann JN, Vollmar B, Laschke MW et al (2004) Microhemodynamic and cellular mechanisms of activated protein C action during endotoxemia. Crit Care Med 32:1011–1017PubMedCrossRefGoogle Scholar
  43. 43.
    Lehmann C, Meissner K, Knock A et al (2006) Activated protein C improvesintes tinal microcirculation in experimental endotoxaemia in the rat. Crit Care 10:R157PubMedCrossRefGoogle Scholar
  44. 44.
    Marechal X, Favory R, Joulin O et al (2008) Endothelial glycocalyx damage during endotoxemia coincides with microcirculatory dysfunction and vascular oxidative stress. Shock 29:572–576PubMedGoogle Scholar
  45. 45.
    De Backer D, Verdant C, Chierego M et al (2006) Effects of drotrecogin alfa activated on microcirculatory alterations in patients with severe sepsis. Crit Care Med 34:1918–1924PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Italia 2011

Authors and Affiliations

  • D. De Backer
  • K. Donadello
  • S. Scolletta

There are no affiliations available

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