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Published in: Critical Care 4/2005

01-08-2005 | Review

Clinical manifestations of disordered microcirculatory perfusion in severe sepsis

Authors: Stephen Trzeciak, Emanuel P Rivers

Published in: Critical Care | Special Issue 4/2005

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Abstract

Microcirculatory dysfunction plays a pivotal role in the development of the clinical manifestations of severe sepsis. Prior to the advent of new imaging technologies, clinicians had been limited in their ability to assess the microcirculation at the bedside. Clinical evidence of microcirculatory perfusion has historically been limited to physical examination findings or surrogates that could be derived from global parameters of oxygen transport. This review explores: (1) the clinical manifestations of severe sepsis that can be linked to microcirculatory dysfunction; (2) the relationship between conventional hemodynamic parameters and microcirculatory blood flow indices; (3) the incorporation of microcirculatory function into the definition of 'shock' in the sepsis syndrome; (4) the role of the microcirculation in oxygen transport; and (5) the potential impact of novel sepsis therapies on microcirculatory flow. Although the study of the microcirculation has long been the domain of basic science, newly developed imaging technologies, such as orthogonal polarization spectral imaging, have now given us the ability to directly visualize and analyze microcirculatory blood flow at the bedside, and see the microcirculatory response to therapeutic interventions. Disordered microcirculatory flow can now be associated with systemic inflammation, acute organ dysfunction, and increased mortality. Using new technologies to directly image microcirculatory blood flow will help define the role of microcirculatory dysfunction in oxygen transport and circulatory support in severe sepsis.
Literature
1.
go back to reference De Backer D, Creteur J, Preiser JC, Dubois MJ, Vincent JL: Microvascular blood flow is altered in patients with sepsis. Am J Respir Crit Care Med 2002, 166: 98-104. 10.1164/rccm.200109-016OCCrossRefPubMed De Backer D, Creteur J, Preiser JC, Dubois MJ, Vincent JL: Microvascular blood flow is altered in patients with sepsis. Am J Respir Crit Care Med 2002, 166: 98-104. 10.1164/rccm.200109-016OCCrossRefPubMed
2.
go back to reference Spronk PE, Ince C, Gardien MJ, Mathura KR, Oudemans-van Straaten HM, Zandstra DF: Nitroglycerin in septic shock after intravascular volume resuscitation. Lancet 2002, 360: 1395-1396. 10.1016/S0140-6736(02)11393-6CrossRefPubMed Spronk PE, Ince C, Gardien MJ, Mathura KR, Oudemans-van Straaten HM, Zandstra DF: Nitroglycerin in septic shock after intravascular volume resuscitation. Lancet 2002, 360: 1395-1396. 10.1016/S0140-6736(02)11393-6CrossRefPubMed
3.
go back to reference 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 2004, 32: 1825-1831. 10.1097/01.CCM.0000138558.16257.3FCrossRefPubMed 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 2004, 32: 1825-1831. 10.1097/01.CCM.0000138558.16257.3FCrossRefPubMed
4.
go back to reference Bateman RM, Sharpe MD, Ellis CG: Bench-to-bedside review: microvascular dysfunction in sepsis – hemodynamics, oxygen transport, and nitric oxide. Crit Care 2003, 7: 359-373. 10.1186/cc2353PubMedCentralCrossRefPubMed Bateman RM, Sharpe MD, Ellis CG: Bench-to-bedside review: microvascular dysfunction in sepsis – hemodynamics, oxygen transport, and nitric oxide. Crit Care 2003, 7: 359-373. 10.1186/cc2353PubMedCentralCrossRefPubMed
5.
go back to reference Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B, Peterson E, Tomlanovich M, Early Goal-Directed Therapy Collaborative Group: Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 2001, 345: 1368-1377. 10.1056/NEJMoa010307CrossRefPubMed Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B, Peterson E, Tomlanovich M, Early Goal-Directed Therapy Collaborative Group: Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 2001, 345: 1368-1377. 10.1056/NEJMoa010307CrossRefPubMed
6.
go back to reference Aird WC: The role of the endothelium in severe sepsis and multiple organ dysfunction syndrome. Blood 2003, 101: 3765-3777. 10.1182/blood-2002-06-1887CrossRefPubMed Aird WC: The role of the endothelium in severe sepsis and multiple organ dysfunction syndrome. Blood 2003, 101: 3765-3777. 10.1182/blood-2002-06-1887CrossRefPubMed
7.
go back to reference Yan SB, Helterbrand JD, Hartman DL, Wright TJ, Bernard GR: Low levels of protein C are associated with poor outcome in severe sepsis. Chest 2001, 120: 915-922. 10.1378/chest.120.3.915CrossRefPubMed Yan SB, Helterbrand JD, Hartman DL, Wright TJ, Bernard GR: Low levels of protein C are associated with poor outcome in severe sepsis. Chest 2001, 120: 915-922. 10.1378/chest.120.3.915CrossRefPubMed
8.
go back to reference Ince C: Microcirculation in distress: a new resuscitation end point? Crit Care Med 2004, 32: 1963-1964. 10.1097/01.CCM.0000139617.88704.B9CrossRefPubMed Ince C: Microcirculation in distress: a new resuscitation end point? Crit Care Med 2004, 32: 1963-1964. 10.1097/01.CCM.0000139617.88704.B9CrossRefPubMed
10.
go back to reference Dellinger RP: Cardiovascular management of septic shock. Crit Care Med 2003, 31: 946-955. 10.1097/01.CCM.0000057403.73299.A6CrossRefPubMed Dellinger RP: Cardiovascular management of septic shock. Crit Care Med 2003, 31: 946-955. 10.1097/01.CCM.0000057403.73299.A6CrossRefPubMed
11.
go back to reference Nguyen HB, Rivers EP, Knoblich BP, Jacobsen G, Muzzin A, Ressler JA, Tomlanovich MC: Early lactate clearance is associated with improved outcome in severe sepsis and septic shock. Crit Care Med 2004, 32: 1637-1642. 10.1097/01.CCM.0000132904.35713.A7CrossRefPubMed Nguyen HB, Rivers EP, Knoblich BP, Jacobsen G, Muzzin A, Ressler JA, Tomlanovich MC: Early lactate clearance is associated with improved outcome in severe sepsis and septic shock. Crit Care Med 2004, 32: 1637-1642. 10.1097/01.CCM.0000132904.35713.A7CrossRefPubMed
12.
go back to reference Wo CC, Shoemaker WC, Appel PL, Bishop MH, Kram HB, Hardin E: Unreliability of blood pressure and heart rate to evaluate cardiac output in emergency resuscitation and critical illness. Crit Care Med 1993, 21: 218-223.CrossRefPubMed Wo CC, Shoemaker WC, Appel PL, Bishop MH, Kram HB, Hardin E: Unreliability of blood pressure and heart rate to evaluate cardiac output in emergency resuscitation and critical illness. Crit Care Med 1993, 21: 218-223.CrossRefPubMed
13.
go back to reference LeDoux D, Astiz ME, Carpati CM, Rackow EC: Effects of perfusion pressure on tissue perfusion in septic shock. Crit Care Med 2000, 28: 2729-2732. 10.1097/00003246-200008000-00007CrossRefPubMed LeDoux D, Astiz ME, Carpati CM, Rackow EC: Effects of perfusion pressure on tissue perfusion in septic shock. Crit Care Med 2000, 28: 2729-2732. 10.1097/00003246-200008000-00007CrossRefPubMed
14.
go back to reference Bourgoin A, Leone M, Delmas A, Garnier F, Albanese J, Martin C: Increasing mean arterial pressure in patients with septic shock: effects on oxygen variables and renal function. Crit Care Med 2005, 33: 780-786. 10.1097/01.CCM.0000157788.20591.23CrossRefPubMed Bourgoin A, Leone M, Delmas A, Garnier F, Albanese J, Martin C: Increasing mean arterial pressure in patients with septic shock: effects on oxygen variables and renal function. Crit Care Med 2005, 33: 780-786. 10.1097/01.CCM.0000157788.20591.23CrossRefPubMed
15.
go back to reference Donnino MW, Nguyen HB, Jacobsen G, Tomlanovich M, Rivers EP: Cryptic septic shock: a sub-analysis of early goal-directed therapy [abstract]. Chest 2003, 124: 90S. 10.1378/chest.124.1.90CrossRef Donnino MW, Nguyen HB, Jacobsen G, Tomlanovich M, Rivers EP: Cryptic septic shock: a sub-analysis of early goal-directed therapy [abstract]. Chest 2003, 124: 90S. 10.1378/chest.124.1.90CrossRef
16.
go back to reference Dellinger RP, Carlet JM, Masur H, Gerlach H, Calandra T, Cohen J, Gea-Banacloche J, Keh D, Marshall JC, Parker MM, Surviving Sepsis Campaign Management Guidelines Committee, et al.: Surviving sepsis campaign guidelines for management of severe sepsis and septic shock. Crit Care Med 2004, 32: 858-873. 10.1097/01.CCM.0000117317.18092.E4CrossRefPubMed Dellinger RP, Carlet JM, Masur H, Gerlach H, Calandra T, Cohen J, Gea-Banacloche J, Keh D, Marshall JC, Parker MM, Surviving Sepsis Campaign Management Guidelines Committee, et al.: Surviving sepsis campaign guidelines for management of severe sepsis and septic shock. Crit Care Med 2004, 32: 858-873. 10.1097/01.CCM.0000117317.18092.E4CrossRefPubMed
17.
go back to reference Vincent JL, Abraham E, Annane D, Bernard G, Rivers E, Van den Berghe G: Reducing mortality in sepsis: new directions. Crit Care 2002,6(suppl 3):S1-18. 10.1186/cc1860PubMedCentralCrossRefPubMed Vincent JL, Abraham E, Annane D, Bernard G, Rivers E, Van den Berghe G: Reducing mortality in sepsis: new directions. Crit Care 2002,6(suppl 3):S1-18. 10.1186/cc1860PubMedCentralCrossRefPubMed
18.
19.
go back to reference Aduen J, Bernstein WK, Khastgir T, Miller J, Kerzner R, Bhatiani A, Lustgarten J, Bassin AS, Davison L, Chernow B: The use and clinical importance of a substrate-specific electrode for rapid determination of blood lactate concentrations. JAMA 1994, 272: 1678-1685. 10.1001/jama.272.21.1678CrossRefPubMed Aduen J, Bernstein WK, Khastgir T, Miller J, Kerzner R, Bhatiani A, Lustgarten J, Bassin AS, Davison L, Chernow B: The use and clinical importance of a substrate-specific electrode for rapid determination of blood lactate concentrations. JAMA 1994, 272: 1678-1685. 10.1001/jama.272.21.1678CrossRefPubMed
20.
go back to reference Bakker J, Coffernils M, Leon M, Gris P, Vincent JL: Blood lactate levels are superior to oxygen-derived variables in predicting outcome in human septic shock. Chest 1991, 99: 956-962.CrossRefPubMed Bakker J, Coffernils M, Leon M, Gris P, Vincent JL: Blood lactate levels are superior to oxygen-derived variables in predicting outcome in human septic shock. Chest 1991, 99: 956-962.CrossRefPubMed
21.
go back to reference Bakker J, Gris P, Coffernils M, Kahn RJ, Vincent JL: Serial blood lactate levels can predict the development of multiple organ failure following septic shock. Am J Surg 1996, 171: 221-226. 10.1016/S0002-9610(97)89552-9CrossRefPubMed Bakker J, Gris P, Coffernils M, Kahn RJ, Vincent JL: Serial blood lactate levels can predict the development of multiple organ failure following septic shock. Am J Surg 1996, 171: 221-226. 10.1016/S0002-9610(97)89552-9CrossRefPubMed
22.
23.
go back to reference Krogh A: The number and the distribution of capillaries in muscle with the calculation of the oxygen pressure necessary for supplying tissue. J Physiol 1919, 52: 409-515.PubMedCentralCrossRefPubMed Krogh A: The number and the distribution of capillaries in muscle with the calculation of the oxygen pressure necessary for supplying tissue. J Physiol 1919, 52: 409-515.PubMedCentralCrossRefPubMed
24.
go back to reference Ellsworth ML, Pittman RN: Arterioles supply oxygen to capillaries by diffusion as well as by convection. Am J Physiol 1990, 258: H1240-H1243.PubMed Ellsworth ML, Pittman RN: Arterioles supply oxygen to capillaries by diffusion as well as by convection. Am J Physiol 1990, 258: H1240-H1243.PubMed
25.
go back to reference Beal AL, Cerra FB: Multiple organ failure syndrome in the 1990s. Systemic inflammatory response and organ dysfunction. JAMA 1994, 271: 226-233. 10.1001/jama.271.3.226CrossRefPubMed Beal AL, Cerra FB: Multiple organ failure syndrome in the 1990s. Systemic inflammatory response and organ dysfunction. JAMA 1994, 271: 226-233. 10.1001/jama.271.3.226CrossRefPubMed
26.
go back to reference Karimova A, Pinsky DJ: The endothelial response to oxygen deprivation: biology and clinical implications. Intensive Care Med 2001, 27: 19-31. 10.1007/s001340000790CrossRefPubMed Karimova A, Pinsky DJ: The endothelial response to oxygen deprivation: biology and clinical implications. Intensive Care Med 2001, 27: 19-31. 10.1007/s001340000790CrossRefPubMed
28.
go back to reference Ince C, Sinaasappel M: Microcirculatory oxygenation and shunting in sepsis and shock. Crit Care Med 1999, 27: 1369-1377. 10.1097/00003246-199907000-00031CrossRefPubMed Ince C, Sinaasappel M: Microcirculatory oxygenation and shunting in sepsis and shock. Crit Care Med 1999, 27: 1369-1377. 10.1097/00003246-199907000-00031CrossRefPubMed
29.
go back to reference Rivers EP, Rady MY, Martin GB, Fenn NM, Smithline HA, Alexander ME, Nowak RM: Venous hyperoxia after cardiac arrest. Characterization of a defect in systemic oxygen utilization. Chest 1992, 102: 1787-1793.CrossRefPubMed Rivers EP, Rady MY, Martin GB, Fenn NM, Smithline HA, Alexander ME, Nowak RM: Venous hyperoxia after cardiac arrest. Characterization of a defect in systemic oxygen utilization. Chest 1992, 102: 1787-1793.CrossRefPubMed
30.
go back to reference Rivers EP, Wortsman J, Rady MY, Blake HC, McGeorge FT, Buderer NM: The effect of the total cumulative epinephrine dose administered during human CPR on hemodynamic, oxygen transport, and utilization variables in the postresuscitation period. Chest 1994, 106: 1499-1507.CrossRefPubMed Rivers EP, Wortsman J, Rady MY, Blake HC, McGeorge FT, Buderer NM: The effect of the total cumulative epinephrine dose administered during human CPR on hemodynamic, oxygen transport, and utilization variables in the postresuscitation period. Chest 1994, 106: 1499-1507.CrossRefPubMed
31.
go back to reference Macias WL, Yan SB, Williams ND, Um SL, Sandusky GE, Ballard DW, Planquois J-MS: New insights into the protein C pathway: potential implications for the biological activities of drotrecogin alfa (activated). Critical Care 2005,9(suppl 4):S38-S45.PubMedCentralCrossRefPubMed Macias WL, Yan SB, Williams ND, Um SL, Sandusky GE, Ballard DW, Planquois J-MS: New insights into the protein C pathway: potential implications for the biological activities of drotrecogin alfa (activated). Critical Care 2005,9(suppl 4):S38-S45.PubMedCentralCrossRefPubMed
32.
go back to reference Buwalda M, Ince C: Opening the microcirculation: can vasodilators be useful in sepsis? Intensive Care Med 2002, 28: 1208-1217. 10.1007/s00134-002-1407-2CrossRefPubMed Buwalda M, Ince C: Opening the microcirculation: can vasodilators be useful in sepsis? Intensive Care Med 2002, 28: 1208-1217. 10.1007/s00134-002-1407-2CrossRefPubMed
33.
go back to reference De Backer D, Berre J, Zhang H, Kahn RJ, Vincent JL: Relationship between oxygen uptake and oxygen delivery in septic patients: effects of prostacyclin versus dobutamine. Crit Care Med 1993, 21: 1658-1664.CrossRefPubMed De Backer D, Berre J, Zhang H, Kahn RJ, Vincent JL: Relationship between oxygen uptake and oxygen delivery in septic patients: effects of prostacyclin versus dobutamine. Crit Care Med 1993, 21: 1658-1664.CrossRefPubMed
34.
go back to reference Pittet JF, Lacroix JS, Gunning K, Laverriere MC, Morel DR, Suter PM: Prostacyclin but not phentolamine increases oxygen consumption and skin microvascular blood flow in patients with sepsis and respiratory failure. Chest 1990, 98: 1467-1472.CrossRefPubMed Pittet JF, Lacroix JS, Gunning K, Laverriere MC, Morel DR, Suter PM: Prostacyclin but not phentolamine increases oxygen consumption and skin microvascular blood flow in patients with sepsis and respiratory failure. Chest 1990, 98: 1467-1472.CrossRefPubMed
35.
go back to reference Bihari D, Smithies M, Gimson A, Tinker J: The effects of vasodilation with prostacyclin on oxygen delivery and uptake in critically ill patients. N Engl J Med 1987, 317: 397-403.CrossRefPubMed Bihari D, Smithies M, Gimson A, Tinker J: The effects of vasodilation with prostacyclin on oxygen delivery and uptake in critically ill patients. N Engl J Med 1987, 317: 397-403.CrossRefPubMed
36.
go back to reference Radermacher P, Buhl R, Santak B, Klein M, Kniemeyer HW, Becker H, Tarnow J: The effects of prostacyclin on gastric intramucosal pH in patients with septic shock. Intensive Care Med 1995, 21: 414-421. 10.1007/BF01707410CrossRefPubMed Radermacher P, Buhl R, Santak B, Klein M, Kniemeyer HW, Becker H, Tarnow J: The effects of prostacyclin on gastric intramucosal pH in patients with septic shock. Intensive Care Med 1995, 21: 414-421. 10.1007/BF01707410CrossRefPubMed
37.
go back to reference Secchi A, Wellmann R, Martin E, Schmidt H: Dobutamine maintains intestinal villus blood flow during normotensive endotoxemia: an intravital microscopic study in the rat. J Crit Care 1997, 12: 137-141. 10.1016/S0883-9441(97)90043-5CrossRefPubMed Secchi A, Wellmann R, Martin E, Schmidt H: Dobutamine maintains intestinal villus blood flow during normotensive endotoxemia: an intravital microscopic study in the rat. J Crit Care 1997, 12: 137-141. 10.1016/S0883-9441(97)90043-5CrossRefPubMed
38.
go back to reference Duranteau J, Sitbon P, Teboul JL, Vicaut E, Anguel N, Richard C, Samii K: Effects of epinephrine, norepinephrine, or the combination of norepinephrine and dobutamine on gastric mucosa in septic shock. Crit Care Med 1999, 27: 893-900. 10.1097/00003246-199905000-00021CrossRefPubMed Duranteau J, Sitbon P, Teboul JL, Vicaut E, Anguel N, Richard C, Samii K: Effects of epinephrine, norepinephrine, or the combination of norepinephrine and dobutamine on gastric mucosa in septic shock. Crit Care Med 1999, 27: 893-900. 10.1097/00003246-199905000-00021CrossRefPubMed
39.
go back to reference Shoemaker WC, Appel PL, Kram HB: Hemodynamic and oxygen transport effects of dobutamine in critically ill general surgical patients. Crit Care Med 1986, 14: 1032-1037.CrossRefPubMed Shoemaker WC, Appel PL, Kram HB: Hemodynamic and oxygen transport effects of dobutamine in critically ill general surgical patients. Crit Care Med 1986, 14: 1032-1037.CrossRefPubMed
40.
go back to reference De Backer D, Dubois MJ, Creteur J, Sakr Y, Vincent JL: Microcirculatory alterations are an independent outcome predictor in patients with severe sepsis and septic shock [abstract]. Crit Care Med 2003, 31: A117.CrossRef De Backer D, Dubois MJ, Creteur J, Sakr Y, Vincent JL: Microcirculatory alterations are an independent outcome predictor in patients with severe sepsis and septic shock [abstract]. Crit Care Med 2003, 31: A117.CrossRef
Metadata
Title
Clinical manifestations of disordered microcirculatory perfusion in severe sepsis
Authors
Stephen Trzeciak
Emanuel P Rivers
Publication date
01-08-2005
Publisher
BioMed Central
Published in
Critical Care / Issue Special Issue 4/2005
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/cc3744

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