Bench-to-bedside review: Mechanisms of critical illness – classifying microcirculatory flow abnormalities in distributive shock

Over 30 years ago Weil and Shubin proposed a re-classification of shock states and identified hypovolemic, cardiogenic, obstructive and distributive shock. The first three categories have in common that they are associated with a fall in cardiac output. Distributive shock, such as occurs during sepsis and septic shock, however, is associated with an abnormal distribution of microvascular blood flow and metabolic distress in the presence of normal or even supranormal levels of cardiac output. This Bench-to-bedside review looks at the recent insights that have been gained into the nature of distributive shock. Its pathophysiology can best be described as a microcirculatory and mitochondrial distress syndrome, where time and therapy form an integral part of the definition. The clinical introduction of new microcirculatory imaging techniques, such as orthogonal polarization spectral and side-stream dark-field imaging, have allowed direct observation of the microcirculation at the bedside. Images of the sublingual microcirculation during septic shock and resuscitation have revealed that the distributive defect of blood flow occurs at the capillary level. In this paper, we classify the different types of heterogeneous flow patterns of microcirculatory abnormalities found during different types of distributive shock. Analysis of these patterns gave a five class classification system to define the types of microcirculatory abnormalities found in different types of distributive shock and indicated that distributive shock occurs in many other clinical conditions than just sepsis and septic shock. It is likely that different mechanisms defined by pathology and treatment underlie these abnormalities observed in the different classes. Functionally, however, they all cause a distributive defect resulting in microcirculatory shunting and regional dysoxia. It is hoped that this classification system will help in the identification of mechanisms underlying these abnormalities and indicate optimal therapies for resuscitating septic and other types of distributive shock.

[1]  J. Vincent,et al.  Persistent microcirculatory alterations are associated with organ failure and death in patients with septic shock* , 2004, Critical care medicine.

[2]  Can Ince,et al.  Quantifying bedside-derived imaging of microcirculatory abnormalities in septic patients: a prospective validation study , 2005, Critical care.

[3]  Jean-Charles Preiser,et al.  Microvascular blood flow is altered in patients with sepsis. , 2002, American journal of respiratory and critical care medicine.

[4]  D. Lidington,et al.  Lipopolysaccharide‐induced reductions in cellular coupling correlate with tyrosine phosphorylation of connexin 43 , 2002, Journal of cellular physiology.

[5]  S. Marsch,et al.  Inducible nitric oxide synthase inhibition improves intestinal microcirculatory oxygenation and CO2 balance during endotoxemia in pigs , 2005, Intensive Care Medicine.

[6]  M. Pinsky,et al.  Functional hemodynamic monitoring , 2005, Critical care.

[7]  P. T. Phang,et al.  Heterogeneity of gut capillary transit times and impaired gut oxygen extraction in endotoxemic pigs. , 1996, Journal of applied physiology.

[8]  Can Ince,et al.  Direct Observation of the Human Cerebral Microcirculation During Aneurysm Surgery Reveals Increased Arteriolar Contractility , 2004, Stroke.

[9]  M. Brezis,et al.  Determinants of intrarenal oxygenation. II. Hemodynamic effects. , 1994, The American journal of physiology.

[10]  W. Sibbald,et al.  Effect of a maldistribution of microvascular blood flow on capillary O2 extraction in sepsis , 2002 .

[11]  C. Ince,et al.  Sidestream dark field imaging: an improved technique to observe sublingual microcirculation , 2005, Critical Care.

[12]  H J Meiselman,et al.  Red blood cell aggregation in experimental sepsis. , 1997, The Journal of laboratory and clinical medicine.

[13]  S. Trzeciak,et al.  Clinical manifestations of disordered microcirculatory perfusion in severe sepsis , 2005, Critical care.

[14]  Can Ince,et al.  Nitroglycerin in septic shock after intravascular volume resuscitation , 2002, The Lancet.

[15]  M. Gladwin,et al.  Nitrite reduction to nitric oxide by deoxyhemoglobin vasodilates the human circulation , 2003, Nature Medicine.

[16]  A. Grover,et al.  Effects of peroxynitrite on sarco/endoplasmic reticulum Ca2+ pump isoforms SERCA2b and SERCA3a. , 2003, American journal of physiology. Cell physiology.

[17]  Can Ince,et al.  Thrombolysis in fulminant purpura: Observations on changes in microcirculatory perfusion during succesful treatment , 2006, Thrombosis and Haemostasis.

[18]  Christopher G Ellis,et al.  The microcirculation as a functional system , 2005, Critical care.

[19]  C. Ince,et al.  Functional heterogeneity of oxygen supply-consumption ratio in the heart. , 1999, Cardiovascular research.

[20]  C. Ince,et al.  Sublingual microcirculatory flow is impaired by the vasopressin‐analogue terlipressin in a patient with catecholamine‐resistant septic shock , 2005, Acta anaesthesiologica Scandinavica.

[21]  J. Vincent,et al.  The effects of dobutamine on microcirculatory alterations in patients with septic shock are independent of its systemic effects* , 2006, Critical care medicine.

[22]  K. Messmer,et al.  Orthogonal polarization spectral imaging: A new method for study of the microcirculation , 1999, Nature Medicine.

[23]  K. Silamut,et al.  Red blood cell deformability as a predictor of anemia in severe falciparum malaria. , 1999, The American journal of tropical medicine and hygiene.

[24]  M. Fink Bench-to-bedside review: Cytopathic hypoxia , 2002, Critical care.

[25]  K. Müller,et al.  Heterogeneous expression of cell adhesion molecules by endothelial cells in ARDS , 2002, The Journal of pathology.

[26]  P. Cabrales,et al.  Oxygen release from arterioles with normal flow and no-flow conditions. , 2006, Journal of applied physiology.

[27]  E. Rackow,et al.  Effects of perfusion pressure on tissue perfusion in septic shock , 2000, Critical care medicine.

[28]  R. Heine,et al.  Endothelial glycocalyx damage coincides with microalbuminuria in type 1 diabetes. , 2006, Diabetes.

[29]  Can Ince,et al.  The microcirculation is the motor of sepsis , 2005, Critical care.

[30]  C. Ince,et al.  Opening the microcirculation: can vasodilators be useful in sepsis? , 2002, Intensive Care Medicine.

[31]  C. Ince,et al.  Redistribution of intestinal microcirculatory oxygenation during acute hemodilution in pigs. , 2005, Journal of applied physiology.

[32]  Aleksander S Golub,et al.  Erythrocyte-associated transients in PO2 revealed in capillaries of rat mesentery. , 2005, American journal of physiology. Heart and circulatory physiology.

[33]  S. Segal,et al.  Regulation of Blood Flow in the Microcirculation , 2005, Microcirculation.

[34]  M. Sharpe,et al.  Effect of a maldistribution of microvascular blood flow on capillary O2 extraction in sepsis , 2002, American journal of physiology. Heart and circulatory physiology.

[35]  M. Ellsworth,et al.  Arterioles supply oxygen to capillaries by diffusion as well as by convection. , 1990, The American journal of physiology.

[36]  P. Liss,et al.  Intrarenal oxygen tension measured by a modified Clark electrode at normal and low blood pressure and after injection of x-ray contrast media , 1997, Pflügers Archiv.

[37]  J. Vincent,et al.  Sublingual capnometry tracks microcirculatory changes in septic patients , 2006, Intensive Care Medicine.

[38]  K. Suzuki,et al.  Response of intra-acinar pulmonary microvessels to hypoxia, hypercapnic acidosis, and isocapnic acidosis. , 1998, Circulation research.

[39]  J. Vincent Hemodynamic support in septic shock , 2001, Intensive Care Medicine.

[40]  J. Vincent,et al.  Effect of vasopressin on sublingual microcirculation in a patient with distributive shock , 2003, Intensive Care Medicine.

[41]  John Land,et al.  Association between mitochondrial dysfunction and severity and outcome of septic shock , 2002, The Lancet.

[42]  R. Shonat,et al.  Oxygen tension gradients and heterogeneity in venous microcirculation: a phosphorescence quenching study. , 1997, The American journal of physiology.

[43]  A. Taylor,et al.  Capillary fluid exchange. , 1999, The American journal of physiology.

[44]  E. Vicaut,et al.  Microcirculation in intestinal villi: a comparison between hemorrhagic and endotoxin shock. , 2001, American journal of respiratory and critical care medicine.

[45]  Wanchun Tang,et al.  Increases in tissue Pco2 during circulatory shock reflect selective decreases in capillary blood flow* , 2006, Critical care medicine.

[46]  Can Ince,et al.  Abnormal microcirculation in brain tumours during surgery , 2001, The Lancet.

[47]  C. Ince,et al.  Microcirculatory oxygenation and shunting in sepsis and shock. , 1999, Critical care medicine.

[48]  J. Vincent,et al.  Inflammatory response to cardiopulmonary bypass: mechanisms involved and possible therapeutic strategies. , 1997, Chest.

[49]  J. Vincent,et al.  Effects of drotrecogin alfa activated on microcirculatory alterations in patients with severe sepsis , 2006, Critical care medicine.

[50]  Marcos Intaglietta,et al.  Microvascular oxygen distribution in awake hamster window chamber model during hyperoxia. , 2003, American journal of physiology. Heart and circulatory physiology.

[51]  M. Weil,et al.  Proposed reclassification of shock states with special reference to distributive defects. , 1971, Advances in experimental medicine and biology.