Sepsis is associated with a marked intravascular fluid deficit caused by vasodilatation, venous pooling, and increased microvascular leak. The most striking clinical feature is fluid imbalance and the associated hemodynamic instability despite extensive fluid therapy. So far, the treatment options are fairly unspecific. It seems to be most important to guarantee adequate volume replacement in septic patients aiming at restoration and maintenance of intravascular volume in order to improve organ perfusion and nutritive microcirculatory flow. The type of fluid used is apparently less important. Despite new information, the current understanding of the complex, dynamic pathophysiol-ogy of sepsis-induced microvascular leak is still incomplete. Therefore, at present, neither standardized criteria for assessment of sepsis-induced microvascular leak, nor any specific therapeutic interventions are available. Promising agents for the treatment of microvascular leak have been developed in animal models. It remains to be seen whether they can be incorporated clinically.


Edema: Excessive amount of watery fluid accumulated in the intercellular spaces, most commonly present in subcutaneous tissue.

Microvasculature leakage: Leakage of intravascular fluids into the extravascular space. This syndrome is observed in patients who demonstrate a state of generalized leaky capillaries following shock syndromes, low-flow states, ischemia-reperfusion injuries, toxemias, or poisoning. It can lead to generalized edema and multiple organ failure.

Multiple organ failure: Progressive condition usually characterized by combined failure of several organs such as the lungs, liver, and kidney, along with some clotting mechanisms.

Sepsis: Presence of pathogenic microorganisms or their toxins in tissues or in the blood.

Septic shock: Infection-induced hypotension not reversed with fluid resuscitation and associated with organ dysfunction or hypoperfusion abnormalities.

Severe sepsis: Infection-induced organ dysfunction or hypoperfusion abnormalities.


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2. Groeneveld, A. B., Bronsveld, W., and Thijs, L. G. (1986). Hemody-namic determinants of mortality in human septic shock. Surgery 99, 140-153.

3. Aird, W. C. (2003). The role of the endothelium in severe sepsis and multiple organ dysfunction syndrome. Blood 101, 3765-3777. A review article with a special emphasis on the role of the endothelium in the host response in sepsis.

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5. Michel, C. C., and Curry, F. E. (1999). Microvascular permeability. Physiol. Rev. 79, 703-761. A detailed review of the mechanisms involved in the pathogenesis of microvascular permeability.

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7. Marx. G., Vangerow. B., Burczyk. C., Gratz. K. F., Maassen. N., Cobas Meyer. M., Leuwer. M., Kuse. E., and Rueckoldt. H. (2000). Evaluation of noninvasive determinants for capillary leakage syndrome in septic shock patients. Intensive Care Med. 26, 1252-1258.

8. Marx, G., Cobas Meyer, M., Schuerholz, T., Vangerow, B., Gratz, K. F., Hecker, H., Sumpelmann, R., Rueckoldt, H., and Leuwer, M. (2002). Hydroxyethyl starch and modified fluid gelatin maintain plasma volume in a porcine model of septic shock with capillary leakage. Intensive Care Med. 28, 629-635. This study demonstrates that plasma volume can be maintained in septic pigs despite increased microvascular permeability by artificial colloids but not by crystalloids.

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Capsule Biography

Dr. G. Marx has been Senior Lecturer at the University Department of Anaesthesia in Liverpool and Honorary Consultant in Intensive Care Medicine at the Royal Liverpool University Hospital since 2000. His key research topics are clinical and preclinical aspects of sepsis and increased microvascular leak syndrome. He has a particular interest in the development of new colloids and their potential therapeutic implications.

M. Leuwer has been Professor of Anaesthesia and Head of the University Department of Anaesthesia in Liverpool since 2000. His research interests are the interactions of phenol derivates with ion channels in view of their potential as a new class of local anesthetic/antidysrhythmic and clinical and preclinical aspects of sepsis and increased microvascular leak syndrome.

Essentials of Human Physiology

Essentials of Human Physiology

This ebook provides an introductory explanation of the workings of the human body, with an effort to draw connections between the body systems and explain their interdependencies. A framework for the book is homeostasis and how the body maintains balance within each system. This is intended as a first introduction to physiology for a college-level course.

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