Liver Perfusion in Sepsis, Septic Shock, and Multiorgan Failure

Authors

  • Herbert Spapen

    Corresponding author
    1. Intensive Care Department, University Hospital, Vrije Universiteit Brussels, Brussels, Belgium
    • Intensive Care Department. University Hospital, Vrije Universiteit Brussels, Laarbeeklaan 101, B-1090 Brussels, Belgium
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Abstract

Sepsis causes significant alterations in the hepatic macro- and microcirculation. Diverging views exist on global hepatic blood flow during experimental sepsis because of the large variety in animal and sepsis models. Fluid-resuscitated clinical sepsis is characterized by ongoing liver ischemia due to a defective oxygen extraction despite enhanced perfusion. The effects of vasoactive agents on the hepatosplanchnic circulation are variable, mostly anecdotal, and depend on baseline perfusion, time of drug administration, and use of concomitant medication. Microvascular blood flow disturbances are thought to play a pivotal role in the development of sepsis-induced multiorgan failure. Redistribution of intrahepatic blood flow in concert with a complex interplay between sinusoidal endothelial cells, liver macrophages, and passing leukocytes lead to a decreased perfusion and blood flow velocity in the liver sinusoids. Activation and dysfunction of the endothelial cell barrier with subsequent invasion of neutrophils and formation of microthrombi further enhance liver tissue ischemia and damage. Substances that regulate (micro)vascular tone, such as nitric oxide, endothelin-1, and carbon monoxide, are highly active during sepsis. Possible interactions between these mediators are not well understood, and their therapeutic manipulation produces equivocal or disappointing results. Whether and how standard resuscitation therapy influences the hepatic microvascular response to sepsis is unknown. Indirect evidence supports the concept that improving the microcirculation may prevent or ameliorate sepsis-induced organ failure. Anat Rec, 291:714–720, 2008. © 2008 Wiley-Liss, Inc.

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