• Frank Hinder, Henning D Stubbe, Hugo Van Aken, Hideo A Baba, Ulrich R Jahn, Gerhard Brodner, Christian August, Michael Erren, and Michael Booke.
• Klinik und Poliklinik für Anästhesiologie und operative Intensivmedizin, Universitätsklinikum Münster, Germany.
• Crit. Care Med. 2003 Mar 1; 31 (3): 903-9.

ObjectiveCritically ill patients who develop multiple organ failure during systemic inflammatory states are often predisposed to hypovolemia and vasoconstrictor therapy. Although numerous investigations have evaluated the sequelae of systemic inflammation, no data are available on the contribution of chronic vasoconstrictor-masked hypovolemia to organ dysfunction and morphology.DesignProspective, randomized laboratory investigation.SettingUniversity research laboratory.SubjectsEighteen adult chronically instrumented sheep.InterventionsThe animals were randomly assigned to one of three groups. In the norfenefrine-masked hypovolemia plus endotoxemia (NMH+ENDO) group, mean arterial pressures of 80 mm Hg were maintained by using the alpha1-adrenergic catecholamine norfenefrine for 52 hrs during hypovolemia. Hypovolemia was induced by hemorrhage (about 23 mL x kg(-1)) until mean arterial pressures reached 40 mm Hg. Endotoxin (0.5 microg x k(-1)) was then injected after 4, 16, 28, and 40 hrs. The NMH group received norfenefrine-masked hypovolemia but no endotoxin. In the ENDO group, recurrent endotoxemia was induced during normovolemia.Measurements And Main ResultsDespite profound differences in fluid management, cardiovascular filling pressures were not statistically different between groups. Endotoxemia induced norfenefrine-refractory shock (p < .05 vs. the other groups) and contributed to renal dysfunction only during vasoconstrictor-masked hypovolemia. Norfenefrine-masked hypovolemia caused disseminated cardiac cell necrosis independent of endotoxemia (p < .05 vs. ENDO).ConclusionsHypovolemia can be masked when volume status is monitored by filling pressures. In this new model of endotoxemia-associated multiple organ failure, chronic vasoconstrictor-masked hypovolemia turned systemic inflammation into a life-threatening condition with renal and cardiovascular failure. Cardiomyocyte necroses were caused by vasoconstrictor-masked hypovolemia but were unrelated to cardiovascular failure.

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