title: Early multiple organ failure after recurrent endotoxemia in the presence of vasoconstrictor-masked hypovolemia.
abstract: OBJECTIVE
  Critically 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.
  
  
  METHODS
  Prospective, randomized laboratory investigation.
  
  
  METHODS
  University research laboratory.
  
  
  METHODS
  Eighteen adult chronically instrumented sheep.
  
  
  METHODS
  The 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.
  
  
  RESULTS
  Despite 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).
  
  
  CONCLUSIONS
  Hypovolemia 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.
authors.affiliation: Klinik und Poliklinik für Anästhesiologie und operative Intensivmedizin, Universitätsklinikum Münster, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Hinder
authors.forename: Henning D
authors.initials: HD
authors.lastname: Stubbe
authors.forename: Hugo
authors.initials: H
authors.lastname: Van Aken
authors.forename: Hideo A
authors.initials: HA
authors.lastname: Baba
authors.forename: Ulrich R
authors.initials: UR
authors.lastname: Jahn
authors.forename: Gerhard
authors.initials: G
authors.lastname: Brodner
authors.forename: Christian
authors.initials: C
authors.lastname: August
authors.forename: Michael
authors.initials: M
authors.lastname: Erren
authors.forename: Michael
authors.initials: M
authors.lastname: Booke
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000009:adverse effects*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001810:Blood Volume / Q000187:drug effects; D016638:Critical Illness; D004195:Disease Models, Animal; D019446:Endotoxemia / Q000150:complications* / Q000188:drug therapy*; D004731:Endotoxins / Q000009:adverse effects; D005260:Female; D020896:Hypovolemia / Q000175:diagnosis / Q000209:etiology* / Q000401:mortality; D015994:Incidence; D009102:Multiple Organ Failure / Q000175:diagnosis / Q000209:etiology* / Q000401:mortality; D009655:Octopamine / Q000009:adverse effects* / Q000031:analogs & derivatives*; D011446:Prospective Studies; D011897:Random Allocation; D012008:Recurrence; D012307:Risk Factors; D012485:Salmonella typhi; D012756:Sheep; D016019:Survival Analysis; D018746:Systemic Inflammatory Response Syndrome / Q000150:complications* / Q000188:drug therapy*; D014655:Vascular Resistance / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000009:adverse effects*
chemical_list: D000316:Adrenergic alpha-Agonists; D004731:Endotoxins; D014662:Vasoconstrictor Agents; D009655:Octopamine; C005310:norfenefrine