title: Inflammatory and circulatory effects of the reduction of endotoxin concentration in established porcine endotoxemic shock--a model of endotoxin elimination.
abstract: OBJECTIVE
  To study whether a reduction of the endotoxin load, once a generalized inflammatory state has been established, reduces the inflammatory response and endotoxin-induced effects on circulation, hypoperfusion, and organ dysfunction.
  
  
  METHODS
  Prospective parallel-grouped placebo-controlled randomized interventional experimental study.
  
  
  METHODS
  University research unit.
  
  
  METHODS
  Healthy pigs.
  
  
  METHODS
  The animals were subjected to a continuous endotoxin infusion rate of either 4.0 or 0.063 microg endotoxin x kg x h for 1, 2, or 6 hours. The 1- and 2-hour infusion groups represented the applied therapy by a reduction of the endotoxin load of 5/6 and 2/3, respectively.
  
  
  RESULTS
  During a 6-hour experiment, laboratory and physiologic parameters were recorded hourly in 26 anesthetized and mechanically ventilated pigs. Primary end point was to detect differences in tumor necrosis factor-alpha (TNF-alpha) concentration during the last 3 hours of the experiment. Despite the early reduction of the endotoxin load, no effect on TNF-alpha concentration was observed. Similarly, in circulatory parameters, such as mean arterial pressure and oxygen delivery, and in platelet count and renal function, no effects were noted. However, there was some improvement in pulmonary compliance and function as determined by Pao2, Paco2, and pH. These changes were associated with slight improvements in leukocyte response and capillary leakage.
  
  
  CONCLUSIONS
  Termination of the endotoxin infusion represents an incontestable model of endotoxin concentration reduction. Endotoxin elimination strategies applied at the TNF-alpha peak or later will have very little or no effect on TNF-alpha-mediated toxicity. Nevertheless, there was an effect on the leukocyte response that was associated with an improvement in respiratory function and microcirculation, making it impossible to rule out fully the beneficial effect of this strategy. However, the effects were limited in relation to the magnitude of the endotoxin concentration reduction and the very early application of the antiendotoxin measure.
authors.affiliation: Department of Anesthesiology and Intensive Care, Eskilstuna County Hospital, Mälarsjukhuset, Sweden.
authors.forename: Markus
authors.initials: M
authors.lastname: Carlsson
authors.forename: Miklós
authors.initials: M
authors.lastname: Lipcsey
authors.forename: Anders
authors.initials: A
authors.lastname: Larsson
authors.forename: Eva
authors.initials: E
authors.lastname: Tano
authors.forename: Sten
authors.initials: S
authors.lastname: Rubertsson
authors.forename: Mats
authors.initials: M
authors.lastname: Eriksson
authors.forename: Jan
authors.initials: J
authors.lastname: Sjölin
mesh_terms: D000818:Animals; D001775:Blood Circulation / Q000187:drug effects*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004731:Endotoxins / Q000008:administration & dosage* / Q000097:blood; D006439:Hemodynamics / Q000187:drug effects; D007249:Inflammation; D012772:Shock, Septic / Q000097:blood / Q000276:immunology* / Q000503:physiopathology*; D013552:Swine
chemical_list: D004731:Endotoxins