• Kevin Sherer, Yan Li, Xizhong Cui, Xuemei Li, Mani Subramanian, Michael W Laird, Mahtab Moayeri, Stephen H Leppla, Yvonne Fitz, Junwu Su, and Peter Q Eichacker.
• Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, MD, USA.
• Crit. Care Med. 2007 Jun 1; 35 (6): 1560-7.

ObjectiveThe aim of this study was to test the effects of normal saline treatment either alone or in combination with protective antigen-directed monoclonal antibody in a lethal toxin-infused rat model of anthrax sepsis.DesignProspective controlled animal study.SettingAnimal research laboratory.SubjectsSprague-Dawley rats (n = 539).InterventionsWe initially tested the efficacy of three normal saline doses (5, 10, or 20 mL/kg/hr intravenously for 24 hrs) or none (controls) started when rats were treated with either lethal toxin (24-hr infusion) or, for comparison, lipopolysaccharide (24-hr infusion) or Escherichia coli (intravenous bolus). We then investigated delaying normal saline for 6 hrs or combining it with protective antigen-directed monoclonal antibody following lethal toxin challenge.Measurements And Main ResultsDose did not alter the effects of normal saline with any challenge (p not significant for all) or when combined with protective antigen-directed monoclonal antibody, so this variable was averaged in analysis. In initial studies, normal saline decreased mortality (mean hazards ratio of survival +/- SE) significantly with E. coli challenge (-0.66 +/- 0.25, p = .009 averaged over normal saline dose) but not lipopolysaccharide (-0.17 +/- 0.20). In contrast, normal saline increased mortality significantly with lethal toxin (0.69 +/- 0.20, p = .001) in a pattern different from E. coli and lipopolysaccharide (p ConclusionsThese findings raise the possibility that normal saline treatment may actually worsen outcome with anthrax lethal toxin. Furthermore, lethal toxin-directed therapies may not be as beneficial when used in combination with this type of fluid support.

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