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- Title
The individual survival benefits of tumor necrosis factor soluble receptor and fluid administration are not additive in a rat sepsis model.
- Authors
Ping Qiu; Yan Li; Yi Ding; Jia Weng; Banks, Steven; Kern, Steven; Fitz, Yvonne; Suffredini, Anthony; Eichacker, Peter; Xizhong Cui
- Abstract
Background: Tumor necrosis factor (TNF) antagonists [e.g., TNF soluble receptor (TNFsr)] improved survival in preclinical but not clinical sepsis trials. However fluid support-itself beneficial-is standard clinically but rarely employed in preclinical sepsis models. We hypothesized that these therapies may not have additive benefit. Methods and results: Antibiotic-treated rats ( n = 156) were randomized to intratracheal or intravenous Escherichia coli challenges (>LD50) and either placebo or TNFsr and 24 h fluid treatments alone or together. The survival effects of these therapies did not differ significantly comparing challenge routes. When averaged across route, while TNFsr or fluid alone decreased the hazard ratio of death significantly [ln ± standard error (SE): −0.65 ± 0.30 and −0.62 ± 0.30, respectively, p ≤ 0.05], together they did not ( p = 0.16). Furthermore, the observed effect of TNFsr and fluid together on reducing the hazard ratio was significantly less than estimated (−0.37 ± 0.29 versus −1.27 ± 0.43, respectively, p = 0.027) based on TNFsr and fluid alone. While each treatment increased central venous pressure at 6 and 24 h, the observed effects of the combination were also less than estimated ones ( p ≤ 0.0005). Conclusions: The individual survival benefits of TNFsr and fluids were not additive in this rat sepsis model. Investigating new sepsis therapies together with conventional ones during preclinical testing may be informative.
- Subjects
TUMOR necrosis factors; SEPTICEMIA treatment; CLINICAL trials; ESCHERICHIA coli; LABORATORY rats
- Publication
Intensive Care Medicine, 2011, Vol 37, Issue 10, p1688
- ISSN
0342-4642
- Publication type
Article
- DOI
10.1007/s00134-011-2324-z