A robust scoring system to evaluate sepsis severity in an animal model

BMC Research Notes

Tina Mele¹  John K McCormick²  SM Mansour Haeryfar²  Marisa Donnelly³  Stacey X Xu²  Ram V Anantha²  Bradly Shrum³ 

[1] Division of General Surgery and Critical Care, Room A8-124, London Health Sciences Centre-University Hospital, 339 Windermere Road, London, ON N6A 5A5, Canada;Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada;Division of General Surgery, Department of Surgery, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada

关键词: Infectious diseases;    Cytokine analysis;    Animal model;    Peritonitis;    Septic shock;    Sepsis;    Sepsis score;   

Others  :  1133755
DOI  :  10.1186/1756-0500-7-233

 received in 2014-02-26, accepted in 2014-04-09,  发布年份 2014

【 摘 要 】

Background

The lack of a reliable scoring system that predicts the development of septic shock and death precludes comparison of disease and/or treatment outcomes in animal models of sepsis. We developed a murine sepsis score (MSS) that evaluates seven clinical variables, and sought to assess its validity and reliability in an experimental mouse model of polymicrobial sepsis.

Methods

Stool collected from the cecum of C57BL/6 (B6) mice was dissolved in 0.9% normal saline (NS) and filtered, resulting in a fecal solution (FS) which was injected intraperitoneally into B6 mice. Disease severity was monitored by MSS during the experimental timeline. Blood and tissue samples were harvested for the evaluation of inflammatory changes after sepsis induction. The correlation between pro-inflammatory markers and MSS was assessed by the Spearman rank correlation coefficient.

Results

Mice injected with FS at a concentration of 90 mg/mL developed polymicrobial sepsis with a 75% mortality rate at 24 hours. The MSS was highly predictive of sepsis progression and mortality, with excellent discriminatory power, high internal consistency (Cronbach alpha coefficient = 0.92), and excellent inter-rater reliability (intra-class coefficient = 0.96). An MSS of 3 had a specificity of 100% for predicting onset of septic shock and death within 24 hours. Hepatic dysfunction and systemic pro-inflammatory responses were confirmed by biochemical and cytokine analyses where the latter correlated well with the MSS. Significant bacterial dissemination was noted in multiple organs. Furthermore, the liver, spleen, and intestine demonstrated histopathological evidence of injury.

Conclusions

The MSS reliably predicts disease progression and mortality in an animal model of polymicrobial sepsis. More importantly, it may be used to assess and compare outcomes among various experimental models of sepsis, and serve as an ethically acceptable alternative to death as an endpoint.

【 授权许可】

   
2014 Shrum et al.; licensee BioMed Central Ltd.

【 图 表 】

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