A Novel Scoring System for Humane Endpoints in Mice with Cecal Ligation and Puncture-Induced Sepsis

Area of Science:

• Veterinary Medicine
• Animal Models
• Sepsis Research

Background:

• Animal models are crucial for sepsis research but face challenges with high mortality and predicting death.
• Accurate prediction of death is needed to establish humane endpoints in animal studies.
• Visual scoring systems require high interobserver agreement for reliable results.

Purpose of the Study:

• To develop and validate a visual scoring system for mice with cecal ligation and puncture (CLP)-induced sepsis.
• To assess the system's ability to predict mortality and identify humane endpoints.
• To evaluate interobserver agreement for the scoring system's parameters.

Main Methods:

• A scoring system was developed using three visual parameters: respiratory status, activity and response to stimulus (ASR), and eye appearance (scores 0-3).
• Interobserver agreement was assessed using the weighted Cohen κ statistic on 283 mice.
• The scoring system and temperature were used to monitor 80 mice post-CLP, with data analyzed for prediction of death.

Main Results:

• Substantial to near-perfect interobserver agreement was achieved for all scoring parameters.
• The scoring system accurately discriminated between surviving and nonsurviving septic mice (AUC = 0.8997).
• Key parameters (ASR, eye appearance) and a combined score predicted death, as did temperature, with high sensitivity and specificity.

Conclusions:

• The developed visual scoring system is a reliable tool for predicting death in the mouse CLP model.
• This system facilitates the identification of humane endpoints, refining the CLP model and avoiding spontaneous deaths.
• The scoring system improves the systematic assessment and management of animal welfare in sepsis research.