Evaluation of surrogate markers of impending death in the galactosamine-sensitized murine model of bacterial endotoxemia

Background and Purpose: When evaluating vaccines for efficacy against gram- negative endotoxemia, the challenge has historically required death of a la rge percentage of test subjects. We attempted to identify surrogate markers of impending death to allow for early euthanasia without interfering with experimental data collection. Methods: Galactosamine- sensitized mice (n = 140) were inoculated intraperi toneally with various dosages of endotoxin, and development of clinical sig ns of disease-body temperature, body weight, hunched posture, ruffled coat, inability to ambulate, and loss of consciousness-was evaluated. Results: Wide fluctuations in body temperature (+/- 4 degrees C) were obser ved in survivors and nonsurvivors, Posture, coat, and body weight were not accurate predictors of death. Only inability to ambulate, with a positive p redictive value of 100% (11 of 11), accurately predicted death in the exper imental mice of this study. Conclusion: Using this surrogate marker, loss of ability to ambulate, 11 of 13 mice that developed this sign could have been euthanized early, prevent ing anywhere from 2 to 22 h of potential distress prior to death.