A novel antibiotic based long-term model of ovine smoke inhalation injury and septic shock

Abstract

We modified our established and clinically relevant ARDS model of smoke inhalation injury and septic shock by administration of combined antibiotics (AB) such as piperacillin and ciprofloxacin, to more closely mimic the clinical intensive care setting. Twenty-three sheep were subjected to the injury, and allocated to four groups for a 96 h study period: sham (n=5 non-injured); control (n=6: injured); AB6h (n=6: injured, antibiotics started 6 h post-injury); AB12h (n=6: injured, antibiotics started 12 h post-injury). All sham animals survived 96 h. Control, AB6h, AB12h groups reached criteria of septic shock within 12 h post-injury. All controls died within 36 h. Eighty three percent of AB6h and fifty percent of AB12h survived 96 h. Median survival times were significantly improved in the treated groups compared with the control group: 24 h in control vs. 80.5 h in AB6h, and 65 h in AB12h animals. Combined ciprofloxacin and piperacillin therapy was effective, reduced nitric oxide production and mortality, and will allow future long-term studies in this model.

Fig. 1

A Time point of protocol. After 5 to 7 days of recovery from surgical preparation, injury was induced. The injured group became septic before 6hrs post injury and septic shock before 12hrs post injury. AB6h and AB12h groups started antibiotics at 6hrs and 12hrs, respectively. P+C = Piperacillin + Ciprofloxacin, P = Piperacillin B Survival in Sham, Control, and Treated animals. Kaplan-Meier curve of sham (n=5), control (n=6), AB6h (n=6), and AB12h (n=6) animals is shown. Animal survival for 96hrs (4days) were considered survivors and sacrificed. There were statistically significant differences for survival between control and AB6h (p=0.0015), and control and AB12h groups (p=0.026) at 96hrs. C/D Changes in PaO₂/FiO₂-ratio and pulmonary shunt fraction (Qs/Qt). Data are expressed as mean ± SEM. Significance was assumed when p was less than 0.05; *vs. sham; †vs. control.

Fig. 2

Changes in HR, MAP, CI, and PNOx. HR, heart rate; MAP, mean arterial pressure; CI, cardiac index; PNOx, plasma nitrate-to-nitrite level. Data are expressed as mean ± SEM. Significance was assumed when p was less than 0.05; *vs. sham; †vs. control.