Effects of combined antibiotic therapy in an ovine model of septic shock with smoke inhalation

Abstract

OBJECTIVE: Sepsis increases morbidity and mortality of smoke inhalation victims. We test the effect of ciprofloxacin and piperacillin combination therapy in an ovine model of Ps. aeruginosa sepsis with smoke inhalation. METHODS: Sheep were surgically prepared for study. After a tracheotomy, acute lung injury was induced by cotton smoke and instillation of Ps. aeruginosa into lung. After the injury, all sheep were awakened, mechanically ventilated, and resuscitated with fluid. Groups: Control (n=6: injured, untreated); Treated (n=6: injured, treated with ciprofloxacin [0.4g, every 12 h] and piperacillin [3g, every 6h] started 12h post injury). RESULTS: All control sheep died before 36h. 50% treated sheep survived over 96h. All sheep showed severe cardiopulmonary dysfunctions and plasma nitrate/nitrite (NOx) level significantly increased at 12h and peaked at 18h. PaO2/FiO2 ratio, mean arterial pressure, NOx were 167±32, 77±8, 14.0±1.3 at 18h vs. 160±42, 109±7, 5.6±1.8, respectively at 30h in treated group. CONCLUSIONS: The combined antibiotic therapy significantly improved the survival, hemodynamics, plasma NOx, but not improved pulmonary function at 30h post-injury. This combined therapy may be an effective treatment option against Ps. aeruginosa-induced sepsis even with delayed onset. SUPPORT: NIH PO12GM066312, R01GM060688, Shriners Hospitals for Children 8450, 8954, 8820