Abstract 2537: Recombinant Human Antithrombin III Improves Myocardial Function and Reduces Systemic Vascular Permeability After Combined Burn and Smoke Inhalation Injury
Introduction: With more than 1 billion injuries every year, burns represent a major source of morbidity and mortality in the United States.
Hypothesis: We hypothesized that a continuous intravenous (iv) infusion of recombinant human antithrombin III (rhAT III) reduces the myocardial depression and the vascular permeability associated with combined burn and smoke inhalation injury. Therefore, the present prospective, randomized experiment was conducted using an established ovine model.
Methods: After instrumentation for chronic hemodynamic monitoring and 5 days of recovery, a tracheostomy as well as a 40% total body surface area 3rd° cutaneous burn and smoke inhalation injury (48 breaths of cold cotton smoke <40°C) were performed in 12 sheep under deep anesthesia. The sheep were then randomized to receive either an iv infusion of 6 IU·kg−1·h−1 rhAT III (started 1 h after injury) or normal saline (n=6 each). All sheep were awake, mechanically ventilated and fluid resuscitated according to standard formula during the 48 h study period. Data are expressed as mean±SEM.
Results: No statistical differences could be shown at baseline. Mean arterial pressure and cardiac index remained at baseline values in both groups. Heart rate was lower and myocardial contractility was increased in rhAT III treated sheep as represented by higher left ventricular stroke work indexes at lower left atrial pressures (table 1⇓). While protein levels (24h: 4.6±0.1 vs 4.0±0.0 mg·dL−1; 48h: 4.9±0.2 vs 3.7±0.2 mg·dL−1; p<0.01 each) and oncotic pressures (24h: 13±1 vs 10±0 cmH2O; 48h: 14±1 vs 9±0 cmH2O, p<0.02 each) in plasma were higher, lung lymph flow (24h: 12±5 vs 53±4 mL·h−1, 48h: 16±7 vs 50±4 mL·h−1, p<0.001 each), hematocrit (p<0.03 at 36 h) and cumulative net fluid balance (table 1⇓) were lower in rhAT III than in control animals.
Conclusion: Continuous iv infusion of rhAT III improves myocardial function and reduces systemic vascular permeability after combined burn and smoke inhalation injury.