HYPOTENSIVE RESUSCITATION OF CASUALTIES IN THE FAR-FORWARD COMBAT ENVIRONMENT: EFFECTS OF SELECT CRYSTALLOIDS AND COLLOIDS ON SIGNAL TRANSDUCTION MEDIATORS IN A SWINE MODEL OF SEVERE HEMORRHAGE

Despite years of treating trauma patients, the optimal fluid and strategy for the resuscitation of hemorrhagic hypovolemia remains unknown. Hypotensive resuscitation is a rational approach for the military due to logistic constraints to treat casualties on the battlefield, and to minimize rebleeding from penetrating injuries. In the present study anesthetized, splenectomized and instrumented 40 kg swine (n=8-10/gp) were subjected to a controlled hemorrhage of 20 ml/kg over about 5 min that duplicated the blood loss profile of an uncontrolled hemorrhage. After 30 min, fluid resuscitation was initiated along with a second hemorrhage of 8 ml/kg. Fluid infusion was controlled to return systolic blood pressure to 80 mmHg, as necessary throughout the experiment. Hemodynamic and metabolic variables were monitored continuously and blood samples were drawn at baseline (BL), and at select times throughout the 3.5 hr experimental period or until death. Tissues were collected at necropsy, homogenized and the content of total and phosphorylated EGF-R was determined by Western blot analysis. Evidence for lipid peroxidation or free radical generation was also determined. Hemorrhage reduced MAP to about 36 mmHg and lowered cardiac output (CO) to 36% of BL in all groups. CO improved the most in the Hextend group. PolyHeme infusion resulted in the highest blood pressure and lowest CO in surviving animals compared with the other fluids, but differences were not statistically significant among groups. Base deficit and plasma lactate increased during the 3.5 hr experiment in all groups. In the PolyHeme and Hextend groups, duodenal EGF-R levels were 73% and 33%, respectively, of the levels observed in LR treated pigs. EGF-R activation was about 50% higher in Hextend treated pigs compared to the LR and PolyHeme groups. As a result, about 60% of the EGF-R in duodenum from PolyHeme treated pigs was in the activated form compared to 37% and 18% in the Hextend and LR groups, respectively. In summary, all fluids improved hemodynamics and resulted in similar short term survival in this model of severe hemorrhage. Biochemical analyses suggest that resuscitation fluids can have different effects on signal transduction mediators that should be considered in designing the optimal fluid for long term improved outcome.