Assessment of ethynylestradiol-3-sulfate on coagulation, metabolism, and survival in pigs with traumatic hemorrhage

Abstract

BACKGROUND The beneficial effects of estrogens on survival from hemorrhage have been suggested in some preclinical models. This study investigated the effects of ethynylestradiol-3-sulfate (EE-3-S) on coagulation, metabolism and survival in pigs following traumatic hemorrhage. METHODS Twenty-six pigs were randomized into: normal saline group (NS, n = 10), EE-3-S group (EE-3, n = 11) groups, and no resuscitation group (NR, n = 5). Femur fracture was performed in each pig's left leg, followed by hemorrhage of 55% of estimated blood volume and a 10-minute shock period. Afterward, pigs were resuscitated with a small volume of either NS alone (4 mL/kg) or EE-3-S with NS (1 mL/kg at concentration of 1 mg/mL, plus NS solution of 3 mL/kg). Pigs in NR group were not resuscitated with any fluid. All pigs were then monitored for 6 hours or until death, with hemodynamics and survival times recorded. Blood samples were taken during the study for measurements of oxygen metabolism (oxygen delivery, extraction, and consumption) and coagulation function (using Rotem with Extem reagents). RESULTS All baseline measurements were similar among the three groups. In the NS group, femur fracture and hemorrhage immediately reduced mean arterial pressure (MAP, 74 ± 3 mm Hg to 44 ± 4 mm Hg) and increased heart rate (97 ± 5 bpm to 218 ± 14 bpm, both p < 0.05). Similar changes in MAP and heart rate were observed in the EE-3 and NR groups. There were no differences observed in changes of Rotem® measurements or oxygen metabolism among the groups during the study. At 6 hours, four pigs in NS, four pigs in EE-3-S, and two pigs in the NR group survived to the end of the study. The mean survival times were similar among the NS (212 ± 43 minutes), EE-3 (212 ± 39 minutes), and NR (223 ± 63 minutes) groups (p = 0.9845). CONCLUSION Following severe traumatic hemorrhage, hypotensive resuscitation with EE-3-S did not impact coagulation, metabolism, or survival in pigs.