Effects of Intraosseous Erythropoietin during Hemorrhagic Shock in Swine

OBJECTIVE: To determine whether erythropoietin given during hemorrhagic shock (HS) ameliorates organ injury while improving resuscitation and survival. METHODS: Three series of 24 pigs each were studied. In an initial series, 50% of the blood volume (BV) was removed in 30 minutes and normal saline (threefold the blood removed) started at minute 90 infusing each third in 30, 60, and 150 minutes with shed blood reinfused at minute 330 (HS-50(BV)). In a second series, the same HS-50(BV) protocol was used but removing an additional 15% of BV from minute 30 to 60 (HS-65(BV)). In a final series, blood was removed as in HS-65(BV) and intraosseous vasopressin given from minute 30 (0.04 U/kg min(−1)) until start of shed blood reinfusion at minute 150 (HS-65(BV)+VP). Normal saline was reduced to half the blood removed and given from minute 90 to 120 in half of the animals. In each series, animals were randomized 1∶1 to receive erythropoietin (1,200 U/kg) or control solution intraosseously after removing 10% of the BV. RESULTS: In HS-50(BV), O(2) consumption remained near baseline yielding minimal lactate increases, 88% resuscitability, and 60% survival at 72 hours. In HS-65(BV), O(2) consumption was reduced and lactate increased yielding 25% resuscitability. In HS-65(BV)+VP, vasopressin promoted hemodynamic stability yielding 92% resuscitability and 83% survival at 72 hours. Erythropoietin did not affect resuscitability or subsequent survival in any of the series but increased interleukin-10, attenuated lactate increases, and ameliorated organ injury based on lesser troponin I, AST, and ALT increases and lesser neurological deficits in the HS-65(BV)+VP series. CONCLUSIONS: Erythropoietin given during HS in swine failed to alter resuscitability and 72 hour survival regardless of HS severity and concomitant treatment with fluids and vasopressin but attenuated acute organ injury. The studies also showed the efficacy of vasopressin and restrictive fluid resuscitation for hemodynamic stabilization and survival.