Effects of Intraosseous Erythropoietin during Hemorrhagic Shock in Swine

Abstract

ObjectiveTo determine whether erythropoietin given during hemorrhagic shock (HS) ameliorates organ injury while improving resuscitation and survival.MethodsThree 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-50BV). In a second series, the same HS-50BV protocol was used but removing an additional 15% of BV from minute 30 to 60 (HS-65BV). In a final series, blood was removed as in HS-65BV and intraosseous vasopressin given from minute 30 (0.04 U/kg min−1) until start of shed blood reinfusion at minute 150 (HS-65BV+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.ResultsIn HS-50BV, O2 consumption remained near baseline yielding minimal lactate increases, 88% resuscitability, and 60% survival at 72 hours. In HS-65BV, O2 consumption was reduced and lactate increased yielding 25% resuscitability. In HS-65BV+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-65BV+VP series.ConclusionsErythropoietin 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.

Vasopressin Infusion with Small-Volume Fluid Resuscitation during Hemorrhagic Shock Promotes Hemodynamic Stability and Survival in Swine

“…As discussed above, the addition of vasopressin infusion in an series from a previous study markedly improved initial resuscitation and subsequent 72 hour survival relative to a preceding series in which only fluid resuscitation with normal saline was used before blood reinfusion for the same hemorrhagic shock severity [ 9 ]. For the present study, pigs were randomized 2:1 to vasopressin or no vasopressin.…”

“…The preceding study [ 9 ] also showed that in the presence of vasopressin initial resuscitability and 72 hour survival could be achieved successfully administering a reduced amount of normal saline (corresponding to half the amount of blood withdrawn) or no fluids at all. Thus, for the present series we also examined whether normal saline could be required.…”

“…In previous work, we had hypothesized that administration of erythropoietin (EPO) early during hemorrhagic shock could minimize tissue injury through activation of mitochondrial protective mechanisms and help improve resuscitability and survival [ 8 , 9 ]. Although EPO attenuated transient tissue injury it failed to elicit survival benefits [ 9 ].…”

“…In previous work, we had hypothesized that administration of erythropoietin (EPO) early during hemorrhagic shock could minimize tissue injury through activation of mitochondrial protective mechanisms and help improve resuscitability and survival [ 8 , 9 ]. Although EPO attenuated transient tissue injury it failed to elicit survival benefits [ 9 ]. While conducting these studies we observed that vasopressin infusion was highly effective for hemodynamic stabilization and promoted survival under conditions of severe hemorrhagic shock in which aggressive fluid resuscitation had failed.…”

Resuscitative therapy with erythropoietin reduces oxidative stress and inflammatory responses of vital organs in a rat severe fixed-volume hemorrhagic shock model

“…Erythropoietin (EPO), a well-known hormone for red blood cell proliferation, has been reported to protect organs and tissues against ischemia-reperfusion injuries. Recently, it is administered in low-flow states such as HS and has shown beneficial effects in this condition (Borovnik-Lesjak et al 2014). Therefore, erythropoietin was added into the resuscitative fluid to evaluate its protective effects on organs following HS.…”