Intraosseous Erythropoietin for Acute Tissue Protection in Battlefield Casualties Suffering Hypovolemic Shock.

摘要

The project compared in a swine model of hemorrhagic shock (HS) the effects of vasopressin (VP) infusion and low-volume fluid resuscitation using normal saline (NS) on 72 hour survival, with erythropoietin (EPO) administration and HS severity as confounders. Twenty-four male pigs (36-41 kg) were anesthetized with isoflurane and nitrous oxide in oxygen and instrumented to assess hemodynamic function and advance a 23-F cannula into the right atrium for blood withdrawal (BW) and blood reinfusion using a custom developed system that allowed modeling spontaneous bleeding as a mono-exponential decay function. Twenty-four pigs were randomized 2:1 to receive an intraosseous infusion of VP (0.04 U/kg min-1) or vehicle control starting 7 minutes into BW until the start of blood reinfusion at minute 210. Pigs were also randomized 1:1 to receive NS (half the amount of BW) or no fluids. Pigs assigned to VP were also randomized 1:1 to EPO (1,200 U/kg) or vehicle control and to have 65% or 75% of their blood volume withdrawn. Randomization proceeded by blocks ensur-ing balanced distribution in all the subsets. Survival analysis to 72 hours showed that survival was influenced by VP and NS but not by EPO or HS severity with the highest survival rate in the group VP-NS (100%) followed by VP-noNS (37.5%), noVP-NS (25%), and noVP-noNS (0%) with a high overall statistical significance (p=0.009 by the log-rank test) with each subset different than VP-NS by the Holm-Sidak s test. Accordingly, these findings support an approach to the initial management of severe HS in the field that entails early initiation of VP infusion through the intraosseous route followed by low-volume fluid resuscitation (e.g., small boluses of normal saline).