Research Article: Effects of Intraosseous Erythropoietin during Hemorrhagic Shock in Swine

Date Published: November 3, 2014

Publisher: Public Library of Science

Author(s): Vesna Borovnik-Lesjak, Kasen Whitehouse, Alvin Baetiong, Yang Miao, Brian M. Currie, Sathya Velmurugan, Jeejabai Radhakrishnan, Raúl J. Gazmuri, Raghavan Raju.


To determine whether erythropoietin given during hemorrhagic shock (HS) ameliorates organ injury while improving resuscitation and survival.

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-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.

In 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.

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.

Partial Text

Acute hemorrhage resulting from traumatic injury is responsible for a high percentage of death in military personnel engaged in combat operations [1]. A recent report including 4,596 battlefield fatalities from Operation Iraqi Freedom and Operation Enduring Freedom between October 2001 and June 2011 showed that 87.3% of all injury related deaths occurred before arriving to a medical treatment facility [2]. Of these deaths, 24.3% were deemed potentially survivable with acute mortality associated with hemorrhage in 90.9%. The current acute management of hemorrhage focuses on hemostasis, hemodynamic stabilization, and rapid transfer to a medical treatment facility.

The studies were approved by the Institutional Animal Care and Use Committee (IACUC) at Rosalind Franklin University of Medicine and Science (approval number 12–23) and by the United States Army Medical Research and Materiel Command Animal Care and Use Review Office (ACURO) and were conducted according to institutional guidelines.

No unexpected adverse events occurred. Demise occurred attributed to hemorrhagic shock consequent to hemodynamic compromise during the acute phase and to organ dysfunction during the 72 hour observation interval.

The present study failed to demonstrate a beneficial (or detrimental) effect of EPO on initial resuscitability or subsequent survival in a swine model of HS regardless of its severity. The work was conducted in three consecutive HS series modeling mild severity, high severity with high fatality despite aggressive fluid resuscitation, and high severity with low fatality associated with vasopressin infusion and low-fluid or no-fluid resuscitation. EPO in the last series featuring high severity with low fatality increased plasma levels of the anti-inflammatory cytokine IL-10, attenuated lactatemia, and lessened transient injury to the liver, heart, and brain based on enzyme release and clinical neurological deficit. In addition, the study addressed several current aspects of HS management showing the efficacy of vasopressin infusion and restrictive fluid resuscitation.