Date Published: June 24, 2015
Publisher: Public Library of Science
Author(s): Raúl J. Gazmuri, Kasen Whitehouse, Karla Whittinghill, Alvin Baetiong, Jeejabai Radhakrishnan, Raghavan Raju.
Current management of hemorrhagic shock (HS) in the battlefield and civilian settings favors small-volume fluid resuscitation before controlling the source of bleeding. We investigated in a swine model of HS the effects of vasopressin infusion along with small-volume fluid resuscitation; with erythropoietin (EPO) and HS severity as additional factors.
HS was induced in 24 male domestic pigs (36 to 41 kg) by blood withdrawal (BW) through a right atrial cannula modeling spontaneous bleeding by a mono-exponential decay function. The initial 12 pigs received no fluids; the last 12 pigs received normal saline (NS) half the BW volume. Pigs were randomized 2:1 to receive intraosseously vasopressin (0.04 U/kg·min-1) or vehicle control from minute 7 to minute 210. Pigs assigned to vasopressin were further randomized 1:1 to receive EPO (1,200 U/kg) or vehicle control and 1:1 to have 65% or 75% BW of their blood volume. Shed blood was reinfused at 210 minutes and the pigs recovered from anesthesia.
Survival at 72 hours was influenced by vasopressin and NS but not by EPO or % BW. Vasopressin with NS promoted the highest survival (8/8) followed by vasopressin without NS (3/8), NS without vasopressin (1/4), and neither treatment (0/4) with overall statistical significance (log-rank test, p = 0.009) and each subset different from vasopressin with NS by Holm-Sidak test. Vasopressin increased systemic vascular resistance whereas NS increased cardiac output.
Vasopressin infusion with small-volume fluid resuscitation during severe HS was highly effective enabling critical hemodynamic stabilization and improved 72 hour survival.
Hemorrhagic shock after penetrating trauma in the battlefield accounts for a high percentage of potentially survivable injuries . A report from operations Iraqi Freedom and Enduring Freedom between October 2001 and June 2011 showed that 87% of battlefield fatalities occurred before arrival to a medical treatment facility with 24% deemed potentially survivable . Of these potentially survivable injuries, 91% were associated with hemorrhagic shock.
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 was the consequence of hemorrhagic shock severity during the acute phase. Animals that survived the acute phase and were recovered from anesthesia survived the 72 hour observation interval recovering baseline neurological function and overall performance.
The present study demonstrates a marked survival benefit associated with early and sustained administration of vasopressin in conjunction with small-volume fluid resuscitation in a swine model of severe hemorrhagic shock. Vasopressin acted by increasing systemic vascular resistance whereas normal saline acted by increasing cardiac index through a preload effect. Although vasopressin intensified lactic acidosis, this effect was counterbalanced by normal saline. The combination of vasopressin and normal saline averted early demise and secured sufficient hemodynamic stability for the 210 minutes of hemorrhagic shock before blood reinfusion, modeled to simulate delayed arrival to a medical treatment facility where control of the bleeding source and resuscitation with blood products could be performed. Administration of EPO conferred no additional survival benefit.
The present findings support the concept that early and sustained administration of vasopressin could be highly effective for hemodynamic stabilization in the setting of severe hemorrhagic shock and work in conjunction with small-volume fluid resuscitation to initiate and maintain critical hemodynamic stability until arrival to a medical treatment facility.