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

Abstract

IntroductionCurrent 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.MethodsHS 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.ResultsSurvival 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.ConclusionVasopressin infusion with small-volume fluid resuscitation during severe HS was highly effective enabling critical hemodynamic stabilization and improved 72 hour survival.

Real‐Time Ventricular Fibrillation Amplitude‐Spectral Area Analysis to Guide Timing of Shock Delivery Improves Defibrillation Efficacy During Cardiopulmonary Resuscitation in Swine

“…Blood samples collected from the aorta and pulmonary artery were processed on site for pH, Po 2 , Pco 2 , hemoglobin, base excess, and lactate using a cartridge‐based device (OPTI CCA‐TS Blood Gas and Electrolyte Analyzer; OPTI Medical Systems, Roswell, GA) and for common hemoglobin types (oxy‐, met‐, carboxy‐, and reduced‐) using a co‐oximeter (AVOXimeter 4000; A‐VOX Systems Inc, San Antonio, TX). Pertinent indices of cardiovascular and metabolic function were derived from these primary measurements as previously described …”

“…Pertinent indices of cardiovascular and metabolic function were derived from these primary measurements as previously described. [32][33][34] Outcomes…”

Evaluation of the clinical effect of small-volume resuscitation on uncontrolled hemorrhagic shock in emergency

“…Small-volume resuscitation, which refers to the resuscitation using hypertonic NaCl solution (mass fraction =7.2%–7.5%) with a dosage of ~4 mL/kg, could rapidly expand the blood volume and effectively stabilize the hemodynamics 7–10. During the small-volume resuscitation, there existed an instantaneous mobilization of endogenous fluid along the osmotic gradient from the intracellular to the intravascular compartment 9.…”

Supplemental arginine vasopressin during the resuscitation of severe hemorrhagic shock preserves renal mitochondrial function

“…First, we only investigated the use of high dose AVP given at a single time point. While high dose vasopressin has been shown to improve survival in a lethal model of hemorrhagic shock in swine [ 44 , 45 ], its long-term benefit remains unknown and alternative dosing regimens, including the use of a continuous infusion targeting a physiologic endpoint such as MAP, may provide a better supplementation strategy. Second, we only evaluated the impact of AVP on one tissue type.…”