Fibrinogen Concentrate Improves Survival During Limited Resuscitation of Uncontrolled Hemorrhagic Shock in a Swine Model

Abstract

The purpose of this study was to evaluate the effect of fibrinogen concentrate, as a hemostatic agent, on limited resuscitation of uncontrolled hemorrhagic shock. We use a swine model of hemorrhagic shock with free bleeding from a 4mm aortic tear to test the effect of adding a one-time dose of fibrinogen concentrate given at the onset of limited fluid resuscitation. Immature female swine were anesthetized and subjected to catheter hemorrhage and aortic tear to induce uniform hemorrhagic shock. Animals (N=7 per group) were then randomized to receive either; 1. No fluid resuscitation (Neg Control), 2. Limited resuscitation in the form of two boluses of 10ml/kg of 6% hydroxyethyl starch solution (HEX) given 30 minutes apart, or 3. The same fluid regimen with one dose of 120mg/kg fibrinogen concentrate given with the first HEX bolus (FBG). Animals were then observed for a total of 6 hours with aortic repair and aggressive resuscitation with shed blood taking place at 3 hours. Survival to 6 hours was significantly increased with FBG (7/8, 86%) vs. HEX (2/7, 29%), and Neg Control (0/7, 0%) (FBG vs. HEX, Kaplan Meier LR p=0.035). Intraperitoneal blood loss adjusted for survival time was increased in HEX (0.4ml/kg/min) when compared to FBG (0.1mg/kg/min, p=0.047) and Neg Control (0.1ml/kg/min, p=0.041). Systemic and cerebral hemodynamics also showed improvement with FBG vs. HEX. Fibrinogen concentrate may be a useful adjunct to decrease blood loss, improve hemodynamics, and prolong survival during limited resuscitation of uncontrolled hemorrhagic shock.

A Multifunctional, Low-Volume Resuscitation Cocktail Improves Vital Organ Blood Flow and Hemostasis in a Pig Model of Polytrauma with Traumatic Brain Injury

“…These findings are in keeping with prior human and animal studies showing that fibrinogen supplementation improves coagulation profile and hemostasis [ 16 , 17 , 27 , 28 , 29 , 30 ]. Our model shows its effectiveness in severe polytrauma that is meant to represent the most drastic battlefield injuries with limited access to volume resuscitation or surgical repair for several hours.…”

“…Fibrinogen plays a critical role in hemostasis after injury because low fibrinogen levels are associated with increased mortality in trauma patients, and it is the first coagulation factor to reach a critically low level after trauma [ 13 , 14 , 15 ]. Fibrinogen supplementation has demonstrated benefit by decreasing blood loss and improving survival in experimental models of both solid organ and arterial hemorrhage [ 16 , 17 ].…”

Platelets and Fibrinogen: Emerging Complexity in Trauma-Induced Coagulopathy

“…[109][110][111] Aggressive fibrinogen replacement can improve thrombin generation, increase clot formation, and decrease blood loss when used in porcine trauma models. [112][113][114] Early high-dose fibrinogen therapy also does not appear to have a significant adverse effect on blood fibrinogen concentration during the first 7 days of trauma care. 115 Fibrinogen replacement is typically achieved using either the blood component cryoprecipitate or lyophilized fibrinogen concentrates.…”

Association between the effect of controlled fluid resuscitation on massive hemorrhage and expression of human neutrophil lipocalin

“…Also, the traumatic hemorrhagic shock is closely related to the mortality rate of patients and incidence rate of complications ( 13 ). However, before the active bleeding could be effectively controlled, a large amount of fluid resuscitation would result in the rise of blood loss leading to the dilution of coagulation dysfunction ( 14 ). Also, a recent report observed significant damage to the mitochondrial function along with the reduction in the oxygen supply to tissues causing acidosis ( 15 ).…”