Double-blinded, placebo-controlled study of early tranexamic acid treatment in swine uncontrolled hemorrhage model.

Background: Tranexamic acid (TXA) is an antifibrinolytic drug that was shown to increase survival in trauma patients, but the mechanisms remain unclear. The purpose of this double-blinded, randomized placebo-controlled study was to determine if TXA with hypotensive resuscitation with Hextend (HEX) or fresh frozen plasma (FFP) reduced blood loss (BL) and improved survival in a model of uncontrolled hemorrhage.

Methods: Instrumented, anesthetized pigs (n = 11 per group) were subjected to 24-mL/kg controlled hemorrhage, followed by transection of the spleen.

Comparison of Noninvasive pH and Blood Lactate as Predictors of Mortality in a Swine Hemorrhagic Shock with Restricted Volume Resuscitation Model.

Recent clinical studies have demonstrated that high blood lactate in the prehospital setting and poor lactate clearance in the emergency department are predictive of in-hospital mortality. This analysis of data collected from a swine model of hemorrhage and restricted volume resuscitation investigated the hypotheses that noninvasive muscle pH (pHm) and H clearance would predict mortality, and the responses would be similar between pHm and lactate. Data from a set of 57 swine were analyzed over the first 2 h after controlled hemorrhage and uncontrolled splenic bleeding.

Systemic and microvascular effects of resuscitation with blood products after severe hemorrhage in rats.

Background: Severe hemorrhage is associated with the disruption of the endothelial glycocalyx (EG), a key component of the endothelium. The effects of blood components on the EG are unknown. The present study furthers our investigations into the effects of resuscitation with blood products on the skeletal muscle microcirculation of hemorrhaged rats, focusing on packed red blood cells (PRBCs) or fresh whole blood (FWB).

Blood-banking techniques for plateletpheresis in swine.

During the past several years, trauma resuscitation in human patients has evolved from decreased use of crystalloids to increased use of blood products. Of high interest is the role of platelets in trauma resuscitation. Because conducting prehos- pital resuscitation in human trauma patients is very difficult, swine are often the animal model of choice for such studies because their coagulation and hemodynamic systems are similar to those in humans.

Investigation of noninvasive muscle pH and oxygen saturation during uncontrolled hemorrhage and resuscitation in swine.

This study evaluated noninvasively determined muscle pH (pHm) and muscle oxygen saturation (SmO2) in a swine shock model that used uncontrolled hemorrhage and restricted volume resuscitation. Anesthetized 40-kg female swine underwent hemorrhage until 24 mL/kg of blood was removed (n = 26), followed by transection of the spleen, causing uncontrolled hemorrhage throughout the remainder of the protocol. After 15 min, 15 mL/kg of resuscitation fluid (Hextend, fresh-frozen plasma or platelets) was given for 30 min.

Evaluation of resuscitation fluids on endothelial glycocalyx, venular blood flow, and coagulation function after hemorrhagic shock in rats.

Background: Endothelial glycocalyx (EG) plays an essential role in endothelium integrity and may be compromised by hemorrhagic shock. The effects of currently available resuscitation fluids such as Hextend (HEX) or lactated Ringer's solution (LR) on vascular function and coagulation are not well understood. The aim of the present study was to compare the effects of fresh frozen plasma (FFP) with HEX or LR in their ability to repair EG structure, promote volume expansion, increase blood flow, and prevent coagulopathy.

Comparison between human and porcine thromboelastograph parameters in response to ex-vivo changes to platelets, plasma, and red blood cells.

In the acute care setting, both the tracings and numeric outputs (R time, angle, and MA) of thrombelastography (TEG) may be used to inform treatment decisions. The objective was to determine the sensitivity of TEG to isolated changes in platelet count, hematocrit and fibrinogen concentration in human blood. As pigs have a similar coagulation system, we also compared the responses of the pig blood.

Stability of tranexamic acid after 12-week storage at temperatures from -20°c to 50°c.

Background: Tranexamic acid (TXA) is an antifibrinolytic agent that reduces blood loss during surgery, decreases mortality in civilian and military trauma populations, was adopted for prehospital use by the British military, and is now issued to U.S. Special Operations Forces for use on the battlefield.

In vivo evaluation of venular glycocalyx during hemorrhagic shock in rats using intravital microscopy.

Hemorrhage is responsible for a large percentage of trauma-related deaths but the mechanisms underlying tissue ischemia are complex and not well understood. Despite the evidence linking glycocalyx degradation and hemorrhagic shock, there is no direct data obtained in vivo showing glycocalyx thickness reduction in skeletal muscle venules after hemorrhage. We hypothesize that damage to the endothelial glycocalyx is a key element in hemorrhage pathophysiology and tested the hypothesis that hemorrhage causes glycocalyx degradation in cremaster muscle microvessels.

Influence of asymptomatic pneumonia on the response to hemorrhage and resuscitation in swine.

Introduction: Investigation of resuscitation fluids in our swine hemorrhage model revealed moderate to severe chronic pneumonia in five swine at necropsy. Our veterinary staff suggested that we perform a retrospective analysis of prospectively collected data from these animals. We compared the data to that of ten healthy swine to determine the physiologic consequences of the added stress on our hemorrhage/resuscitation model.

Red blood cells accelerate the onset of clot formation in polytrauma and hemorrhagic shock.

Background: Hemorrhage and coagulopathy are major contributors to death after trauma. The contribution of red blood cells (RBCs) in correcting coagulopathy is poorly understood. Current methods of measuring coagulopathy may fail to accurately characterize in vivo clotting.

Testing of blood products in a polytrauma model: results of a multi-institutional randomized preclinical trial.

Introduction: Trauma-induced coagulopathy, acidosis, and hypothermia form a "lethal triad" that is difficult to treat and is associated with extremely high mortality. This study was performed at three academic centers to evaluate whether resuscitation with blood components could reverse the coagulopathy in a complex polytrauma model.

Methods: Yorkshire swine (40 +/- 5 kg) were subjected to a three-phase protocol: (a) "Prehospital" phase = femur fracture, hemorrhage (60% blood volume), and 30 minutes shock + infusion of saline (3x shed blood) + induction of hypothermia (33 degrees C); (b) "Early hospital" phase = grade V liver injury; and (c) "Operative" phase= liver packing.

Lyophilized plasma for resuscitation in a swine model of severe injury.

Hypothesis: Lyophilized plasma (LP) is as safe and effective as fresh frozen plasma (FFP) for resuscitation after severe trauma.

Design: Multicenter animal study.

Setting: Animal laboratories, 2 level I trauma centers.

Development and testing of freeze-dried plasma for the treatment of trauma-associated coagulopathy.

Background: Trauma-induced coagulopathy is associated with an extremely high mortality. We have recently shown that survival can be improved by correction of coagulopathy through early, aggressive infusion of Fresh Frozen Plasma (FFP). However, FFP is a perishable product, and its use is impractical in challenging environments such as a battlefield.

Reproducibility of an animal model simulating complex combat-related injury in a multiple-institution format.

We developed a complex combat-relevant model of abdominal and extremity trauma, hemorrhagic shock, hypothermia, and acidosis. We then simulated injury, preoperative, and operative phases. We hypothesized that this model is reproducible and useful for randomized multicenter preclinical trials.

Recombinant factor VIIa reduces rebleed hemorrhage volume in a swine aortotomy model: a randomized double-blinded study.

Noncompressible hemorrhage requires hypotensive resuscitation until definitive measures can be taken to prevent rebleeding by sustaining blood pressure at subphysiological levels. Previous studies have demonstrated that a 180- or 720-microg kg(-1) dose of recombinant factor VIIa (rFVIIa) increases the MAP at which rebleeding occurs in a swine aortotomy model. The purpose of the current study was to determine the efficacy of a lower dose of 90 microg kg(-1) given prophylactically to prevent or reduce rebleeding in a prospective, randomized, blinded study using a porcine model of uncontrolled hemorrhage and resuscitation.

Closed-loop control of fluid therapy for treatment of hypovolemia.

Closed-loop algorithms and resuscitation systems are being developed to control IV infusion rate during early resuscitation of hypovolemia. Although several different physiologic variables have been suggested as an endpoint to guide fluid therapy, blood pressure remains the most used variable for the initial assessment of hemorrhagic shock and the treatment response to volume loading. Closed-loop algorithms use a controller function to alter infusion rate inversely to blood pressure.

Uncontrolled hemorrhage differs from volume- or pressure-matched controlled hemorrhage in swine.

Controversy continues as to whether uncontrolled or controlled hemorrhage is the most appropriate for the study of hemorrhagic shock and resuscitation. To appraise differences between these models, we evaluated the relationship between blood volume loss and blood pressure in controlled versus uncontrolled hemorrhage. Anesthetized, instrumented, immature female pigs (40 kg) were assigned to one of three groups: (1) group U, uncontrolled aortotomy hemorrhage from a 2-mm aortotomy; (2) group P, controlled hemorrhage matched to the blood pressure profile of group U; or (3) group V, controlled hemorrhage matched to the blood volume loss profile of group U.

Effects of hemorrhage and lactated Ringer's resuscitation on coagulation and fibrinogen metabolism in swine.

Hemorrhagic coagulopathy is a significant complication after traumatic injury, and much of the underlying mechanism remains unclear. We investigated the changes in fibrinogen metabolism and coagulation after a moderate hemorrhage and resuscitation. Pigs of either sex (weight, 40.

Effects of an inspiratory impedance threshold device on blood pressure and short term survival in spontaneously breathing hypovolemic pigs.

Background: The inspiratory impedance threshold device (ITD) has been shown to improve hemodynamic variables and survival outcomes during cardiopulmonary resuscitation in animals and humans. We hypothesized that use of an ITD, with a resistance of -10 cm H2O, will improve hemodynamics and short-term survival rates during hypovolemic hypotension in spontaneously breathing pigs.

Methods: Female farm pigs ( approximately 26 kg) were intubated and anesthetized with propofol with the dose adjusted to permit spontaneous respirations.

Hemostatic efficacy of two advanced dressings in an aortic hemorrhage model in Swine.

Background: An effective hemostatic agent capable of stopping severe arterial bleeding and sustaining hemostasis over a prolonged time is required. The U.S.

Recombinant factor VIIa increases the pressure at which rebleeding occurs in porcine uncontrolled aortic hemorrhage model.

In trauma patients, resuscitation to endpoints below normal blood pressure (BP) levels may reduce further blood loss due to the rebleeding often caused by more aggressive resuscitation. However, patients whose BP is maintained at lower levels for extended periods are at increased risk for organ failure. The purpose of this study was to determine whether recombinant activated factor VII (rFVIIa) raises the BP level at which rebleeding occurs in a prospective, randomized, blinded study using a porcine model of uncontrolled hemorrhage and resuscitation.

Evaluation of renal cortical perfusion by noninvasive power Doppler ultrasound during vascular occlusion and reperfusion.

Background: Urine output, a frequently used resuscitation end point, is presumed to represent renal cortical perfusion. However, no noninvasive method for direct measurement of renal perfusion exists. Power Doppler ultrasound (PDUS) is a method that reportedly is sensitive to low-velocity and microvascular blood flow and can depict it.

Advanced hemostatic dressing development program: animal model selection criteria and results of a study of nine hemostatic dressings in a model of severe large venous hemorrhage and hepatic injury in Swine.

Background: An advanced hemostatic dressing is needed to augment current methods for the control of life-threatening hemorrhage. A systematic approach to the study of dressings is described. We studied the effects of nine hemostatic dressings on blood loss using a model of severe venous hemorrhage and hepatic injury in swine.