CAN POLYETHYLENE GLYCOL-20K REPLACE ALBUMIN FOR PREHOSPITAL TREATMENT OF HEMORRHAGIC SHOCK WHEN FULL RESUSCITATION IS UNAVAILABLE?

A solution of high concentration albumin has been used for temporal volume expansion when timely resuscitation was unavailable after hemorrhagic shock. However, during prolonged hemorrhagic shock, cell edema and interstitial dehydration can occur and impede the volume expansion effect of albumin. Polyethylene glycol-20K (PEG) can establish an osmotic gradient from swollen cells to capillary lumens and thus facilitate capillary fluid shift and volume expansion.

Effects of extremity trauma on physiological responses to hemorrhage in conscious rats.

Although physiological responses to hemorrhage are well-studied, hemorrhage is often accompanied by trauma, and it remains unclear how injury affects these responses. This study examined effects of extremity trauma on cardiorespiratory responses and survival to moderate (37%; H-37) or severe (50%; H-50) hemorrhage in rats. Transmitter and carotid catheter implantation and extremity trauma (fibular fracture and muscle injury) were conducted 2 wk, 24 h, and 90 min, respectively, before conscious hemorrhage.

A novel animal model to study delayed resuscitation following traumatic hemorrhage.

A focus of combat casualty care research is to develop treatments for when full resuscitation after hemorrhage is delayed. However, few animal models exist to investigate such treatments. Given the kidney's susceptibility to ischemia, we determined how delayed resuscitation affects renal function in a model of traumatic shock.

Extremity trauma exacerbates acute kidney injury following prolonged hemorrhagic hypotension.

Background: The incidence of and mortality due to acute kidney injury is high in patients with traumatic shock. However, it is unclear how hemorrhage and trauma synergistically affect renal function, especially when timely volume resuscitation is not available.

Method: We hypothesized that trauma impairs renal tolerance to prolonged hemorrhagic hypotension.

Effects of ketamine analgesia on cardiorespiratory responses and survival to trauma and hemorrhage in rats.

Ketamine is the recommended analgesic on the battlefield for soldiers with hemorrhage, despite a lack of supportive evidence from laboratory or clinical studies. Hence, this study determined the effects of ketamine analgesia on cardiorespiratory responses and survival to moderate (37% blood volume; = 8/group) or severe hemorrhage (50% blood volume; = 10/group) after trauma in rats. We used a conscious hemorrhage model with extremity trauma (fibular fracture + soft tissue injury) while measuring mean arterial pressure (MAP), heart rate (HR), and body temperature (T) by telemetry, and respiration rate (RR), minute volume (MV), and tidal volume (TV) via whole body plethysmography.

Fentanyl impairs but ketamine preserves the microcirculatory response to hemorrhage.

Background: Peripheral vasoconstriction is the most critical compensating mechanism following hemorrhage to maintain blood pressure. On the battlefield, ketamine rather than opioids is recommended for pain management in case of hemorrhage, but effects of analgesics on compensatory vasoconstriction are not defined. We hypothesized that fentanyl impairs but ketamine preserves the peripheral vasoconstriction and blood pressure compensation following hemorrhage.

Long-term consequences of abdominal aortic and junctional tourniquet for hemorrhage control.

Background: Specialized tourniquets have been deployed to the battlefield for the control of junctional/pelvic hemorrhage despite limited knowledge concerning their safety and duration of use. This study investigated long-term effects of abdominal application of the abdominal aortic and junctional tourniquet (AAJT) in a swine survival model.

Methods: Anesthetized spontaneously air-breathing swine were subjected to bilateral femoral artery injuries and subsequent 40% hemorrhage.

A novel rat model of extremity trauma for prehospital pain management research.

Background: Pain management is important in prehospital care of patients with extremity trauma (ET). The goal of this study was to establish a rat model of ET for prehospital pain research and validate it using pain behaviors and analgesics.

Methods: Rats were anesthetized using isoflurane, and ET was induced in one hindlimb via clamping retrofemoral tissues for 30 seconds, followed by closed fibula fracture.

Do vented chest seals differ in efficacy? An experimental evaluation using a swine hemopneumothorax model.

Objective: Airways compromise was the second leading cause of potentially preventable death among combat casualties. We investigated the ability of five Food and Drug Administration-approved nonocclusive chest seals (CSs) to seal a bleeding chest wound and prevent tension hemopneumothorax (HPTX) in a swine model.

Methods: Following instrumentation, an open chest wound was created in the left thorax of spontaneously air-breathing anesthetized pigs (n = 26; 43 kg).

Relationship between Plasma Albumin Concentration and Plasma Volume in 5 Inbred Rat Strains.

Using the Evans Blue procedure, we previously found strain-related differences in plasma volumes in 5 inbred rat strains. Because albumin binds strongly with Evans blue, this protein is important in the Evans blue method of plasma volume determination. Therefore, we speculated that interstrain differences in plasma albumin concentration (PAC) could distort calculated plasma volumes.

Vented versus unvented chest seals for treatment of pneumothorax and prevention of tension pneumothorax in a swine model.

Background: Unvented chest seals (CSs) are currently recommended for the management of penetrating thoracic injuries in the battlefield. Since no supporting data exist, we compared the efficacy of a preferred unvented with that of a vented CS in a novel swine model of pneumothorax (PTx).

Methods: An open chest wound was created in the left thorax of spontaneously air-breathing anesthetized pigs (n = 8).

Arterial blood gases, electrolytes, and metabolic indices associated with hemorrhagic shock: inter- and intrainbred rat strain variation.

We have previously shown interstrain variation (indicating a genetic basis), and intrastrain variation in survival time after hemorrhage (STaH) among inbred rat strains. To assist in understanding physiological mechanisms associated with STaH, we analyzed various arterial blood measures (ABM; pH, Paco2, oxygen content, sodium, potassium, glucose, bicarbonate, base excess, total CO2, and ionized calcium) in inbred rats. Rats from five inbred strains (n = 8-10/strain) were catheterized and, ≈ 24 h later, subjected to a conscious, controlled, 47% hemorrhage.

Cardiac mitochondrial proteomic expression in inbred rat strains divergent in survival time after hemorrhage.

We have previously identified inbred rat strains differing in survival time to a severe controlled hemorrhage (StaH). In efforts to identify cellular mechanisms and ultimately genes that are important contributors to enhanced STaH, we conducted a study to characterize potential differences in cardiac mitochondrial proteins in these rats. Inbred rats from three strains [Brown Norway/Medical College of Wisconsin (BN); Dark Agouti (DA), and Fawn Hooded Hypertensive (FHH)] with different StaH (DA = FHH > BN) were assigned to one of three treatment groups (n = 4/strain): nonoperated controls, surgically catheterized rats, or rats surgically catheterized and hemorrhaged 24 h postsurgery.

Life or death? A physiogenomic approach to understand individual variation in responses to hemorrhagic shock.

Severe hemorrhage due to trauma is a major cause of death throughout the world. It has often been observed that some victims are able to withstand hemorrhage better than others. For decades investigators have attempted to identify physiological mechanisms that distinguish survivors from nonsurvivors for the purpose of providing more informed therapies.

Genetic influences on survival time after severe hemorrhage in inbred rat strains.

To find a genetic basis for differential ability to survive severe hemorrhage, we previously showed eightfold differences in survival times among inbred rat strains. We assumed that rat strains had similar normalized blood volumes (NBV; ml/100 g body wt). As NBV might vary among strains and constitute one genetic variable affecting survival time to hemorrhage, in experiment 1 of the current studies we first measured total blood volumes and calculated NBV in specific inbred rat strains (Brown Norway/Medical College of Wisconsin, BN; Dark Agouti, DA; Fawn Hooded Hypertensive, FHH; Lewis, LEW; and Dahl Salt-Sensitive, SS) previously found to be divergent in survival time.

Rat strains bred for low and high aerobic running capacity do not differ in their survival time to hemorrhage.

Hemorrhagic shock reflects low tissue perfusion that is inadequate to maintain normal metabolic functions. Often associated with this condition are impairments in cellular oxygen delivery and utilization. Rat strains divergent in their running endurance have been artificially selected over 12 generations.

Comparison of new hemostatic granules/powders with currently deployed hemostatic products in a lethal model of extremity arterial hemorrhage in swine.

Background: HemCon bandage (HC) and QuikClot granules (QC) have been deployed for the past 5 years for treating external hemorrhage in combat casualties. We examined efficacy and initial safety of three new hemostatic granules/powders in a swine extremity arterial hemorrhage model that was 100% fatal with army standard gauze treatment. The new products were compared with the most advanced forms of HC and QC products.

Is survival time after hemorrhage a heritable, quantitative trait?: an initial assessment.

Enhancing survival to hemorrhage of both civilian and military patients is a major emphasis for trauma research. Previous observations in humans and outbred rats show differential survival to similar levels of hemorrhage. In an initial attempt to determine potential genetic components of such differential outcomes, survival time after a controlled hemorrhage was measured in 15 inbred strains of rats.

A novel swine model for evaluation of potential intravascular hemostatic agents.

Because uncontrolled hemorrhage is a leading cause of battlefield mortality, finding an intravenous treatment that could assist endogenous clotting mechanisms is a major mission for military researchers. Evaluation of potential intravenous hemostatic agents requires both in vitro and in vivo tests. For in vivo evaluation, we have developed a novel swine model in which 1) bleeding times (BT) and coagulation function could be ascertained after multiple doses of hemostatic drug administration and 2) a subsequent exsanguinating injury could be performed in the same animal, yielding screening information regarding the effects of drug pretreatment on blood loss and survival.

Evaluation of FloSeal as a potential intracavitary hemostatic agent.

Background: Noncompressible hemorrhage is a major cause of death in combat and civilian trauma. When surgery is unavailable, one potential solution to such hemorrhage might be the introduction of an agent into the closed body cavity to provide hemostasis via a combination of coagulative and tamponade effects. FloSeal is an agent containing collagen and thrombin with proven hemostatic efficacy when applied with manual pressure to a bleeding site.

Effect of recombinant FVIIa in hypothermic, coagulopathic pigs with liver injuries.

Background: Previous experiments with diverse pig models to evaluate the ability of rFVIIa to reduce hemorrhage have provided divergent results. The current study was conducted to address concerns related to previous work by using larger sample sizes, and an extended observational period of 4 hours post-injury. The objectives were to evaluate further the hemostatic efficacy and safety of rFVIIa administration after traumatic, uncontrolled hemorrhage.