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A recent large civilian randomized controlled trial on the use of tranexamic acid (TXA) for trauma reported important survival benefits. Subsequently, successful use of TXA for combat casualties in Afghanistan was also reported. As a result of these promising studies, there has been growing interest in the use of TXA for trauma. Potential adverse effects of TXA have also been reported. A US Department of Defense committee conducted a review and assessment of knowledge gaps and research requirements regarding the use of TXA for the treatment of casualties that have experienced traumatic hemorrhage. We present identified knowledge gaps and associated research priorities. We believe that important knowledge gaps exist and that a targeted, prioritized research effort will contribute to the refinement of practice guidelines over time.

BACKGROUND A critical immediate determinant of survival after exposure to blast overpressure (BOP) is cardiovascular and respiratory impairment related to disruption of the alveolar septa and pulmonary capillaries and resulting in acute pulmonary hemorrhage. Hemoglobin (Hb) released from red cells can contribute to lethality by activation of oxidative stress reactions and severe vasoconstriction associated with hypoperfusion in the pulmonary microcirculation. Heme oxygenase-1 (HO-1) is activated by hemin, a product of Hb degradation and may confer protection against hemoglobin-mediated oxidative cell and tissue damage. METHODS Rats were injected intraperitoneally with hemin (50 mg/kg) or phosphate buffered saline (PBS). Twenty hours later, animals were placed in a shock tube and exposed to blast overpressure with mean intensity of approximately 160 kPa. Nonblasted sham-injected animals served as controls. RESULTS HO-1 mRNA and HO-1 protein in lungs was induced by injection of hemin. Exposure to blast resulted in confluent lung hemorrhage and mortality ( approximately 65%). Hemin injection significantly improved the survival rate of animals compared with PBS injected animals (p = 0.01). CONCLUSIONS The protection by hemin against blast may involve antioxidative and vasodilatory effects of HO-1, although, the precise mechanisms of the protection are unknown.

QuikClot is a zeolite-based dressing approved and deployed by military for the arrest of severe combat-induced hemorrhage. A novel formulation (bagged QuikClot [ACS]) of the original granular QuikClot (QC) has been proposed to facilitate the application of the hemostatic dressings under battlefield conditions. This study compares the hemostatic efficacy of ACS and QC in controlling blood loss and improving survival in a swine model of uncontrolled hemorrhage induced by complex groin injury.After transection of the femoral vasculature, anesthetized Yorkshire pigs (n = 32) were hemorrhaged for 3 minutes and randomized into four groups: no treatment (NONE) or application of standard dressing (SD), QC, or ACS. At 15 minutes, resuscitation was initiated by infusion of 500 mL Hextend during a span of 30 minutes. Vital signs were continuously recorded throughout the 4-hour experimental period. In addition, blood loss and temperature at the dressing and tissue interface were continuously recorded.After 3 minutes, average blood loss was 44.7% +/- 11.9% estimated blood volume (EBV) for all animals (34.1 +/- 3.2 kg). Posttreatment blood loss was significantly higher (p0.01) for NONE- and SD-treated animals (31.5% +/- 21.8% and 22.3% +/- 12.6% EBV, respectively) as compared with animals treated with QC and ACS (7.4% +/- 7.1% and 10.3% +/- 6.9%, respectively). All NONE animals died at approximately 60 minutes. Times until death were slightly greater for animals treated with SD (96.8 minutes) and significantly greater for animals treated with QC (188 minutes) and ACS (194 minutes). Overall survival to 4 hours for SD (1 of 8, 12.5%) was significantly lower (p0.02) than for QC (6 of 8, 75%) and for ACS (6 of 8, 75%) treatments. Elevated temperatures at the dressing and tissue interface were seen in animals treated with QC and ACS (average at 8 minutes was 58.1 +/- 4.5 degrees C and 58.2 +/- 5.3 degrees C, respectively) compared with SD treated animals (38.8 +/- 2.7 degrees C). Histologic examination revealed more edema in muscular tissue of animals treated with ACS as compared with in QC-treated animals.ACS was as efficacious as original granular QC in inducing hemostasis and improving survival as compared with the efficacy of SD. Easier and more rapid application and complete removal of ACS may offer a distinct advantage in battlefield resuscitation efforts to enhance a clean wound site and eventual surgical repair.

An inhalation chamber for behavioral toxicology studies is described. Complete and uniform diffusion of test atmospheres throughout the chamber is achieved, thus solving a dead-airspace problem prevalent in extant chamber designs. Modular attachments to the chamber allow for a variety of uses, including physiological-pathological and classical or operant conditioning. The chamber design and size are appropriate for testing most small laboratory animals (e.g., birds, rodents, and small primates), but the chamber is easily modified for use with larger vertebrates. Despite the versatility of design, the chamber is relatively inexpensive and easy to build.