Tranexamic acid and trauma: current status and knowledge gaps with recommended research priorities.

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.

Protection against blast-induced mortality in rats by hemin.

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.

Comparative efficacy of granular and bagged formulations of the hemostatic agent QuikClot.

BACKGROUND: 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. METHODS: 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. RESULTS: 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 (p < 0.01) 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 (p < 0.02) 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. CONCLUSIONS: 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.

Measurement of blast wave by a miniature fiber optic pressure transducer in the rat brain.

Exposure to blast wave that is generated during an explosion may result in brain damage and related neurological impairments. The aim of this study was to investigate pressure changes induced by exposure to blast inside the rat brain. For intracranial pressure measurement we used a miniature optic fiber sensor (o.d. 550 microm) with a computer recording system. The sensor was placed in the third cerebral ventricle of anesthetized rats exposed to 40 kPa blast wave in a pneumatic-pressure driven shock tube. Short pressure waves lasting several ms were detected inside the brain with the magnitude that might result in nervous tissue damage.

Lung injury and recovery after exposure to blast overpressure.

BACKGROUND: A critical immediate determinant of survival after exposure to blast overpressure (BOP) is pulmonary damage, but mechanisms of injury and the course of recovery are not well understood. The objective of this study was to characterize the progression of oxidative and inflammatory responses in lungs as well as the activation of consequent protective mechanisms after exposure to medium intensity BOP. METHODS: Rats were exposed to a moderate (approximately 120 kPa) level of BOP in a pneumatically driven shock tube. At different times (2-192 hours) after exposure, lungs were examined for pathologic signs of injury, markers of inflammatory responses, and indicators of oxidative and nitrative damage. RESULTS: The results showed a postblast activation of inflammatory response (increase of myeloperoxidase activity, CINC-1, ICAM-1, and iNOS), increase in protein oxidation and nitration, and development of gross diffused hemorrhage in lungs. The initial phase of lung damage that peaked at 24 to 48 hours after exposure to BOP was followed by gradual dissolution of inflammation and oxidation that were complete by 192 hours. Resolution of morphologic damage and inflammation in lungs concurred with activation of expression of antioxidant enzymes heme oxygenase-1 (HO-1) and manganese superoxide dismutase (MnSOD). Plasma level of gelsolin, a marker of acute lung damage was decreased at 24 hours postblast and later returned to the control level. CONCLUSIONS: The study shows the role of adaptive anti-oxidant and anti- inflammatory mechanisms in lung recovery after injury caused by exposure to BOP.