Jonathan J. Morrison

Military Application of Tranexamic Acid in Trauma Emergency Resuscitation (MATTERs) Study

OBJECTIVES To characterize contemporary use of tranexamic acid (TXA) in combat injury and to assess the effect of its administration on total blood product use, thromboembolic complications, and mortality. DESIGN Retrospective observational study comparing TXA administration with no TXA in patients receiving at least 1 unit of packed red blood cells. A subgroup of patients receiving massive transfusion (≥10 units of packed red blood cells) was also examined. Univariate and multivariate regression analyses were used to identify parameters associated with survival. Kaplan-Meier life tables were used to report survival. SETTING A Role 3 Echelon surgical hospital in southern Afghanistan. PATIENTS A total of 896 consecutive admissions with combat injury, of which 293 received TXA, were identified from prospectively collected UK and US trauma registries. MAIN OUTCOME MEASURES Mortality at 24 hours, 48 hours, and 30 days as well as the influence of TXA administration on postoperative coagulopathy and the rate of thromboembolic complications. RESULTS The TXA group had lower unadjusted mortality than the no-TXA group (17.4% vs 23.9%, respectively; P = .03) despite being more severely injured (mean [SD] Injury Severity Score, 25.2 [16.6] vs 22.5 [18.5], respectively; P < .001). This benefit was greatest in the group of patients who received massive transfusion (14.4% vs 28.1%, respectively; P = .004), where TXA was also independently associated with survival (odds ratio = 7.228; 95% CI, 3.016-17.322) and less coagulopathy (P = .003). CONCLUSIONS The use of TXA with blood component-based resuscitation following combat injury results in improved measures of coagulopathy and survival, a benefit that is most prominent in patients requiring massive transfusion. Treatment with TXA should be implemented into clinical practice as part of a resuscitation strategy following severe wartime injury and hemorrhage.

Association of cryoprecipitate and tranexamic acid with improved survival following wartime injury: findings from the MATTERs II Study

OBJECTIVE To quantify the impact of fibrinogen-containing cryoprecipitate in addition to the antifibrinolytic tranexamic acid on survival in combat injured. DESIGN Retrospective observational study comparing the mortality of 4 groups: tranexamic acid only, cryoprecipitate only, tranexamic acid and cryoprecipitate, and neither tranexamic acid nor cryoprecipitate. To balance comparisons, propensity scores were developed and added as covariates to logistic regression models predicting mortality. SETTING A Role 3 Combat Surgical Hospital in southern Afghanistan. PATIENTS A total of 1332 patients were identified from prospectively collected U.K. and U.S. trauma registries who required 1 U or more of packed red blood cells and composed the following groups: tranexamic acid (n = 148), cryoprecipitate (n = 168), tranexamic acid/cryoprecipitate (n = 258), and no tranexamic acid/cryoprecipitate (n = 758). MAIN OUTCOME MEASURE In-hospital mortality. RESULTS Injury severity scores were highest in the cryoprecipitate (mean [SD], 28.3 [15.7]) and tranexamic acid/cryoprecipitate (mean [SD], 26 [14.9]) groups compared with the tranexamic acid (mean [SD], 23.0 [19.2]) and no tranexamic acid/cryoprecipitate (mean [SD], 21.2 [18.5]) (P < .001) groups. Despite greater Injury Severity Scores and packed red blood cell requirements, mortality was lowest in the tranexamic acid/cryoprecipitate (11.6%) and tranexamic acid (18.2%) groups compared with the cryoprecipitate (21.4%) and no tranexamic acid/cryoprecipitate (23.6%) groups. Tranexamic acid and cryoprecipitate were independently associated with a similarly reduced mortality (odds ratio, 0.61; 95% CI, 0.42-0.89; P = .01 and odds ratio, 0.61; 95% CI, 0.40-0.94; P = .02, respectively). The combined tranexamic acid and cryoprecipitate effect vs. neither in a synergy model had an odds ratio of 0.34 (95% CI, 0.20-0.58; P < .001), reflecting nonsignificant interaction (P = .21). CONCLUSIONS Cryoprecipitate may independently add to the survival benefit of tranexamic acid in the seriously injured requiring transfusion. Additional study is necessary to define the role of fibrinogen in resuscitation from hemorrhagic shock.

Aortic balloon occlusion is effective in controlling pelvic hemorrhage

BACKGROUND The objective of this study was to evaluate the efficacy of resuscitative endovascular aortic balloon occlusion (REBOA) of the distal aorta in a porcine model of pelvic hemorrhage. METHODS Swine were entered into three phases of study: injury (iliac artery), hemorrhage (45 s), and intervention (180 min). Three groups were studied: no intervention (NI, n = 7), a kaolin-impregnated gauze (Combat Gauze) (CG, n = 7), or REBOA (n = 7). The protocol was repeated with a dilutional coagulopathy (CG-C, n = 7, and REBOA-C, n = 7). Measures of physiology, rates of hemorrhage, and mortality were recorded. RESULTS Rate of hemorrhage was greatest in the NI group, followed by the REBOA and CG groups (822 ± 415 mL/min versus 11 ± 13 and 0.2 ± 0.4 mL/min respectively; P < 0.001). MAP following intervention (at 15 min) was the same in the CG and REBOA groups and higher than in the NI group (70 ± 4 and 70 ± 11 mm Hg versus 5 ± 13 mm Hg respectively; P < 0.001). There was 100% mortality in the NI group, with no deaths in the CG or REBOA group. In the setting of coagulopathy, the rate of bleeding was higher in the CG-C versus the REBOA-C group (229 ± 295 mL/min versus 20 ± 7 mL/min, P = 0.085). MAP following intervention (15 min) was higher in the REBOA-C than the CG-C group (71 ± 12 mm Hg versus 28 ± 31 mm Hg; P = 0.005). There were 5 deaths (71.4%) in the CG-C group, but none in the REBOA-C group (P = 0.010). CONCLUSION Balloon occlusion of the aorta is an effective method to control pelvic arterial hemorrhage. This technique should be further developed as an adjunct to manage noncompressible pelvic hemorrhage.

En-Route Care Capability From Point of Injury Impacts Mortality After Severe Wartime Injury

Objective: The objective of this study is to characterize modern point-of-injury (POI) en-route care platforms and to compare mortality among casualties evacuated with conventional military retrieval (CMR) methods to those evacuated with an advanced medical retrieval (AMR) capability. Background: Following a decade of war in Afghanistan, the impact of en-route care capabilities from the POI on mortality is unknown. Methods: Casualties evacuated from POI to one level III facility in Afghanistan (July 2008–March 2012) were identified from UK and US trauma registries. Groups comprised those evacuated by a medically qualified provider-led, AMR and those by a medic-led CMR capability. Outcomes were compared per incremental Injury Severity Score (ISS) bins. Results: Most casualties (n = 1054; 61.2%) were in the low-ISS (1–15) bracket in which there was no difference in en-route care time or mortality between AMR and CMR. Casualties in the mid-ISS bracket (16–50) (n = 583; 33.4%) experienced the same median en-route care time (minutes) on AMR and CMR platforms [78 (58) vs 75 (93); P = 0.542] although those on AMR had shorter time to operation [110 (95) vs 117 (126); P < 0.001]. In this mid-ISS bracket, mortality was lower in the AMR than in the CMR group (12.2% vs 18.2%; P = 0.035). In the high-ISS category (51–75) (n = 75; 4.6%), time to operation was lower in the AMR than the CMR group (66 ± 77 vs 113 ± 122; P = 0.013) but there was no difference in mortality. Conclusions: This study characterizes en-route care capabilities from POI in modern combat. Conventional platforms are effective in most casualties with low injury severity. However, a definable injury severity exists for which evacuation with an AMR capability is associated with improved survival.

A novel fluoroscopy-free, resuscitative endovascular aortic balloon occlusion system in a model of hemorrhagic shock.

BACKGROUND Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a potentially lifesaving maneuver in the setting of hemorrhagic shock. However, emergent use of REBOA is limited by existing technology, which requires large sheath arterial access and fluoroscopy-guided balloon positioning. The objectives of this study were to describe a new, fluoroscopy-free REBOA system and to compare its efficacy to existing technology. An additional objective was to characterize the survivability of 60 minutes of REBOA using these systems in a model of hemorrhagic shock. METHODS Swine (70–88 kg) in shock underwent 60 minutes of REBOA using either a self-centering, one component prototype balloon system (PBS, n = 8) inserted (8 Fr) and inflated without fluoroscopy or a two-component, commercially available balloon system (CBS, n = 8) inserted (14 Fr) with fluoroscopic guidance. Following REBOA, resuscitation occurred for 48 hours with blood, crystalloid, and vasopressors. End points included accurate balloon positioning, hemodynamics, markers of ischemia, resuscitation requirements, and mortality. RESULTS Posthemorrhage mean arterial pressure (mm Hg) was similar in the CBS and PBS groups (35 [8] vs. 34 [5]; p = 0.89). Accurate balloon positioning and inflation occurred in 100% of the CBS and 88% of the PBS group. Following REBOA, mean arterial pressure increased comparably in the CBS and PBS groups (81 [20] vs. 89 [16]; p = 0.21). Lactate peaked in the CBS and PBS groups (10.8 [1.4] mmol/L vs. 13.2 [2.1] mmol/L; p = 0.01) 45 minutes following balloon deflation but returned to baseline by 24 hours. Mortality was similar between the CBS and PBS groups (12% vs. 25%, p = 0.50). CONCLUSION This study reports the feasibility and efficacy of a novel, fluoroscopy-free REBOA system in a model of shock. Despite a significant physiologic insult, 60 minutes of REBOA is tolerated and recoverable. Development of lower profile, fluoroscopy-free endovascular balloon occlusion catheters may allow proactive aortic control in patients at risk for hemorrhagic shock and cardiovascular collapse.

Physiologic tolerance of descending thoracic aortic balloon occlusion in a swine model of hemorrhagic shock

BACKGROUND Resuscitative endovascular balloon occlusion of the aorta (REBOA) is an emerging technique in trauma; however, the physiologic sequelae have not been well quantified. The objectives of this study were to characterize the burden of reperfusion and organ dysfunction of REBOA incurred during 30 or 90 min of class IV shock in a survivable porcine model of hemorrhage. METHODS After induction of shock, animals were randomized into 4 groups (n = 6): 30 min of shock alone (30-Shock) or with REBOA (30-REBOA) and 90 min of shock alone (90-Shock) or with REBOA (90-REBOA). Cardiovascular homeostasis was then restored with blood, fluid, and vasopressors for 48 h. Outcomes included mean central aortic pressure (MCAP), lactate concentration, organ dysfunction, histologic evaluation, and resuscitation requirements. RESULTS Both REBOA groups had greater MCAPs throughout their shock phase compared to controls (P < .05) but accumulated a significantly greater serum lactate burden, which returned to control levels by 150 min in the 30-REBOA groups and 320 min in the 90-REBOA group. There was a greater level of renal dysfunction and evidence of liver necrosis seen in the 90-REBOA group compared to the 90-Shock group. There was no evidence of cerebral or spinal cord necrosis in any group. The 90-REBOA group required more fluid resuscitation than the 90-Shock group (P = .05). CONCLUSION REBOA in shock improves MCAP and is associated with a greater lactate burden; however, this lactate burden returned to control levels within the study period. Ultimately, prolonged REBOA is a survivable and potentially life-saving intervention in the setting of hemorrhagic shock and cardiovascular collapse in the pig.

A systematic review of the use of resuscitative endovascular balloon occlusion of the aorta in the management of hemorrhagic shock.

BACKGROUND Torso hemorrhage remains a leading cause of potentially preventable death within trauma, acute care, vascular, and obstetric practice. A proportion of patients exsanguinate before hemorrhage control. Resuscitative endovascular balloon occlusion of the aorta (REBOA) is an adjunct designed to sustain the circulation until definitive hemostasis. A systematic review was conducted to characterize the current clinical use of REBOA and its effect on hemodynamic profile and mortality. METHODS A systematic review (1946–2015) was conducted using EMBASE and MEDLINE. Original studies on human subjects, published in English language journals, were considered. Articles were included if they reported data on hemodynamic profile and mortality. RESULTS A total of 83 studies were identified; 41 met criteria for inclusion. Clinical settings included postpartum hemorrhage (5), upper gastrointestinal bleeding (3), pelvic surgery (8), trauma (15), and ruptured aortic aneurysm (10). Of the 857 patients, overall mortality was 423 (49.4%); shock was evident in 643 (75.0%). Pooled analysis demonstrated an increase in mean systolic pressure by 53 mm Hg (95% confidence interval, 44–61 mm Hg) following REBOA use. Data exhibited moderate heterogeneity with an I2 of 35.5. CONCLUSION REBOA has been used in a variety of clinical settings to successfully elevate central blood pressure in the setting of shock. Overall, the evidence base is weak with no clear reduction in hemorrhage-related mortality demonstrated. Formal, prospective study is warranted to clarify the role of this adjunct in torso hemorrhage. LEVEL OF EVIDENCE Systematic review, level IV.

Noncompressible Torso Hemorrhage : A Review with Contemporary Definitions and Management Strategies

Trauma resulting in hemorrhage from vascular disruption within the torso is a challenging scenario, with a propensity to be lethal in the first hour following trauma. The term noncompressible torso hemorrhage (NCTH) was only recently coined as part of contemporary studies describing the epidemiology of wounding during the wars in Afghanistan and Iraq. This article provides a contemporary review of NCTH, including a unifying definition to promote future study as well as a description of resuscitative and operative management strategies to be used in this setting, and sets a course for research to improve mortality following this vexing injury pattern.

Use of resuscitative endovascular balloon occlusion of the aorta in a highly lethal model of noncompressible torso hemorrhage

ABSTRACT Noncompressible torso hemorrhage is a leading cause of death in trauma, with many patients dying before definitive hemorrhage control. Resuscitative endovascular balloon occlusion of the aorta (REBOA) is an adjunct than can be used to expand the window of salvage in patients with end-stage hemorrhagic shock. The aim of this study was to evaluate the effect of continuous and intermittent REBOA (iREBOA) on mortality using a highly lethal porcine model of noncompressible torso hemorrhage. Male splenectomized pigs (70–90 kg) underwent a laparoscopic liver injury (80% resection of left lobe) followed by a 10-min free-bleed period. Animals were then divided into three groups (n = 8) for a 60-min intervention phase (n = 8): continuous occlusion (cREBOA), iREBOA, or no occlusion (nREBOA). Groups then underwent whole blood resuscitation, damage control surgery, and further critical care. Endpoints were mortality and hemodynamic and circulating measures of shock and resuscitation. Systolic blood pressure (in mmHg) at the end of the free-bleed period for cREBOA, iREBOA, and nREBOA was 31 ± 14, 48 ± 28, and 28 ± 17, respectively (P = 0.125). Following the start of the intervention phase, systolic blood pressure was higher in the iREBOA and cREBOA groups compared with the nREBOA (85 ± 37 and 96 ± 20 vs. 42 ± 4; P < 0.001). Overall mortality for the cREBOA, iREBOA, and nREBOA groups was 25.0%, 37.5%, and 100.0% (P = 0.001). Resuscitative endovascular balloon occlusion of the aorta can temporize exsanguinating hemorrhage and restore life-sustaining perfusion, bridging critical physiology to definitive hemorrhage control. Prospective observational studies of REBOA as a hemorrhage control adjunct should be undertaken in appropriate groups of human trauma patients.

Endovascular management of axillo-subclavian arterial injury: A review of published experience

BACKGROUND The role of endovascular treatment for vascular trauma, including injury to the subclavian and axillary arteries, continues to evolve. Despite growing experience with the utilization of these techniques in the setting of artherosclerotic and aneurysmal disease, published reports in traumatic subclavian and axillary arterial injuries remain confined to sporadic case reports and case series. METHODS We conducted a review of the medical literature from 1990 to 2012 using Pubmed and OVID Medline databases to search for all reports documenting the use of endovascular stenting for the treatment of subclavian or axillary artery injuries. Thirty-two published reports were identified. Individual manuscripts were analysed to abstract data regarding mechanism, location and type of injury, endovascular technique and endograft type utilized, follow-up, and radiographic and clinical outcomes. RESULTS The use of endovascular stenting for the treatment of subclavian (150) or axillary (10) artery injuries was adequately described for only 160 patients from 1996 to the present. Endovascular treatment was employed after penetrating injury (56.3%; 29 GSW; 61 SW), blunt trauma (21.3%), iatrogenic catheter-related injury (21.8%) and surgical injury (0.6%). Injuries treated included pseudoaneurysm (77), AV fistula (27), occlusion (16), transection (8), perforation (22), dissection (6), or other injuries otherwise not fully described (4). Initial endovascular stent placement was successful in 96.9% of patients. Radiographic and clinical follow-up periods ranging from hospital discharge to 70 months revealed a follow-up patency of 84.4%. No mortalities related to endovascular intervention were reported. New neurologic deficits after the use of endovascular modalities were reported in only one patient. CONCLUSION Endovascular treatment of traumatic subclavian and axillary artery injuries continues to evolve. Early results are promising, but experience with this modality and data on late follow-up remain limited. Additional multicenter prospective study and capture of data for these patients is warranted to further define the role of this treatment modality in the setting of trauma.