Joseph DuBose

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.

A Clinical Series of Resuscitative Endovascular Balloon Occlusion of the Aorta for Hemorrhage Control and Resuscitation

BACKGROUND A requirement for improved methods of hemorrhage control and resuscitation along with the translation of endovascular specialty skills has resulted in reappraisal of resuscitative endovascular balloon occlusion of the aorta (REBOA) for end-stage shock. The objective of this report was to describe implementation of REBOA in civilian trauma centers. METHODS Descriptive case series of REBOA (December 2012 to March 2013) used in scenarios of end-stage hemorrhagic shock at the University of Maryland, R. Adams Cowley Shock Trauma Center, Baltimore, Maryland, and Herman Memorial Hospital, The Texas Trauma Institute, Houston, Texas. RESULTS REBOA was performed by trauma and acute care surgeons for blunt (n = 4) and penetrating (n = 2) mechanisms. Three cases were REBOA in the descending thoracic aorta (Zone I) and three in the infrarenal aorta (Zone III). Mean (SD) systolic blood pressure at the time of REBOA was 59 (27) mm Hg, and mean (SD) base deficit was 13 (5). Arterial access was accomplished using both direct cutdown (n = 3) and percutaneous (n = 3) access to the common femoral artery. REBOA resulted in a mean (SD) increase in blood pressure of 55 (20) mm Hg, and the mean (SD) aortic occlusion time was 18 (34) minutes. There were no REBOA-related complications, and there was no hemorrhage-related mortality. CONCLUSION REBOA is a feasible and effective means of proactive aortic control for patients in end-stage shock from blunt and penetrating mechanisms. With available technology, this method of resuscitation can be performed by trauma and acute care surgeons who have benefited from instruction on a limited endovascular skill set. Future work should be aimed at devices that allow easy, fluoroscopy-free access and studies to define patients most likely to benefit from this procedure. LEVEL OF EVIDENCE Therapeutic study, level V.

Endovascular stenting for the treatment of traumatic internal carotid injuries: expanding experience.

BACKGROUND The role of endovascular techniques in the treatment of traumatic vascular injuries, including injury to the internal carotid artery, continues to evolve. Despite growing experience with the usage of these techniques in the setting of artherosclerotic disease, published results in traumatic carotid injuries remain sporadic and confined to case reports and case series. METHODS We conducted a review of the medical literature from 1990 to the present date using the Pubmed and OVID Medline databases to search for all reports documenting the use of endovascular stenting for the treatment of carotid injuries. Thirty-one published reports were analyzed to abstract data regarding mechanism, location, and type of injury; use and type of anticoagulation used in conjunction with stenting; type and timing of radiographic and clinical follow-up; and radiographic and clinical outcomes. RESULTS The use of endovascular stenting for the treatment of internal carotid injuries was reported for only 113 patients from 1994 to the present date. Stenting was most commonly used after a blunt mechanism of injury (77.0%). The injury types treated by stenting included pseudoaneurysm (60.2%), arteriovenous fistula (16.8%), dissection (14.2%), partial transection (4.4%), occlusion (2.7%), intimal flap (0.9%), and aneurysm (0.9%). Initial endovascular stent placement was successful in 76.1% of patients. Radiographic and clinical follow-up periods ranging from 2 weeks to 2 years revealed a follow-up patency of 79.6%. No stent-related mortalities were reported. New neurologic deficits after stent placement occurred in 3.5%. CONCLUSION Endovascular treatment of traumatic internal carotid artery injury continues to evolve. Early results are encouraging, but experience with this modality and data on late follow-up are still very limited. A large prospective randomized trial is warranted to further define the role of this treatment modality in the setting of trauma.

Role of Anemia in Traumatic Brain Injury

BACKGROUND Few studies have investigated the effects of anemia in patients with traumatic brain injury (TBI). The objective of this study was to examine the role of anemia and blood transfusion on outcomes in TBI patients. STUDY DESIGN We performed a retrospective review of all blunt trauma patients with TBI admitted to the ICU from July 1998 to December 2005. Admission and daily ICU blood hemoglobin (hemoglobin) levels and blood transfusions during the first week of hospitalization were measured. Anemia was defined as a hemoglobin<9 g/dL occurring on 3 consecutive blood draws. The role of anemia and blood transfusion was investigated using logistic regression adjusting for factors, with p<0.2 from the bivariate analysis. RESULTS During the study period, 1,150 TBI patients were admitted to the ICU. When both anemia and blood transfusion were included in the full model, blood transfusion was significantly associated with higher mortality (adjusted odds ratio [AOR], 2.19 [95% CI, 1.27, 3.75]; p=0.0044) and more complications (AOR, 3.67 [95% CI, 2.18, 6.17]; p<0.0001), but anemia was not. But when transfusion was not included in the full model, anemia was a significant risk factor for mortality (AOR, 1.59 (95% CI, 1.13, 2.24); p=0.007) and for complications (AOR, 1.95 [95% CI, 1.42, 2.70]; p<0.0001). CONCLUSIONS Blood transfusion is associated with significantly worse outcomes in traumatic brain injured patients. In addition, blood transfusion is a major contributing factor to worse outcomes in TBI patients who are anemic. We caution against the liberal use of blood in TBI patients.

The AAST prospective Aortic Occlusion for Resuscitation in Trauma and Acute Care Surgery (AORTA) registry: Data on contemporary utilization and outcomes of aortic occlusion and resuscitative balloon occlusion of the aorta (REBOA)

INTRODUCTION Aortic occlusion (AO) for resuscitation in traumatic shock remains controversial. Resuscitative endovascular balloon occlusion of the aorta (REBOA) offers an emerging alternative. METHODS The American Association for the Surgery of Trauma Aortic Occlusion for Resuscitation in Trauma and Acute Care Surgery registry prospectively identified trauma patients requiring AO from eight ACS Level 1 centers. Presentation, intervention, and outcome variables were collected and analyzed to compare REBOA and open AO. RESULTS From November 2013 to February 2015, 114 AO patients were captured (REBOA, 46; open AO, 68); 80.7% were male, and 62.3% were blunt injured. Aortic occlusion occurred in the emergency department (73.7%) or the operating room (26.3%). Hemodynamic improvement after AO was observed in 62.3% [REBOA, 67.4%; open OA, 61.8%); 36.0% achieving stability (systolic blood pressure consistently >90 mm Hg, >5 minutes); REBOA, 22 of 46 (47.8%); open OA, 19 of 68 (27.9%); p =0.014]. Resuscitative endovascular balloon occlusion of the aorta (REBOA) access was femoral cut-down (50%); US guided (10.9%) and percutaneous without imaging (28.3%). Deployment was achieved in Zones I (78.6%), II (2.4%), and III (19.0%). A second AO attempt was required in 9.6% [REBOA, 2 of 46 (4.3%); open OA, 9 of 68 (13.2%)]. Complications of REBOA were uncommon (pseudoaneurysm, 2.1%; embolism, 4.3%; limb ischemia, 0%). There was no difference in time to successful AO between REBOA and open procedures (REBOA, 6.6 ± 5.6 minutes; open OA, 7.2 ± 15.1; p = 0.842). Overall survival was 21.1% (24 of 114), with no significant difference between REBOA and open AO with regard to mortality [REBOA, 28.2% (13 of 46); open OA, 16.1% (11 of 68); p = 0.120]. CONCLUSION Resuscitative endovascular balloon occlusion of the aorta has emerged as a viable alternative to open AO in centers that have developed this capability. Further maturation of the American Association for the Surgery of Trauma Aortic Occlusion for Resuscitation in Trauma and Acute Care Surgery database is required to better elucidate optimal indications and outcomes. LEVEL OF EVIDENCE Therapeutic/care management study, level IV.

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.

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.

Open abdominal management after damage-control laparotomy for trauma: A prospective observational American Association for the Surgery of Trauma multicenter study

BACKGROUND We conducted a prospective observational multi-institutional study to examine the natural history of the open abdomen (OA) after trauma and identify risk factors for failure to achieve definitive primary fascial closure (DPC) after OA use in trauma. METHODS Adults requiring OA for trauma were enrolled during a 2-year period. Demographics, presentation, and management variables were used to compare primary fascial closure and non–primary fascial closure patients, with logistic regression used to identify independent risk factors for failure to achieve primary fascial closure. RESULTS A total of 572 patients from 14 American College of Surgeons–verified Level I trauma centers were enrolled. The majority were male (79%), mean (SD) age 39 (17) years. Injury Severity Score (ISS) was 15 or greater in 85% of patients and 84% had an abdominal Abbreviated Injury Scale (AIS) score of 3 or greater. Overall mortality was 23%. Initial primary fascial closure with unaltered native fascia was achieved in 379 patients (66%). Patients surviving at least 48 hours were grouped into those achieving DPC and those who did not achieve DPC after OA use. After logistic regression, independent risk factors for failure to achieve DPC included the number of reexplorations required (adjusted odds ratio [AOR], 1.3; 95% confidence interval (CI), 1.2–1.6; p < 0.001) the development of intra-abdominal abscess/sepsis (AOR, 2.4; 95% CI, 1.2–4.8; p = 0.011) bloodstream infection (AOR, 2.6; 95% CI, 1.2–5.7; p = 0.017), acute renal failure (AOR, 2.3; 95% CI, 1.2–5.7; p = 0.007), enteric fistula (AOR, 6.4; 95% CI, 1.2–32.8; p = 0.010) and ISS of greater than 15 (AOR, 2.5; 95% CI, 1.1–5.9; p = 0.037). CONCLUSION Our study identifies independent risk factors associated with failure to achieve primary fascial closure during initial hospitalization after OA use for trauma. Additional study is required to validate appropriate algorithms that optimize the opportunity to achieve primary fascial closure and outcomes in this population. LEVEL OF EVIDENCE Prognostic study, level III.

A prospective multicenter comparison of levetiracetam versus phenytoin for early posttraumatic seizure prophylaxis.

BACKGROUND Brain Trauma Foundation guidelines recommend seizure prophylaxis for preventing early posttraumatic seizure (PTS). Phenytoin (PHE) is commonly used. Despite a paucity of data in traumatic brain injury, levetiracetam (LEV) has been introduced as a potential replacement, which is more costly but does not require serum monitoring. The purpose of this study was to compare the efficacy of PHE with that of LEV for preventing early PTS. METHODS Consecutive blunt traumatic brain injury patients undergoing seizure prophylaxis were prospectively enrolled at two Level 1 trauma centers during a 33-month period. Seizure prophylaxis was administered according to local protocol. Patients were monitored prospectively throughout their hospital stay for clinical evidence of seizure activity. PHE was compared with LEV with clinical early PTS as the primary outcome measure, defined as a seizure diagnosed clinically, occurring within 7 days of admission. RESULTS A total of 1,191 patients were screened for enrollment, after excluding 378 (31.7%) who did not meet inclusion criteria; 813 (68.3%) were analyzed (406 LEV and 407 PHE). There were no significant differences between LEV and PHE in age (51.7 [21.3] vs. 53.6 [22.5], p = 0.205), male (73.9% vs. 68.8%, p = 0.108), Injury Severity Score (ISS) (20.0 [10.0] vs. 21.0 [10.6], p = 0.175), Marshall score of 3 or greater (18.5% vs. 14.7%, p = 0.153), or craniectomy (8.4% vs. 11.8%, p = 0.106). There was no difference in seizure rate (1.5% vs.1.5%, p = 0.997), adverse drug reactions (7.9% vs. 10.3%, p = 0.227), or mortality (5.4% vs. 3.7%, p = 0.236). CONCLUSION In this prospective evaluation of early PTS prophylaxis, LEV did not outperform PHE. Cost and need for serum monitoring should be considered in guiding the choice of prophylactic agent. LEVEL OF EVIDENCE Therapeutic study, level III.

Isolated severe traumatic brain injuries sustained during combat operations: demographics, mortality outcomes, and lessons to be learned from contrasts to civilian counterparts.

BACKGROUND Severe traumatic brain injuries occurring in the context of modern military conflict are entities about which little has been reported. We reviewed the epidemiology of these injuries from the Joint Trauma Theater Registry (JTTR), contrasting these results with civilian counterparts from the National Trauma Databank (NTDB). METHODS Isolated severe brain injuries (defined as head abbreviated injury scale [AIS] ≥3 and no other body region AIS>2) were queried from the JTTR over a period from 2003 to 2007. The demographics and outcomes of these injuries were reviewed. These results were then contrasted to findings of similar patients, age 18 years to 55 years, over the same period from the NTDB using propensity score matching derived from age, gender, systolic blood pressure, Glasgow Coma Scale, and AIS. RESULTS JTTR review identified 604 patients meeting study criteria, with a mean age of 25.7 years. Glasgow Coma Scale was ≤8 in 27.8%, and 98.0% were men. Hypotension at presentation was noted in 5.5%. Blast (61.9%) and gunshot wound (19.5%) mechanisms accounted for the majority of combat injuries. Intracranial pressure monitoring was used in 15.2%, and 27.0% underwent some form of operative cranial decompression, lobectomy, or debridement. When compared with matched civilian NTDB counterparts, JTTR patients were significantly more likely to undergo intracranial pressure monitoring (13.8% vs. 1.7%; p<0.001) and operative neurosurgical intervention (21.5% vs. 7.2%; p<0.001). Mortality was also significantly better among military casualties overall (7.7% vs. 21.0%; p<0.001; odds ratio, 0.32 [0.16-0.61]) and particularly after penetrating mechanisms of injury (5.6% vs. 47.9%; p<0.001; odds ratio, 0.07 [0.02-0.20]) compared with propensity score-matched NTDB counterparts. CONCLUSION Patients sustaining severe traumatic brain injury during military operations represent a unique population. Comparison with civilian counterparts has inherent limitations but reveals higher rates of neurosurgical intervention performed after penetrating injuries and a corresponding improvement in survival. Many factors likely contribute to these findings, which highlight the need for additional research on the optimal management of penetrating brain injury.