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Background: Traumatic haemorrhage is common after severe injury, leading to disability and death. Cryoprecipitate, a source of fibrinogen, may improve outcomes for patients with traumatic haemorrhage., Objective: To investigate the effects of early fibrinogen supplementation in the form of 3 pools (15 units, approximately 6 g of fibrinogen) of cryoprecipitate on 28-day mortality., Design: A randomised, parallel-group, unblinded, multicentre, international trial and economic evaluation. Patients were randomised to either the intervention (early cryoprecipitate) or the comparator (standard major haemorrhage protocol) arm via opaque, sealed envelopes in the emergency department or the transfusion laboratory/blood bank. All analyses were performed on an intention-to-treat basis. A cost-effectiveness analysis was undertaken., Setting: Twenty-five major trauma centres in the UK and one level 1 trauma centre in the USA., Participants: Adults who had traumatic haemorrhage following severe injury requiring activation of the major haemorrhage protocol and had received a blood transfusion., Intervention: Early cryoprecipitate - 3 pools (equivalent to 15 single units of cryoprecipitate or 6 g of fibrinogen supplementation), infused as rapidly as possible, within 90 minutes of arrival at hospital in addition to standard major haemorrhage protocol or standard major haemorrhage protocol only., Main Outcome Measures: The primary outcome was all-cause mortality at 28 days. The secondary outcomes were all-cause mortality at 6 hours, 24 hours, 6 months and 12 months from admission; death from bleeding at 6 hours and 24 hours; transfusion requirements at 24 hours from admission; destination of participant at discharge; quality-of-life measurements (EuroQol-5 Dimensions, five-level version and Glasgow Outcome Scale) at discharge/day 28 and 6 months after injury; and hospital resource use up to discharge or day 28 (including ventilator-days, hours spent in critical care and inpatient stays)., Results: Eight hundred and five patients were randomised to receive the standard major haemorrhage protocol (control arm). Seven hundred and ninety-nine patients were randomised to receive an additional three pools of cryoprecipitate in addition to standard care (intervention arm). Baseline characteristics appeared well matched. Patients had a median age of 39 (interquartile range 26-55) years, and the majority (79%) were male. All-cause 28-day mortality ( n  = 1531 patients; intention to treat) was 25.3% in the intervention arm compared with 26.1% in the control arm (odds ratio 0.96; p  = 0.74)., Limitations: There was variability in the timing of cryoprecipitate administration, with overlap between the treatment arms, limiting the degree of intervention separation., Conclusions: There was no evidence that early empiric administration of high-dose cryoprecipitate reduced the risk of death in unselected patients with traumatic haemorrhage. There was also no difference in adverse events. The cost-effectiveness of the intervention was similar to that of standard care., Future Work: Research to evaluate if fibrinogen replacement is more beneficial for selected patients, for example those with low fibrinogen blood levels, is needed, as is further exploration of whether there is a difference in outcome according to mechanism of injury., Trial Registration: This trial is registered as ISRCTN14998314., Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 15/57/02) and is published in full in Health Technology Assessment ; Vol. 28, No. 76. See the NIHR Funding and Awards website for further award information.

Introduction: With the use of resuscitative endovascular balloon occlusion of the aorta (REBOA) comes the potential for vascular access site complications (VASCs) and limb ischemic sequelae. We aimed to determine the prevalence of VASC and associated clinical and technical factors., Methods: A retrospective cohort analysis of 24-h survivors undergoing percutaneous REBOA via the femoral artery in the American Association for the Surgery of Trauma Aortic Occlusion for Resuscitation in Trauma and Acute care surgery registry between Oct 2013 and Sep 2021 was performed. The primary outcome was VASC, defined as at least one of the following: hematoma, pseudoaneurysm, arteriovenous fistula, arterial stenosis, or the use of patch angioplasty for arterial closure. Associated clinical and procedural variables were examined. Data were analyzed using Fisher exact test, Mann-Whitney-U tests, and linear regression., Results: There were 34 (7%) cases with VASC among 485 meeting inclusion criteria. Hematoma (40%) was the most common, followed by pseudoaneurysm (26%) and patch angioplasty (21%). No differences in demographics or injury/shock severity were noted between cases with and without VASC. The use of ultrasound (US) was protective (VASC, 35% versus no VASC, 51%; P = 0.05). The VASC rate in US cases was 12/242 (5%) versus 22/240 (9.2%) without US. Arterial sheath size >7 Fr was not associated with VASC. US use increased over time (R 2  = 0.94, P < 0.001) with a stable rate of VASC (R 2  = 0.78, P = 0.61). VASC were associated with limb ischemia (VASC, 15% versus no VASC, 4%; P = 0.006) and arterial bypass procedures (VASC 3% versus no VASC 0%; P < 0.001) but amputation was uncommon (VASC, 3% versus no VASC, 0.4%; P = 0.07)., Conclusions: Percutaneous femoral REBOA had a 7% VASC rate which was stable over time. VASC are associated with limb ischemia but need for surgical intervention and/or amputation is rare. The use of US-guided access appears to be protective against VASC and is recommended for use in all percutaneous femoral REBOA procedures., (Published by Elsevier Inc.)

Introduction: Severe COVID-19 illness can lead to thrombotic complications, organ failure, and death. Antithrombin (AT) regulates thromboinflammation and is a key component of chemical thromboprophylaxis. Our goal was to examine the link between AT activity and responsiveness to thromboprophylaxis, markers of hypercoagulability, and inflammation among severe COVID-19 patients., Methods: This was a single-center, prospective observational study enrolling SARS-CoV-2-positive patients admitted to the intensive care unit on prophylactic enoxaparin. Blood was collected daily for 7 days to assess AT activity and anti-factor Xa levels. Patient demographics, outcomes, and hospital laboratory results were collected. Continuous variables were compared using Mann-Whitney tests, and categorical variables were compared using χ2 tests. Multivariable logistic regression was used to determine the association between AT activity and mortality., Results: In 36 patients, 3 thromboembolic events occurred, and 18 (50%) patients died. Patients who died had higher fibrinogen, D-dimer, and C-reactive protein (CRP) levels and lower AT activity. Reduced AT activity was independently associated with mortality and correlated with both markers of hypercoagulability (D-dimer) and inflammation (CRP)., Conclusion: Low AT activity is associated with mortality and persistent hypercoagulable and proinflammatory states in severe COVID-19 patients. The anti-thromboinflammatory properties of AT make it an appealing therapeutic target for future studies., (© 2022 S. Karger AG, Basel.)

Importance: Venous thromboembolism (VTE) affects 2% to 20% of recovering trauma patients, despite aggressive prophylaxis with enoxaparin. Antithrombin is a primary circulating anticoagulant and crucial component of enoxaparin thromboprophylaxis. Approximately 20% of trauma patients present with antithrombin deficiency (antithrombin activity <80%)., Objective: To examine time-dependent changes in antithrombin activity, responsiveness to enoxaparin, as measured by anti-factor Xa (anti-FXa) levels, and incidence of VTE after severe trauma and to assess the association of ex vivo antithrombin supplementation with patients' sensitivity to enoxaparin prophylaxis., Design, Setting, and Participants: This single-center, prospective cohort study was performed at a level 1 trauma center between January 7, 2019, and February 28, 2020. Adult trauma patients admitted to the trauma service at high risk for VTE, based on injury pattern and severity, were screened and enrolled. Patients who were older than 70 years, were pregnant, had a known immunologic or coagulation disorder, or were receiving prehospital anticoagulants were excluded., Exposures: Blood samples were collected on emergency department arrival and daily for the first 8 days of hospitalization., Main Outcomes and Measures: Patients' antithrombin activity and anti-FXa levels were measured by a coagulation analyzer, and thrombin generation was measured by calibrated automated thrombography. Responsiveness to enoxaparin was assessed by measuring anti-FXa levels 4 to 6 hours after the first daily enoxaparin dose and compared between patients who developed VTE and who did not. In addition, the associations of ex vivo supplementation of antithrombin with plasma anti-FXa levels were assessed., Results: Among 150 patients enrolled (median [IQR] age, 35 [27-53] years; 37 [24.7%] female and 113 [75.3%] male; 5 [3.3%] Asian, 32 [21.3%] Black, and 113 [75.3%] White; and 51 [34.0%] of Hispanic ethnicity), 28 (18.7%) developed VTE. Patients with VTE had significantly lower antithrombin activity on admission compared with patients without VTE (median [IQR], 91% [79%-104%] vs 100% [88%-112%]; P = .04), as well as lower antithrombin activity on hospital days 5 (median (IQR), 90% [83%-99%] vs 114% [99%-130%]; P = .011), 6 (median [IQR], 97% [81%-109%] vs 123% [104%-134%]; P = .003), 7 (median [IQR], 82% [74%-89%] vs 123% [110%-140%]; P < .001), and 8 (median [IQR], 99% [85%-100%] vs 123% [109%-146%]; P = .011). Anti-FXa levels were significantly lower in patients with VTE vs those without VTE at hospital day 4 (median [IQR], 0.10 [0.05-0.14] IU/mL vs 0.18 [0.13-0.23] IU/mL; P = .006), day 6 (median [IQR], 0.12 [0.08-0.14] IU/mL vs 0.22 [0.13-0.28] IU/mL; P = .02), and day 7 (median [IQR], 0.11 [0.08-0.12] IU/mL vs 0.21 [0.13, 0.28] IU/mL; P = .002). Multivariable analyses found that for every 10% decrease in antithrombin activity during the first 3 days, the risk of VTE increased 1.5-fold., Conclusions and Relevance: The results of this cohort study suggest that after severe trauma, antithrombin deficiency is common and contributes to enoxaparin resistance and VTE. Interventional studies are necessary to determine the efficacy of antithrombin supplementation in the reduction of VTE incidence.

Background: Aortic occlusion (AO) to facilitate the acute resuscitation of trauma and acute care surgery patients in shock remains a controversial topic. Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) is an increasingly deployed method of AO. We hypothesized that in patients with non-compressible hemorrhage below the aortic bifurcation, the use of REBOA instead of open AO may be associated with a survival benefit., Methods: From the AAST Aortic Occlusion for Resuscitation in Trauma and Acute Care Surgery (AORTA) registry, we identified 1494 patients requiring AO from 45 Level I and 4 Level II trauma centers. Presentation, intervention, and outcome variables were analyzed to compare REBOA vs open AO in patients with non-compressible hemorrhage below the aortic bifurcation., Results: From December 2014 to January 2019, 217 patients with Zone 3 REBOA or Open AO who required pelvic packing, pelvic fixation or pelvic angio-embolization were identified. Of these, 109 AO patients had injuries isolated to below the aortic bifurcation (REBOA, 84; open AO, 25). Patients with intra-abdominal or thoracic sources of bleeding, above deployment Zone 3 were excluded. Overall mortality was lower in the REBOA group (35.% vs 80%, p <.001). Excluding patients who arrived with CPR in progress, the REBOA group had lower mortality (33.33% vs. 68.75%, p = 0.012). Of the survivors, systemic complications were not significantly different between groups. In the REBOA group, 16 patients had complications secondary to vascular access. Intensive care lengths of stay and ventilator days were both significantly shorter in REBOA patients who survived to discharge., Conclusions: This study compared outcomes for patients with hemorrhage below the aortic bifurcation treated with REBOA to those treated with open AO. Survival was significantly higher in REBOA patients compared to open AO patients, while complications in survivors were not different. Given the higher survival in REBOA patients, we conclude that REBOA should be used for patients with hemorrhagic shock secondary to pelvic trauma instead of open AO., Level Iii Evidence: Therapeutic., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to report. No financial support was received for the conduct of this study., (Copyright © 2022. Published by Elsevier Ltd.)

Background: Resuscitative endovascular balloon occlusion of the aorta (REBOA) is increasingly used in some trauma settings. Arterial access-related limb ischemic complications (ARLICs) resulting from the femoral arterial access required for REBOA are largely under reported. We sought to describe the incidence of these complications and the clinical, technical, and device factors associated with their development., Methods: This was a retrospective cohort study of records of adult trauma patients from the American Association for the Surgery of Trauma Aortic Occlusion for Resuscitation in Trauma and Acute care surgery registry between October 2013 and September 2020 who had REBOA and survived at least 48 hours. The primary outcome was ARLIC, defined as clinically relevant extremity ischemia or distal embolization. Relevant factors associated with ARLIC were also analyzed., Results: Of 418 identified patients, 36 (8.6%) sustained at least one ARLIC; 22 with extremity ischemia, 25 with distal embolism, 11 with both. Patient demographics and injury characteristics were similar between ARLIC and no ARLIC groups. Access-related limb ischemic complication was associated with larger profile devices (p = 0.009), cutdown access technique (p = 0.02), and the presence of a pelvic external fixator/binder (p = 0.01). Patients with ARLIC had higher base deficit (p = 0.03) and lactate (p = 0.006). One hundred fifty-six patients received tranexamic acid (TXA), with 22 (14%) ARLICs. The rate of TXA use among ARLIC patients was 61% (vs. 35% TXA for non-ARLIC patients, p = 0.002). Access-related limb ischemic complication did not result in additional in-hospital mortality, however, ARLIC had prolonged hospital LOS (31 vs. 24 days, p = 0.02). Five ARLIC required surgical intervention, three patch angioplasty (and two with associated bypass), and four ARLIC limbs were amputated., Conclusion: Femoral artery REBOA access carries a risk of ARLIC, which is associated with unstable pelvis fractures, severe shock, and strongly with the administration of TXA. Use of lower-profile devices and close surveillance for these complications is warranted in these settings and caution should be exercised when using TXA in conjunction with REBOA., Level of Evidence: Prognostic and Epidemiologic, Level III., (Copyright © 2021 American Association for the Surgery of Trauma.)

Objective: To describe the current use of the ER-REBOA catheter and associated outcomes and complications., Introduction: Noncompressible truncal hemorrhage is the leading cause of potentially preventable death in trauma patients. Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a novel strategy to obtain earlier temporary hemorrhage control, supporting cardiac, and cerebral perfusion before definitive hemostasis., Methods: Prospective, observational study conducted at 6 Level 1 Trauma Centers over 12-months. Inclusion criteria were age >15 years of age with evidence of truncal hemorrhage below the diaphragm and decision for emergent hemorrhage control intervention within 60 minutes of arrival. REBOA details, demographics, mechanism of injury, complications, and outcomes were collected., Results: A total of 8166 patients were screened for enrollment. In 75, REBOA was utilized for temporary hemorrhage control. Blunt injury occurred in 80% with a median injury severity score (ISS) 34 (21, 43). Forty-seven REBOAs were placed in Zone 1 and 28 in Zone 3. REBOA inflation increased systolic blood pressure from 67 (40, 83) mm Hg to 108 (90, 128) mm Hg 5 minutes after inflation (P = 0.02). Cardiopulmonary resuscitation was ongoing during REBOA insertion in 17 patients (26.6%) and 10 patients (58.8%) had return of spontaneous circulation after REBOA inflation. The procedural complication rate was 6.6%. Overall mortality was 52%., Conclusion: REBOA can be used in blunt and penetrating trauma patients, including those in arrest. Balloon inflation uniformly improved hemodynamics and was associated with a 59% rate of return of spontaneous circulation for patients in arrest. Use of the ER-REBOA catheter is technically safe with a low procedural complication rate., Competing Interests: The authors declare no conflict of interests., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Importance: Emergency research is challenging to do well as it involves time sensitive interventions in unstable patients. There is limited time to obtain informed consent from the patient or their legally authorized representative (LAR). Such research is permitted under exception from informed consent (EFIC) if specific criteria are met, including notification after enrollment. Some question whether the risks of EFIC outweighs its benefits. To date, there is limited empiric information about time to notification (TTN) and rates of withdrawal in such trials., Objective: To describe variation in TTN and rates of withdrawal among that patients enrolled in EFIC trials over a twelve-year period., Design: We performed post hoc descriptive analyses of data from five trials conducted under EFIC., Setting: Emergency medical services and receiving hospitals participating in the Resuscitation Outcomes Consortium in the United States and Canada., Participants: Patients with out-of-hospital cardiac arrest or life-threatening traumatic injury., Exposures: Notification strategies were specified at each site before initiation of enrollment by a local institutional review board. We monitored TTN within each site centrally throughout each study's enrollment period., Outcomes: TTN was defined as time from randomization to first-reported notification of patient or LAR of enrollment. Withdrawal was defined as patient or LAR opt out of ongoing participation at the time of notification., Results: Of 35,442 patients enrolled in five trials, 33,805 had cardiac arrest; and 1636 had traumatic injury. TTN varied overall and by patient outcome. Among those with cardiac arrest, TTN ranged from median (5%ile, 95%ile) of 6 (1,27) days to 28 (2, 53) days across sites. 0.3% of notified patients with cardiac arrest withdrew. Among those with traumatic injury, TTN ranged from 0 (0, 5) days to 36 (5, 68) days across sites. 7.7% of notified patients with traumatic injury withdrew., Conclusions and Relevance: There is large variation in TTN in trials conducted under EFIC for emergency research. This may be due to several factors. It may or may not be modifiable. Overall rates of withdrawal are low, which suggests current practices related to EFIC are acceptable to those who have participated in emergency research., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021. Published by Elsevier B.V.)

Introduction: Reliable, accurate, and non-invasive hemoglobin measurements would be useful in the trauma setting. The aim of this study was to re-examine the ability of the Masimo Radical 7 in this setting after recent hardware and software improvements., Methods: Level 1 Trauma patients were prospectively enrolled in the study over a 9-mo period with the goal of obtaining 3 paired data points from 150 patients admitted to the ICU or IMU. Hospital laboratory hemoglobin values were compared with cyanomethemoglobin (HiCN) and Masimo device hemoglobin (SpHb) values using comparison plots and Bland-Altman analysis., Results: A total of 380 patients were enrolled in the study with 150 of those being admitted to the ICU or IMU. Comparison of hospital lab hemoglobin and HiCN (n = 494) found a correlation of R2 = 0.92. Comparison of hospital lab hemoglobin and Masimo device hemoglobin (n = 218) found a correlation of R2 = 0.27. Bland-Altman analysis of the 218 of the comparable hospital hemoglobin and Masimo device hemoglobin values had a bias of 0.505 g/dL with 95% of values within the limits of agreement of 4.06 g/dL to -3.60 g/dL., Conclusions: The Masimo Radical 7 device has the potential to provide timely, useful clinical information, but it is not currently able to serve as an initial noninvasive diagnostic tool for trauma patients. There was poor correlation between clinical Hgb and SpHb, and because of that, SpHb should not be used to evaluate hemoglobin levels in trauma patients., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Backdrop: Clinicians intuitively recognize that faster time to hemostasis is important in bleeding trauma patients, but these times are rarely reported., Methods: Prospectively collected data from the Pragmatic Randomized Optimal Platelet and Plasma Ratios trial were analyzed. Hemostasis was predefined as no intraoperative bleeding requiring intervention in the surgical field or resolution of contrast blush on interventional radiology (IR). Patients who underwent an emergent (within 90 minutes) operating room (OR) or IR procedure were included. Mixed-effects Poisson regression with robust error variance (controlling for age, Injury Severity Score, treatment arm, injury mechanism, base excess on admission [missing values estimated by multiple imputation], and time to OR/IR as fixed effects and study site as a random effect) with modified Bonferroni corrections tested the hypothesis that decreased time to hemostasis was associated with decreased mortality and decreased incidence of acute kidney injury (AKI), acute respiratory distress syndrome (ARDS), multiple-organ failure (MOF), sepsis, and venous thromboembolism., Results: Of 680 enrolled patients, 468 (69%) underwent an emergent procedure. Patients with decreased time to hemostasis were less severely injured, had less deranged base excess on admission, and lower incidence of blunt trauma (all p < 0.05). In 408 (87%) patients in whom hemostasis was achieved, every 15-minute decrease in time to hemostasis was associated with decreased 30-day mortality (RR, 0.97; 95% confidence interval [CI], 0.94-0.99), AKI (RR, 0.97; 95% CI, 0.96-0.98), ARDS (RR, 0.98; 95% CI, 0.97-0.99), MOF (RR, 0.94; 95% CI, 0.91-0.97), and sepsis (RR, 0.98; 95% CI, 0.96-0.99), but not venous thromboembolism (RR, 0.99; 95% CI, 0.96-1.03)., Conclusion: Earlier time to hemostasis was independently associated with decreased incidence of 30-day mortality, AKI, ARDS, MOF, and sepsis in bleeding trauma patients. Time to hemostasis should be considered as an endpoint in trauma studies and as a potential quality indicator., Level of Evidence: Therapeutic/care management, level III.

Background: Exception from informed consent (EFIC) allows clinician scientists to perform much needed emergency research. Obtaining this exception, however, requires many meetings with community groups for consultation, which can make the process time-consuming and expensive. We aim to determine the impact of using social media in lieu of some community meetings in an effort to obtain an EFIC., Materials and Methods: An economic analysis of four randomized clinical trials was performed. Costs were conservatively estimated using personnel costs, social media costs, and adjusted to 2016 US dollars. People were considered reached if they attended a community meeting or were directed to the study website by social media and spent ≥1 min., Results: The Early Whole Blood study required 14 meetings, reached 272 people, and cost $8260 ($30/person reached). The Pragmatic, Randomized Optimal Platelet and Plasma Ratios study required 14 meetings, reached 260 people, and cost $7479 overall ($29/person reached). The Prehospital Tranexamic Acid Use for Traumatic Brain Injury study required 12 meetings, reached 198 people, and cost $6340 ($32/person reached). Only the damage control laparotomy trial utilized social media in lieu of some community meetings. The damage control laparotomy trial required six meetings at which 137 people were reached. The $1000 social media campaign reached 229 people. The cost was $3977 overall and $11/person reached., Conclusions: Including a social media campaign during the EFIC process increased the number of potential patients reached and reduced total and per person costs reached costs. Obtaining an EFIC for future emergency clinical trials may be facilitated by the inclusion of a social media campaign., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Laboratory-based evidence of coagulopathy (LC) is observed in 25-35% of trauma patients, but clinically-evident coagulopathy (CC) is not well described., Methods: Prospective observational study of adult trauma patients transported by helicopter from the scene to nine Level 1 trauma centers in 2015. Patients meeting predefined highest-risk criteria were divided into CC+ (predefined as surgeon-confirmed bleeding from uninjured sites or injured sites not controllable by sutures) or CC-. We used a mixed-effects, Poisson regression with robust error variance to test the hypothesis that abnormalities on rapid thrombelastography (r-TEG) and international normalized ratio (INR) were independently associated with CC+., Results: Of 1,019 highest-risk patients, CC+ (n=41, 4%) were more severely injured (median ISS 32 vs 17), had evidence of LC on r-TEG and INR, received more transfused blood products at 4 hours (37 vs 0 units), and had greater 30-day mortality (59% vs 12%) than CC- (n=978, 96%). The overall incidence of LC was 39%. 30-day mortality was 22% vs 9% in those with and without LC. In two separate models, r-TEG K-time >2.5 min (RR 1.3, 95% CI 1.1-1.7), r-TEG mA <55 mm (RR 2.5, 95% CI 2.0-3.2), platelet count <150 x 10 9 /L (RR 1.2, 95% CI 1.1-1.3), and INR >1.5 (RR 5.4, 95% CI 1.8-16.3) were independently associated with CC+. A combined regression model was not generated because too few patients underwent both r-TEG and INR., Conclusion: CC was rare compared to LC. CC was associated with poor outcomes and impairment of both clotting factor and platelet-mediated coagulation components., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Earlier use of in-hospital plasma, platelets, and red blood cells (RBCs) has improved survival in trauma patients with severe hemorrhage. Retrospective studies have associated improved early survival with prehospital blood product transfusion (PHT). We hypothesized that PHT of plasma and/or RBCs would result in improved survival after injury in patients transported by helicopter., Methods: Adult trauma patients transported by helicopter from the scene to nine Level 1 trauma centers were prospectively observed from January to November 2015. Five helicopter systems had plasma and/or RBCs, whereas the other four helicopter systems used only crystalloid resuscitation. All patients meeting predetermined high-risk criteria were analyzed. Patients receiving PHT were compared with patients not receiving PHT. Our primary analysis compared mortality at 3 hours, 24 hours, and 30 days, using logistic regression to adjust for confounders and site heterogeneity to model patients who were matched on propensity scores., Results: Twenty-five thousand one hundred eighteen trauma patients were admitted, 2,341 (9%) were transported by helicopter, of which 1,058 (45%) met the highest-risk criteria. Five hundred eighty-five of 1,058 patients were flown on helicopters carrying blood products. In the systems with blood available, prehospital median systolic blood pressure (125 vs 128) and Glasgow Coma Scale (7 vs 14) was significantly lower, whereas median Injury Severity Score was significantly higher (21 vs 14). Unadjusted mortality was significantly higher in the systems with blood products available, at 3 hours (8.4% vs 3.6%), 24 hours (12.6% vs 8.9%), and 30 days (19.3% vs 13.3%). Twenty-four percent of eligible patients received a PHT. A median of 1 unit of RBCs and plasma were transfused prehospital. Of patients receiving PHT, 24% received only plasma, 7% received only RBCs, and 69% received both. In the propensity score matching analysis (n = 109), PHT was not significantly associated with mortality at any time point, although only 10% of the high-risk sample were able to be matched., Conclusion: Because of the unexpected imbalance in systolic blood pressure, Glasgow Coma Scale, and Injury Severity Score between systems with and without blood products on helicopters, matching was limited, and the results of this study are inconclusive. With few units transfused to each patient and small outcome differences between groups, it is likely large, multicenter, randomized studies will be required to detect survival differences in this important population., Level of Evidence: Level II.

Background: Rational development of technology for rapid control of noncompressible torso hemorrhage (NCTH) requires detailed understanding of what is bleeding. Our objectives were to describe the anatomic location of truncal bleeding in patients presenting with NCTH and compare endovascular (ENDO) management versus open (OPEN) management., Methods: This is a retrospective study of adult trauma patients with NCTH admitted to four urban Level I trauma centers in the Houston and San Antonio metropolitan areas in 2008 to 2012. Inclusion criteria include named axial torso vessel disruption, Abbreviated Injury Scale chest or abdomen score of 3 or higher with shock (base excess, <-4) or truncal operation in 90 minutes or less, or pelvic fracture with ring disruption. Exclusion criteria include isolated hip fractures, falls from standing, or prehospital cardiopulmonary resuscitation. After dichotomizing into OPEN, ENDO, and resuscitative thoracotomy (RT) groups based on the initial approach to control NCTH, a mixed-effects Poisson regression with robust error variance (controlling for age, mechanism, Injury Severity Score, shock, hypotension, and severe head injury as fixed effects and site as a random effect) was used to test the hypothesis that ENDO was associated with reduced in-hospital mortality in NCTH patients., Results: Five hundred forty-three patients with NCTH underwent ENDO (n = 166, 31%), OPEN (n = 309, 57%), or RT (n = 68, 12%). Anatomic bleeding locations were 25% chest, 41% abdomen, and 31% pelvis. ENDO was used to treat relatively few types of vascular injuries, whereas OPEN and RT injuries were more diverse. ENDO patients had more blunt trauma (95% vs. 34% vs. 32%); severe injuries (median Injury Severity Score, 34 vs. 27 vs. 21), and increased time to intervention (median, 298 vs. 92 vs. 51 minutes) compared with OPEN and RT. Mortality was 15% versus 20% versus 79%. ENDO was associated with decreased mortality compared to OPEN (relative risk, 0.58; 95% confidence interval, 0.46-0.73)., Conclusion: Although ENDO may reduce mortality in NCTH patients, significant group differences limit the generalizability of this finding., Level of Evidence: Therapeutic, level V.

Background: Early identification of patients with pelvic fractures at risk of severe bleeding requiring intervention is critical. We performed a multi-institutional study to test our hypothesis that pelvic fracture patterns predict the need for a pelvic hemorrhage control intervention., Methods: This prospective, observational, multicenter study enrolled patients with pelvic fracture due to blunt trauma. Inclusion criteria included shock on admission (systolic blood pressure <90 mm Hg or heart rate >120 beats/min and base deficit >5, and the ability to review pelvic imaging). Demographic data, open pelvic fracture, blood transfusion, pelvic hemorrhage control intervention (angioembolization, external fixator, pelvic packing, and/or REBOA [resuscitative balloon occlusion of the aorta]), and mortality were recorded. Pelvic fracture pattern was classified according to Young-Burgess in a blinded fashion. Predictors of pelvic hemorrhage control intervention and mortality were analyzed by univariate and multivariate regression analyses., Results: A total of 163 patients presenting in shock were enrolled from 11 Level I trauma centers. The most common pelvic fracture pattern was lateral compression I, followed by lateral compression I, and vertical shear. Of the 12 patients with an anterior-posterior compression III fracture, 10 (83%) required a pelvic hemorrhage control intervention. Factors associated with the need for pelvic fracture hemorrhage control intervention on univariate analysis included vertical shear pelvic fracture pattern, increasing age, and transfusion of blood products. Anterior-posterior compression III fracture patterns and open pelvic fracture predicted the need for pelvic hemorrhage control intervention on multivariate analysis. Overall in-hospital mortality for patients admitted in shock with pelvic fracture was 30% and did not differ based on pelvic fracture pattern on multivariate analysis., Conclusion: Blunt trauma patients admitted in shock with anterior-posterior compression III fracture patterns or patients with open pelvic fracture are at greatest risk of bleeding requiring pelvic hemorrhage control intervention., Level of Evidence: Prognostic/epidemiologic study, level III.

Background: There is no consensus as to the optimal treatment paradigm for patients presenting with hemorrhage from severe pelvic fracture. This study was established to determine the methods of hemorrhage control currently being used in clinical practice., Methods: This prospective, observational multi-center study enrolled patients with pelvic fracture from blunt trauma. Demographic data, admission vital signs, presence of shock on admission (systolic blood pressure < 90 mm Hg or heart rate > 120 beats per minute or base deficit < -5), method of hemorrhage control, transfusion requirements, and outcome were collected., Results: A total of 1,339 patients with pelvic fracture were enrolled from 11 Level I trauma centers. Fifty-seven percent of the patients were male, with a mean ± SD age of 47.1 ± 21.6 years, and Injury Severity Score (ISS) of 19.2 ± 12.7. In-hospital mortality was 9.0 %. Angioembolization and external fixator placement were the most common method of hemorrhage control used. A total of 128 patients (9.6%) underwent diagnostic angiography with contrast extravasation noted in 63 patients. Therapeutic angioembolization was performed on 79 patients (5.9%). There were 178 patients (13.3%) with pelvic fracture admitted in shock with a mean ± SD ISS of 28.2 ± 14.1. In the shock group, 44 patients (24.7%) underwent angiography to diagnose a pelvic source of bleeding with contrast extravasation found in 27 patients. Thirty patients (16.9%) were treated with therapeutic angioembolization. Resuscitative endovascular balloon occlusion of the aorta was performed on five patients in shock and used by only one of the participating centers. Mortality was 32.0% for patients with pelvic fracture admitted in shock., Conclusion: Patients with pelvic fracture admitted in shock have high mortality. Several methods were used for hemorrhage control with significant variation across institutions. The use of resuscitative endovascular balloon occlusion of the aorta may prove to be an important adjunct in the treatment of patients with severe pelvic fracture in shock; however, it is in the early stages of evaluation and not currently used widely across trauma centers., Level of Evidence: Prognostic study, level II; therapeutic study, level III.

Background: The Pragmatic, Randomized Optimal Platelets and Plasma Ratios (PROPPR) trial was a randomized clinical trial comparing survival after transfusion of two different blood component ratios for emergency resuscitation of traumatic massive hemorrhage. Transfusion services supporting the study were expected to provide thawed plasma, platelets, and red blood cells within 10 minutes of request., Study Design and Methods: At the 12 Level 1 trauma centers participating in PROPPR, blood components transfused and delivery times were tabulated, with a focus on universal donor (UD) plasma management. The adequacy of site plans was assessed by comparing the bedside blood availability times to study goals and the new American College of Surgeons guidelines., Results: Eleven of 12 sites were able to consistently deliver 6 units of thawed UD plasma to their trauma-receiving unit within 10 minutes and 12 units in 20 minutes. Three sites used blood group A plasma instead of AB for massive transfusion without complications. Approximately 4700 units of plasma were given to the 680 patients enrolled in the trial. No site experienced shortages of AB plasma that limited enrollment. Two of 12 sites reported wastage of thawed AB plasma approaching 25% of AB plasma prepared., Conclusion: Delivering UD plasma to massively hemorrhaging patients was accomplished consistently and rapidly and without excessive wastage in high-volume trauma centers. The American College of Surgeons Trauma Quality Improvement Program guidelines for massive transfusion protocol UD plasma availability are practicable in large academic trauma centers. Use of group A plasma in trauma resuscitation needs further study., (© 2015 AABB.)

Background: In 2011, supported by data from two separate trauma centers, we implemented a protocol to administer tranexamic acid (TXA) in trauma patients with evidence of hyperfibrinolysis (HF) on admission. The purpose of this study was to examine whether the use of TXA in patients with HF determined by admission rapid thrombelastography was associated with improved survival., Methods: Following institutional review board approval, we evaluated all trauma patients 16 years or older admitted between September 2009 and September 2013. HF was defined as LY-30 of 3% or greater. Patients with LY-30 less than 3.0% were excluded. Patients were divided into those who received TXA (TXA group) and those who did not (no-TXA group). After univariate analyses, a purposeful, logistic regression model was developed a priori to evaluate the impact of TXA on mortality (controlling for age, sex, Injury Severity Score (ISS), arrival physiology, and base deficit)., Results: A total of 1,032 patients met study criteria. Ninety-eight (10%) received TXA, and 934 (90%) did not. TXA patients were older (median age, 37 years vs. 32 years), were more severely injured (median ISS, 29 vs. 14), had a lower blood pressure (median systolic blood pressure 103 mm Hg vs. 125 mm Hg), and were more likely to be in shock (median, base excess, -5 mmol/dL vs. -2 mmol/dL), all p < 0.05. Twenty-three percent of the patients had a repeat thrombelastography within 6 hours; 8.8% of the TXA patients had LY-30 of 3% or greater on repeat rapid thrombelastography (vs. 10.1% in the no-TXA group, p = 0.679). Unadjusted in-hospital mortality was higher in the TXA group (40% vs. 17%, p < 0.001). There were no differences in venous thromboembolism (3.3% vs. 3.8%). Logistic regression failed to find a difference in in-hospital mortality among those receiving TXA (odds ratio, 0.74; 95% confidence interval, 0.38-1.40; p 0.80)., Conclusion: In the current study, the use of TXA was not associated with a reduction in mortality. Further studies are needed to better define who will benefit from an administration of TXA., Level of Evidence: Therapeutic study, level IV.

Importance: Severely injured patients experiencing hemorrhagic shock often require massive transfusion. Earlier transfusion with higher blood product ratios (plasma, platelets, and red blood cells), defined as damage control resuscitation, has been associated with improved outcomes; however, there have been no large multicenter clinical trials., Objective: To determine the effectiveness and safety of transfusing patients with severe trauma and major bleeding using plasma, platelets, and red blood cells in a 1:1:1 ratio compared with a 1:1:2 ratio., Design, Setting, and Participants: Pragmatic, phase 3, multisite, randomized clinical trial of 680 severely injured patients who arrived at 1 of 12 level I trauma centers in North America directly from the scene and were predicted to require massive transfusion between August 2012 and December 2013., Interventions: Blood product ratios of 1:1:1 (338 patients) vs 1:1:2 (342 patients) during active resuscitation in addition to all local standard-of-care interventions (uncontrolled)., Main Outcomes and Measures: Primary outcomes were 24-hour and 30-day all-cause mortality. Prespecified ancillary outcomes included time to hemostasis, blood product volumes transfused, complications, incidence of surgical procedures, and functional status., Results: No significant differences were detected in mortality at 24 hours (12.7% in 1:1:1 group vs 17.0% in 1:1:2 group; difference, -4.2% [95% CI, -9.6% to 1.1%]; P = .12) or at 30 days (22.4% vs 26.1%, respectively; difference, -3.7% [95% CI, -10.2% to 2.7%]; P = .26). Exsanguination, which was the predominant cause of death within the first 24 hours, was significantly decreased in the 1:1:1 group (9.2% vs 14.6% in 1:1:2 group; difference, -5.4% [95% CI, -10.4% to -0.5%]; P = .03). More patients in the 1:1:1 group achieved hemostasis than in the 1:1:2 group (86% vs 78%, respectively; P = .006). Despite the 1:1:1 group receiving more plasma (median of 7 U vs 5 U, P < .001) and platelets (12 U vs 6 U, P < .001) and similar amounts of red blood cells (9 U) over the first 24 hours, no differences between the 2 groups were found for the 23 prespecified complications, including acute respiratory distress syndrome, multiple organ failure, venous thromboembolism, sepsis, and transfusion-related complications., Conclusions and Relevance: Among patients with severe trauma and major bleeding, early administration of plasma, platelets, and red blood cells in a 1:1:1 ratio compared with a 1:1:2 ratio did not result in significant differences in mortality at 24 hours or at 30 days. However, more patients in the 1:1:1 group achieved hemostasis and fewer experienced death due to exsanguination by 24 hours. Even though there was an increased use of plasma and platelets transfused in the 1:1:1 group, no other safety differences were identified between the 2 groups., Trial Registration: clinicaltrials.gov Identifier: NCT01545232.

Abstract Objective. Earlier use of plasma and red blood cells (RBCs) has been associated with improved survival in trauma patients with substantial hemorrhage. We hypothesized that prehospital transfusion (PHT) of thawed plasma and/or RBCs would result in improved patient coagulation status on admission and survival. Methods. Adult trauma patient records were reviewed for patient demographics, shock, coagulopathy, outcomes, and blood product utilization from September 2011 to April 2013. Patients arrived by either ground or two different helicopter companies. All patients transfused with blood products (either pre- or in-hospital) were included in the study. One helicopter system (LifeFlight, LF) had thawed plasma and RBCs while the other air (OA) and ground transport systems used only crystalloid resuscitation. Patients receiving PHT were compared with all other patients meeting entry criteria to the study cohort. All comparisons were adjusted in multilevel regression models. Results. A total of 8,536 adult trauma patients were admitted during the 20-month study period, of which 1,677 met inclusion criteria. They represented the most severely injured patients (ISS = 24 and mortality = 26%). There were 792 patients transported by ground, 716 by LF, and 169 on OA. Of the LF patients, 137 (19%) received prehospital transfusion. There were 942 units (244 RBCs and 698 plasma) placed on LF helicopters, with 1.9% wastage. PHT was associated with improved acid-base status on hospital admission, decreased use of blood products over 24 hours, a reduction in the risk of death in the sickest patients over the first 6 hours after admission, and negligible blood products wastage. In this small single-center pilot study, there were no differences in 24-hour (odds ratio 0.57, p = 0.117) or 30-day mortality (odds ratio 0.71, p = 0.441) between LF and OA. Conclusions. Prehospital plasma and RBC transfusion was associated with improved early outcomes, negligible blood products wastage, but not an overall survival advantage. Similar to the data published from the ongoing war, improved early outcomes are associated with placing blood products prehospital, allowing earlier infusion of life-saving products to critically injured patients.

Objective: Complex dismounted blast injuries from (improvised) explosive devices have caused amputations of the lower extremities associated with open injuries to the pelvic ring, resulting in life-threatening hemorrhage from disruption of blood vessels near the pelvic ring. Provisional stabilization of the skeletal pelvis by circumferential pelvic compression provides stability for intrapelvic clots and reduces the volume of the pelvis, thereby limiting the amount of hemorrhage. The Junctional Emergency Treatment Tool (JETTtm; North American Rescue Products, http://www.narescue.com) is a junctional hemorrhage control device developed to treat pelvic and lower extremity injuries sustained in high-energy trauma on the battlefield and in the civilian environment. Our purpose was to evaluate the compressive function of the JETT in the reduction of pelvic ring injuries in a cadaveric model., Methods: Radiographic comparison of pre (intact) and post pelvic ring disruption and injury was compared with radiographic measurements post reduction with the JETT device in two cadavers. The device's ability to reduce pelvic disruption and injury in a human cadaver model was assessed through measurements of the anteroposterior (AP) and transverse diameters obtained at the inlet and outlet of the pelvis., Results: Computed tomography (CT) scans demonstrated that JETT application effectively induced circumferential soft tissue compression that was evoked near anatomic reduction of the sacroiliac joint and symphysis pubis., Conclusions: The JETT is capable of effectively reducing an AP compression type III injury (APC III) pelvic ring disruption and injury by approximating the inlet and outlet dimensions toward predisruption measurements. Such a degree of reduction suggests that the JETT device may be suitable in the acute setting for provisional pelvic stabilization., (2014.)

Background: Forty percent of in-hospital deaths among injured patients involve massive truncal haemorrhage. These deaths may be prevented with rapid haemorrhage control and improved resuscitation techniques. The Pragmatic Randomized Optimal Platelet and Plasma Ratios (PROPPR) Trial was designed to determine if there is a difference in mortality between subjects who received different ratios of FDA approved blood products. This report describes the design and implementation of PROPPR., Study Design: PROPPR was designed as a randomized, two-group, Phase III trial conducted in subjects with the highest level of trauma activation and predicted to have a massive transfusion. Subjects at 12 North American level 1 trauma centres were randomized into one of two standard transfusion ratio interventions: 1:1:1 or 1:1:2, (plasma, platelets, and red blood cells). Clinical data and serial blood samples were collected under Exception from Informed Consent (EFIC) regulations. Co-primary mortality endpoints of 24h and 30 days were evaluated., Results: Between August 2012 and December 2013, 680 patients were randomized. The overall median time from admission to randomization was 26min. PROPPR enrolled at higher than expected rates with fewer than expected protocol deviations., Conclusion: PROPPR is the largest randomized study to enrol severely bleeding patients. This study showed that rapidly enrolling and successfully providing randomized blood products to severely injured patients in an EFIC study is feasible. PROPPR was able to achieve these goals by utilizing a collaborative structure and developing successful procedures and design elements that can be part of future trauma studies., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: Despite a well-described association of age and injury with mortality and decreased functional status, inpatient mortality studies have traditionally not included analysis of do not resuscitate (DNR) status. We hypothesized that the increased likelihood of DNR status in older patients alters age-adjusted mortality rates in trauma., Methods: The trauma registry was queried for adult patients admitted to our Level I trauma center (January 2005-December 2008) and divided into eight age groups by decade. Ages 15-44 years were collapsed because of the lack of variation. We compared age, case fatality rate, and DNR status by univariate analysis and trends by χ (p < 0.05)., Results: Of the 15,227 adult patients admitted, 13% were elderly (≥65) and 7% died. DNR status was known in 75% of deaths, and 42% of those had active DNR orders on the chart at time of death. DNR likelihood increased with age (p < 0.05), from 5% to 18%. With DNRs excluded, mortality variability across all ages was markedly diminished (4-7%)., Conclusion: DNR status among trauma patients varies significantly because of inconsistent implementation and meaning between hospitals, and successive decades are more likely to have an active DNR order at time of death. When DNR patients were excluded from mortality analysis, age was minimally associated with an increased risk of death. The inclusion of DNR patients within mortality studies likely skews those analyses, falsely indicating failed resuscitative efforts rather than humane decisions to limit care after injury.

Aim: Early death due to hemorrhage is a major consequence of traumatic injury. Transfusion practices differ among hospitals and it is unknown which transfusion practices improve survival. This report describes the experience of the PRospective Observational Multicenter Major Trauma Transfusion (PROMMTT) Study Data Coordination Center in designing and coordinating a study to examine transfusion practices at ten Level 1 trauma centers in the US., Methods: PROMMTT was a multisite prospective observational study of severely injured transfused trauma patients. The clinical sites collected real-time information on the timing and amounts of blood product infusions as well as colloids and crystalloids, vital signs, initial diagnostic and clinical laboratory tests, life saving interventions and other clinical care data., Results: Between July 2009 and October 2010, PROMMTT screened 12,561 trauma admissions and enrolled 1245 patients who received one or more blood transfusions within 6h of Emergency Department (ED) admission. A total of 297 massive transfusions were observed over the course of the study at a combined rate of 5.0 massive transfusion patients/week., Conclusion: PROMMTT is the first multisite study to collect real-time prospective data on trauma patients requiring transfusion. Support from the Department of Defense and collaborative expertise from the ten participating centers helped to demonstrate the feasibility of prospective trauma transfusion studies. The observational data collected from this study will be an invaluable resource for research in trauma surgery and it will guide the design and conduct of future randomized trials., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)